Newmark, J. Therapy for nerve agent poisoning. Arch Neurol 2004; 61:649-652
Nerve agents include tabun (GA), sarin (GB), soman (GD), cyclosarin (GF) and VX. All evaporate and are gone within 24 hours, except VX which is oily and the only one which is persistent. VX is the most lethal substance known to man. The drugs were weaponized in Nazi Germany, used by Iraq against Iran in the Iraq-Iran war, and used in 2 subway attacks in Japan in 1994-5.
Clinical scenario-- in a shopping mall, you hear a "pop" and see smoke, your vision dims and nose runs severely. People may collapse, breathing heavily or seizing, with constricted pupils.
The mechanism is similar to organophosphate pesticides, although they are much less fat soluble and therefore more toxic. Theyinhibit AchE, acetylcholinesterase, producing a cholinergic crisis. Most exposures occur through the vapor route and act within seconds to minutes. The initial symptoms are miosis and rhinorhhea and salivation. Later, brochorrhea and bronchospasm occur. They are absorbed at the alveoli, and although they are not important clinically, the gold standard of diagnosis is RBC AChE. Circulating toxin first affects the GIT causing cramping, pain, nausea and defecation. It will affect the heart variably with unpredictable effects on BP and HR. They cause massive overstimulation of peripheral neuromuscular synapses witha progression from fasciculation to twitching that may be misinterpreted as a seizure. When ATP is depleted (a late finding) the patient will eventually have flaccid paralysis. Rapid CND cholinergic stimulation will cause LOC, seizures, inhibition of medullary respiratory center with central apnea. Death is due to respiratory failure (combined) due to bronchospasm, bronchorhhea, inadequate function of respiratorymuscles, and central apnea.
Liquid exposure has a longer slower onset and offset than vapor. Skin decontamination may not suffice if not done immediately, as nerve agent may be trapped subcutaneously and continue to penetrate.
Patients recovered frommild poisoning have a neurobehavioral syndrome including HA, personalitychange, depression, and higher order problemswith memory and reading. It may resemblePTSD or postanoxic encephalopathy. Chronic effects are few, with one report of a PN and a few of vestibular problems.
THERAPY:
Ventilatory support can be lifesaving even for someone in full arrest, if an antidote is given. Treatment has not changed since 1945 and includes an anticholinergic drug to counteract crisis, an oxime to reactivate inhibited AChE, and an AED to prevent seizures. In the field,atropine is used with i-m autoinjectorswith an initial therapy of 2,4,or 6 mg with retreatment every 5-10 minutes as needed. 0.5 or 1.0 mg ampules are available for children. In the hospital it may be given intravenously. Atropine binds to muscarinicreceptorsbut not nicotinic receptors, so twitching and dyscoordination will continue. The respiratory problems are life threatening and atropine saves lives,per the Iranian experience.
The fielded oxime is 2-pralidoximm chloride (2 PAM). The i-m dose is 600 mg per autoinjector. The upper limit is 2000 mg/hr due to the risk of sudden elevation of blood pressure. Oximes reactivate catalytic cholinesterase and simultaenously split nerve agent or organophosphate insectisides into harmless, rapidly metabolized fragments. After nerve agent binds AChE , the resultant complex spontaneously loses a side chain ("aging") rendering the remaining enzyme-inhibitor complex unable to be reactivated by oxime. Most nerve agents age slowly and the reaction can be ignores (sarin over hours, VX over days to weeks) but soman over two minutes. Once the complex has aged, the oximes are useless although not harmful to the patient.
The MARK 1 set (Meridian Medical Technologies, Columbia, MS) has a 2 mg atropine and 600 mg 2-PAM autoinjectors and is already approved by the FDA for the general use.
Standard AED's (antiepileptic drugs) are not useful for seizures due to nerve agents. Only benzodiazepines are effective. The military uses diazepam 10mg autoinjectors. Midazolam is the most effective, given i-v, in terms of speed of actions, low dose required, and broad spectrum. Epilepsy does not develop and chonic AED's are not advised.
The fourth drug available is pyridostigmine bromide, which may be useful if soldiers are concerned about a rapidly aging poison (soman) . Pyridostigmine will sequester a percentage of the patients excess AChE and render it unavailable to be irreversibly inhibited by a a nerve agent. Therefore a lethal dose becomes survivable with antidotes.
Care must be provided inthe field, not in the hospital (too late). Additional information is available at the chemical casualty division website at http://ccc.apgea.army.mil or the Army Medical Research Institute of Chemical Defense at (410) 436-3276.
Sunday, December 02, 2007
Multiple auras: clinical significanceand pathophysiology
Widdiss-Walsh P, Kotagel P et al. Multiple auras: clinical significance and pathophysiology. Neurology 2007; 69:755-761.
Ninety percent of those with two aura types and 100 % of those with three aura types have right hemisphere localization of their seizures. Some examples were rising epigastric sensation with a simultaneous unpleasant odor or visual field distortion. Multiple auras previously are considered commoner in in patients "alien tissue" (v. mesial temporal sclerosis).
Ninety percent of those with two aura types and 100 % of those with three aura types have right hemisphere localization of their seizures. Some examples were rising epigastric sensation with a simultaneous unpleasant odor or visual field distortion. Multiple auras previously are considered commoner in in patients "alien tissue" (v. mesial temporal sclerosis).
Thursday, November 15, 2007
Miscellaneous drug facts most people do not know
Antiepileptic drug random facts
1. Phenytoin (more misc. on than we already new)- a. increases HDL levels.
b. Formula to adjust PTN dose. In zero order kinetics, a fixed AMOUNT not percentage of phenytoin is metabolized. Vd= .7 L/kg Loading dose = (Vd) x (desired change in concentration) so eg. raise the level from 5 to 18 in a 100 kg man would mean Vd=70L, loading dose = 70 x 13= 910 mg. Phenytoin is saturably absorbed in duodenum and affected by food and by antacids
2. Cerebyx has the same Tmax as Dilantin due to time required to cleave the "fos" of fos phenytoin. Cerebyx also has some cardiac toxicity despite the absent phenylene glycol adjuvant. Infusion can be faster than Dilantin but not more than 150 mg/min. It prevents the purple glove but not time to treat SE.
3. PTN, CBZ and PB block efficacy of some chemotherapeutic agents (see post)http://neurologyminutiae.blogspot.com/2007/11/drug-interactionsenzyme-inducers-and.html
4. Depakote
a. may be useful in brain tumor treatment irrespective of AED effect (see post) http://neurologyminutiae.blogspot.com/2007/07/valproic-acid-and-brain-tumors.html
b. Depakote is highly bound but not to albumen; and free levels are difficult to measure. Its level rises in cirrhosis. Its path is 80 % direct glucuronidation, 17 % is in same oxidative path as free fatty acids and enters the carnitine shuffle, leading to 4, en VPA. Many ICU patients are carnitine deficient which shunts VPA to toxic metabolism so give these patients carnitine 25 mg/kg png over six hours leads to less NH4+.
5. Vimpat can cause angioedema
DRUGS FOR DEMENTIA
1. Rivastigmine patches can be left on for more than 24 hours as they have a 24 hour half life (in effect, patients are throwing away active drug). Wearing multiple patches, duly labelled, is one way to dispense a higher dose, usually with limited adverse effects
2. Memantine has histamine blocking properties and its use may limit GI adverse events of individuals taking rivastigmine or other drugs.
3. Cholinesterase inhibitors inhibit metabolism of suxamethonium, prolonging neuromuscular blockade
OTHER
1. Prazosin is highly effective for post-traumatic stress disorder
2. Levodopa-carbidopa and gabapentin are two rare drugs that are gastric absorbed and in fact compete with each other. Better to stop the gabapentin in Parkinson patients.3. Protease inhibitors potentiate toxicity of GHB, so HIV patients attending circuit parties are at extra high risk of coma and death.
4. Drug rash to Sinemet is due to yellow dye not levodopa carbidopa (see post) http://neurologyminutiae.blogspot.com/2007/04/rash-to-yellow-dye-in-levodopa.html
5. Natalizumab also blocks trafficking of B cells into CNS
6. . Atorvastatin, even brief exposure, causes a marked decrease in blood Co Q 10 concentration (shares the synthetic pathway of cholesterol). Primary CoQ10 deficiency causes mitochondrial encephalomyopathy with recurrent myoglobinuria; this may pertain to AE's of atorvastatin. Also, CoQ10 is an excellent free radical scavenger and the effects on degenerative disease are not known. Rundek et al,. Arch Neurol 2004; 61: 889-892.
1. Phenytoin (more misc. on than we already new)- a. increases HDL levels.
b. Formula to adjust PTN dose. In zero order kinetics, a fixed AMOUNT not percentage of phenytoin is metabolized. Vd= .7 L/kg Loading dose = (Vd) x (desired change in concentration) so eg. raise the level from 5 to 18 in a 100 kg man would mean Vd=70L, loading dose = 70 x 13= 910 mg. Phenytoin is saturably absorbed in duodenum and affected by food and by antacids
2. Cerebyx has the same Tmax as Dilantin due to time required to cleave the "fos" of fos phenytoin. Cerebyx also has some cardiac toxicity despite the absent phenylene glycol adjuvant. Infusion can be faster than Dilantin but not more than 150 mg/min. It prevents the purple glove but not time to treat SE.
3. PTN, CBZ and PB block efficacy of some chemotherapeutic agents (see post)http://neurologyminutiae.blogspot.com/2007/11/drug-interactionsenzyme-inducers-and.html
4. Depakote
a. may be useful in brain tumor treatment irrespective of AED effect (see post) http://neurologyminutiae.blogspot.com/2007/07/valproic-acid-and-brain-tumors.html
b. Depakote is highly bound but not to albumen; and free levels are difficult to measure. Its level rises in cirrhosis. Its path is 80 % direct glucuronidation, 17 % is in same oxidative path as free fatty acids and enters the carnitine shuffle, leading to 4, en VPA. Many ICU patients are carnitine deficient which shunts VPA to toxic metabolism so give these patients carnitine 25 mg/kg png over six hours leads to less NH4+.
5. Vimpat can cause angioedema
DRUGS FOR DEMENTIA
1. Rivastigmine patches can be left on for more than 24 hours as they have a 24 hour half life (in effect, patients are throwing away active drug). Wearing multiple patches, duly labelled, is one way to dispense a higher dose, usually with limited adverse effects
2. Memantine has histamine blocking properties and its use may limit GI adverse events of individuals taking rivastigmine or other drugs.
3. Cholinesterase inhibitors inhibit metabolism of suxamethonium, prolonging neuromuscular blockade
OTHER
1. Prazosin is highly effective for post-traumatic stress disorder
2. Levodopa-carbidopa and gabapentin are two rare drugs that are gastric absorbed and in fact compete with each other. Better to stop the gabapentin in Parkinson patients.3. Protease inhibitors potentiate toxicity of GHB, so HIV patients attending circuit parties are at extra high risk of coma and death.
4. Drug rash to Sinemet is due to yellow dye not levodopa carbidopa (see post) http://neurologyminutiae.blogspot.com/2007/04/rash-to-yellow-dye-in-levodopa.html
5. Natalizumab also blocks trafficking of B cells into CNS
6. . Atorvastatin, even brief exposure, causes a marked decrease in blood Co Q 10 concentration (shares the synthetic pathway of cholesterol). Primary CoQ10 deficiency causes mitochondrial encephalomyopathy with recurrent myoglobinuria; this may pertain to AE's of atorvastatin. Also, CoQ10 is an excellent free radical scavenger and the effects on degenerative disease are not known. Rundek et al,. Arch Neurol 2004; 61: 889-892.
A 16 year old girl with progressive weakness of the let leg
Hahn AF, Mauermann ML, Dyck PJB, Keegan BM/ CPC. Neurology2007;69:84-90. Insidious onset of left LE weakness started at age 13, progressing to complete footdrop. She had normal sensation and reflexes. She had gobs of negative tests. Motor exam showed mild weakness in posterior tibialis and hamstring, severe weakness in the tibialis anterior, to extensors and peroneii, and normal gastrocnemius and toe flexors. She had mild pes cavus. EMG showed normal left tibial nerve conductions, left peroneal motor and surals were absent or severely abnormal. Needle testing showed marked denervation distal to the short head of the biceps. QST's were normal. MRI showed mild increase int he size and signal intensity of the left peroneal nerve in the peroneal division only. Anatomic localization implicated the common peroneal nerve or divisional sciatic nerve. Discussant notes that the tibial and peroneal divisions of the sciatic nerve are segregated as the sciatic nerve passes from the sciatic notch, so a sciatic lesion can mimic a peroneal neuropathy. In such cases needle EMG of the short head of the biceps is crucial. MRI neuronography showed enlarged peroneal nerve ipsilaterally. The diagnosis on biopsy of the nerve was intraneural perineuroma (aka localized hypertrophic mononeuropathy). It presents as a painless motor mononeuropathy in younger patients in a variety of nerves (posterior interosseous, radial ulnar). MRI differentiates from fibrolipomatous hamartoma, but not intraneural ganglion cysts. Intraoperatively, internal neurolysis can suggest the diagnosis also. Unlike true onion bulbs, which are S100 positive, these are S100 negative and EMA positive.
Friday, November 09, 2007
SSPE
Cole AJ, Henson JW, Roehrl MHA et al. Case 24-1007: A 20 year old pregnant woman with altered mental status. NEJM 2007; 357: 589-600.
Case showed a young pregnant woman with clinical presentation of aseptic meningitis: confusion, lymphocytic pleocytosis in CSF, FIRDA on EEG, ,MRI showing dysfunction in a non hSVE pattern affecting internal capsule and cerebellar outflow tract, gads of negative tests. MRI affected left temporal lobe and pons. The patient had chorea which brought up Strep infection and Syndenham's chorea but ASO was only minimally positive and ACL's were negative. There was marked increase in CSF IgG levels, IgG index and oligoclonal bands. According to Dr. Cole, that narrowed it to syphilis, chronic rubella encephalitis, and SSPE.
Measles causes 3 different CNS diseases: postinfectious encephalomyelitis, subacute measles encephalitis, and SSPE. SSPE occurs 7-10 years after infection with behavioral changes, headache, adventitious movements, and sometimes seizures. Myoclonic jerks and PLEDs on EEG may occur. It may occur from childhood until fifth decade of life. It persists in places where measles vaccination remains uncommon. It is more common if measles occurred at age < 2 years, and may be more common in pregnancy. The diagnostic test is measles specific CSF IgG antibody index compared to serum. Iit maybe compared to a control infection such as mumps. This patients was treated with interferon and pranobex for eight weeks, delivered a healthy baby and then expired. SSPE is considered almost always a progressive disease. This patient may have shown signs in a prior pregnancy of a movement disorder.
Case showed a young pregnant woman with clinical presentation of aseptic meningitis: confusion, lymphocytic pleocytosis in CSF, FIRDA on EEG, ,MRI showing dysfunction in a non hSVE pattern affecting internal capsule and cerebellar outflow tract, gads of negative tests. MRI affected left temporal lobe and pons. The patient had chorea which brought up Strep infection and Syndenham's chorea but ASO was only minimally positive and ACL's were negative. There was marked increase in CSF IgG levels, IgG index and oligoclonal bands. According to Dr. Cole, that narrowed it to syphilis, chronic rubella encephalitis, and SSPE.
Measles causes 3 different CNS diseases: postinfectious encephalomyelitis, subacute measles encephalitis, and SSPE. SSPE occurs 7-10 years after infection with behavioral changes, headache, adventitious movements, and sometimes seizures. Myoclonic jerks and PLEDs on EEG may occur. It may occur from childhood until fifth decade of life. It persists in places where measles vaccination remains uncommon. It is more common if measles occurred at age < 2 years, and may be more common in pregnancy. The diagnostic test is measles specific CSF IgG antibody index compared to serum. Iit maybe compared to a control infection such as mumps. This patients was treated with interferon and pranobex for eight weeks, delivered a healthy baby and then expired. SSPE is considered almost always a progressive disease. This patient may have shown signs in a prior pregnancy of a movement disorder.
Saturday, November 03, 2007
Drug interactions,enzyme inducers and anticancer
PTN, CBZ and PB induce cytochome P450 and reduces bioavailability of many chemotherapeutic drugs and warfarin. The former include camptothecins (topotecan and irinotecan) and taxanes (paclitaxol).
Mayo Clin Prcds combination of risperidol and gingko caused priaprism
Mayo Clin Prcds combination of risperidol and gingko caused priaprism
Friday, July 06, 2007
Valproic acid and brain tumors
Besides its antiepileptic effects, valproic acid promotes differentiation of neurons into mature cell liens and inhibits proliferation of neuroectodermal lines. This has led to the use of valproic acid in pediatric patients who are s/p chemotherapy and radiation therapy for malignant glioma (Driever etal. al Klin Ped 1999; 21:323-8). Valproic acide also inhibits histone deacetylases, as do topamax and one of the metabolites of levitiracetam (PBA).
MGMT gene silencing and temozolamide in GBM
Hegi et al. NEJM 2005; 352:997-1003
Epigenetic gene silencing of the MGMT (06 methylguanine DNA methyltransferase) DNA repair gene by promoter methylation compromises DNA repair and is associated with longer survival in GBM patients receiving chemotherapy. This was also found to be true in radiotherapy; patietns with a methylated MGMT promoter had a survival benefit.
Epigenetic gene silencing of the MGMT (06 methylguanine DNA methyltransferase) DNA repair gene by promoter methylation compromises DNA repair and is associated with longer survival in GBM patients receiving chemotherapy. This was also found to be true in radiotherapy; patietns with a methylated MGMT promoter had a survival benefit.
Oligodendroglioma: towards definition and treatment
Reifenberger G, Louis DN. Oligodendroglioma: towards molecular definitions in diagnostic neurooncology. Journal of Neuropathology and Experimental Neurology. 2003; 62:111-126.
Since 1988 the treatment options have differed for different types of gliomas. Recurrent anaplastic astrocytomas sometimes respond dramatically to PCV (procarbazine, lomustine and vincristine). Since 1990 the same is true for newly diagnosed analplastic oligodendrogliomas. The response may be durable and may also occur with temozolomide, an oral agent.
Diagnostic markers such as Olig1 and Olig2 are not reliable. Microtubule associated protein (MAP2) is not specific although it is sensitive. In 1998 Cairncross reported response to chemo is strongly related to allelic losses on 1p or 19q in resected tumor tissue. The correspond to WHO grade II tumors. Testing is performed at a few specialized labs and is not considered routine. At MGH LOH 1p and 19q testing costs $800. In another study, Kim and Kim (Acta Neuropath 2005) found two light microscopy histological features, tumor cellularity and perinuclear halo were associated with the two markers above.
