Neurology Minutiae

AED selection for patients taking antiretrovirals

2012-01-18T18:01:00.003-08:00

Due to interactions, dose adjustments are often needed. This is a position paper with mostly level C recommendations.

1. If taking PTN, may need to increase lopinavir/ritonavir dosage up to 50 % to maintain levels
2. Patients on VPA may need to reduce zidovudine dose to maintain zid. levels in serum
3. Coadministration of VPA and efavirenz does not require dose adjustment of ef.
4. Patients on ritonavir/ atazanavir may need 50 % lamotrigine dose increase to maintain LTG levels
5. Coadministration of raltegravir/atazanavir and LTG may not require LTG dose adjustment
6. Coadministration of raltegravir and midazolam may not require midazolam dose adjustment
7. Counsel patients its unclear whether combinations of AED's and ARV's require dose adjustments esp enzyme inducers. They may lead to virologic failure, esp protease inhibitors and nonnucleoside reverse transcriptase inhibitors

Combination AED therapy with Depakote and lamotrigine

2012-01-18T16:58:00.000-08:00

Neurology 2012; 78: 62-68 Combing records of 148 disabled adults in state run institutions, authors analyzed whether any combination of AED's were superior to others. Out of 32 AED combinations, only the combination of lamotrigine and valproate was superior to others,AND the addition of a third AED aggregately did not add to epileptic control over the use of two medicines

Central pontine myelinolysis PEARLS and SURPRISING FINDINGS

2011-12-01T10:58:00.000-08:00

Graff-Radford J, Fugate JE, Kaufmann TJ et al. Clinical and radiologic correlations of central pontine myelinolysis. Mayo Clin Proc 2011; 86: 1063-1067.

Authors did a chart review of patients with definite CPM seen at Mayo over 11 years and found 24 cases. Key points:

1. MRI T2 signal abnormality even if extensive does not predict clinical outcome as some patients with bad MRI recovered.

2, Half had CPM only, half also had extrapontine myelinolysis especially thalamic

3. Causes were rapid correction of Na (67%), hyperosmolar hyperglycemia (4 %), hyperammonemia (n=1) and unknown (n=6). 75 % were alcoholics and 50 % were malnourished with albumen mean 2.6. Half were chronically hypertensive, one third were taking diuretics, 17 % had DM and 1 had ahad liver-kidney transplant. Forty percent of hyponatremic patients also were hypokalemic, and mean nadir of Na was 114.

4. Presentations included encephalopathy (75 %), ataxia (46 %), dysarthria (29 %), eom abnormalities (25 %), seizures (21 %), eps including chorea.

5. Initial MRI was negative in 5 patients and became positive later.

6. Four of 14 patients so tested had Gd+ lesion on MRI

7. Ten of 24 patients achieved favorable outcome (mRS<2) at discharge, 15/24 were favorable at 22 months.

8. Many patients did not have prior IWMD

Treximet v. Fiorecet favors the industry over the generic

2011-11-29T15:41:00.001-08:00

Sumatriptan-Naproxen and Butalbital: A Double-Blind, Placebo-Controlled Crossover Study; Derosier F, Sheftell F, Silberstein S, Cady R, Ruoff G, Krishen A, Peykamian M; Headache (Nov 2011)

Objectives.- The primary objective was to compare the efficacy of a sumatriptan and naproxen combination medication (SumaRT/Nap-85 mg sumatriptan and 500 mg naproxen sodium), a butalbital-containing combination medication (BCM-50 mg butalbital, 325 mg acetaminophen, 40 mg caffeine), and placebo when used to treat moderate to severe migraine headache pain in subjects who used BCMs in the past. Background.- Despite the lack of Food and Drug Administration approval and the absence of placebo-controlled trials to demonstrate efficacy, butalbital-containing medications are among the most commonly prescribed acute migraine treatments in the United States. Butalbital-containing medications are associated with serious and undesirable side effects, and have been linked to the chronification of migraine and development of medication-overuse headaches. This study compares the relative efficacy, safety, and tolerability of a fixed dose SumaRT/Nap versus a BCM and placebo. Methods.- Enrolled subjects were required to have treated at least 1 migraine with a butalbital medication in the past. Enrolled subjects treated 3 moderate to severe migraines using each of the 3 study treatments once in a randomized sequence. The primary endpoint compared SumaRT/Nap versus BCM for sustained pain freedom at 2-24 hours without the use of any rescue medication. This study combines data from 2 identical outpatient, randomized, multicenter, double-blind, double-dummy, 3 attack crossover studies in adult migraineurs (International Classification of Headache Disorders, 2nd edition). Results.- A total of 442 subjects treated at least 1 attack with study medication. The majority of the treated subjects were female (88%) with a mean age 43 years, who reported that their migraines had a severe impact on their lives (78% with Headache Impact Test-6 of>59). At screening, 88% of subjects reported current butalbital use; 68% had used butalbital for more than 6 weeks; and 82% reported satisfaction with butalbital. Across treatment groups, 28-29% of subjects took study medication within 15 minutes of migraine onset, 34-37% of subjects took study medication>15 minutes to 2 hours after onset, and 32-36% of subjects took study medication more than 2 hours after onset. This study did not detect a difference at the nominal 0.05 level in percent sustained pain-free between SumaRT/Nap (8%), BCM (6%), and placebo (3%). SumaRT/Nap was superior to BCM for pain free at 2, 4, 6, 8, 24, 48 hours (P ≤ .044); pain relief (mild or no pain) at 2, 4, 6, 8, 24, 48 hours (P ≤ .01); sustained pain relief 2-24 hours (P < .001); migraine free (pain free with no nausea, photophobia, or phonophobia) at 4, 6, 8, 24, 48 hours (P ≤ .046); and complete symptom free (migraine free with no neck/sinus pain) at 4, 6, 8, 48 hours (P ≤ .031). Adverse event incidence was similar for all treatments (10%, 12%, and 9% for placebo, SumaRT/Nap, and BCM, respectively). Nausea was the most frequent adverse event (2%, 2%, and<1% for placebo, SumaRT/Nap, and BCM, respectively). Five serious adverse events were reported by 3 subjects: viral meningitis and colon neoplasm (placebo); chest pain and hypertension 17 days postdose (SumaRT/Nap); and breast cancer (BCM). Investigators judged no serious adverse events related to study medication. Conclusions.- This study primarily included subjects whose migraines significantly impacted their lives. Before the study, these subjects used butalbital-containing medications as part of their current migraine treatment regimen and were satisfied with it, suggesting they were butalbital responders who had found a workable treatment strategy for themselves. When treated with SumaRT/Nap versus BCM in this study, however, a significant proportion of subjects reported better treatment outcomes for themselves for both migraine pain and associated symptoms. Use of SumaRT/Nap was also associated with less rescue medication use and a longer time before use of rescue medication compared with both BCM and placebo.