Since 1988 the treatment options have differed for different types of gliomas. Recurrent anaplastic astrocytomas sometimes respond dramatically to PCV (procarbazine, lomustine and vincristine). Since 1990 the same is true for newly diagnosed analplastic oligodendrogliomas. The response may be durable and may also occur with temozolomide, an oral agent.
Diagnostic markers such as Olig1 and Olig2 are not reliable. Microtubule associated protein (MAP2) is not specific although it is sensitive. In 1998 Cairncross reported response to chemo is strongly related to allelic losses on 1p or 19q in resected tumor tissue. The correspond to WHO grade II tumors. Testing is performed at a few specialized labs and is not considered routine. At MGH LOH 1p and 19q testing costs $800. In another study, Kim and Kim (Acta Neuropath 2005) found two light microscopy histological features, tumor cellularity and perinuclear halo were associated with the two markers above.
Sunday, June 17, 2007
Saturday, May 19, 2007
Listeria encephalitis
case discussion in Reviews in Neurological Diseases. The typical presentation is rhombencephalitis with a fever. It affects often pons and medulla in middle aged adults who are not immunocompromised. The prodrome is low grade fever, headache, encephalitis, vomiting and malaise lasting up to two weeks, followed by abrupt onset of cranial nerve palsies and encephalopathy. The cranial nerve palsies are often strikingly assymetric. The most common findings are dysphagia, dysphonia, dysarthria, facial weakness, diplopia and nystagmus. INO is described in those with a pontine abscess. Urinary retention is described due to involvement of Barrington's nucleus. CSF gram stain is often negative and diagnosis may require serologic tests. There is 75 % chance of survival if treatment is initiated promptly.
Saturday, May 05, 2007
Brain MRI findings in mitochondrial cytopathies
Barragan-Campos H et al. Arch Neurol 2005; 62:737-742. 21 patients were described, including 7 with CPEO, 7 with Kearns-Sayre, 6 with mitochondrial neurogastrointestinal encephalopathy, and 1 with myoclonic epilepsy with ragged red fiber myopathy. MRi showed widespread white matter hyperintensity in 90 %, supracortical atrophy in 18, cerebellar atrophy in 13 ABSENT BASAL GANGLIA HYPERINTENSITY CORRELATED WITH KEARNS SAYRE AND SUPRATENTORIAL ATROPHY WITH mitochondrial neurogastrointestinal encephalopathy.
Clinical criteria: CPEO-- ext opthalmopledia, proximal myopathy and RRF. KS-- ext opthalmoplegia, heart block, pigmentary retinopathy, cerebellar ataxia, eolevated CSF protein (the latter two were "optional"). MNGIE-- leukoencephalopathy, CPEO, PN, chronic intestinal pseudoobstruction MERRF- myoclonic epilepsy, myoclonic ataxia, dementia, and RRF.
Clinical criteria: CPEO-- ext opthalmopledia, proximal myopathy and RRF. KS-- ext opthalmoplegia, heart block, pigmentary retinopathy, cerebellar ataxia, eolevated CSF protein (the latter two were "optional"). MNGIE-- leukoencephalopathy, CPEO, PN, chronic intestinal pseudoobstruction MERRF- myoclonic epilepsy, myoclonic ataxia, dementia, and RRF.
Wednesday, May 02, 2007
Cryptococcus/fungals/meningoencephalitis pearls (Dr Perfect AAN 2007 lecture)
1. Cryptococcus neoformans serotype A and D (grubii and neofomans) and serotype B and C (Cr. gattii) are major serotypes. Gattii affects more normal hosts and has more torulomas.
2. Consider IRIS (immune reconstition syndrome) in HIV patients starting HAART or with any CHANGE in immunosuppressive regiment. If patient seems to be getting worse in spite of treatment, this may be one of the few times to pay attention to the Crypto antigen titer. If it is dropping the patient may have IRIS and may not be failing therapy.
3. Don't put a shunt in until the patient is already on treatment-- you'll just have to replace it later. Increased ICP can occur on presentation chronic and indolent, acutely during early therapy, or classic hydrocephalus with therapy. Consider increased ICP if frequent and severe headaches, pappilledema, hearing loss, or pathologic reflexes present. Consider repeat LP's as a treatment modality. Shunts don't work often in comatose patients.
4. Indications for surgery include diagnostic biopsy, toruloma greater than 3 mm, zygomycetes and infarcted tissue, phaeohyphomycosis, shunt placement.
5. Diagnosis of other fungi clues: neutrophilic meningitis (aspergillus, scedosporium, blastomyces, zygomycetes), large volume CSF cultures (Blasto/histo/coccidio). Histoplasmosis antigen, sporotrix CSF antibodies, cocciiodes CFA, aspergillus galactomannan.
6. Wangiella (Exophiala) dermatitidis meningitis occurs due to injectable steroids that are contaminated, with a 1-11 month incubation period. Therapy with voriconazole.
7. Hyalohyphomycosis-- occurs in near fresh water drownings, due to steroids, and diabetes, usually from sinus disease, causes abscesses, surgery is critical for diagnosis and debulking.
8. Drug resistance is rare but it occurs.
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Leprosy Pearls-- lecture by Dr Swift at AAN 1007
1. Most people (95 %) have immunity to leprosy and cannot get it.
2. Leprosy is only infection that invades the peripheral nerve. Palpation of nerves is important.
3. Invasion can take form of nodular or diffuse infiltration.
4. Erythema nodosum leprosum is an immune reaction that occurs with treatment than can result in severe damage of skin, anterior eye, testes, and nerves and cause infarction/ulcers especially of skin.
5. The three types are tuberculous ( immune reaction present), lepromatous (immune reaction absent) and intermediate or borderline. Borderline is unstable and tends towards lepromatous or tuberculous (reversal reaction).
6. Signs include affected cool areas with involvement of upper lip (cooler than lower lip), tip of nose, ears, extensor surfaces of extremities, scrotum and testes, anterior third of eye. May have sparing between toes (warmer). Failure to close eyes results in corneal drying and lower lid hangs away (lagopthalmos). Buccinator wrinkles since buccinator is deep. Ulnar clawing, acute angle glaucoma, or corneal abrasions due to eyelids turning in. Knee and ankle jerks are normal. Scalp is only affected in bald patients.
7. Treatment of paucibacillary (tuberculoid) leprosy is with a combination of rifamycin, ofloxacin, and minocycline (check standards which always change). In paucibacillary intermediate disease use rifamycine 600 mg monthly and dapsone 100 mg daily for 6 months. In multibacillary (lepromatous) use triple therapy with dapsone 100 mg/day, rifamycine 600 mg/mo, and clofazimine 50 mg per day for 12-14 months. Also treat reactions with prednisone 60 mg/day or equivalent. Rehab procedures of affected skin are helpful. Patients are at high risk of osteomyelitis due to neuropathy. Casting has been tried.
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Cerebral Abscess-- Quick Hits from AAN (Bartt lecture) 2007
1. Mortality has declined in recent years. In a recent review of 94 patients admitted to intensive care, 26 % died and 36 % had long term morbidity. Recent rates of death are 13-14 % in both children and adults. Factors that predicted mortality (independently) were sepsis and GCS < 9 , not location, deficits, organism or need for surgery. (Tattevin et al., 2003, AM J MED).
2. Resolution of ring enhancing MRI is longer than the six weeks needed to treat the abscess with intravenous antibiotics.
3. The purpose of surgery is to treat mass effect.
4. Do not treat mycotic aneurysms (or worry excessively about them) until 4-6 weeks of treatment has already occurred.
5. Steroids can reduce antibiotic penetration through the blood brain barrier and are not proven in abscess.
6. Risk factors for abscess 1.7 % for acute or chronic sinusitis (esp ethmoid or sphenoid), 1-2 % for HIV, 4 % for stem cell or bone marrow transplant, 2.1 % of cyanotic heart disease, and 3.1-37.5 for pulmonary AVM's (worse with multiple AVMS's).
7. Otitis is more common in young males as a cause.
8. The most common cause is headache in 70-80 % and less than half have HA, fever and focal deficit. Less than half have pappilledema. Nausea, vomiting, pappilledema are more common in otogenic with symptoms in posterior fossa and of increased intracranial pressure.
9. Sed rate and blood cultures may be positive in less than 20 % and especially if bacterial endocarditis is present.
10. Factors on imaging favoring abscess over tumor (metastasis) include a more regular rim, homogenous enhancement, a thinner wall towards the ventricular surface, daughter satellite lesions and RESTRICTED DIFFUSION ON DIFFUSION WEIGHTED SEQUENCES all favor abscess.
11. Do a TEE to look for paradoxical abscess and PFO in patients with a cryptogenic abscess.
12. Therapy suggestions:
Immunocompromised with lobar pneumonia, TMP-SMX; antifungals if bug not identified.
Listeria--PCN
Frontal (sinus, odontogenic)-- aer/anaer-- PCN + Flagyl or 3rd gen ceph + Flagyl
Temporal (Otogenic) - Str, Entero, Bacter.-- PCN + Flagyl + 3rd gen ceph.
Metastatic/ hematogenous-- nafcillin, Flagyl, cefotaxime
Penetrating trauma/ postop--Steph, enterob, pse.-- vancomycin + ceftazadime
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Monday, April 30, 2007
Swallowing rehab measures in dysphagia due to inflammatory myopathy
Diet -- oral, nonoral (PEG) or both
Feeding instructions-- chew food well, swallow twice, small bites, alternate solids and liquids, sit upright during the meal.
Compensation-- Chin tuck, head turn (right and left) , effootful swallow, Mendelsohn maneuver, supraglottic swallow
Exercises-- tongue base retraction, effortful swallow, Mendelsohn maneuver, falsetto, supraglottice swallow.
Interventions done-- cricopharyngeal myotomies most helpful and were most frequently done in IBM Other procedures done were cricopharyngeal or esophageal dilatation, and PEG.
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Malignant transformation of monoclonal gammopathy
Rosinol L. et al. Mayo Clin Proc 2007;82:428-434.
The authors cite a NEJM article (2006) showing a prevalence of 3.2 % and 5.7 % in patients greater than 50 and 70, respectively. The patients can transform after years of stability. To determine the rate of transformation, the authors took into account both the presenting clinical finding and the evolutionary pattern of the M protein. They excluded patients diagnosed in the first 3 years, or with smoldering myeloma. 537 were diagnosed with MGUS, 178 were lost to followup or were followed les than three years, 359 were followed more than 3 years. Patients received a SPEP, UPEP and bonemarrow aspirate. On followup they got an M protein measurement on pep yearly. Evolving type was defined as patients with an increase in the M protein size on electropheresis in each annual visit over three years. 330 patients were nonevolving and 29 were evolving. 32 developed malignancies. Risk factors were the evolving typeand M protein concentration. Of the 32 malignancies, 20 had multiple myeloma and 2 had Waldenstrom's macroglobulinemia after a median followup of 93 months (7 and a half years, just under ten percent). However, 14/29 with evolving MGUS (48 %) developed symptomatic disease, and 18 (5%) on nonevolving progressed. The rate of transformation in the evolving and nonevolving groups after ten and twenty years, respectively, were, 55 and 10, and 80 and 13, respectively.
Initial factors associated with transformation were M protein size greaterthn 15 g/L, proportion of BMPCs (bonemarrow plasma cells) greater than 5 %; higher incidence of IgA v. IgG, and evolving MGUS. No nonevolving patients transformed after twelve years.
The actuarial rate of progression is 1.5 % per year, 17 % at 10 years, 34 % at 20 years, 39 % at 25 years (Kyle et al., different paper). Baldini et al. (Blood, 1996) emphasizes BMPC's as an important risk factor with followup of patients with BMPC ranging from 10-30 percent (normal was around 4) having a 5-6 year followup, having a rate of malignant transformation of 37 v. 7 percent. Cesana et al. (J Clin Oncol 2002) found bm plasmacytosis greater than 5 percent, presence of light chains proteinuria, polyclonal serum immunoglobulin reduction and high ESR as independent factors affecting transformation. Kyle et al. found thatM protein size and non IgG type were the most important predictors of progression. (Kappa v. lambda had relative risk of 4.1). Rajkumar et al.(Blood 2005)found non IgG MGUS, M protein > 15 g/L, abnormal k/l light chain ratio had an actuarial probability of transforming of 58 % at 20 years, whereas patients who lacked all of the above risk factors had a rate of transformation at 20 years of only 6 percent.
Kyle and Greipp(NEJM 1980) described SMM (smouldering multiple myeloma), defined as M protein > 30 and BMPC> 10 % without end organ impairment. Patients with the evolving SMM type show a progressive increase in M protein until myeloma develops, whereas nonevolving types have stable M protein until the onset of disease with a longer time till disease develops. 59 % of SMM patients who were evolving previously had an evolving MGUS, whereas only 4 % of nonevolving SMM had a previously noted MGUS . This is due to genomic hybridization, with high chromosomal losses and iq gains in the evolving patients.
The authors hypothesize that there are two types oo MGUS evolving and nonevolving, and all patients with the evolving type will eventially get disease.
See what's free at AOL.com.
Sunday, April 22, 2007
Internuclear opthalmoplegia: Unusual causes in 114/410
Keane JR. Arch Neurol. 2005; 62:714-717. Uunusual causes not stroke or MS occur in 28 % overall, 42 % of unilateral cases the author has seen over three plus decades in practice. Of 410 cases, 38 % (157)were due to stroke (5.157 due to cardiac emboli), 139 (34 %) due to MS, and 114 (28%) due to "unusual" causes. These included 16 patients with blunt head injury, one gunshot wound, and one with blood loss after a stabbing. Two motor vehicular collisions led to vertebral artery injury after cervical spine fracture. Tentorial herniation after CNS infection occurred in 2; one had a subdural empyema , bilateral SDH, TB meningitis There were two cases of brainstem toxoplasmosis, 1 lymphoma and 3 brainstem encephalitis, all inHIV patients. 4 patients with cysticercosis had lesions in caudal aqueduct or fourth ventricle. Two patients had neurosyphilis. 12 patients had iatrogenic injury including angiography, tumor emobolization, CEA, cardiac catheterization, 1 hydrocephalus, 1 Wernicke's encephalopathy, 1 brainstem atrophy, one carbamazepine overdose, one cerebellar hemorrhagic infarct with pontine compression, one spinocerebellar atrophy with pigmentary changes.
Pseudo INO was seen in 27/182 patients with myasthenia gravis, 2 patients with GBS, 1/38 with Fisher s, 1 with abetalipoporoteninemia, andcalorics showed an INO pattern in several comatose patients. PSP shows preferential weakness of the medial rectus with improvement with caloric stimulation.
Pseudo INO was seen in 27/182 patients with myasthenia gravis, 2 patients with GBS, 1/38 with Fisher s, 1 with abetalipoporoteninemia, andcalorics showed an INO pattern in several comatose patients. PSP shows preferential weakness of the medial rectus with improvement with caloric stimulation.
Delirium due to consuming toner cartridge cleaner
Tancredi DN , Shannon MW. Case 30-2003: A 21 year old man with sudden alteration of mental status. The patient was a 21 year old who b had been drinking, then acted strangely, smelled of urine, awake and noncommunicative. Pupils were reactive. Iv droperidol resulted in coma, then hyperagitation. He had consumed laser printer toner cartridge cleaner to augment the effects of alcohol, that is metabolized to GABA. He awoke and insisted on leaving.
Discussion comments on gamma hydroxybutyrate that was used in the 1980s by bodybuilders, enhanced ethanol,date rape drug, but is still manufactured illegally, quite easily, at home. Criminalization led to the use of congeners. Gamma butyrolactone has since been restricted. Gamma valerolactone is a solvent in industrial applications. This patient took 1,4 butanediol which is used in compact disc and printer cleaners, but is legal. It metabolizes to gamma hydroxybutyrate which acts at specific receptors and at the GABA b receptor. Intoxication shows about one third have hypothermia, bradycardia, or both, are inebriated with an agitated delirium. Severe effects are coma and apnea, which uniquely, resolves extremely rapidly with a return to awareness. Amnesia occurs. Ethanol inhibits alcohol dehydrogenase, halting the metabolism of 1,4 butanediol. There may be a biphasic period of risk of coma due to interactions and patients should have prolonged observation. Treatment is supportive. Studies are underway using 4-methylpyrazole (fomepazole) an alcohol dehydrogenase inhibitor also being studied in methanol and ethylene glycol intoxication. More clinical information can be found here: http://neurologistnotes.blogspot.com/2007/12/ghb.html
See discussion of SSADH here: http://neurologyminutiae.blogspot.com/2008/02/succinic-semialdehyde-dehydrogenase.html
Discussion comments on gamma hydroxybutyrate that was used in the 1980s by bodybuilders, enhanced ethanol,date rape drug, but is still manufactured illegally, quite easily, at home. Criminalization led to the use of congeners. Gamma butyrolactone has since been restricted. Gamma valerolactone is a solvent in industrial applications. This patient took 1,4 butanediol which is used in compact disc and printer cleaners, but is legal. It metabolizes to gamma hydroxybutyrate which acts at specific receptors and at the GABA b receptor. Intoxication shows about one third have hypothermia, bradycardia, or both, are inebriated with an agitated delirium. Severe effects are coma and apnea, which uniquely, resolves extremely rapidly with a return to awareness. Amnesia occurs. Ethanol inhibits alcohol dehydrogenase, halting the metabolism of 1,4 butanediol. There may be a biphasic period of risk of coma due to interactions and patients should have prolonged observation. Treatment is supportive. Studies are underway using 4-methylpyrazole (fomepazole) an alcohol dehydrogenase inhibitor also being studied in methanol and ethylene glycol intoxication. More clinical information can be found here: http://neurologistnotes.blogspot.com/2007/12/ghb.html
See discussion of SSADH here: http://neurologyminutiae.blogspot.com/2008/02/succinic-semialdehyde-dehydrogenase.html
Cavernous carotid aneurysms
One third are asymptomatic at diagnosis, one third have headaches, and one third have cranial neuropathy (3,4,5,6). HA may resolve with gabapentin. Associations of include htn, multiple aneurysms, connective tisue diseases such as Ehler-Danlos s. type 4 and xanthoma elasticum.
Differential of trigeminal headaches &blink reflex
SUNCT (see separate entry)
Cluster
cervical (c2) myelitis with occipital headache
cavernous sinus syndrome-- aneurysms
pituitary tumor
cavernous sinus malignancy
MG
Evaluation of:
Blink reflexes were abnormal in 15 % of patients with atypical facial pain . 35 % of patients showed decreased habituation of the blink reflex. Thermal QST was abnormal in 55 % with abnormal facial pain and in all with trigeminal neuropathy. Blinks could help sort out brainstem and peripheral lesions, the trigeminal neuropathy patients. Source Forssell H et al. Neurology 2007; 69:1451-9. (authors are Finnish, and so am I)
Cluster
cervical (c2) myelitis with occipital headache
cavernous sinus syndrome-- aneurysms
pituitary tumor
cavernous sinus malignancy
MG
Evaluation of:
Blink reflexes were abnormal in 15 % of patients with atypical facial pain . 35 % of patients showed decreased habituation of the blink reflex. Thermal QST was abnormal in 55 % with abnormal facial pain and in all with trigeminal neuropathy. Blinks could help sort out brainstem and peripheral lesions, the trigeminal neuropathy patients. Source Forssell H et al. Neurology 2007; 69:1451-9. (authors are Finnish, and so am I)
Smallpox and bioterrorism and the neurologist
Variola infection requires only a few drops inhaled from oral, nasal or pharyngeal mucosa. Infected patients may shed virions one or two days before symptoms until all scabs and crusts are shed. They are most infectious in first ten days. It produces an asymptomatic viremia, followed by a toxic viremia when it spreads to the spleen and other organs.
Neurologic symptoms include splitting headaches with pain over whole or just lumbar spine, hallucinations, delirium, depressive psychosis, manic depressive states that all may last into convalescence. Ocular disease (variola residua) may be bilateral with loss of sight from leukoma adherens or complications causing enucleation .
Intravenous cidofavir which is nephrotoxic may be useful. Smallpox vaccine (vaccinia virus) within seven days after exposure (incubation period) can prevent or attenuate the disease. Contraindications to preexposure vaccination are immunosuppression, HIV infection, pregnancy, or household sexual contacts with contraindications. Such patients should get vaccinia immune globulin with smallpox vaccine, but it may be unavailable.
Postvaccinial encephalitis is seen almost exclusively in those getting primary vaccination. In kids younger than 2 it can occur in 6-10 days,with most patients dying. In those older than 2, it has 35 % mortality, or those who recover do so within two weeks. Strain used may be important. Authors favor preexposure vaccination and stockpiling of vaccinia immune globulin. Eczema vaccinatum results from vaccinating an atopic patient or contacts of someone with eczema.
Pitfalls-- confusing generalized vaccinia, vaccinia necrosum or eczema vaccinatum with true smallpox, therefore rapid development of a pcr test is needed. Another pitfall is vaccinating an immunocompromised individual, that may have a 33 % mortality.
Neurologic symptoms include splitting headaches with pain over whole or just lumbar spine, hallucinations, delirium, depressive psychosis, manic depressive states that all may last into convalescence. Ocular disease (variola residua) may be bilateral with loss of sight from leukoma adherens or complications causing enucleation .
Intravenous cidofavir which is nephrotoxic may be useful. Smallpox vaccine (vaccinia virus) within seven days after exposure (incubation period) can prevent or attenuate the disease. Contraindications to preexposure vaccination are immunosuppression, HIV infection, pregnancy, or household sexual contacts with contraindications. Such patients should get vaccinia immune globulin with smallpox vaccine, but it may be unavailable.
Postvaccinial encephalitis is seen almost exclusively in those getting primary vaccination. In kids younger than 2 it can occur in 6-10 days,with most patients dying. In those older than 2, it has 35 % mortality, or those who recover do so within two weeks. Strain used may be important. Authors favor preexposure vaccination and stockpiling of vaccinia immune globulin. Eczema vaccinatum results from vaccinating an atopic patient or contacts of someone with eczema.
Pitfalls-- confusing generalized vaccinia, vaccinia necrosum or eczema vaccinatum with true smallpox, therefore rapid development of a pcr test is needed. Another pitfall is vaccinating an immunocompromised individual, that may have a 33 % mortality.
Neurologic symptoms of anthrax
The major one is fulminant and rapidly fatal hemorrhagic meningoencephalitis. Fever with neurologic deterioration and dark necrotic pustules on the extremities, gram postive rods in CSF and multifocal cerebral bleeding, anthrax should be considered. Inhalational form is muchmore likely to cause the above than cutaneous forms. Death usually occurs within one week. Conversely, headache and confusion are common presenting signs.
Posterior thalamic hemorrhage and pusher syndrome
Karnath HO et al Posterior thalamic hemorrhage induces "pusher syndrome." Neurology 2005; 64: 1014-1019.
The syndrome occurs when stroke patients use an unaffected limb to "push" away from nonparalyzed side. Authors have found subjects with posterior thalamic stroke experience their body as upright when it is actually are tilted 20 degrees towards the lesional side. The result of the contraversive pushing is loss of postural balance and falling. The study involved about 46 thalamic stroke patients.
The syndrome occurs when stroke patients use an unaffected limb to "push" away from nonparalyzed side. Authors have found subjects with posterior thalamic stroke experience their body as upright when it is actually are tilted 20 degrees towards the lesional side. The result of the contraversive pushing is loss of postural balance and falling. The study involved about 46 thalamic stroke patients.
Forearm exercise screening test for mitochondria myopathy
Jensen TD et al. A forearm exercise screening test for mitochondrial myopathy. Neurology 2002; 58:1533-1538. Authors comapred 12 patients with MM to 10 with mucular dystrophy and 12 normal controls. All subjects performed intermittent handgrip exercise (squeeze one second, rest one second) for 3 minutes. Blood samples were collected from median cubital vein before during and after exercise to measure oxygen saturation and lactate levels. MM patients did not have the normal oxygen desaturation seen in other subjects. The lactate test did not show a significant change. The authors propose this as a sensitive and specific screening test for MM, almoot as good as muscle biopsy.
Localization of orgasmic seizures (aura)
Janszky J et al. Orgasmic aura originates from the right hemisphere Neurology 2002; 58:302-304. The authors reviewed 2 new cases and 22 already published. Among 15 with unilateral eeg foci, 13 (87%) had right and 2 (13%) had left hemisphere focus. The lesions included right temporal AVM, 3 had right postcentral parasaggittal focus. Authors comment on the rarity of auras have lateralizing value and this being an exception among epilepsies. Reviewing the chart, several patients had left hand or leg jerking, ictal speech, sitting, automatism, a sensation of fear. Authors believe amygdala is important, but that parasaggittal cases are due to stimulation of the cortical areas important for genital sensation.
Localizing value of the abdominal aura
and its evolution. A study in focal epilepsies. Henkel et al. Neurology 2002; 58:271-276. Abdominal auras were more common in TLE than in extratemporal epilepsy. (52 % v 12 %). They also were more frequent in mesial TLE and than cortical TLE. Abdominal auras were followed by oral and manual automatisms in 100 % of patients with TLE and only 2/13 patients with extratemporal epilepsy. The evolution of an abdominal aura into an automotor seizure increases the likelihood (probability) of TLE to 98.3 %.
Immune reconstitution s. ass c PML/AIDS
MArtinez JV et al. Neurology 2006; 67:1692-1694. A patient with PML due to HIV received HAART and deteriorated. He developed enhancing lesions. HAART wa stopped for 2 weeks, and he was given dexamethasone 32 mg/day with slow taper, and partially imnproved.
Paraneoplastic syndromes involving the nervous system
Darnell R B and Posner JB. NEJM2003; 349:1543-54. Review article . Mechanisms of disease.
Authors discuss immune mediated diseases, affecting 0.01 percent of patients with cancer. However some are more common. LEMS affects 3 % of patients with small cell lung cancer, and mg affects 15 % of patients with thymoma, and demyelinating neuropathy affects 50 % of patients with sclerotic form of multiple myeloma (rare form).
Neurologic condition usually appears first, and cancer searches may be unrewarding, and whole body PET scan should be considered. CSF pleocytosis may dissipate but elevated IgG may persist. The predominant cell type is T cells.
Clinical conditions include
Limbic encephalitis
brain stem encephalitis
cerebrellar degeneration
opsoclonus-myoclonus
visual syndromes ((cancer associated retinopathy and ON)
Parkinsonism
necrotizing myelopathy
inflammatory myelitis
motor neuron disease
subacute motor neuropathy
stiff person syndrome
sensory neuronopathy
autonomic neuropathy
acute sensorimotor neuropathy
polyradiculpathy (GBS)
brachial neuritis
chronic sensorimotor neuropathy
vasculitic neuropathy
neuromyotonia
LEMS
myasthenia gravis
polymyositis
dermatomyositis
necrotizing myopathy
myotonia.
Antigens that are present do not cause neurologic disease unless they cross the blood brain barrier and react with neurons expressing the onconeural antigen.
Pearls
patients with Hu antigens mayhave small cell lung cancer restricted to a nodule despite that most small cell lung cancers are metastatic at diagnosis. The prognosis of the cancer may also be better, even, eg. among patients with anti Hu antibodies who lack a paraneoplastic syndrome. T cells are critical elements of the response. They may be activated by apoptotic tumor cells. In a few conditions, antibody responses are more important, including LEMS, MG and a rare form of cerebellar degeneration. These forms have antigens that are cell surface receptors. Anti Sox antibodies are thought predictive of SCCL in LEMS
Immune treatments are widely used but not known to be effective. Keine-Guibert protocols IVIG .5 g/kg for five days, iv methylprednisolone at 1 g/d for 3 days and iv cyclophosphamide at 600 mg/m(2) of body surface area for one day on day 4. The treatment can be repeated if it appears effective, at 3 week intervals, or if prednisolone was effective, using one day per month of ivig/steroid/cytoxan together. Also used is tacrolimus, .15 mg/kg/d for 14 days, then .3 mg/kg for 7 days.
Authors discuss immune mediated diseases, affecting 0.01 percent of patients with cancer. However some are more common. LEMS affects 3 % of patients with small cell lung cancer, and mg affects 15 % of patients with thymoma, and demyelinating neuropathy affects 50 % of patients with sclerotic form of multiple myeloma (rare form).
Neurologic condition usually appears first, and cancer searches may be unrewarding, and whole body PET scan should be considered. CSF pleocytosis may dissipate but elevated IgG may persist. The predominant cell type is T cells.
Clinical conditions include
Limbic encephalitis
brain stem encephalitis
cerebrellar degeneration
opsoclonus-myoclonus
visual syndromes ((cancer associated retinopathy and ON)
Parkinsonism
necrotizing myelopathy
inflammatory myelitis
motor neuron disease
subacute motor neuropathy
stiff person syndrome
sensory neuronopathy
autonomic neuropathy
acute sensorimotor neuropathy
polyradiculpathy (GBS)
brachial neuritis
chronic sensorimotor neuropathy
vasculitic neuropathy
neuromyotonia
LEMS
myasthenia gravis
polymyositis
dermatomyositis
necrotizing myopathy
myotonia.
Antigens that are present do not cause neurologic disease unless they cross the blood brain barrier and react with neurons expressing the onconeural antigen.
Pearls
patients with Hu antigens mayhave small cell lung cancer restricted to a nodule despite that most small cell lung cancers are metastatic at diagnosis. The prognosis of the cancer may also be better, even, eg. among patients with anti Hu antibodies who lack a paraneoplastic syndrome. T cells are critical elements of the response. They may be activated by apoptotic tumor cells. In a few conditions, antibody responses are more important, including LEMS, MG and a rare form of cerebellar degeneration. These forms have antigens that are cell surface receptors. Anti Sox antibodies are thought predictive of SCCL in LEMS
Immune treatments are widely used but not known to be effective. Keine-Guibert protocols IVIG .5 g/kg for five days, iv methylprednisolone at 1 g/d for 3 days and iv cyclophosphamide at 600 mg/m(2) of body surface area for one day on day 4. The treatment can be repeated if it appears effective, at 3 week intervals, or if prednisolone was effective, using one day per month of ivig/steroid/cytoxan together. Also used is tacrolimus, .15 mg/kg/d for 14 days, then .3 mg/kg for 7 days.
Saturday, April 21, 2007
SUNCT syndrome and SUNA syndrome & PH
These are grouped as trigeminal autonomic cephalgias, together with cluster headache. (TACs)
SUNCT= short acting unilateral neuralgiform headache with conjunctival injection and tearing. Usually SUNCT headaches are retroorbital with stabs, groups of stabs or sawtooth pain and may occur 3-200 times per day and last 15-240 seconds. They are strictly unilateral and may resemble paroxysmal hemicrania, cluster headache or trigeminal neuralgia. They may resist treatment although in one case in Neurology a patient responded to topiramate, AAN2009 lamictal was reported as drug of choice. Men experience it more in a 2:1 ratio, whereas paroxysmal hemicrania occurs more in women and last 15 minutes v. less than a minute for SUNCT. The location of the pain is supraorbital, orbital, retroorbital, temporal, in the top or side of the head, in a V2 or V3 distribution, or in the teeth, neck or ear. All patients have conjunctival injection and tearing. GBN also has been used. Neurology(2002) patients with pituitary tumors (adenomas) after beginning therapy with bromocriptene. Other cases are triggered by exercise. In the above series, authors speculate that extension of the tumor into the cavernous sinus may be contributory.
In Cohen AS et al, Brain 2006 (129:2746-2760) a series of 43 patients were reported with SUNCT and 9 with the less known SUNA syndrome. 2 SUNA patients had tearing, 4 had conjunctival injection but none had both. Other cranial autonomic features seen include nasal blockage, rhinorrhea, eyelid edema, facial sweating, flushing or ear flushing. Most patients did not have a refractory period between attacks and were agitated with the attacks. Pain severity is greater in SUNCT than SUNA. In general analgesic overuse ought to be avoided.
SUNA stands for "Short-lasting Unilateral Neuralgiform headache Attacks with cranial autonomic symptoms." Occassionally it can present with Horner's syndrome.
Other pearls for diagnosis: ipsilateral photophobia and phonophobia differentiates TACS from migraines. Interictal pain occurs in one third, often those with personal/family history of migraine. In patients with cluster headache, more than half have OSA so do a sleep study. TAC like pain occurs at a very high rate with pituitary tumors, so MRI with pituitary thin cuts is indicated.
Paroxysmal hemicrania (PH) has a unilateral brief headache attack that occurs several times daily. It most often but not exclusively affects first division of trigeminal nerve. It lasts 2-30 minutes (longer than SUNCT/SUNA) with 1-40 attacks per day, and may be episodic in 20 percent (attacks for up to a week with a month or more remission between) or chronic in 8- percent with no remission of remission of less than a month. Distinctively, it responds to indomethacin.
(I try to AVOID basic science but) common to all 3 is activation of posterior hypothalamus on all syndromes.
Symptomatic (or secondary) TACs occur rarely, and clinical features alerting to possibility include atypical phenotype, abnormal exam, and refractory to treatment. Summarized by Cittadini et al (Neurologist 2009; 15: 305-312) include historical points such as unusual triggers such as postprandial, or sitting or standing; altered consciousness, impotence, galactorrhea, acromegaly, fever, and purulent nasal discharge. Physical signs included opthalmoplegia, optic atrophy, temporal hemianopia, Adie syndrome, swelling of the eye, persistent partial or complete Horner's syndrome, absent nasal tickle reflex, signs of acromegaly, testicular atrophy, and absent radial pulse. In PH atypical features included onset with carotid massage (gangliocytoma extending to carotid artery from pituitary lesion).
Since one in ten patients may have incidental pituitary microadenoma and one in 500 an incidental macroadenoma, the role of imaging may be less certain, with decided risk of unknown importance of discovering and treating an incidental finding.
AAN 2010 suggested SUNCT/SUNA responsive to occipital stimulator
SUNCT= short acting unilateral neuralgiform headache with conjunctival injection and tearing. Usually SUNCT headaches are retroorbital with stabs, groups of stabs or sawtooth pain and may occur 3-200 times per day and last 15-240 seconds. They are strictly unilateral and may resemble paroxysmal hemicrania, cluster headache or trigeminal neuralgia. They may resist treatment although in one case in Neurology a patient responded to topiramate, AAN2009 lamictal was reported as drug of choice. Men experience it more in a 2:1 ratio, whereas paroxysmal hemicrania occurs more in women and last 15 minutes v. less than a minute for SUNCT. The location of the pain is supraorbital, orbital, retroorbital, temporal, in the top or side of the head, in a V2 or V3 distribution, or in the teeth, neck or ear. All patients have conjunctival injection and tearing. GBN also has been used. Neurology(2002) patients with pituitary tumors (adenomas) after beginning therapy with bromocriptene. Other cases are triggered by exercise. In the above series, authors speculate that extension of the tumor into the cavernous sinus may be contributory.
In Cohen AS et al, Brain 2006 (129:2746-2760) a series of 43 patients were reported with SUNCT and 9 with the less known SUNA syndrome. 2 SUNA patients had tearing, 4 had conjunctival injection but none had both. Other cranial autonomic features seen include nasal blockage, rhinorrhea, eyelid edema, facial sweating, flushing or ear flushing. Most patients did not have a refractory period between attacks and were agitated with the attacks. Pain severity is greater in SUNCT than SUNA. In general analgesic overuse ought to be avoided.
SUNA stands for "Short-lasting Unilateral Neuralgiform headache Attacks with cranial autonomic symptoms." Occassionally it can present with Horner's syndrome.
Other pearls for diagnosis: ipsilateral photophobia and phonophobia differentiates TACS from migraines. Interictal pain occurs in one third, often those with personal/family history of migraine. In patients with cluster headache, more than half have OSA so do a sleep study. TAC like pain occurs at a very high rate with pituitary tumors, so MRI with pituitary thin cuts is indicated.
Paroxysmal hemicrania (PH) has a unilateral brief headache attack that occurs several times daily. It most often but not exclusively affects first division of trigeminal nerve. It lasts 2-30 minutes (longer than SUNCT/SUNA) with 1-40 attacks per day, and may be episodic in 20 percent (attacks for up to a week with a month or more remission between) or chronic in 8- percent with no remission of remission of less than a month. Distinctively, it responds to indomethacin.
(I try to AVOID basic science but) common to all 3 is activation of posterior hypothalamus on all syndromes.
Symptomatic (or secondary) TACs occur rarely, and clinical features alerting to possibility include atypical phenotype, abnormal exam, and refractory to treatment. Summarized by Cittadini et al (Neurologist 2009; 15: 305-312) include historical points such as unusual triggers such as postprandial, or sitting or standing; altered consciousness, impotence, galactorrhea, acromegaly, fever, and purulent nasal discharge. Physical signs included opthalmoplegia, optic atrophy, temporal hemianopia, Adie syndrome, swelling of the eye, persistent partial or complete Horner's syndrome, absent nasal tickle reflex, signs of acromegaly, testicular atrophy, and absent radial pulse. In PH atypical features included onset with carotid massage (gangliocytoma extending to carotid artery from pituitary lesion).