Blogger note: this is an interesting study, but begs the question that the most common reason neurologists prescribe fiorecet is that the patient is considered unsafe to receive triptans for various reasons.

Ketamine: to induce coma in cases of brain injury?

2011-11-29T15:37:00.001-08:00

BET 3: Is ketamine a viable induction agent for the trauma patient with potential brain injury; Emergency Medicine Journal 28 (12), 1076-7 (Dec 2011)

A short cut review was carried out to establish whether ketamine is a viable induction agent in trauma patients with potential brain injuries. 276 papers were found using the reported searches, of which 5 presented the best evidence to answer the clinical question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these best papers are tabulated. It is concluded that there is no evidence to suggest harm with Ketamine use as induction agent for the patient with potential traumatic brain injury. The drug has major advantages in those patients with associated haemodynamic compromise and should potentially be regarded as the agent of choice.

Blogger note: Always beware when a meta-analysis tries to answer questions not posed by the papers meta-analyzed. As always, the devil is in the details.

Skull based osteomyelitis

2011-11-29T15:27:00.001-08:00

Skull base osteomyelitis]; Benoudiba F, Toulgoat F, Sarrazin JL; Journal de Radiologie 92 (11), 987-94 (Nov 2011)

Skull base osteomyelitis is a rare but serious infection. It typically afflicts immunosuppressed patients and should be suspected in patients with persistent otitis complicated by cranial nerve palsy (VII, IX and XII). The most frequent germ is pseudomonas aeruginosa. Contiguous spread of infection occurs along neurovascular structures and weaker regions of the skull base, then into the soft tissue compartments of the face and nasopharynx. Diagnosis and treatment should be made early for this disease with poor prognosis and high mortality.

Blogger note: Hopefully neurologists won't miss that there is something wrong when they examine this patient, but in case they forget, the germ to treat is pseudomonas.

the fourteen review of systems are.... (drumroll)

2011-08-20T01:53:00.001-07:00

I hate to waste my few remaining neurons on memorizing this but its clear that failure to document will cost not one but two levels of reimbursement (and no one cannot attest in aggregate " a fourteen point ROS was done and was negative") and one cannot make up your own 14 ROS or state there are 17 or 35 there are only 14 defined by PAYORS (no matter how retarded the categories) here they are

1. General/Constitutional

2. Eyes

3. ENT

4. Heart/CV

5. Respiratory

6. GIT

7. GU

8. Musculoskeletal

9. Neurologic

10.Heme/Onc

11. Psychiatric

12. All/immunologic

13. Skin

14. Endocrine

Health screening

prolonged visit codes

2011-07-09T20:07:00.001-07:00

Must document time for all of these codes

code 99354 extended care code for outpatients first hour

99356/99357 extended care for inpatients

Consider using if you are doing a prolonged consult on someone who has been seen in last 3 years, not eligible for new patient code. If took 1 hour 15 minutes, bill at highest level established patient (99215) for first forty minutes, and 99354 for subsequent face to face time . Over 74 minutes can use additional code for time.

IF ARNP sees patient first (CE) then MD sees or vice versa.

99239 code for discharge codes more than 30 minutes.

Critical care 99291/'99292 first hour (31-74 minutes for 99291 and 99292 for each subsequent half hour). Tpa good choice, add all your time together. document time.Includes time with radiologist, time on unit.

Use modifier 25 for LP if done on same day as E and M service.

Lamotrigine in pregnancy and absent major malformations

2011-06-11T17:20:00.000-07:00

Cunningham MC et al. Final results from 18 years of the Lamotrigine Pregnancy Registry. Neurology 2011; 76: 1817-1823.

1558 first trimester exposures occurred. There were 35 infants (2.2 %) with major congenital malformations. This is similar to population based cohorts. However, the number was 10.7%ammmong the 150 exposed both to lamotrigine and valproate in the first trimester and 2.8 % in 430 patients exposed to lamotrigine polytherapy without valproate. Among patients with first trimester monopharmacy with lamotrigine, there were 3 cases of anencephaly, all of which were electively terminated.