Since one in ten patients may have incidental pituitary microadenoma and one in 500 an incidental macroadenoma, the role of imaging may be less certain, with decided risk of unknown importance of discovering and treating an incidental finding.
AAN 2010 suggested SUNCT/SUNA responsive to occipital stimulator
Applause sign is specific clinical test for PSP
Dubois B et al. "Applause sign" helps to discriminate PSP from FTRD and PD. Neurology 2005;64: 2132-2133. When asked to clap three and only three times as quickly as possible, after demonstration by examiner, an inability to stop clapping indicates PSP. Clapping from 4->10 times is abnormal. An applause sign was seen in 71 % of patients with PSP but none with FTD or PD.
a separate article described superior cerebellar atrophy in PSP
a separate article described superior cerebellar atrophy in PSP
Drop attacks due to superior canal dehiscence
Brantberg K, Ishiyama A, Baloh RW. Drop attacks secondary to superior canal dehiscence syndrome. Authors describe 2 patients. They note drop attacks occur in late Meniere's syndrome but can be early as well with vestibular dysfunction and normal hearing. They are in these cases associated with a sensation of being pushed or environmental tilts.
SCD is a peripheral audivestibular disorder manifested by sound and pressure induced vertigo due to absent bone coverage at the apex of the semicircular canal. The diagnosis is by inducing vertical or torsional eye movements in the plane of the superior canal when exposed to sounds or pressure changes. High resolution CT shows bony dehiscence in canal. Audiological tests show increased threshold in the low frequency range for air but not bone conduction.
The 2 patients described with unprovoked drop attacks not provoked by coughing, straining or loud noises (Tullio phenomenon).
SCD is a peripheral audivestibular disorder manifested by sound and pressure induced vertigo due to absent bone coverage at the apex of the semicircular canal. The diagnosis is by inducing vertical or torsional eye movements in the plane of the superior canal when exposed to sounds or pressure changes. High resolution CT shows bony dehiscence in canal. Audiological tests show increased threshold in the low frequency range for air but not bone conduction.
The 2 patients described with unprovoked drop attacks not provoked by coughing, straining or loud noises (Tullio phenomenon).
Malignant transformation in MGUS
Eurelings M et al. Maligannt transformation in polyneuropathy associated with monoclonal gammopathy. Neurology 2005; 64:2079-2084.
Of 193 patients with MGUS and polyneuropathy, 17 had a hematologic diagnosis at onset. The rate of transformation in the remaining patients was 2.7 % per year. Independent predicting factors associated with transformation were progressive neuropathy, weight loss, fevers, night sweats and Mm-protein level.
Notes: diagnotic criteria for MGUS include M proteinlevel< 30 g/dl, bm plasma cell infiltrate of less than 10 %, absent lytic lesions in bone, anemia, hypercalcemia, renal insufficiency, and stable M protein level, as well as absent fatigue, weight loss, bone pain or susceptibility to infections. There was no effect of IgG v IgA or kappa v lambda
Of 193 patients with MGUS and polyneuropathy, 17 had a hematologic diagnosis at onset. The rate of transformation in the remaining patients was 2.7 % per year. Independent predicting factors associated with transformation were progressive neuropathy, weight loss, fevers, night sweats and Mm-protein level.
Notes: diagnotic criteria for MGUS include M proteinlevel< 30 g/dl, bm plasma cell infiltrate of less than 10 %, absent lytic lesions in bone, anemia, hypercalcemia, renal insufficiency, and stable M protein level, as well as absent fatigue, weight loss, bone pain or susceptibility to infections. There was no effect of IgG v IgA or kappa v lambda
Intermittent third nerve palsy ddx
Cluster HA
cryptococcus n. infection meningitis
aneurysm
cavernous sinus lesion
pituitary lesion
trauma
diabetes
cryptococcus n. infection meningitis
aneurysm
cavernous sinus lesion
pituitary lesion
trauma
diabetes
Laryngospasm in Kennedy Syndrome
Sperfeld AD et al. Laryngospasm. An underdiagnosed symptom of x-linked spinobulbar muscular atrophy. Neurology 2005;64: 753-4. L is defined as the sudden onset of the sensation of the inability to move air in and out, lasting a few seconds and followed by stridor. It occurred in 23/49 patients surveyed with KS. Itsalso associated with GERD.
Paparounas K. Kennedy disease: insights and conclusions. Arch neurol (correspondence) 2004;61: 603. Distinctive features that are virtually pathognomic of the disease include (in the originally cited article) endocrine features such as gynecomastia. The author states that perioral fasciculations and facial fasciclations are present in 95 % of patients and are "highly characteristic if not pathognomonic." Its not found in any other disease. KD patients also have decreased vibratory sense, especially in the feet, even among patients without sensory dysfunction. The original author responded that perioral fasciculations are a late finding.
The diagnosis of Kennedy syndrome or SBMA (spinal bulbar muscular atrophy) by a simple blood test (Athena) is important because SBMA has a much more benign course with a 10 year survival of 82 % with no PEG use and only rare CPAP use. (Chahin et al. Neurology 2008:70:1967-1971.
Paparounas K. Kennedy disease: insights and conclusions. Arch neurol (correspondence) 2004;61: 603. Distinctive features that are virtually pathognomic of the disease include (in the originally cited article) endocrine features such as gynecomastia. The author states that perioral fasciculations and facial fasciclations are present in 95 % of patients and are "highly characteristic if not pathognomonic." Its not found in any other disease. KD patients also have decreased vibratory sense, especially in the feet, even among patients without sensory dysfunction. The original author responded that perioral fasciculations are a late finding.
The diagnosis of Kennedy syndrome or SBMA (spinal bulbar muscular atrophy) by a simple blood test (Athena) is important because SBMA has a much more benign course with a 10 year survival of 82 % with no PEG use and only rare CPAP use. (Chahin et al. Neurology 2008:70:1967-1971.
Segawa disease DYT 5
AD guanosine triphosphate cyclohydrolase I (GTP-1_ deficiency. Thsi is a hereditary doap response generalized dystonia, typically with onset in childhood, that responds to low dose levodopa. It is due to partial deficiency of tetrahydrobiopterin.
Clinical pearls include the presentation with equinovarus by age 6, and four extremity dystonia by teens, difficulty with hand pronation/supination, marked diurnal fluctuation, and rarer findings such as writer's cramp or guitarist's cramp. Adult onset may have bradykinesia,, tremor mimicking PD, or focal hand dystonia.
Clinical pearls include the presentation with equinovarus by age 6, and four extremity dystonia by teens, difficulty with hand pronation/supination, marked diurnal fluctuation, and rarer findings such as writer's cramp or guitarist's cramp. Adult onset may have bradykinesia,, tremor mimicking PD, or focal hand dystonia.
Rheumatoid pachymeningitis
Starosta MA et al. Clinical manifestations and treatment of r.p. Neurology 2007;68:1079-1080.
Disorder can occur early or after many years of RA, RF and ESR are usually elevated but the esr may be only middling. The usual presentation is headache or cn palsy esp cn 8. On biopsy, unlike autopsy, nodules are infrequently found, in dura, and path showsx inflammatory cells, fibrosis. In autopsy series, the finding is nodules with central necrosis with histiocytes and mononuclear esp. plasma cells. Treatment with prednisone and other drugs (MTX, cytoxan) are effective.
Disorder can occur early or after many years of RA, RF and ESR are usually elevated but the esr may be only middling. The usual presentation is headache or cn palsy esp cn 8. On biopsy, unlike autopsy, nodules are infrequently found, in dura, and path showsx inflammatory cells, fibrosis. In autopsy series, the finding is nodules with central necrosis with histiocytes and mononuclear esp. plasma cells. Treatment with prednisone and other drugs (MTX, cytoxan) are effective.
Rash to yellow dye in levodopa-carbidopa
Chou KL , Stacy MA. Skin rash associated with simemet does not equal levodopa allergy. Neurology 2007; 68: 1078-9. Patients experiencing a rash on sinemet requiring stopping and rechallenging were actually allergic to a yellow dye (D&C Yellow 10 and FD&C Yellow 6) and were able to tolerate forms of levodopa not containing the dye. The safe forms included C/L 25/250 or 10/100 , CR forms of Sinemet, Stalevo and Parcopa, or Madopar (benserazide/levodopa).
Thursday, March 08, 2007
ALS pearls-- ALS mimics
spondylitic myelopathy -- limb fibs should go away within six months of fixing spine
inclusion body myositis pearl check finger flexors esp FPL FDP, forearm atrophy and check for absent fascics and symmetry
spinal cord AVM
heavy metal intoxication -- lead-- check for basophilic stippling and consider treatment with dmpa
lymphoproliferative disorder
multifocal motor neuropathy with conduction block (anti GM1 seen in about half) rsponds to IVIG
vasculitis
motor polyradiculopathy
infectious (polio, WNV)-- EMG shows poor recruitment, then fibs in 4-6 weeks
Bulbospinal mononeuropathy (Kennedy's syndrome) X linked, presents in men with symmetrical weakness, atrophy and fasciculations of bulbar and proximal limb muscles, testicular atrophy and gynecomastia.Occurs early, diagnosed by a CAG repeat, and is associated with a normal lifespan. Consider in males with slow course. Fascics are more pronounced in this disorder, but its all LMN.
Spinal muscular atrophy (Werdnig Hoffman, Kugelberg Welander)-- kids, young and old adults
Progressive lateral sclerosis (UMN variety) is associated with a normal lifespan
Benign fasciculations
cramp fasciculation syndrome-- easily treated with membrane stabilizers
Monomelic atrophy-- focal variant
frontotemporal dementia- identical path finding seen by Neumann ALS spectrun disorder?
Machado Jospeh disease= spinocerebellar atrophy tpe 3. See prominent anterior horn disorder plus ataxia and myelopathy
polyglucosan body disease-- rare UMN and LMN findings plus sensory changes and shite matter changes on MRI, with rare glucosan bodies seen on sural nerve biopsy.
Acid maltase deficiency may mimic PM abnormal respiratory muscles.
Syrinx
true neurologic TOS thoracic outlet syndrome -- shows decreased median CMAP, normal median SNAP, decreased ulnar SNAP, decreased medial antebrachial SNAP; needle shows median > ulnar hand involvement; lower trunk median/radial innervated forearm muscles (FPL, EIP)
myofibrillar myopathy-- = Desmond's myopathy-- mimics IBM. Get quad atrophy, medial gastroc, dysphagia, atrophy of VM/VL but rectus femoris is spared and is normal
inclusion body myositis pearl check finger flexors esp FPL FDP, forearm atrophy and check for absent fascics and symmetry
spinal cord AVM
heavy metal intoxication -- lead-- check for basophilic stippling and consider treatment with dmpa
lymphoproliferative disorder
multifocal motor neuropathy with conduction block (anti GM1 seen in about half) rsponds to IVIG
vasculitis
motor polyradiculopathy
infectious (polio, WNV)-- EMG shows poor recruitment, then fibs in 4-6 weeks
Bulbospinal mononeuropathy (Kennedy's syndrome) X linked, presents in men with symmetrical weakness, atrophy and fasciculations of bulbar and proximal limb muscles, testicular atrophy and gynecomastia.Occurs early, diagnosed by a CAG repeat, and is associated with a normal lifespan. Consider in males with slow course. Fascics are more pronounced in this disorder, but its all LMN.
Spinal muscular atrophy (Werdnig Hoffman, Kugelberg Welander)-- kids, young and old adults
Progressive lateral sclerosis (UMN variety) is associated with a normal lifespan
Benign fasciculations
cramp fasciculation syndrome-- easily treated with membrane stabilizers
Monomelic atrophy-- focal variant
frontotemporal dementia- identical path finding seen by Neumann ALS spectrun disorder?
Machado Jospeh disease= spinocerebellar atrophy tpe 3. See prominent anterior horn disorder plus ataxia and myelopathy
polyglucosan body disease-- rare UMN and LMN findings plus sensory changes and shite matter changes on MRI, with rare glucosan bodies seen on sural nerve biopsy.
Acid maltase deficiency may mimic PM abnormal respiratory muscles.
Syrinx
true neurologic TOS thoracic outlet syndrome -- shows decreased median CMAP, normal median SNAP, decreased ulnar SNAP, decreased medial antebrachial SNAP; needle shows median > ulnar hand involvement; lower trunk median/radial innervated forearm muscles (FPL, EIP)
myofibrillar myopathy-- = Desmond's myopathy-- mimics IBM. Get quad atrophy, medial gastroc, dysphagia, atrophy of VM/VL but rectus femoris is spared and is normal
Thursday, February 15, 2007
Sensory Guillian-Barre Syndrome
Oh SJ, LaGanke C, Claussen GC. Sensory Guillian Barre. Neurology 2001; 56:82-82. Describes eight patients collected with a sensory equivalent of classical GBS. These patients had acute onset of a sensory ascending neuropathy that peaked within 4 weeks, generally had an antecedent viral illness, areflexia, CSF albumen-cytologic dissociation, demyelination in at least two nerves, (esp MOTOR nerves), favorable outcome. 3 patients were treated with immunomodulatory treatments.
Monday, February 12, 2007
Neck pain and calcium deposition
Nodera et al. Neurology 2007; 68:383 (Neuroimages). Japanese. A 43 year old man had neck pain, sore throat, dysphagia, and low grade fever upon awakening. He had limited ROM of the neck. CT showed calcification ANTERIOR to C1-2 with thickened prevertebral tissues due to effusion. Retropharyngeal calcific tendinitis is uncommon and confused with abscess but the characteristic calcium deposit is diagnostic. It is self limiting.
Paraneoplastic cerebellar degeneration antibodies
Anti Yo (PCA-1) ovarian and breast cancer; anti Tr antibodies -- Hodgkin's lymphoma; also for Hodgkin's lymphoma: Anti-mGluR1 and Anti Zic4 antibodies. Above are PREDOMINANTLY associated with PCD. SOMETIMES associated with PCD are anti VGCC (LEMS, small cell lung cancer); anti Hu (ANNA-1)(encephalomyelitis, PCD, sensory neuronopathy) (small cell lung and other CA); anti Ri (ANNA 2) (PCD, brainstem encephalitis; paraneoplastic opsoclonus/myoclonus)(breast, gyne and small cell CA);anti CV2/CRMP (encephalomyelitis, PCD, chorea, PN, uveitis)(small cell lung, thymoma, others); anti MA protein (limbic, hypothalamic, brainstem encephalitis, infrequently PCD)( testicular, lung and other cancers); antiamphiphysin (stiff person s, encephalomyelitis, PCD) (breast and small cell) CHART is FROM NEJM 2007; 356:612-620. MORE Tumors with anti Yo antibodies express Yo antigen which is a cytoplasmic protein called CDR2 that interacts with c-Myc. It is expressed in the Purkinje cells of the cerebellum and the large neurons of the brainstem. It sequesters c Myc and downregulates; disruption with antibodies may increase c Myc activity leading to apoptosis (although the T cell immune response may also be important).
rapidly progressive ataxia ddx
in immunocompentent patients:
stroke,
multiple sclerosis
sarcoidosis,
primary or metastatic diseases,
paraneoplastic disorders,
toxins/drugs (lead, anticonvulsants, salicyclates, aminoglycosides, sedatives, fluorouuacil, cytarabine),
Miller Fisher syndrome,
infection (HIV, viral/postviral cerebellitis, Creutzfeld Jacob disease, progressive multifocal leukoencephalopathy),
alcoholic cerebellar degeneration, thiamine deficiency,
autoimmune ( SLE, Sjogrens, Hashimoto's disease, cerebellar ataxia with anti GAD or antigliadin antibodies).
stroke,
multiple sclerosis
sarcoidosis,
primary or metastatic diseases,
paraneoplastic disorders,
toxins/drugs (lead, anticonvulsants, salicyclates, aminoglycosides, sedatives, fluorouuacil, cytarabine),
Miller Fisher syndrome,
infection (HIV, viral/postviral cerebellitis, Creutzfeld Jacob disease, progressive multifocal leukoencephalopathy),
alcoholic cerebellar degeneration, thiamine deficiency,
autoimmune ( SLE, Sjogrens, Hashimoto's disease, cerebellar ataxia with anti GAD or antigliadin antibodies).
Sunday, February 04, 2007
Lack of utility/overuse of muscle biopsy
Filosto M et al. The role of muscle biopsy in investigating isolated muscle pain. Neurology 2007; 68:181-186.
editorial Kissel JT. Muscle biopsy in patients with myalgia. Neurology2007; 68:170-171.
Filosto et al. reviewed clinicals and neuropath on 240 patients presenting with muscle pain isolated or cramping. 80 % had biopsy abnormalities but only 20 %got a specific diagnosis and only 6 % a specific myopathy. Patients with obvious causes eg. statin use were excluded before analysis. CK levels and EMG did not predict pathology. Patients need to go under rigorous selection prior to biopsy.
editorial Kissel JT. Muscle biopsy in patients with myalgia. Neurology2007; 68:170-171.
Filosto et al. reviewed clinicals and neuropath on 240 patients presenting with muscle pain isolated or cramping. 80 % had biopsy abnormalities but only 20 %got a specific diagnosis and only 6 % a specific myopathy. Patients with obvious causes eg. statin use were excluded before analysis. CK levels and EMG did not predict pathology. Patients need to go under rigorous selection prior to biopsy.
Saturday, February 03, 2007
cryoglobulinemic vasculitis PN
Gemignani F et al. Clinical spectrum of cryoglobulinemic neuropathy. JNNP 2005; 76:1410-1414.
Most common presentation is middle aged female patients who develop small fiber sensory neuropathy (73%). Less often, then sensorimotor neuropathy (18 %) then least often, mononeuritis multiplex (8%) occurs. Symptoms were tingling paresthesias (55%), sensory ataxia (38%), thermal dysesthesias (42%) pain (42%) and RLS (45 %). 29 % were asymmetrical. Patients did not have autonomic dysfunction.
Study occurred of 71 patients referred to academic center. Cryoglobulnemic syndrome was defined as intense recurring purpura and cryocrit>5 %, and "mild" syndrome with minimal purpura and cryocrit <5%. 46 % presented with PN. Hepatitis C caused the cryoglobulinemia in more than 90 %.
Comment--most cases were noo biopsied.
Most common presentation is middle aged female patients who develop small fiber sensory neuropathy (73%). Less often, then sensorimotor neuropathy (18 %) then least often, mononeuritis multiplex (8%) occurs. Symptoms were tingling paresthesias (55%), sensory ataxia (38%), thermal dysesthesias (42%) pain (42%) and RLS (45 %). 29 % were asymmetrical. Patients did not have autonomic dysfunction.