Postictal wandering localizes to temporal> extratemporal focus

2011-06-11T16:55:00.000-07:00

Tai P. et al. Postictal wandering (PIW) is common after temporal lobe seizures. Neurology 2010; 74:11:924-931.

PIW occurs in 4 % of seizures, and 13 % of seizures of patients who experienced PIW (n=42 patients admitted to an epilepsy monitoring unit in Toronto. It occurred in 9/20 with TLE and 2/22 with non TLE, and 18/186 temporal seizures, and 2/266 non temporal lobe seizures.

Literature tends to emphasize frontal seizures, contrary to these results, but may reflect selection bias of a different group.

Cryptococcosis in non-immunosuppressed

2011-06-11T16:06:00.000-07:00

Bestard J, Siddiqi ZA. Cryptococcal meningoencephalitis in immunocompetent patients: changing trends in Canada. Neurology 74:15 April 13, 2010 pp 1233-1234

Cryptococcus neoformans have 3 subtypes : var grubii and var neoformans affect immunosuppressed, whereas CN var gatii affects non-immunosuppressed, especially males. Its found in decaying heartwood of decaying tree species in tropics and also Vancouver Island, exclusively in British Columbia.

Bob Daroff's exam of a patient with Whipple's mimicking PSP

2011-05-29T06:34:00.001-07:00

http://stream.utah.edu/m/dp/frame.php?f=53f176fbc7618354812

h/t NOVEL

neurodoc

Flail arm and flail leg variants of ALS

2011-04-25T17:55:00.000-07:00

Neurology 2009; 72: 1087-1094

These are phenotypic variants of ALS that have been described a century or more ago that have unique characteristics including

1. In flail arm, proximal wasting and weakness, in flail leg, distal weakness or wasting
2. LMN variant with no clonus, hypertonia or UMN signs, or involvement of other extremity (leg + arm) or bulbar involvement
3. 4:1 male predominance in FA, 1:1 gender equality in FL in London; 10:1 and 5:1 respectively in Melbourne series
4. Relatively longer prognosis than other forms of ALS with lifespan of around 6 years

Synonyms FA: Vulpian-Bernhardt syndrome, hanging arm syndrome, neurogenic man in a barrel syndrome, or amyotrophic brachial diplegia
Synonyms FL: Marie -Patrikios variant, pseudopolyneuritic variant of ALS, peroneal form of ALS

Delayed cerebral thrombosis after initial good recovery from pc meningitis

2011-04-25T05:50:00.000-07:00

Schut ES, Brouwer MC, de Gan J, Florquin S, et al. Neurology 2009; 73: 1988-1995.

Dutch authors have small case series of patients who recovered apparently from meningitis then developed stroke on a delayed basis 2-3 weeks after recovery. 6 patients, including 5 males 30-73 got dexamethasone for pneumococcal meningitis. After 7-19 days patients suddenly deteriorated with headache, fever, loss of consciousness, brainstem signs and had thalamic or brainstem strokes in penetrating artery territory. LP's were sterile.
In discussion, authors note they surveyed a similar population in the predexamethasone days and found no delayed strokes. Authors speculate that withdrawing corticosteroids may be compromising and suggest reinstating high dose steroids in these patients, as well repeating LP promptly, treating with antibiotics again, and checking for endocarditis.

treatment of photosensitive seizures

2011-04-23T15:08:00.001-07:00

Take Home Points
• Light-induced seizures are not uncommon.
• Most patient with epilepsy can safely watch
television or play video games (using easy
preventive measures in those who are lightsensitive).
• Blue sunglasses can be very effective (and
documented with EEG & photic stimulation).
• Valproate & levetiracetam are the two most
effective treatments currently available, and the
drug selection for a given epilepsy syndrome
should consider if photosensitivity is present.
• Follow-up EEG with photic stimulation is helpful to
access the patient's response to treatment.
9

neurodoc

photosensitive seizures

2011-04-23T15:05:00.001-07:00

Photosensitivity
• 4.1 to 8.9% prevalence of photosensitivity
(without other seizures) in population
- 49% television induced
- 43% video game induced
• 76% of children with photosensitive
seizures to Pokemon had never had a prior
seizure, and 90% of these did not go on to
develop seizures.
• Broadcasting guidelines have dramatically
decreased photosensitive seizures
Takahashi Y et al. Neurology, 2004; 62: 990-993.

neurodoc

Epilepsy Syndromes Associatedwith Photosensitivity

2011-04-23T15:04:00.001-07:00

Epilepsy Syndromes Associated
with Photosensitivity

– Benign myoclonic epilepsy in infancy
– Severe myoclonic epilepsy of infancy (Dravet Syndrome)
(40%)
– Myoclonic-astatic epilepsy (Doose Syndrome)
– Childhood absence & juvenile absence (13-18%)
– Juvenile myoclonic epilepsy (30-35%)
– Epilepsy with GTC seizures on awakening (13%)
– Primary reading epilepsy (<10%)
– Jeavons syndrome (eyelid myoclonia and absences)
– Progressive myoclonic epilepsies (NCLFs, Lafora's
disease, Unverricht-Lundborg disease, MERRF)
– Idiopathic photosensitive occipital lobe epilepsy.
Guerrini R, Genton P. Epilepsia, 2004; 45 (Suppl 1): 14-18.
Photosensitivity: Types of
Seizures Induced
• Prevalence based on the literature:
– GTC (55-84%)
– Absences (6-20%)
– Myoclonic jerks (2-8%)
– Focal seizures (2.5%)
• Reports may over-exaggerate GTCs in
relation to "minor" seizure events.
• Clinical experience: Myoclonic jerks >
absences > GTCs.
Panayiotopoulos C. Epileptic Syndromes and Their Treatment. Springer. London 2009.
Photosensitivity Historical Timeline
1885 Gowers described girl with seizures when going into
bright sunlight
1932 Radovici described eyelid myoclonias and absence
seizures in response to eyelid closure while looking
at bright light
1952 Livingston reported TV-induced seizures for 1st time
1962 Gastaut studied 35 patients with TV induced
seizures
1981 Rushton reports "Space-Invader epilepsy"
1993 TV commercial caused 3 seizures in UK. Guidelines
for photic stimulation in commercials introduced.
1997 Pokemon Episode (Pikachu) induced seizures in
560 Japanese children.
3

neurodoc

Aggravation of Severe Myoclonic Epilepsy (SMEI) by Lamotrigine

2011-04-23T14:44:00.001-07:00

v Twenty-one SMEI patients (age 2-18 years, mean
9 years)

v Convulsive seizures increased by >50% in 8 of 20
pts, myoclonic seizures worsened in 6 of 18 pts.

v Of 5 pts with improvement in one seizure type, 4
had concomitant worsening of more disabling
seizures

v Lamotrigine was withdrawn in 19 pts, with
consequent improvement in 18

R. Guerrini et al, Epilepsia 1998;39, 508-12

neurodoc

myoclonus fromgabapentin

2011-04-23T14:43:00.001-07:00

Myoclonus Associated with the Use of Gabapentin

v Of 104 consecutive patients treated with
gabapentin, 13 (12.5%) developed myoclonus

v All patients (age 14 to 41 years) had refractory
partial epilepsy, 6 had a static encephalopathy

v Myoclonus was multifocal in 10, contralateral to
the epilepticus focus in 3

v Myoclonus persisted for as long as gabapentin
was continued. Disappeared on drug withdrawal.

v An EEG recording in 3 patients showed no
correlate

J. Asconapé et al., Epilepsia 2000:41:479-82

neurodoc

risk factors for statin myopathy; antibodies of

2011-02-17T06:08:00.003-08:00

The field of autoantibodies related to immune-mediated inflammatory myopathies has expanded in recent years and there is now a host of antibodies that have relevance to these myopathies. The 1975 Bohan and Peter criteria for the classification of immune-mediated inflammatory myopathies do not reflect many newer insights, and several newer classification schemes exist, but none enjoy uniform acceptance.¹² Some controversy remains as to the pathophysiology behind dermatomyositis, but this disease is probably the most consistently defined. Conversely, polymyositis has several varied definitions, and in the Bohan and Peter criteria it was not delineated from inclusion body myopathy (IBM). The antisynthetase syndrome associated with antibodies described in this section does not cleanly sort under either the dermato- or polymyositis labels. The inflammatory myopathies associated with SRP and 200/100 antibodies do not even necessarily have the inflammatory muscle infiltrates that we traditionally associate with inflammatory myopathies. While IBM has prominent inflammatory features, none of the described autoantibodies are linked to IBM, nor is immunomodulatory treatment of any benefit. For these and other reasons, many authorities believe IBM to be more of a myodegenerative disease with secondary inflammation.¹³ Granulomatous myopathy, HIV-associated myositis, and graft vs host disease are other immune-mediated inflammatory myopathies without associated muscle-directed antibodies.

There are also the overlap syndromes in which another defined autoimmune condition exists and overlaps with a myositis. This can occur in diseases such as systemic sclerosis, rheumatoid arthritis, systemic lupus erythematosus, and Sjögren syndrome. Distinguishing the primary inflammatory myopathies from the overlap syndromes is done by excluding the conditions causing overlap syndromes, but there are also autoantibodies that are almost unique to the immune-mediated inflammatory myopathies referred to as muscle-specific autoantibodies (MSA). Other antibodies are frequently seen in other connective tissue disorders, and these can be referred to as myositis-associated autoantibodies (MAA). All of these antibodies can help establish the diagnosis of myositis when the muscle biopsy is inconclusive, and the MSAs as well as some of the MAAs are listed in table 2.

The most prevalent MSA is the anti-Jo antibody, which is directed against histidyl-tRNA synthetase. Anti-Jo is detected in about 20% of patients with myositis in most populations. Anti-Jo can be detected in both dermatomyositis and polymyositis and is frequently associated with interstitial lung disease and mechanic's hands. This clinical and laboratory constellation is referred to as the antisynthetase syndrome. Interstitial lung disease is a potentially fatal comorbidity that often requires more aggressive immunomodulatory treatment. Histologically, the inflammation is often more perimysial rather than endomysial.¹⁴ There are other newer antisynthetase antibodies with similar clinical features including those that recognize threonyl-tRNA synthetase (anti-PL-7), alanyl-tRNA synthetase (anti-PL-12), glycyl-tRNA synthetase (anti-EJ), isoleucyl-tRNA synthetase (anti-OJ), asparaginyl-tRNA synthetase (anti-KS), anti-tyrosyl-tRNA synthetase, and antiphenylalanyl synthetase (anti-Zo). These other antibodies are each present in a few percent of patients, but there is essentially no overlap between them and patients do not express more than one antisynthetase antibody. A different type of antibody is the Anti-Mi-2 autoantibody. This nuclear antibody is directed against a component of the nucleosome-remodeling deacetylase, is seen more often in dermatomyositis, and is infrequent in most populations.