Study occurred of 71 patients referred to academic center. Cryoglobulnemic syndrome was defined as intense recurring purpura and cryocrit>5 %, and "mild" syndrome with minimal purpura and cryocrit <5%. 46 % presented with PN. Hepatitis C caused the cryoglobulinemia in more than 90 %.
Comment--most cases were noo biopsied.
Wednesday, January 24, 2007
Mimics of GBS Part II
Chemical toxins
vacor (rodenticide)ingested due to homicidal or suicidal intent. Impairs fast axon transport. Clinical findings are initially abdominal pain, nausea, vomiting, necrosis of pancreas beta cells causes hyperglycemia, rapid distal motor/sensory/Autonomic neuropathy with weakness, areflexia, dysesthesias, OH, urine retention, and cranial neuropathy, then later stupor, EEG changes, DKA, EKG changes. Long term residua often include DM and ANS dysfunction. Acute tx is gastric lavage and induced emesis.
Organophosphates -- found in malathion, parathion, dursban. 10-20 days after exposure they produce a distal axonopathy, calf cramps, extremity paresthesias and distal weaknesss. A SEPARATE syndrome is NMJ disorder with cholinergic toxicity and respiratory insufficiency.
n-Hexane solvent associated with glue sniffing and industrial exposure. Clinical includes distal sensory loss and severe weakness that progresses for months after exposure ends.
Drugs
CV-- amiodorone, streptokinase
Hem-- cytarabine, suramin.
amiodoarone chronic progressive predominantly distal s-m neuropathy. NCS show distal latency prolongation and slowing to 11 m/s. Dose is 200-400 mg per day.
streptokinase-- 10-20 cases, 10-20 days after exposure, paresthesias of hands and feet, cndxn blocks, elevated CSF protein, coincident to peak SKN titers, dramatic response to IVIG.
cytarabine-- 0.6 % of cases with doses more than 200 mg/m2/d. progressive distal sensorimotor neuropathy, hours to days after last treatment.
Suramin -- PN in 40 % of patients with levels> 350 ug/ml Rarely GBS like presentation.
Vasculitis
Churg-Strauss s-- may resemble GBS. Eosinophilia is seen. Tx with pred/MTX. Asthma, vasculitic lung involvment, eosinophilia and mononeuropathy are common but not universal.
Other cryoglobulinemia, PAN.
AIP-- Motor PN.
Refsums
Diptheria ("extinct" in US, present in developing countries)
Poliomyelitis--
West Nile Virus
Botulism
WNV
CMV polyradiculopathy
critical illness myopathy
critical illness neuropathy
Myelopathy
vacor (rodenticide)ingested due to homicidal or suicidal intent. Impairs fast axon transport. Clinical findings are initially abdominal pain, nausea, vomiting, necrosis of pancreas beta cells causes hyperglycemia, rapid distal motor/sensory/Autonomic neuropathy with weakness, areflexia, dysesthesias, OH, urine retention, and cranial neuropathy, then later stupor, EEG changes, DKA, EKG changes. Long term residua often include DM and ANS dysfunction. Acute tx is gastric lavage and induced emesis.
Organophosphates -- found in malathion, parathion, dursban. 10-20 days after exposure they produce a distal axonopathy, calf cramps, extremity paresthesias and distal weaknesss. A SEPARATE syndrome is NMJ disorder with cholinergic toxicity and respiratory insufficiency.
n-Hexane solvent associated with glue sniffing and industrial exposure. Clinical includes distal sensory loss and severe weakness that progresses for months after exposure ends.
Drugs
CV-- amiodorone, streptokinase
Hem-- cytarabine, suramin.
amiodoarone chronic progressive predominantly distal s-m neuropathy. NCS show distal latency prolongation and slowing to 11 m/s. Dose is 200-400 mg per day.
streptokinase-- 10-20 cases, 10-20 days after exposure, paresthesias of hands and feet, cndxn blocks, elevated CSF protein, coincident to peak SKN titers, dramatic response to IVIG.
cytarabine-- 0.6 % of cases with doses more than 200 mg/m2/d. progressive distal sensorimotor neuropathy, hours to days after last treatment.
Suramin -- PN in 40 % of patients with levels> 350 ug/ml Rarely GBS like presentation.
Vasculitis
Churg-Strauss s-- may resemble GBS. Eosinophilia is seen. Tx with pred/MTX. Asthma, vasculitic lung involvment, eosinophilia and mononeuropathy are common but not universal.
Other cryoglobulinemia, PAN.
AIP-- Motor PN.
Refsums
Diptheria ("extinct" in US, present in developing countries)
Poliomyelitis--
West Nile Virus
Botulism
WNV
CMV polyradiculopathy
critical illness myopathy
critical illness neuropathy
Myelopathy
AIDP atypical forms and mimics PT I
Levin KH. Variants and mimics ocf Guillian Barre Syndrome.The Neurologist 2004;10:61-74
typical case AIDP: febrile antecedent esp. campylobacter jej, CMV, EBV, infl, mycoplasma, coxsackie, hepatitis virus. Other noninfectious causes include Hodgkins dis, and events such as surgery, childbirth, and immunization. Within 2 weeks, get symmetric leg paresthesiae, tingling, crawling sensations, pain esp in back (50%), ascending weakness. 50 % develop weakness diaphragmand cranial nn. > 50 % have autonomic findings. CSF dissociation acellularity, increased protein, and typical NCS (not detailed here).
Variants: asymmetric; pure motor; prominent sensory loss; preserved DTR's; regional presentations (pharyngeal/brachial/cervical); paraparetic; facial diplegia with paresthesias; pure sensory neuropathy; pure autonomic neuropathy; Miller Fisher variant; axon loss variants (AMAN, AMSAN).
Miller Fisher syndrome-- triad opthalmoplegia, areflexia, ataxia (follows sensory loss). NCS show loss of SNAP amplitude. Course is often benign,maynot require IVIG/Plasmapx. may include facial weakness, dysarthria, dysphagia, abnormal pupils, limb weakness. 95 % have ANTI GQ1B antibodies.
AMAN-- Chinese disease-- NCS show motor amplitude loss without demyelination. High correlation with campylobacter. Antibodies to GD1a and GM1 at node of Ranvier. Involves complement activation and macrophage infiltration.
AMSAN-- cannot differentiate from AMAN until enough time has elapsed to show NCS findings. Typically this does not respond to IVIG/plasmapx.
Mimics:
tick paralysis-- notoriously overlooked in children, esp preadolescent girls. Ticks may infest scalp. Symptoms develop 2-4 days later including paresthesias, gait ataxia, diplopia, dysarthria, rapid weakness. Tick is dermocenter andersonii. Paralysis reverses within 24 hours of tick removal. Australian ticks cause paralysis that lasts longer. NCS show reduced CMAP amplitudes.
marine toxins-- ciguatoxin (diflagellates eaten by algae), tetrodotoxin (pufferfish) and saxitoxin
(dinoflagellates eaten by shellfish)cause paresthesias and weakness within hours. NCS show slow motor/sensory responses (mimics GBS) and dispersed CMAP.
buckthorn berry-- in SW USA and Mexico. Affects children and cattle causing rapid weakness within a few weeks. Limited amt published.
heavy metals (esp arsenic, gold, thallium).
Arsenic-- 7-14 days after ingestion. presents with N/V/D paresthesias, burning, then stocking glove loss small and large fibers. Weakness is distal to proximal and lead to footdrop. Predominant axon loss, Occassional ans dysfunction.
Gold-- usually secondary to RA treatment. PN, with pain, may be sudden or slow, with or without dermatitis and stomatitis.
Thallium-- usually deliberate ingestion (may be accidental in kids) or due to mal intent. Causes dermatitis, alopecia (usually a LATE finding), GI (N/V/D), CNS (ON, confusion, movement disorders, psych), acute and chronic PN. Starts with painful paresthesias and painful joints, ascending weakness, possibly normal DTR's, autonomic dysfunction
typical case AIDP: febrile antecedent esp. campylobacter jej, CMV, EBV, infl, mycoplasma, coxsackie, hepatitis virus. Other noninfectious causes include Hodgkins dis, and events such as surgery, childbirth, and immunization. Within 2 weeks, get symmetric leg paresthesiae, tingling, crawling sensations, pain esp in back (50%), ascending weakness. 50 % develop weakness diaphragmand cranial nn. > 50 % have autonomic findings. CSF dissociation acellularity, increased protein, and typical NCS (not detailed here).
Variants: asymmetric; pure motor; prominent sensory loss; preserved DTR's; regional presentations (pharyngeal/brachial/cervical); paraparetic; facial diplegia with paresthesias; pure sensory neuropathy; pure autonomic neuropathy; Miller Fisher variant; axon loss variants (AMAN, AMSAN).
Miller Fisher syndrome-- triad opthalmoplegia, areflexia, ataxia (follows sensory loss). NCS show loss of SNAP amplitude. Course is often benign,maynot require IVIG/Plasmapx. may include facial weakness, dysarthria, dysphagia, abnormal pupils, limb weakness. 95 % have ANTI GQ1B antibodies.
AMAN-- Chinese disease-- NCS show motor amplitude loss without demyelination. High correlation with campylobacter. Antibodies to GD1a and GM1 at node of Ranvier. Involves complement activation and macrophage infiltration.
AMSAN-- cannot differentiate from AMAN until enough time has elapsed to show NCS findings. Typically this does not respond to IVIG/plasmapx.
Mimics:
tick paralysis-- notoriously overlooked in children, esp preadolescent girls. Ticks may infest scalp. Symptoms develop 2-4 days later including paresthesias, gait ataxia, diplopia, dysarthria, rapid weakness. Tick is dermocenter andersonii. Paralysis reverses within 24 hours of tick removal. Australian ticks cause paralysis that lasts longer. NCS show reduced CMAP amplitudes.
marine toxins-- ciguatoxin (diflagellates eaten by algae), tetrodotoxin (pufferfish) and saxitoxin
(dinoflagellates eaten by shellfish)cause paresthesias and weakness within hours. NCS show slow motor/sensory responses (mimics GBS) and dispersed CMAP.
buckthorn berry-- in SW USA and Mexico. Affects children and cattle causing rapid weakness within a few weeks. Limited amt published.
heavy metals (esp arsenic, gold, thallium).
Arsenic-- 7-14 days after ingestion. presents with N/V/D paresthesias, burning, then stocking glove loss small and large fibers. Weakness is distal to proximal and lead to footdrop. Predominant axon loss, Occassional ans dysfunction.
Gold-- usually secondary to RA treatment. PN, with pain, may be sudden or slow, with or without dermatitis and stomatitis.
Thallium-- usually deliberate ingestion (may be accidental in kids) or due to mal intent. Causes dermatitis, alopecia (usually a LATE finding), GI (N/V/D), CNS (ON, confusion, movement disorders, psych), acute and chronic PN. Starts with painful paresthesias and painful joints, ascending weakness, possibly normal DTR's, autonomic dysfunction
Saturday, January 06, 2007
CNS complications of HPCT
Denier et al. Spectrum and prognosis of neurologic complications after hematopoeitc transplantation. Neurology 2006;67: 1990-1997.
Modern study. Ablation of bone marrow with allogeneic grafts are treated with prophylaxis against previously common events such as veno-occlusive disease and pulmonary complications. Now neurologic disease is a major cause of M/M. They occurred in about 16 % of patients receiving HPCT, usually opportunistic infections. Toxoplasmosis was the most common cause (33%) with others getting viral encephalitis, HSVE, and less commonly, metabolic encephalopathy, stroke, peripheral nervous system dysfunction.
Modern study. Ablation of bone marrow with allogeneic grafts are treated with prophylaxis against previously common events such as veno-occlusive disease and pulmonary complications. Now neurologic disease is a major cause of M/M. They occurred in about 16 % of patients receiving HPCT, usually opportunistic infections. Toxoplasmosis was the most common cause (33%) with others getting viral encephalitis, HSVE, and less commonly, metabolic encephalopathy, stroke, peripheral nervous system dysfunction.
Spinal epidural abscess
Darouiche RO. Current Concept: Spinal epidural abscess NEJM 35;19 2012 Nov 9 2006
Article concentrates on bacterial causes. Most patients have predisposing risk factors: DM, ETOH, HIV, drug abuse intravenous, DJD, surgery with instrumentation, placement of stimulators, or potential local source of infection (skin, soft tissue, indwelling catheter, UTI, sepsis). Entry is contiguous spread (1/3) or hematogenous (1/3). Two thirds are staph aureus, 40 % of those Methicillin resistant (MRSA). These are especially common a few weeks after implantation of devices.
Other causes: St epidermidis, e coli, Ps aer., rarely actinomyces, nocardia, mycobacteria, fungi, (candida, aspergillus) parasites (echonococcus and dracunculus). A letter writer added brucellosis as a cause in Spain, Italy and the Near East.
Spinal cord injury can occur either by mechanical compression of vascular occlusion due to septic thrombophlebitis.
Clinical staging system: stage 1, back pain at level; stage 2, nerve root pain of affected level; stage 3, motor weakness, sensory loss, or B/B dysfunction at affected level; stage 4, paralysis. 3/4 have back pain, fever present in half, neurologic dysfunction in one third. Stage 2 is "enigmatic" in thoracic cases. Duration/rate of progression is highly variable but can be extremely rapid.
Abscesses favor large epidural spaces with infection prone fat, and therefore are more common in posterior than anterior and thoracolumbar than cervical. Lumbar even more common due to epidural injections. Generally they extend over 3-4 levels or more.
Diagnosis is by drainage. Sed rate is always high. Differential diagnostic conditions ( osteomyelitism discitis, sepsis, endocarditis) also have S aureus bacteremia. CSF cultures are negative in 75%. Blood cultures are usually positive. Risks of LP includes causing meningitis by introducing infection through the meninges or causing deterioration if tapped below a block.
MRI with contrast is preferred procedure although myelography has > 90 % sensitivity. Spine CT can be done in conjunction with and may suggest changes of osteopmyelitis.
Frequent misdiagnoses include: osteomyelitism discitis, meningitis, UTI, sepsis, endocarditis, disc prolapse, DJD, spinal tumor, transverse myelitis, spinal hematoma. These are made because patient is neurologically intact.
Treatment: medical v. surgical. No trials done. Medical treatment indicated if patient has high risk of surgery, has panspinal infection, or paralysis for more than 24 hours, or if agent is identified and his condition is monitored closely. Surgery can be a limited laminectomy if patient has a panspinal infection. Empiric coverage should include coverage against MRSA, against gram negative bacilli (with a third or fourth generation cephalosporin such as ceftazidime). Letter writer added that medical management was safe as long as the patient didnot deteriorate.
Statistics: 4-22% get irreversible paralysis. 11-75 % are initially misdaignosed.
The most important predictor of outcome is patient's status just before surgery. Patients who undergo surgery in stage 1 or 2 are expected to remnain neurologically intact.
Article concentrates on bacterial causes. Most patients have predisposing risk factors: DM, ETOH, HIV, drug abuse intravenous, DJD, surgery with instrumentation, placement of stimulators, or potential local source of infection (skin, soft tissue, indwelling catheter, UTI, sepsis). Entry is contiguous spread (1/3) or hematogenous (1/3). Two thirds are staph aureus, 40 % of those Methicillin resistant (MRSA). These are especially common a few weeks after implantation of devices.
Other causes: St epidermidis, e coli, Ps aer., rarely actinomyces, nocardia, mycobacteria, fungi, (candida, aspergillus) parasites (echonococcus and dracunculus). A letter writer added brucellosis as a cause in Spain, Italy and the Near East.
Spinal cord injury can occur either by mechanical compression of vascular occlusion due to septic thrombophlebitis.
Clinical staging system: stage 1, back pain at level; stage 2, nerve root pain of affected level; stage 3, motor weakness, sensory loss, or B/B dysfunction at affected level; stage 4, paralysis. 3/4 have back pain, fever present in half, neurologic dysfunction in one third. Stage 2 is "enigmatic" in thoracic cases. Duration/rate of progression is highly variable but can be extremely rapid.
Abscesses favor large epidural spaces with infection prone fat, and therefore are more common in posterior than anterior and thoracolumbar than cervical. Lumbar even more common due to epidural injections. Generally they extend over 3-4 levels or more.
Diagnosis is by drainage. Sed rate is always high. Differential diagnostic conditions ( osteomyelitism discitis, sepsis, endocarditis) also have S aureus bacteremia. CSF cultures are negative in 75%. Blood cultures are usually positive. Risks of LP includes causing meningitis by introducing infection through the meninges or causing deterioration if tapped below a block.
MRI with contrast is preferred procedure although myelography has > 90 % sensitivity. Spine CT can be done in conjunction with and may suggest changes of osteopmyelitis.
Frequent misdiagnoses include: osteomyelitism discitis, meningitis, UTI, sepsis, endocarditis, disc prolapse, DJD, spinal tumor, transverse myelitis, spinal hematoma. These are made because patient is neurologically intact.
Treatment: medical v. surgical. No trials done. Medical treatment indicated if patient has high risk of surgery, has panspinal infection, or paralysis for more than 24 hours, or if agent is identified and his condition is monitored closely. Surgery can be a limited laminectomy if patient has a panspinal infection. Empiric coverage should include coverage against MRSA, against gram negative bacilli (with a third or fourth generation cephalosporin such as ceftazidime). Letter writer added that medical management was safe as long as the patient didnot deteriorate.
Statistics: 4-22% get irreversible paralysis. 11-75 % are initially misdaignosed.
The most important predictor of outcome is patient's status just before surgery. Patients who undergo surgery in stage 1 or 2 are expected to remnain neurologically intact.
Thursday, December 28, 2006
Psychotropic effects of New AED's
Ettinger a. Neurology 2006;67: 1916-1925. Review paper. Random notes
Gabapentin--
1. aberrant/aggressive behavior noted in children and patients with developmental disorders. 2. Ineffective for BPAD 3. It does help behaviors in institutionalized patients with AD 4. Useful in epileptic patients with anxiety
Lamotrigine-- 1. It does help mood in depressed patients with epilepsy. 2. Effective in controlling impulsive aggression in one study.
Leviteracetam-- 1. Causes depression or anxiety in up to 15 % of those treated, especially those with preexisting disorders that are exacerbated with the drug. 2. Reversible psychotic symptoms occur in children treated. 3. May be ameliorated with pyridoxine. 4. Tested for treatment of mania and social anxiety syndrome
oxcarbazepine-- too limited information to make conclusions.
pregabalin--similar to gabapentin. Useful for epilepsy patients with anxiety.
topiramate-- related to psychomotor slowing. Used in bPAD for weight reducing side effect. Not proven efffective in BPAD. May be effective for anger/aggression in those with borderline personalities. Other side effects in 1-2 % of patients (7 % of kids) are psychotic symptoms, agitation, aggression, hallucinations, auditory and visual, paranoid and mystical delusions. Does not stabilize moods.
tiagabine-- possibly anxiolytic but not a mood stabilizer.