A clinically useful antibody is the SRP antibody. This antibody can often be found when there is myonecrosis, but little or no inflammation is seen on muscle histology. Identifying the antibody can be helpful in establishing that the myopathy is inflammatory and encourages escalating immunosuppression even if initial attempts are unsuccessful. The target of the new anti-155/140 antibody remains unknown, but this antibody is seen in dermatomyositis and is more common in paraneoplastic dermatomyositis compared to idiopathic autoimmune dermatomyositis.¹⁵ The not yet commercially available anti-200/100 autoantibody appears to have specificity for the necrotizing statin myositis (discussed earlier).⁸ In patients with a myopathy of unclear cause and a nondiagnostic biopsy testing, one should consider testing the anti-Jo antibody and a comprehensive panel of the other MSA, either sequentially or simultaneously

Myopathy: Five New Things

Risk of statin toxicity increases along with increases in their lipophilicity, cholesterol-lowering potency, and dosage.
In immune-mediated statin myopathy, discontinuation does not translate into immediate recovery.
MRI and muscle ultrasound in myopathy may provide detailed anatomic information.
Autoantibody testing may be helpful in defining myopathies of unclear cause.
Enzyme replacement may improve function in Pompe disease.

vincristine neuropathy nuggets and pearls

2010-12-05T09:46:00.001-08:00

Verstappen CCP,Heimans Koeppen S, et al. JJ, Dose-related vincristine-induced peripheral neuropathy with unexpected off-therapy worseningNeurology March 22, 2005 vol. 64 no. 6 1076-1077

Article described microtubule related neuropathy due to vincristine in 114 patients.

1. High dose group experienced more signs and symptoms than low dose group.

2. Off therapy worsening signs and symptoms occurred in about 30 percent, mostly in the first month off. Most patients improved off therapy however.

3. Paresthesias and numbness in both groups developed earlier in hands than feel and were more prominent in hands

4. Paresthesias, numbness and pain occurred at more than 50 percent in both groups

5. Resulting physical limitations include trouble buttoning clothes, climbing stairs, writing and walking

6. The dose intensity of VCR has changed considerably over the years. Studies 30 years ago describe dose intensities of 2 to 4 mg/week, frequently leading to a severe mixed sensorimotor peripheral neuropathy.Today, VCR is usually administered in a dose of ≤2 mg once every 1 to 4 weeks.

7. Off therapy deterioration is also well described in cisplatin and paclitaxol related neuropathy.

Sjogren's Pearls

2010-09-27T07:01:00.000-07:00

J. Birnbaum. Peripheral nervous system manifestations of Sjogren syndrome: clinical patterns, diagnostic paradigms, etiopathogenesis, and therapeutic strategies. The Neurologist 2010; 16:5:287 -- 297 .

1.Syndromes that can cause sicca symptoms and which should be typically excluded, include hepatitis B or hepatitis C, HIV, sarcoidosis, and a history of radiation to either the header the neck.

2. 30% to 50% of patients have negative auto antibodies and require a lip biopsy for diagnosis.

3. Sensory ganglionapathy : aka sensory neuronopathy is dramatic with isolated or disproportionate impairment of kinesthetic awareness, with profound handicap of proprioception, even affecting the larger joints. Sensory deafferentation can cause patients to become wheelchair-bound, or have pseudoathetoid movements which may be misdiagnosed as a movement disorder. The most common presentation is distal dysesthesias. Differential diagnosis includes paraneoplastic syndromes, Bickerstaff brainstem encephalitis, and effect of drugs for example, cisplatin and pyridoxine. Nerve conduction studies typically absent sensory nerve action potential(snaps) and preserved compound motor action potentials (cmap). T2 hyper intensities in the dorsal spinal cord are described. Response to I VIG is inconsistent.

4. Small fiber neuropathy: the cardinal feature can be excruciating burning pain. There is disproportionate or selective impairment in pinprick and temperature with preserved vibratory sense and proprioception. The onset is subacute or chronic usually. The differential diagnosis includes diabetes, amyloidosis, chemotherapy and other medications, genetic syndromes (i.e. Fabry's) and complications from HIV treatment.

5. Patients with findings of small fiber dysfunction disproportionally affecting the proximal extremities, torso or face in unorthodox patterns may have Sjogren's. Patients may also have classic length dependent symptoms.

6. Sjogrens and vasculitis: patients with mononeuritis multiplex should be evaluated for cryoglobulinemia especially with high titer rheumatoid factor, with disproportionate C-4 hypo-complementemia, or normal C-3. Small vessel vasculitis and low levels of C-4 complement in Sjogren's space placed the patient at 6 to 40. fold risk for non-Hodgkin's lymphoma. Therefore the development of systemic features such as fever or weight loss merit close scrutiny. Nerve or muscle biopsy showing vasculitis more likely responds to immunosuppressive therapy. Mori described patients with axonal MMN who also had cranial neuropathies. The most common is trigeminal neuropathy which may be indolent, progressive, or bilateral. The unifying feature may be ganglionapathy. Facial nerve also may be affected. Acute cranial neuropathy plus rapid multiple mono neuropathies may prompt concern for vasculitis.