Gabapentin--
1. aberrant/aggressive behavior noted in children and patients with developmental disorders. 2. Ineffective for BPAD 3. It does help behaviors in institutionalized patients with AD 4. Useful in epileptic patients with anxiety
Lamotrigine-- 1. It does help mood in depressed patients with epilepsy. 2. Effective in controlling impulsive aggression in one study.
Leviteracetam-- 1. Causes depression or anxiety in up to 15 % of those treated, especially those with preexisting disorders that are exacerbated with the drug. 2. Reversible psychotic symptoms occur in children treated. 3. May be ameliorated with pyridoxine. 4. Tested for treatment of mania and social anxiety syndrome
oxcarbazepine-- too limited information to make conclusions.
pregabalin--similar to gabapentin. Useful for epilepsy patients with anxiety.
topiramate-- related to psychomotor slowing. Used in bPAD for weight reducing side effect. Not proven efffective in BPAD. May be effective for anger/aggression in those with borderline personalities. Other side effects in 1-2 % of patients (7 % of kids) are psychotic symptoms, agitation, aggression, hallucinations, auditory and visual, paranoid and mystical delusions. Does not stabilize moods.
tiagabine-- possibly anxiolytic but not a mood stabilizer.
Fludaribine for MGUS
Niermeijer JMF et al. Neurologic and hematologic response to fludaribine treatment in IgM MGUS polyneuropathy. Neurology 2006:67:2076-2079.
Uncontrolled trial of 16 patients with IgM with progressive IgM MGUS treated with fludaribine.
Patients: 6 were MAG positive, 14 had kappa light chain, 2 had lambda light chain, 3 had axonal neuropathy and 13 had demyelinating neuropathy. 9 used ambulation aids.
10/16 were first treated with cyclophosphamide/prednisone
Uncontrolled trial of 16 patients with IgM with progressive IgM MGUS treated with fludaribine.
Patients: 6 were MAG positive, 14 had kappa light chain, 2 had lambda light chain, 3 had axonal neuropathy and 13 had demyelinating neuropathy. 9 used ambulation aids.
10/16 were first treated with cyclophosphamide/prednisone
4-H syndrome
Timmons et al. Peripheral and central hypomyelination with hypogonadotropic hypogonadism and hypodontia. NIH. Neurology 2006; 67:2066-2069.
Pubertal onset dysmyelinating leukodystrophy. Characteristics: young adults, absent spontaneous puberty, normal till age 7-12, borderline iq's (60s-70s), dysarthria, absent pursuit, upbeat or other nystagmus, normal sensory exam, dysmetria, long tract signs.
Sural nerve biopsies showed membraneous and other debris, loss of major and minor dense lines, increased neurofilaments. Decreased galactocerebrosidase and sphingomyelin. Immunostaining for PO protein showed clefted disruption of myelin sheaths and laminar deposits in circumferential distribution. MAG staining was similar but less definitive. Nerve conductions were normal.
MRI showed supratentorial white matter signal approximated cortex on T1, hyperintense WM on T2 (demyelination) atrophic cerebellum and thin corpus callosum.
Heterogenous Holmes-Adie syndrome has described the combination of cerebellar ataxia and hypogonadotropic hypogonadism.
Pubertal onset dysmyelinating leukodystrophy. Characteristics: young adults, absent spontaneous puberty, normal till age 7-12, borderline iq's (60s-70s), dysarthria, absent pursuit, upbeat or other nystagmus, normal sensory exam, dysmetria, long tract signs.
Sural nerve biopsies showed membraneous and other debris, loss of major and minor dense lines, increased neurofilaments. Decreased galactocerebrosidase and sphingomyelin. Immunostaining for PO protein showed clefted disruption of myelin sheaths and laminar deposits in circumferential distribution. MAG staining was similar but less definitive. Nerve conductions were normal.
MRI showed supratentorial white matter signal approximated cortex on T1, hyperintense WM on T2 (demyelination) atrophic cerebellum and thin corpus callosum.
Heterogenous Holmes-Adie syndrome has described the combination of cerebellar ataxia and hypogonadotropic hypogonadism.
Radiation retinopathy
Grimm et al. Retinopathy in survivors of primnary CNS lymphoma. Neurology 2006:67:2060-2062.
Study reports specifically five survivors of PCNSL who developed syndrome, 1.5 % of database. Patients received high dose MTX then WBRT then post-XRT chemo including procarbazine, vincristine, and carmustine. Mean latency to developing syndrome was 27 months. Note- syndrome is also reported in other diseases treated with WBRT.
Presentation was blurred vision (2/5), partial visual loss (3/5) and floaters (1/5). Fluroscein agio confirmed bilateral disease in 3. Treatments given include intraocular steroids and laser therapy. No patients had progressive ocular disease although one had radiation dementia and another had ongoing PCNSL.
Study reports specifically five survivors of PCNSL who developed syndrome, 1.5 % of database. Patients received high dose MTX then WBRT then post-XRT chemo including procarbazine, vincristine, and carmustine. Mean latency to developing syndrome was 27 months. Note- syndrome is also reported in other diseases treated with WBRT.
Presentation was blurred vision (2/5), partial visual loss (3/5) and floaters (1/5). Fluroscein agio confirmed bilateral disease in 3. Treatments given include intraocular steroids and laser therapy. No patients had progressive ocular disease although one had radiation dementia and another had ongoing PCNSL.
dopa responsive disorders
Friedman J, Hyland K, Blau N, MacCollin M. Dopa-responsive hypersomnia and mixed movement disorder due to seriapterin reductase deficiency. Neurology 2006:67:2032-2035.
Defects in monoamine synthesis are associated with phenotypes of developmental delay, diurnal variation in symptom severity, and dopa-responsive dystonia. A subset also with cognitive delay due to SPR (seriapterin reductase ) gene have dopa and serotonergic responsive hypersomnolence and movement disorder responsive.
Case report-- 27 year old woman with "CP" had delayed milestones, abnormal gait, incoordination, and hypersomnolence. Other maternal relatives had abnormal limb posturing. She had FSIQ 60, punctate cataracts, oculomotor apracis, dysarthria, bradykinesia, , PTOSIS, generalized dystonia, myoclonus, normal MRI/PET.
CSF showed decreased 5HIAA and HVA and increased 7,8 dihydropterin c/w SRD. Treatment with Sinemet and selegeline and later combined with sertraline helped.
The same patient was FIRST treated with sertraline alone (akathisia), melatonin (dystonic neck spasms), 5 hydroxytriptophan (helped but led to increased LFT's), levodopa-carbidopa (caused dyskinesias; these are rare in DRD or dopa responsive dystonias).
Inheritance is AR. Further information available at the BIODEF database (www.bh4.org)
Defects in monoamine synthesis are associated with phenotypes of developmental delay, diurnal variation in symptom severity, and dopa-responsive dystonia. A subset also with cognitive delay due to SPR (seriapterin reductase ) gene have dopa and serotonergic responsive hypersomnolence and movement disorder responsive.
Case report-- 27 year old woman with "CP" had delayed milestones, abnormal gait, incoordination, and hypersomnolence. Other maternal relatives had abnormal limb posturing. She had FSIQ 60, punctate cataracts, oculomotor apracis, dysarthria, bradykinesia, , PTOSIS, generalized dystonia, myoclonus, normal MRI/PET.
CSF showed decreased 5HIAA and HVA and increased 7,8 dihydropterin c/w SRD. Treatment with Sinemet and selegeline and later combined with sertraline helped.
The same patient was FIRST treated with sertraline alone (akathisia), melatonin (dystonic neck spasms), 5 hydroxytriptophan (helped but led to increased LFT's), levodopa-carbidopa (caused dyskinesias; these are rare in DRD or dopa responsive dystonias).
Inheritance is AR. Further information available at the BIODEF database (www.bh4.org)
Wednesday, November 15, 2006
stents dangerous
-----------------
Forwarded Message:
Subj: Endarterectomy versus stenting in patients with symptomatic severe carotid stenosis
Date: 11/13/2006 1:42:12 PM Eastern Standard Time
From: BestEvidence@mp.medscape.com
To: djacobs272@aol.com
Sent from the Internet (Details)
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Neurology
Article(s) Relevance Newsworthiness
1 Endarterectomy versus stenting in patients with symptomatic severe carotid stenosis.
N Engl J Med. 2006 Oct 19;355(16):1660-71. ******* *******
2 Efficacy and safety of pramipexole in restless legs syndrome.
Neurology. 2006 Sep 26;67(6):1034-9. Epub 2006 Aug 23. ******* *******
3 Efficacy of cabergoline in restless legs syndrome: a placebo-controlled study with polysomnography (CATOR).
Neurology. 2006 Sep 26;67(6):1040-6. Epub 2006 Aug 23. ******* *******
4 Treatment with interferon beta-1b delays conversion to clinically definite and McDonald MS in patients with clinically isolated syndromes.
Neurology. 2006 Oct 10;67(7):1242-9. Epub 2006 Aug 16. ******* *******
5 Effect of donepezil on motor and cognitive function in Huntington disease.
Neurology. 2006 Oct 10;67(7):1268-71. ******* *******
6 Unification of the revised trauma score.
J Trauma. 2006 Sep;61(3):718-22; discussion 722. ******* *******
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Forwarded Message:
Subj: Endarterectomy versus stenting in patients with symptomatic severe carotid stenosis
Date: 11/13/2006 1:42:12 PM Eastern Standard Time
From: BestEvidence@mp.medscape.com
To: djacobs272@aol.com
Sent from the Internet (Details)
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Dear Dr. JACOBS,
We hope you enjoy this trial issue of the Medscape Best Evidence Neurology weekly newsletter.
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Neurology
Article(s) Relevance Newsworthiness
1 Endarterectomy versus stenting in patients with symptomatic severe carotid stenosis.
N Engl J Med. 2006 Oct 19;355(16):1660-71. ******* *******
2 Efficacy and safety of pramipexole in restless legs syndrome.
Neurology. 2006 Sep 26;67(6):1034-9. Epub 2006 Aug 23. ******* *******
3 Efficacy of cabergoline in restless legs syndrome: a placebo-controlled study with polysomnography (CATOR).
Neurology. 2006 Sep 26;67(6):1040-6. Epub 2006 Aug 23. ******* *******
4 Treatment with interferon beta-1b delays conversion to clinically definite and McDonald MS in patients with clinically isolated syndromes.
Neurology. 2006 Oct 10;67(7):1242-9. Epub 2006 Aug 16. ******* *******
5 Effect of donepezil on motor and cognitive function in Huntington disease.
Neurology. 2006 Oct 10;67(7):1268-71. ******* *******
6 Unification of the revised trauma score.
J Trauma. 2006 Sep;61(3):718-22; discussion 722. ******* *******
Medscape Best Evidence, powered by the McMaster Online Rating of Evidence ("MORE") program, vastly improves the signal-to-noise ratio in keeping up to date. By employing filters for research quality and clinical relevance, these alerts can shrink the approximate 50,000 articles per year that appear in more than 110 journals and might be relevant to your clinical practice down to a manageable amount that is likely to be truly important to your clinical practice.
All alerts are pre-assessed for scientific merit (based on the criteria for Evidence-Based Medicine and ACP Journal Club) and qualifying articles are then rated by at least three clinicians in each pertinent discipline for relevance to clinical practice and how new or "newsworthy" the information is likely to be to practicing clinicians.
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Saturday, November 11, 2006
Prevention of meningococcal disease
Gardner P. NEJM 355: 1466-1473. Clinical Practice section.
N meningitidis colonizes the nasopharyx in 18 % of the population. Transmission is by droplet. Most adults have antibodies to the pathogenic subgroups (A,B,C,Y w-135). Classically infection occurs in crowded conditions, eg. military recruits. Infection occurs within 7-10 days of transmission and can be fatal. Occurrence is 0.5-1.1 per 100,000 population. Case fatality rate is 10 %. Sequelae occur in 11-19 % due to neurologic effects or DIC residua. 62 % occur in kids < 11. Other risk factors include crowding, RTI, active and passive smoking, asplenia, terminal complement deficiency. Travel to endemic areas such as Saudi Arabia or sub Saharan Africa also are risk factors. In year one of college rate is 5.1/100,000 but by year two its 1.4 or almost normal.
Chemoprophylaxs of close contacts: "Close contacts" are defined as people in 3 foot range (droplet range) or exposure through oral secretions including ventilatory tubing. For adults chemoprophylaxis is Copro 500 mg once, rifampin 600 q 12 for two days, or ceftriaxone 125 mg im onc if <15, 250 mg im once if older than 15. Chemoprophylaxis is indicated for vaccinated since vaccine does not cover all strains. Chemoprophylaxis should be undertaken within 24 hours.
Vaccines cover strains A,C, Y W-135 but not B. Two vaccines exist. Number one , Menomune (Sanofi) lasts 3 years and is good for travellers, people with limited risk (army recruits, college kids). Second one Menactra (also Sanofi) just released last two years, is more durable (lasts longer) and revaccination results in booster response. There is a warning on Menactra about GBS but it is not clear the 8 cases were more than would be expected in the population.
N meningitidis colonizes the nasopharyx in 18 % of the population. Transmission is by droplet. Most adults have antibodies to the pathogenic subgroups (A,B,C,Y w-135). Classically infection occurs in crowded conditions, eg. military recruits. Infection occurs within 7-10 days of transmission and can be fatal. Occurrence is 0.5-1.1 per 100,000 population. Case fatality rate is 10 %. Sequelae occur in 11-19 % due to neurologic effects or DIC residua. 62 % occur in kids < 11. Other risk factors include crowding, RTI, active and passive smoking, asplenia, terminal complement deficiency. Travel to endemic areas such as Saudi Arabia or sub Saharan Africa also are risk factors. In year one of college rate is 5.1/100,000 but by year two its 1.4 or almost normal.
Chemoprophylaxs of close contacts: "Close contacts" are defined as people in 3 foot range (droplet range) or exposure through oral secretions including ventilatory tubing. For adults chemoprophylaxis is Copro 500 mg once, rifampin 600 q 12 for two days, or ceftriaxone 125 mg im onc if <15, 250 mg im once if older than 15. Chemoprophylaxis is indicated for vaccinated since vaccine does not cover all strains. Chemoprophylaxis should be undertaken within 24 hours.
Vaccines cover strains A,C, Y W-135 but not B. Two vaccines exist. Number one , Menomune (Sanofi) lasts 3 years and is good for travellers, people with limited risk (army recruits, college kids). Second one Menactra (also Sanofi) just released last two years, is more durable (lasts longer) and revaccination results in booster response. There is a warning on Menactra about GBS but it is not clear the 8 cases were more than would be expected in the population.
Saturday, October 21, 2006
hypothermia after arrest
Bernard et al. Treatment of comatose survivors of our of hospital cardiac arrest with induced hypothermia. NEJM 2002 346:557-63 (Australia) Study done 1996-1999. Candidates men>18, women >50, v fib, coma, cardiogenic shock (BP<90 despite pressors). Basic cooling in ambulance, core cooling in ER to 33 degrees, usual measueres used eg. heparin tpa, lidocaine, versed, pancuronium. Life support withdrawn at 72 hours. n=77 patients, 39/43 assigned to hypothermia received it. 21/43 patients assigned to hypothermia had a good outcome, 9/34 in normothermia group (49 v. 26 %)defined as discharge home or to rehab. Normal disability was achieved in 15 v 7 patients (35 v 21 %). Mortality (51 v. 68 % ) did not reach significance. Factors affecting outcome included age (two years led to 9 % less chance of good outcome)and time till return of circulation also was important.
Paper 2: Hypothermia study group. Mild therapeutix hypothermia to improve the neurologic outcome after cardiac arrest. NEJM 346:549-556. (Austria). Primary endpoint is favorable neurologic outcome at 6 months by Pittsburgh cerebral performance (1 good recover, 2, mod disability, 3 severe disability, 4 veg, 5 death). Criteria: witnessed arrest, VF, no hypotension, comatose. 1996-2001. 275/35551 patients enrolled. 137 to hypothermia group, 138 to control. Of treated group, 75/136 (55%) had good outcome v. 54/137 (39 %) NTT to get one additional good outcome = 6. Death was less in treated group: NTT=7.
Notes
Paper 2: Hypothermia study group. Mild therapeutix hypothermia to improve the neurologic outcome after cardiac arrest. NEJM 346:549-556. (Austria). Primary endpoint is favorable neurologic outcome at 6 months by Pittsburgh cerebral performance (1 good recover, 2, mod disability, 3 severe disability, 4 veg, 5 death). Criteria: witnessed arrest, VF, no hypotension, comatose. 1996-2001. 275/35551 patients enrolled. 137 to hypothermia group, 138 to control. Of treated group, 75/136 (55%) had good outcome v. 54/137 (39 %) NTT to get one additional good outcome = 6. Death was less in treated group: NTT=7.
Notes
Wednesday, September 27, 2006
Tuberous sclerosis complex
Crino et al. NEJM 355:13: 1345-1356 The Tuberous Sclerosis Complex [Review article}
TSC is a multisystem autosomal dominant disorder affecting children and adults, resulting from mutations in one of two genes, TSC1(encoding hamartin) or TSC2 (encoding tuberin).
Neurologic disorders include epilepsy, mental retardation, and autism. Other features are facial angiofibromas (formerly adenoma sebaceum), renal angiomyolipomas, and pulmonary lymphangiomyomatosis. TSC has a wide spectrun of disease ranging from subclinical to severely affected. Clinical trials utilizing tuberin and hamartin are underway.
The diagnosis is made clinically using major and minor criieria. Genetic tests are currently considered corroborative. Diagnosis may be made by developmental stage specific findings.
Renal disease (angiomyolipomas) occur in up to thre fourths, may be vascular, may sometimes be treated with embolization, and are most dangerous if greater than 3 cm in size.
TSC is a multisystem autosomal dominant disorder affecting children and adults, resulting from mutations in one of two genes, TSC1(encoding hamartin) or TSC2 (encoding tuberin).
Neurologic disorders include epilepsy, mental retardation, and autism. Other features are facial angiofibromas (formerly adenoma sebaceum), renal angiomyolipomas, and pulmonary lymphangiomyomatosis. TSC has a wide spectrun of disease ranging from subclinical to severely affected. Clinical trials utilizing tuberin and hamartin are underway.