7. Demyelinating neuropathies are rare but may be noted subclinically. EMG may know isolated prolonged F. waves.
8. Autonomic features are seen in 50% of Sjogren's patients. Inquire about urinary frequency or hesitancy, erectile dysfunction, increased or decreased sweating, orthostatic or temperature intolerance, constipation or increased bowel movements. Adie's pupil , space orthostatic hypotension, and abnormal sweating occurs in 57, 40, and 70% of patients with sensory neuronopathy respectively.

9. Anti-nicotinic ganglionic receptor antibody role is under investigation in Sjogren's. This antibody differs from the anti-muscarinic receptor antibody seen in myasthenia gravis.

10. Inflammatory myopathies occur only in 1 to 2%. Myalgias may be caused by autoimmune thyroid disease, vitamin D. deficiency, or fibromyalgia. Always assess vitamin D level. Vitamin D may be low due to malabsorption, bacterial deconjugation of bile acids due to gastric motility seen in autonomic neuropathies, type one renal tubular acidosis or coexisting celiac sprue.

Clinical spectrum of voltage gated potassium channel (VGKC) autoimmunity

2010-09-19T17:00:00.000-07:00

Tan KM, Lennon et al. Neurology 2008; 70:1883-1890.

80 patients were found, 71 with clinical information available. Mean age 65.

Neurologic symptoms were subacute or chronic including

1. cognitive impairment 71 %-- see below

2. seizures 58 %-- several types

3. dysautonomia 33 %

4. myoclonus 29 %

5. dyssomnia 26 %

6. peripheral nerve dysfunction 25 %

7. EPS 21 %

8. brainstem/cranial nerve dysfunction 19 %-- vision loss/blurred vision, diplopia, dysarthria, hemifacial spasm, facial numbness, anosmia.

9. hypothalamic involvement-- 38 %-- hyponatremia (36 %) , hyperphagia, (8%)

Common misdiagnosis was CJD (14 %).. Other misdiagnoses: viral encephalitis, recurrent TGA, generalized anxiety disorder, conversion disorder.

Associated tumors (paraneoplastic) 33 % confirmed histologically

carcinoma 18, adenoma 5, thymoma1, hematologic 3.

Associations

hyponatremia 36 %

other organ specific autoantibodies 49 %

coexisting autoimmune disorder 33 % (thyroiditis, DM)

34/38 responded to immunotherapy, half "vigorously" so.

Classic reports of association:

1. Morvan's syndrome

2, acquired neuromyotonia

3. epilepsy

4. limbic encephalitis

5. dysatuonomia

6. lung carcinoma

Cognitive presentation:

1. frontosubcortical (personaltiy change, disinhibition, executive dysfunction) 13 %

2. Visual hallucination (10 %)

3. Depression or agitation (13 %)

Treatment of orthostatic hypotension in Parkinson's disease

2010-09-19T16:37:00.001-07:00

Source: Neurology 2009 supplement cited above, p.S83

1. Consider a role for medication, including selegeline, levodopa, DA agonists and MAO inhibitors.

2. Increase sodium intake, especially in daytime.

3. Avoid lying flat which leads to release of renin. Elevate HOB and legs.

4. Postprandial hypotension can be avoided with small meals, with low carbohydrate intake and avoiding alcohol

5. Caffeine with breakfast can be helpful

6. Heat related vasodilatation, vasovagal activities (straining at stool, playing wind instruments, singing all can be considered/limited if applicable.

7. Isometric exercise especially swimming

8. Avoid knee high TEDS, consider waist high Jobst stockings or abdominal binders.

Medication:

1. Florinef up to 0.5 (start with 0.1 mg).

2. DDAVP 5-40 ug intranasally at bedtime can be tried. Monitor Na+ in first 4-5 days of treatment and monthly thereafter. It can cause a severe and life threatening hyponatremia.

3. Midodrine, start at 2.5 mg per day, do not go above 10 tid, and do not give at bedtime.

4. Erythropoietin 4,000 units biw especially if anemic also.

5. End of dose sweating can be an "off" phenomenon and can eb treated with more dopamine.

Treating constipation in Parkinson's disease, and urinary problems

2010-09-19T16:23:00.001-07:00

Regimen suggested in Neurology 72:21:2009 S4 pp S80-81.

Bowel:

Management consists of dietary changes, exercises and pharmacotherapy.

1. Dietary changes-- Increase bulk, and soften stool. Drink 6-8 glasses of water per day. Increase fiber, decrease baked goods. @ meals should have high fiber raw vegetables. Oat bran can be used. Exercise, including walking, is encouraged.

If stools remain hard, docusate, or lactulose 10-20 grams per day can be used. Miraelx (otc) can be used. Patients should be educated about possibble delayed onset and reminded to do the things in paragraph one above.

Third line is milk of magnesia and other laxatives or enemas. Apomorphine rescue therapy can be used.

Urinary:

Nocturia is earliest problem, then urgency, frequency and hesitancy. Consider detrusor hyperreflexia v. incomplete/delayed relaxation of the pelvic floor. Supine hypertension can also cause pressure natriuresis. Incomplete emptying can be an "off" symptom. UTI should be considered if any change occurs in symptoms.