The diagnosis is made clinically using major and minor criieria. Genetic tests are currently considered corroborative. Diagnosis may be made by developmental stage specific findings.
Renal disease (angiomyolipomas) occur in up to thre fourths, may be vascular, may sometimes be treated with embolization, and are most dangerous if greater than 3 cm in size.
transfusion related infections
Blajchman MA and Vamvakas EC. The Contining risk of transfusion-transmitted infections. NEJM 355:13: 1303-1305 Sept 28 2006
Authors remind us of risks to the blood supply. Neurologically speaking, culprits include West Nile Virus which is now mandated to be screened. vCJD (Variant CJD) with an incubation period oo up to 50 years has probably been transmitted in three cases in Britain. HHV8 a herpesvirus akin to CMV causes lifelong infections with periodic reactivations during which virus can circulate in WBC's and be transmitted. Risk factors probably overlap with HBV HCV and HIV andmayinduce Kaposi's sarcoma. No simple screening assay exists. Transfusing leukocyte reduced PRBC's may reduce transmission but this is unproved.
Discussion in blood bank circles includes whether to use pathogen reduction technologies such as methylene blue or solvent detergent, amotosalen for platelets, and UVA for RBC's.
Authors remind us of risks to the blood supply. Neurologically speaking, culprits include West Nile Virus which is now mandated to be screened. vCJD (Variant CJD) with an incubation period oo up to 50 years has probably been transmitted in three cases in Britain. HHV8 a herpesvirus akin to CMV causes lifelong infections with periodic reactivations during which virus can circulate in WBC's and be transmitted. Risk factors probably overlap with HBV HCV and HIV andmayinduce Kaposi's sarcoma. No simple screening assay exists. Transfusing leukocyte reduced PRBC's may reduce transmission but this is unproved.
Discussion in blood bank circles includes whether to use pathogen reduction technologies such as methylene blue or solvent detergent, amotosalen for platelets, and UVA for RBC's.
Friday, September 22, 2006
Neuropathy treatments
MMN distal> proximal, +GM1, +IVIG, Cytoxan, ppx
MADSAM Lewis Sumner syndrome= MMN with sensory symptoms, distal>proximal +IVIG, + prednisone, ?cytoxan, ? Ppx
DADS -- rituxan role?
MADSAM Lewis Sumner syndrome= MMN with sensory symptoms, distal>proximal +IVIG, + prednisone, ?cytoxan, ? Ppx
DADS -- rituxan role?
Saturday, September 09, 2006
Mestinon for OH
Singer et al. Pyridostigmine treatment trial in neurogenic orthostatic hypothension. Arch Neurol 2006; 63:513-518.
Pyridostigmine may improve OH especially diastolic BP without affecting systolic BP due to effect on efferent limb of baroreflex in a 2 neuron system synapsing at the autonomic ganglion.
Study was a 4 way crossover study at Mayo Clinic in MN on 56 patients. Finding was that alone or with low dose midodrine alleviates OH without exacerbating HTN
Pyridostigmine may improve OH especially diastolic BP without affecting systolic BP due to effect on efferent limb of baroreflex in a 2 neuron system synapsing at the autonomic ganglion.
Study was a 4 way crossover study at Mayo Clinic in MN on 56 patients. Finding was that alone or with low dose midodrine alleviates OH without exacerbating HTN
CTX signs and lack thereof
Verrips et al. Presence of diarrhea and absence of tendon xanthomas in patients with cerebrotendinous xanthomatosis. Arch Neurol 2000; 57:520-524
Summary: study of 27 adults and 5 children at Netherlands. Only 41 % had tendon xanthomas at diagnosis. 97 % had premature cataracts and 81 % had long tract signs, 66 % had low intelligence and 56 % had cerebellar signs. Half had severe intractable diarrhea that started in childhood. Suggests CTX is underdiagnosed and should be sought in patients with cataracts and early diarrhea irrespective of neurologic disease.
Summary: study of 27 adults and 5 children at Netherlands. Only 41 % had tendon xanthomas at diagnosis. 97 % had premature cataracts and 81 % had long tract signs, 66 % had low intelligence and 56 % had cerebellar signs. Half had severe intractable diarrhea that started in childhood. Suggests CTX is underdiagnosed and should be sought in patients with cataracts and early diarrhea irrespective of neurologic disease.
Late onset Fabry's disease
Nance et al. Later onset Fabry disease. An adult variant presenting with cramp-fasciculation syndrome. Arch Neurol 2006; 63:453-457.
Fabry disease is an X linked recessively inherited disease due to deficient/absent lysosomal alpha galactosidase and accumulation of globotriaosylceramide (GL-3) and glycososphingolipids in plasma and cellular lysosomes. Classically, male onset occurs in childhood with episodic painful burning sensations in the hands and feets (acroparesthesias), typical skin lesions (angiokeratomas), hypohydrosis, and corneal opacities. Later, patients develop CRF, cardiac valvular disease and strokes, and die by 50s.
Late onset variants typically have renal or cardiac disease without typical neurologic stigmata in sixth decade or later.
Case report is of 34 year old man with activity induced cramps and fasciculations. Nerve biopsy, and pan MRI were negative. Mother had similar syndrome, with painful walking, and had a stroke at 37. Patient's alpha Gal A was deficient, leading to diagnosis.
Other features
Dolichoectasia of cerebral vessels
TIA
Vertigo
Hearing loss
Tinnitus
Cognitive disorders
Small fiber neuropathy
Painful acroparesthesias
Hypohidrosis
Impaired temperature sensation
Intestinal dysmotility
Cardiomyopathy
Cardiac conduction abnormality
Renal failure
Angiokeratomas
Corneal dystrophy
Feathery opacities
Fabry disease is an X linked recessively inherited disease due to deficient/absent lysosomal alpha galactosidase and accumulation of globotriaosylceramide (GL-3) and glycososphingolipids in plasma and cellular lysosomes. Classically, male onset occurs in childhood with episodic painful burning sensations in the hands and feets (acroparesthesias), typical skin lesions (angiokeratomas), hypohydrosis, and corneal opacities. Later, patients develop CRF, cardiac valvular disease and strokes, and die by 50s.
Late onset variants typically have renal or cardiac disease without typical neurologic stigmata in sixth decade or later.
Case report is of 34 year old man with activity induced cramps and fasciculations. Nerve biopsy, and pan MRI were negative. Mother had similar syndrome, with painful walking, and had a stroke at 37. Patient's alpha Gal A was deficient, leading to diagnosis.
Other features
Dolichoectasia of cerebral vessels
TIA
Vertigo
Hearing loss
Tinnitus
Cognitive disorders
Small fiber neuropathy
Painful acroparesthesias
Hypohidrosis
Impaired temperature sensation
Intestinal dysmotility
Cardiomyopathy
Cardiac conduction abnormality
Renal failure
Angiokeratomas
Corneal dystrophy
Feathery opacities
Autoantibodies in MG
Autoantibodies in thymoma-associated myasthenia gravis with myositis or neuromyotonia.
Thymomas are associated with red cell aplasia and in 50 %, with MG. Some patients with MG have inflammatory myopathy of striated and cardiac muscle. Diagnosis is with prosimal muscle weakness, high CPK levels, and myopathic EMG. Cardiac myositis leads to CHF, arrythmia, and sudden death. Patients with thymoma also may have neuromyotonia (NMT) with hyperactive peripheral motor nerves, myokymia, muscle stiffness, cramps, hypertrophy. EMG shows bursts of high frequency motor unit discharges. Antibodies against VGKC have been detected in NMT with or without thymoma. Other antibodies seen are against skeletal muscle calcium release channel (ryanodine receptor RyR) of sarcoplasmic reticulum; and antibodies to cytoplasmic filaments titin or neurofilaments.
There are 3 subgroups of thymoma associated MG with different spectrum of antibodies. 19/19 had AchR antibodies and 17/19 had anti-titin antibodies that did not correlate with symptoms (although anti-titin was higher in patients with antiRyR). Antititin is more or less synonymous with striated muscle antibodies and correlates with the presence of a thymoma.
10/19 had anti RyR, of which five had myositis and 1 had NMT. Myositis is associated with a poorer prognosis, occassionally rippling muscle disease, electrically silent muscle contractions.
7/16 patients tested had anti VGKC, and 4 had NMT, 1 myositis and 2 nothing. RyR and VGKC coexisted only in 2 patients.
Thymic pathology was not correlated, and included thymic ca and carcinoid.
Thymomas are associated with red cell aplasia and in 50 %, with MG. Some patients with MG have inflammatory myopathy of striated and cardiac muscle. Diagnosis is with prosimal muscle weakness, high CPK levels, and myopathic EMG. Cardiac myositis leads to CHF, arrythmia, and sudden death. Patients with thymoma also may have neuromyotonia (NMT) with hyperactive peripheral motor nerves, myokymia, muscle stiffness, cramps, hypertrophy. EMG shows bursts of high frequency motor unit discharges. Antibodies against VGKC have been detected in NMT with or without thymoma. Other antibodies seen are against skeletal muscle calcium release channel (ryanodine receptor RyR) of sarcoplasmic reticulum; and antibodies to cytoplasmic filaments titin or neurofilaments.
There are 3 subgroups of thymoma associated MG with different spectrum of antibodies. 19/19 had AchR antibodies and 17/19 had anti-titin antibodies that did not correlate with symptoms (although anti-titin was higher in patients with antiRyR). Antititin is more or less synonymous with striated muscle antibodies and correlates with the presence of a thymoma.
10/19 had anti RyR, of which five had myositis and 1 had NMT. Myositis is associated with a poorer prognosis, occassionally rippling muscle disease, electrically silent muscle contractions.
7/16 patients tested had anti VGKC, and 4 had NMT, 1 myositis and 2 nothing. RyR and VGKC coexisted only in 2 patients.
Thymic pathology was not correlated, and included thymic ca and carcinoid.
Tuesday, August 29, 2006
DADS
more pn miscellany
rituxan is useful? in DADS
distal acquired demyelinating sensory neuropathy (DADS), M protein differentiates from classical CIDP as does (lack of ) response to treatment. Is large fiber neuropathy in men in fifties or above. Half have anti MAG antibodies, poor response to IVIG. Differentiate DADS-M (monoclonal paraproteinemia present) from DADS no M which is sensory CIDP.
rituxan is useful? in DADS
distal acquired demyelinating sensory neuropathy (DADS), M protein differentiates from classical CIDP as does (lack of ) response to treatment. Is large fiber neuropathy in men in fifties or above. Half have anti MAG antibodies, poor response to IVIG. Differentiate DADS-M (monoclonal paraproteinemia present) from DADS no M which is sensory CIDP.
Miscellany on neuropathy & tests
from Saperstein
B12--may cccur suddenly, 11% hands, 75 % hands and feet, 42 % PN. In evaluating, recall that MMA is increased in renal disease and volume depletion, homocystein in hypothyroidism, age, genetic syndromes, pyridoxine deficiency.
MGUS incidence of monoclonal proteins in population above 50 is 1 %, above 70 is 3 %, in patients with PN is 10 %. SPEP misses 10 percent caught by SIFE. 30 % of MGUS patients eventually develop something (MM, WM, Amyloid). Quantify M protein should be less than 3 g/dl. +/- BM biopsy. Axonal EMG not as bad. DADS also called demyelinating PN, "CIDP" (wrong) IGM neuropathy and anti MAG neuropathy. Usually occurs in older males (> 60). Sensory ataxia, PROLONGED LATENCIES ON NCS are typical. Consider fat biopsy if cardiac,renal, or disease is present.
Celiac disease-- note there are cases with negative duodenal biopsies. Antigliadin antibodies are present in 5-12 percent of normals, but transglutaminase antibodies are more specific. No response to IVIG or poor response to gluten free diet but do it anyway.
antiHU antibodies are best saved for patients with cerebellar ataxia or encephalopathy. NCS show sensorimotor pattern. Less known antibody is CD@ also known as CRMP (collapsing response mediator protein 5). Consider lung cancer, thymoma.
GM1 antibody associates with multifocal motor neuropathy, or at low titers other AI neuropathies not seen in MADSAM.
antiMAG-- small pct dont have igm
B12--may cccur suddenly, 11% hands, 75 % hands and feet, 42 % PN. In evaluating, recall that MMA is increased in renal disease and volume depletion, homocystein in hypothyroidism, age, genetic syndromes, pyridoxine deficiency.
MGUS incidence of monoclonal proteins in population above 50 is 1 %, above 70 is 3 %, in patients with PN is 10 %. SPEP misses 10 percent caught by SIFE. 30 % of MGUS patients eventually develop something (MM, WM, Amyloid). Quantify M protein should be less than 3 g/dl. +/- BM biopsy. Axonal EMG not as bad. DADS also called demyelinating PN, "CIDP" (wrong) IGM neuropathy and anti MAG neuropathy. Usually occurs in older males (> 60). Sensory ataxia, PROLONGED LATENCIES ON NCS are typical. Consider fat biopsy if cardiac,renal, or disease is present.
Celiac disease-- note there are cases with negative duodenal biopsies. Antigliadin antibodies are present in 5-12 percent of normals, but transglutaminase antibodies are more specific. No response to IVIG or poor response to gluten free diet but do it anyway.
antiHU antibodies are best saved for patients with cerebellar ataxia or encephalopathy. NCS show sensorimotor pattern. Less known antibody is CD@ also known as CRMP (collapsing response mediator protein 5). Consider lung cancer, thymoma.
GM1 antibody associates with multifocal motor neuropathy, or at low titers other AI neuropathies not seen in MADSAM.
antiMAG-- small pct dont have igm
Barohn's PN phenotypes
1. Symmetric proximal and distal weakness with sensory loss. GBS or CIDP, is treatable
2. Symmetric distal sensory loss with or without weakness. This is untreatable with immunomodulators and is the most common PN. Within category the most common types are CSPN (cryptogenic sensory peripheral neuropathy) and metabolic, a category that includes diabetic neuropathy and alcoholic neuropathy. Rarer causes include hereditary sensory neuropathies.
3. Asymmetric distal weakness with sensory loss. This includes mononeuritis multiplex, consider vasculitis, motor sensory variant and HNPP (hereditary nerve pressure palsies) or MADSAM (multifocal acquired distal sensory and motor neuropathy, or Lewis Sumner syndrome) which is diagnosed with EMG. Rarer causes are infection (HIV, sarcoid, lyme) or involvement of single nerves or roots (eg. CTS).
4. Asymmetric proximal and distal weakness with sensory loss. Proximal means it may include elbow extensors, hip girdle muscles, neck muscles, knees, covering c5-T1 or L2-S1). Consider polyradiculopathy or plexopathy, due to DM, plexopathies, polyradiculopathy due to neoplasia, carcinoma, lymphoma, and hereditary neuropathy
5. Asymmetric distal weakness without sensory loss eg. progressive footdrop. Category includes ALS (especially with UMN signs), progressive muscular atrophy including regional forms (brachial or leg) juvenile monomelic atrophy, multifocal acquired motor neuropathy
6. Symmetric sensory loss (like number 2) but with UMN signs (crossed adductors, Babinski) think B12 deficiency, ALD, MLD or combination of diabetic/CSPN with cervical spondylosis diagnosis of exclusion)
7. Symmetric weakness without sensory loss-- consider SMA (Kennedy s. includes bulbar, chromosome five includes neck weakness). With bilateral footdrop may have normal EMG. CMT SNAPs are abnormal. overlaps MD and NMJ
8. Focal midline proximal symmetric weakness with neck extensor weakness (ALS, myopathy, MG, oculopharyngeal d., Kennedy s.)
9. Sensory asymmetric proprioceptive loss without weakness. Looks like neuronopathy (CA) but NORMAL SNAPS, abnormal roots on MRI suggest autoimmune, +/- treat with IVIG
10. Autonomic dysfunction
Exceptions to above
1) Mononeuritis multiplex including vasculitis presents symmetrically in one third
2) CIDP -- MMN and MADSAM may be asymmetric distal
3) Demyelinating CMT has no proximal weakness
4) DADS phenotype looks like pattern 2 at bedside but on exam has prolonged latiencies.
2. Symmetric distal sensory loss with or without weakness. This is untreatable with immunomodulators and is the most common PN. Within category the most common types are CSPN (cryptogenic sensory peripheral neuropathy) and metabolic, a category that includes diabetic neuropathy and alcoholic neuropathy. Rarer causes include hereditary sensory neuropathies.
3. Asymmetric distal weakness with sensory loss. This includes mononeuritis multiplex, consider vasculitis, motor sensory variant and HNPP (hereditary nerve pressure palsies) or MADSAM (multifocal acquired distal sensory and motor neuropathy, or Lewis Sumner syndrome) which is diagnosed with EMG. Rarer causes are infection (HIV, sarcoid, lyme) or involvement of single nerves or roots (eg. CTS).
4. Asymmetric proximal and distal weakness with sensory loss. Proximal means it may include elbow extensors, hip girdle muscles, neck muscles, knees, covering c5-T1 or L2-S1). Consider polyradiculopathy or plexopathy, due to DM, plexopathies, polyradiculopathy due to neoplasia, carcinoma, lymphoma, and hereditary neuropathy
5. Asymmetric distal weakness without sensory loss eg. progressive footdrop. Category includes ALS (especially with UMN signs), progressive muscular atrophy including regional forms (brachial or leg) juvenile monomelic atrophy, multifocal acquired motor neuropathy
6. Symmetric sensory loss (like number 2) but with UMN signs (crossed adductors, Babinski) think B12 deficiency, ALD, MLD or combination of diabetic/CSPN with cervical spondylosis diagnosis of exclusion)
7. Symmetric weakness without sensory loss-- consider SMA (Kennedy s. includes bulbar, chromosome five includes neck weakness). With bilateral footdrop may have normal EMG. CMT SNAPs are abnormal. overlaps MD and NMJ
8. Focal midline proximal symmetric weakness with neck extensor weakness (ALS, myopathy, MG, oculopharyngeal d., Kennedy s.)
9. Sensory asymmetric proprioceptive loss without weakness. Looks like neuronopathy (CA) but NORMAL SNAPS, abnormal roots on MRI suggest autoimmune, +/- treat with IVIG
10. Autonomic dysfunction
Exceptions to above
1) Mononeuritis multiplex including vasculitis presents symmetrically in one third
2) CIDP -- MMN and MADSAM may be asymmetric distal
3) Demyelinating CMT has no proximal weakness
4) DADS phenotype looks like pattern 2 at bedside but on exam has prolonged latiencies.