Avoid nighttime water drinking. Try Detrol or Ditropan. Midodrine can worsen symptoms due to increasing sphincter tone. Diazepan, baclofen or dantrolene can be used to relax sphincter tone occassionally.

neurodoc

Diagnosis of parkinsonism

2010-09-19T16:09:00.001-07:00

Classic criteria indicate the triad of resting tremor, akinesia/bradykinesia, and cogwheel rigidity, with two of three being associated with the diagnosis of Parkinson's disease. At the London Brain bank, the diagnosis was not confirmed in 24 of 100 patients with these premorbid clinical symptoms (Hughes et al., JNNP 1992). The alternative triad of parkinsonism, assymetry, and response to levodopa correctly identified 98 % in 73 patients reported in a subsequent trial (Hughes et al., Brain 2002) and was therefore considered better.

neurodoc

Optic atrophy helpful hints

2010-09-11T07:53:00.001-07:00

from AAN 2010 course

differentiate pallor from atrophy

segmental patterns

signs of prior disc-- swelling high water marks and gliosis, fuzzy edges,

collateral venous vessels-- retinal choroid collaterals, AION or post pappilledeme

macular exudates pretty "fireworks" around macula

attenuated arterioles-- "ghost vessels" with gliosis

neurodoc

mimics of optic atrophy

2010-09-11T07:34:00.001-07:00

from aan course 2010

physiologic temporal pallor

aphakia/pseudoaphakia-- after take out lenses after cataract surgery

anemia

myopic discs

optic nerve hypoplasia

myelinated optic nerve fiber layers

neurodoc

neuropthy downloads UTAH

2010-09-10T18:38:00.001-07:00

http://library.med.utah.edu/NOVEL/

neurodoc

MGUS Pearls

2010-07-30T19:32:00.000-07:00

from Ramchandren S, Lewis RA. Monoclonal gammopathy and neuropathy. Curr Opin Neurol 2009; 22:480-485.

Note- search this blog for "MGUS" and various information posted elsewhere will not be repeated

Pearl - Differentiate into subtypes based on type of proteins found, and clinical syndromes

eg. osteosclerotic myeloma has an 85-100 % incidence of neuropathy, depending on whether they have partial syndrome or full POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, M spike and skin changes). In myeloma one third of patients have subclinical PN, and half of these may be small fiber neuropathy, in others, NCS and EMG is required to detect. In contrast, PN is much less frequent in Waldenstrom's macroglobulinemia (5-10 %) and amyloidosis (17 %).

IgM paraprotein patients have half of patients with paraprotein and neuropathy, and 15 % of those with paraprotein and no neuropathy. IgG patients only have 35 % of patients with paraprotein and neuropathy, but 75 % of patients with paraprotein and no neuropathy. IgA patients have 15 % of those with paraprotein and neuropathy, 10 % of those with paraprotein and no neuropathy. Thus IgM is NOT the most common paraprotein, but is the most common to cause neuropathy. Most have MGUS, a few haveWaldenstrom's and other lymphoproliferative disorders. IgM binds myelin sheath and neural antigens in patients with IgM and neuropathy, not in those with IgM and no neuropathy. Of those with IgM paraprotein and neuropathy, half have anti MAG antibodies. Electron microscopy shows deposition on myelin and separation of myelin by MAG via complement. Reducing anti MAG IgM also improves the neuropathy.

IgG paraprotein patients are as above, less likely to develop PN by far, and those that do have all types of neuropathies (distal , length dependent axonal and CIDP). CIDP patients with IgG paraprotein are otherwise identical to those CIDP patients without IgG paraprotein. Unless in a patient with myeloma, amyloid or POEMS, IgG paraprotein is likely to be incidental. A few patients with IgG or IgA paraprotein also have deposition on myelin like IgM patients so previous statement is not absolute.

IgM paraprotein patients with PN usually have kappa light chains and half have anti MAG antibodies. They are older males (60s) with "DADS" which stands for "distal acquired demyelinating sensory neuropathy." Large fibers affecting VS and proprioception cause problems with balance that are progressive. DADS M (DADS with an IgM paraprotein) is probably distinct from DADS no M. A few patients have an aggressive course. EMG in DADS M has accentuated distal slowing and long latency motor nerves and attenuated or absent sensory nerves.

IgG/IgA MGUS have no homogenous presentation, but usually have less balance problems.

2. Myeloma patients have peripheral neuropathy due to perineural or perivascular IgG kappa deposition, or treatment related neuropathy. IgM paraprotein is seen rarely in myeloma, and have sensory > motor symptoms. If amyloid is present, its more likely to be painful. EP is more likely to show axonal damage, but may show demyelinating sometimes.No intervention changes PN but therapy of MM exacerbates PN.

3. POEMS-- Paraprotein is usually IgA or IgG lambda. Synonyms for condition are Crow-Fukase syndrome or Takatsuki syndrome. Patients are younger (40s) with severe sensory and motor features. EMG shows demyelination with secondary axonal loss. Nerve biopsy can show endoneurial deposits. Treatment is for underlying, and PN is reversible for localized process such as plasmacytoma. High dose chemotherapy with autologous blood stem cell rescue is being explored.

4. Waldenstrom's is rarely associated with PN but when it is, its usually IgM kappa with or withour anti MAG antibodies. Its clinically indistinguishable from MGUS related PN with anti MAG or DADS M. Responds to plasma exchange since IgM paraprotein is intravascular, may also use steroids and alkylating agents and Rituxan.