Saturday, August 19, 2006
SE III
Status epilepticus is a neurologic emergency. The first item is medical stablization airway-breathing-circulation. Confused patients should be given thiamine, then glucose (50 grams_, thiamine (100 mg i-v), Narcan (0.4-2.0 mg i-v), and flumazenil (if indicated) 0.2 mg i-v. Labs should be sent, including electrolytes, CBC, diff, Ca, Mg, PO4, extra red top, AED levels, tox screen/ ETOH level.
Several drugs may be used for the acute treatment of SE, but the key is knowing in detail the pharmacokinetic proporties of the chosen drugs. Lorazepam is often given first line, and is considered the most rapidly effective. The dose is 0.5-1.0 mg/kg, Unlike diazepam, is not metabolized by the liver and has a longer half life. Typically, if lorazepam is used a longer acting drug needs to be added immediately. Cerebyx can be given i-v. Unlike i-v Dilantin, Cerebyx can be given rapidly, without cardiac monitoring, can be given i-m if no i-v access is obtained, and does not cause purple hand syndrome (safer and more effective), Dosing is identical to Dilantin. IT IS NOT ONE GRAM. The dosing is 20 mg/kg, about 1500 grams in an average sized patient, and underdosing can cause recurrent seizures. In patients with verified diagnosis of overt GCSE, response rates were as follows: lorazepam, 64.9%; phenobarbital, 58.2%; diazepam and phenytoin, 55.8%; and phenytoin alone, 43.6%. In statistical comparison of the pairs, only the difference between lorazepam and phenytoin alone was significant.
If the patient has a single seizure and is able to swallow pills, they may be orally loaded with Dilantin Kapseals, 100 mg tablets in the 20 mg/kg dosing schedule. Typically for a 80 kg man, 400 mg po q 3 hours times four doses is reasonable. A Dilantin level should be checked the following morning and a daily dose ordered. LIQUID DILANTIN GIVEN THROUGH DOBHOFFS NEVER ACHIEVES THERAPEUTIC LEVELS! (Give Kapseals or i-v Cerebyx).
Alternatives: Depacon (= i-v Depakote) 20 mg/kg i-v over five minutes, phenobarbital 10-20 mg/kg i-v with monitoring over an hour. In refractory SE (ie, that which does not respond to either regimen above), a commonly used protocol is intravenous pentobarbital. A loading dose of 5 mg/kg is followed by 0.5-3 mg/kg/h titrated to cessation of seizures or a burst-suppression pattern on EEG. In a recent study of patients with refractory SE, Krishnamurthy and Drislane concluded that the survival rate was better in patients whose EEG was more suppressed. Hypotension is a risk of pentobarbital infusion. In patients who cannot tolerate pentobarbital, alternatives include continuous infusion of benzodiazepines (eg, midazolam or propofol).
Pitfalls
1. Failure to perform EEG-- may miss nonconvulsive SE and the chance to treat. May miss pseudoseizures and overtreat patient.
2. Failure to perform lumbar puncture-- may miss meningitis
3. Failure to consider a diagnosis of herpes encephalitis-- must be treated early
4. Using above medications incorrectly
5. Failure to order EEG monitoring on admission if patient is not back to normal-- similar to 1-- may miss ongoing SE
6. Discharge from ER prior to patient returning to baseline cognitively-- may miss HSVE
7. Failure to consider differential diagnosis-- intoxication, locked in syndrome, psychogenic SE etc.
Complex partial status epilepticus
Favorable neurologic outcomes of CPSE have been reported regardless of whether medical treatment was successful. Few reports indicate serious sequelae complicating CPSE. Thus, the question of how aggressively to treat CPSE remains controversial. In general, pending a good, randomized trial, CPSE should be treated similarly to GCSE, except that treatment should stop before the use of general anesthesia (eg, pentobarbital coma).
In acute stages and for diagnosis, treatment with an intravenous benzodiazepine may be helpful. Often, out-of-hospital treatment with rectal or oral benzodiazepines aborts an episode. Williamson believes that, since most patients with CPSE have a history of epilepsy, concomitant AED therapy should be optimized.
Walker and Shorvon reported that, although most episodes of CPSE are self-terminating, recurrent episodes are encountered, and medical treatment is often disappointing. Patients who have medically refractory localization-related epilepsy should be evaluated for surgical therapy.
Absence status epilepticus
Walker and Shorvon reported that ASE responds rapidly to intravenous benzodiazepines. D'Agostino and coworkers believe that valproate is the medication of choice for ASE. Although effective, this treatment may result in complications such as sedation and respiratory depression. Kaplan summarized a case of a female with known absence epilepsy in which hospitalization was avoided by treating ASE with intravenous valproate. Snead et al stated that the more atypical the SE, the more difficult it is to control with benzodiazepines and other forms of therapy. Patients with primary generalized epilepsy should have optimized valproate or ethosuximide therapy to prevent recurrent episodes of ASE. Thomas et al reported that long-term anticonvulsant therapy might not be necessary in adults who are middle-aged or older at the onset of de novo ASE.
Li
Several drugs may be used for the acute treatment of SE, but the key is knowing in detail the pharmacokinetic proporties of the chosen drugs. Lorazepam is often given first line, and is considered the most rapidly effective. The dose is 0.5-1.0 mg/kg, Unlike diazepam, is not metabolized by the liver and has a longer half life. Typically, if lorazepam is used a longer acting drug needs to be added immediately. Cerebyx can be given i-v. Unlike i-v Dilantin, Cerebyx can be given rapidly, without cardiac monitoring, can be given i-m if no i-v access is obtained, and does not cause purple hand syndrome (safer and more effective), Dosing is identical to Dilantin. IT IS NOT ONE GRAM. The dosing is 20 mg/kg, about 1500 grams in an average sized patient, and underdosing can cause recurrent seizures. In patients with verified diagnosis of overt GCSE, response rates were as follows: lorazepam, 64.9%; phenobarbital, 58.2%; diazepam and phenytoin, 55.8%; and phenytoin alone, 43.6%. In statistical comparison of the pairs, only the difference between lorazepam and phenytoin alone was significant.
If the patient has a single seizure and is able to swallow pills, they may be orally loaded with Dilantin Kapseals, 100 mg tablets in the 20 mg/kg dosing schedule. Typically for a 80 kg man, 400 mg po q 3 hours times four doses is reasonable. A Dilantin level should be checked the following morning and a daily dose ordered. LIQUID DILANTIN GIVEN THROUGH DOBHOFFS NEVER ACHIEVES THERAPEUTIC LEVELS! (Give Kapseals or i-v Cerebyx).
Alternatives: Depacon (= i-v Depakote) 20 mg/kg i-v over five minutes, phenobarbital 10-20 mg/kg i-v with monitoring over an hour. In refractory SE (ie, that which does not respond to either regimen above), a commonly used protocol is intravenous pentobarbital. A loading dose of 5 mg/kg is followed by 0.5-3 mg/kg/h titrated to cessation of seizures or a burst-suppression pattern on EEG. In a recent study of patients with refractory SE, Krishnamurthy and Drislane concluded that the survival rate was better in patients whose EEG was more suppressed. Hypotension is a risk of pentobarbital infusion. In patients who cannot tolerate pentobarbital, alternatives include continuous infusion of benzodiazepines (eg, midazolam or propofol).
Pitfalls
1. Failure to perform EEG-- may miss nonconvulsive SE and the chance to treat. May miss pseudoseizures and overtreat patient.
2. Failure to perform lumbar puncture-- may miss meningitis
3. Failure to consider a diagnosis of herpes encephalitis-- must be treated early
4. Using above medications incorrectly
5. Failure to order EEG monitoring on admission if patient is not back to normal-- similar to 1-- may miss ongoing SE
6. Discharge from ER prior to patient returning to baseline cognitively-- may miss HSVE
7. Failure to consider differential diagnosis-- intoxication, locked in syndrome, psychogenic SE etc.
Complex partial status epilepticus
Favorable neurologic outcomes of CPSE have been reported regardless of whether medical treatment was successful. Few reports indicate serious sequelae complicating CPSE. Thus, the question of how aggressively to treat CPSE remains controversial. In general, pending a good, randomized trial, CPSE should be treated similarly to GCSE, except that treatment should stop before the use of general anesthesia (eg, pentobarbital coma).
In acute stages and for diagnosis, treatment with an intravenous benzodiazepine may be helpful. Often, out-of-hospital treatment with rectal or oral benzodiazepines aborts an episode. Williamson believes that, since most patients with CPSE have a history of epilepsy, concomitant AED therapy should be optimized.
Walker and Shorvon reported that, although most episodes of CPSE are self-terminating, recurrent episodes are encountered, and medical treatment is often disappointing. Patients who have medically refractory localization-related epilepsy should be evaluated for surgical therapy.
Absence status epilepticus
Walker and Shorvon reported that ASE responds rapidly to intravenous benzodiazepines. D'Agostino and coworkers believe that valproate is the medication of choice for ASE. Although effective, this treatment may result in complications such as sedation and respiratory depression. Kaplan summarized a case of a female with known absence epilepsy in which hospitalization was avoided by treating ASE with intravenous valproate. Snead et al stated that the more atypical the SE, the more difficult it is to control with benzodiazepines and other forms of therapy. Patients with primary generalized epilepsy should have optimized valproate or ethosuximide therapy to prevent recurrent episodes of ASE. Thomas et al reported that long-term anticonvulsant therapy might not be necessary in adults who are middle-aged or older at the onset of de novo ASE.
Li
Thursday, August 03, 2006
SE II
Status epilepticus is a neurologic emergency. The first item is medical stablization airway-breathing-circulation. Confused patients should be given thiamine, then glucose (50 grams_, thiamine (100 mg i-v), Narcan (0.4-2.0 mg i-v), and flumazenil (if indicated) 0.2 mg i-v. Labs should be sent, including electrolytes, CBC, diff, Ca, Mg, PO4, extra red top, AED levels, tox screen/ ETOH level.
Several drugs may be used for the acute treatment of SE, but the key is knowing in detail the pharmacokinetic proporties of the chosen drugs. Lorazepam is often given first line, and is considered the most rapidly effective. The dose is 0.5-1.0 mg/kg, Unlike diazepam, is not metabolized by the liver and has a longer half life. Typically, if lorazepam is used a longer acting drug needs to be added immediately. Cerebyx can be given i-v. Unlike i-v Dilantin, Cerebyx can be given rapidly, without cardiac monitoring, can be given i-m if no i-v access is obtained, and does not cause purple hand syndrome (safer and more effective), Dosing is identical to Dilantin. IT IS NOT ONE GRAM. The dosing is 20 mg/kg, about 1500 grams in an average sized patient, and underdosing can cause recurrent seizures. In patients with verified diagnosis of overt GCSE, response rates were as follows: lorazepam, 64.9%; phenobarbital, 58.2%; diazepam and phenytoin, 55.8%; and phenytoin alone, 43.6%. In statistical comparison of the pairs, only the difference between lorazepam and phenytoin alone was significant.
If the patient has a single seizure and is able to swallow pills, they may be orally loaded with Dilantin Kapseals, 100 mg tablets in the 20 mg/kg dosing schedule. Typically for a 80 kg man, 400 mg po q 3 hours times four doses is reasonable. A Dilantin level should be checked the following morning and a daily dose ordered. LIQUID DILANTIN GIVEN THROUGH DOBHOFFS NEVER ACHIEVES THERAPEUTIC LEVELS! (Give Kapseals or i-v Cerebyx).
Alternatives: Depacon (= i-v Depakote) 20 mg/kg i-v over five minutes, phenobarbital 10-20 mg/kg i-v with monitoring over an hour. In refractory SE (ie, that which does not respond to either regimen above), a commonly used protocol is intravenous pentobarbital. A loading dose of 5 mg/kg is followed by 0.5-3 mg/kg/h titrated to cessation of seizures or a burst-suppression pattern on EEG. In a recent study of patients with refractory SE, Krishnamurthy and Drislane concluded that the survival rate was better in patients whose EEG was more suppressed. Hypotension is a risk of pentobarbital infusion. In patients who cannot tolerate pentobarbital, alternatives include continuous infusion of benzodiazepines (eg, midazolam or propofol).
Pitfalls
1. Failure to perform EEG-- may miss nonconvulsive SE and the chance to treat. May miss pseudoseizures and overtreat patient.
2. Failure to perform lumbar puncture-- may miss meningitis
3. Failure to consider a diagnosis of herpes encephalitis-- must be treated early
4. Using above medications incorrectly
5. Failure to order EEG monitoring on admission if patient is not back to normal-- similar to 1-- may miss ongoing SE
6. Discharge from ER prior to patient returning to baseline cognitively-- may miss HSVE
7. Failure to consider differential diagnosis-- intoxication, locked in syndrome, psychogenic SE etc.
Complex partial status epilepticus
Favorable neurologic outcomes of CPSE have been reported regardless of whether medical treatment was successful. Few reports indicate serious sequelae complicating CPSE. Thus, the question of how aggressively to treat CPSE remains controversial. In general, pending a good, randomized trial, CPSE should be treated similarly to GCSE, except that treatment should stop before the use of general anesthesia (eg, pentobarbital coma).
In acute stages and for diagnosis, treatment with an intravenous benzodiazepine may be helpful. Often, out-of-hospital treatment with rectal or oral benzodiazepines aborts an episode. Williamson believes that, since most patients with CPSE have a history of epilepsy, concomitant AED therapy should be optimized.
Walker and Shorvon reported that, although most episodes of CPSE are self-terminating, recurrent episodes are encountered, and medical treatment is often disappointing. Patients who have medically refractory localization-related epilepsy should be evaluated for surgical therapy.
Absence status epilepticus
Walker and Shorvon reported that ASE responds rapidly to intravenous benzodiazepines. D'Agostino and coworkers believe that valproate is the medication of choice for ASE. Although effective, this treatment may result in complications such as sedation and respiratory depression. Kaplan summarized a case of a female with known absence epilepsy in which hospitalization was avoided by treating ASE with intravenous valproate. Snead et al stated that the more atypical the SE, the more difficult it is to control with benzodiazepines and other forms of therapy. Patients with primary generalized epilepsy should have optimized valproate or ethosuximide therapy to prevent recurrent episodes of ASE. Thomas et al reported that long-term anticonvulsant therapy might not be necessary in adults who are middle-aged or older at the onset of de novo ASE.
Several drugs may be used for the acute treatment of SE, but the key is knowing in detail the pharmacokinetic proporties of the chosen drugs. Lorazepam is often given first line, and is considered the most rapidly effective. The dose is 0.5-1.0 mg/kg, Unlike diazepam, is not metabolized by the liver and has a longer half life. Typically, if lorazepam is used a longer acting drug needs to be added immediately. Cerebyx can be given i-v. Unlike i-v Dilantin, Cerebyx can be given rapidly, without cardiac monitoring, can be given i-m if no i-v access is obtained, and does not cause purple hand syndrome (safer and more effective), Dosing is identical to Dilantin. IT IS NOT ONE GRAM. The dosing is 20 mg/kg, about 1500 grams in an average sized patient, and underdosing can cause recurrent seizures. In patients with verified diagnosis of overt GCSE, response rates were as follows: lorazepam, 64.9%; phenobarbital, 58.2%; diazepam and phenytoin, 55.8%; and phenytoin alone, 43.6%. In statistical comparison of the pairs, only the difference between lorazepam and phenytoin alone was significant.
If the patient has a single seizure and is able to swallow pills, they may be orally loaded with Dilantin Kapseals, 100 mg tablets in the 20 mg/kg dosing schedule. Typically for a 80 kg man, 400 mg po q 3 hours times four doses is reasonable. A Dilantin level should be checked the following morning and a daily dose ordered. LIQUID DILANTIN GIVEN THROUGH DOBHOFFS NEVER ACHIEVES THERAPEUTIC LEVELS! (Give Kapseals or i-v Cerebyx).
Alternatives: Depacon (= i-v Depakote) 20 mg/kg i-v over five minutes, phenobarbital 10-20 mg/kg i-v with monitoring over an hour. In refractory SE (ie, that which does not respond to either regimen above), a commonly used protocol is intravenous pentobarbital. A loading dose of 5 mg/kg is followed by 0.5-3 mg/kg/h titrated to cessation of seizures or a burst-suppression pattern on EEG. In a recent study of patients with refractory SE, Krishnamurthy and Drislane concluded that the survival rate was better in patients whose EEG was more suppressed. Hypotension is a risk of pentobarbital infusion. In patients who cannot tolerate pentobarbital, alternatives include continuous infusion of benzodiazepines (eg, midazolam or propofol).
Pitfalls
1. Failure to perform EEG-- may miss nonconvulsive SE and the chance to treat. May miss pseudoseizures and overtreat patient.
2. Failure to perform lumbar puncture-- may miss meningitis
3. Failure to consider a diagnosis of herpes encephalitis-- must be treated early
4. Using above medications incorrectly
5. Failure to order EEG monitoring on admission if patient is not back to normal-- similar to 1-- may miss ongoing SE
6. Discharge from ER prior to patient returning to baseline cognitively-- may miss HSVE
7. Failure to consider differential diagnosis-- intoxication, locked in syndrome, psychogenic SE etc.
Complex partial status epilepticus
Favorable neurologic outcomes of CPSE have been reported regardless of whether medical treatment was successful. Few reports indicate serious sequelae complicating CPSE. Thus, the question of how aggressively to treat CPSE remains controversial. In general, pending a good, randomized trial, CPSE should be treated similarly to GCSE, except that treatment should stop before the use of general anesthesia (eg, pentobarbital coma).
In acute stages and for diagnosis, treatment with an intravenous benzodiazepine may be helpful. Often, out-of-hospital treatment with rectal or oral benzodiazepines aborts an episode. Williamson believes that, since most patients with CPSE have a history of epilepsy, concomitant AED therapy should be optimized.
Walker and Shorvon reported that, although most episodes of CPSE are self-terminating, recurrent episodes are encountered, and medical treatment is often disappointing. Patients who have medically refractory localization-related epilepsy should be evaluated for surgical therapy.
Absence status epilepticus
Walker and Shorvon reported that ASE responds rapidly to intravenous benzodiazepines. D'Agostino and coworkers believe that valproate is the medication of choice for ASE. Although effective, this treatment may result in complications such as sedation and respiratory depression. Kaplan summarized a case of a female with known absence epilepsy in which hospitalization was avoided by treating ASE with intravenous valproate. Snead et al stated that the more atypical the SE, the more difficult it is to control with benzodiazepines and other forms of therapy. Patients with primary generalized epilepsy should have optimized valproate or ethosuximide therapy to prevent recurrent episodes of ASE. Thomas et al reported that long-term anticonvulsant therapy might not be necessary in adults who are middle-aged or older at the onset of de novo ASE.
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