5. Amyloidosis PN is usually present for a long time first. A. is a multisystem disorder with IgG or IgA lambda paraproteins and deposition of light chains in target organs. Either vascular insufficiency or toxicity of amyloid causes the PN. Painful progressive distal sensory and motor PN often with autonomic findings is seen. NCS show axonal sensory > motor neuropathy. Mean prognosis is 25 months.

6. Patients with DADS and IgG or IgA MGUS respond to treatment regimens used for CIDP patients without MGUS.

7. CANOMAD is a rare disorder (chronic ataxic neuropathy with opthalmoplegia, M protein, cold agglutinins, and anti disialosyl antibodies against gangliosides, including GD1b, GD3, GQ1b, and GT1b. There is a chronic PN with sensory ataxia and areflexia, with sparing of strength. Its similar to Miller Fisher syndrome that has antibodies to GQ1b, but is chronic and progressive rather than monophasic and acute.

Normal pressure hydrocephalus assessments

2010-07-24T12:15:00.000-07:00

Questionnaire/assessment: (from the Neurologist)
http://neuropsychminutiae.blogspot.com/2010/07/nph-questionnaires-for-initial.html

Guidelines for the Initial Management of NPH (published in Neurosurgery) 2005; 57:3.

Links, support groups, information, etc.
http://www.ninds.nih.gov/disorders/normal_pressure_hydrocephalus/normal_pressure_hydrocephalus.htm

Well done powerpoint presentation
http://www.usafp.org/USAFP-Lectures/2007-Lectures/16%20March%20-%20Friday/Ryan%20-%20NPHredo.ppt

MRI criteria:

Maximal frontal horn width divided by diameter of inner table, usually >.33, but often > .4
Lack cortical/hippocampal atrophy/extensive white matter lesions
Callosal angle > 40 degrees
Altered brain water content
Aqueductal and fourth ventricular flow void on MRI

Gait criteria: At least two of the following

Gait/Balance- at least two of following present
Decreased step height
Decreased step length
Decreased cadence/speed
Decreased trunk sway
Widened stance
Toes turned outward while walking
En bloc turning- turns take three or more steps
Impaired balance- two or more corrective steps for eight steps on tandem gait testing

Cognition (at least two of following)

Cognition- two of following present
Psychomotor slowing
Decreased fine motor speed
Decreased fine motor accuracy
Difficulty dividing or maintaining attention
Impaired recall especially for recent events
Impairment of executive functions- multi-step procedures, working memory, formulation of abstractions, insight
Behavioral or personality changes

Urinary symptoms: one of following

Episodic urinary incontinence not attributable to other causes
Persistent urinary incontinence
Fecal and urinary incontinence

OR One of following

Urinary urgency
Urinary frequency- 6 or more voids in 12 hour period
Nocturia- more than two voids in night

Clinical diagnosis

Probable iNPH: Gait or balance impairment, plus cognitive or bladder control disturbance, or both. MRI shows an Evans ratio of greater than .3 with no evidence of obstruction. Diagnosis based on probable NPH predictes 48-64 % of time a good response to surgery.

Possible iNPHL Urinary or cognitive impairment without gait impairment

Pearls:

Rely on family assessment as much as what patient says about gait assessment
Levodopa trial occassionally needed to sort out festination
TInetti Assessment Scale (TAT) for gait assessment screening has a B level of evidence from AAN reviews and is found here: http://agrc.ucsf.edu/files/Tinetti%20AssessmentTool%20(gait%20and%20balance%20test)%20(Week%202%20-Mobility).pdf
TAT misses a velocity component for gait assessment so also use TUG (timed get up and go) and is found here http://www.dhmc.org/dhmc-internet-upload/file_collection/tug_0109.pdf that also has a Level B evidence from AAN
Other instruments that can be used are the ten minute walk, Berg balance test http://www.fallpreventiontaskforce.org/pdf/BergBalanceScale.pdf and the Short Physical Performance Battery http://www.grc.nia.nih.gov/branches/ledb/sppb/index.htm
Urinary incontinence may be described as urinating just before reaching the toilet
Cognitive differentiation from Alzheimer's disease can be accomplished by testing that includes factors that innclude components that should not be affected by NPH, such as Boston Naming Test (in addition to findings that would be affected such as letter fluency and memory and executive function)
Atypical presentations in young may include headache, and poor job performance rather than memory loss.
Obstruction of aqueduct or fourth ventricle due to "late onset aqueductal stenosis" may improve with endoscopic third ventriculostomy (ETV). These patients should NOT undergo LP due to risk of herniation
Thinned / distended callosum may predict shunt responsiveness, may be seen as "bowing" on sagittal views
Presence of "B" waves and increased pulse amplitudes correlate with symptomatic iNPH and responsiveness to shunting. Authors use 48 hours of monitoring followed by 72 hours of drainage.
Behaviorally and by fMRI, increased Stroop testing and finger tapping correlates with SMA functional activity
Response to serial LP's correlates with 88 % response to surgery. Can measure with Tinetti and TUG tests (links above) . With high volume tap, expect improvement in velocity, turning, stride length, number of steps to turn, and tendency to fall, among others. Test immediately before and after shunt, and again q 2-4 hours. Consecutive day LP's x 3 days increased sensitivity to 88 %.
ELD (extended lumbar drainage x 3 days) if no response, very few patients will benefit from surgery.
With ELF and physiologic measurements, authors claim 75-90 % improvement in first year after shunting, and 80 % sustained improvement after two years, with substantial overall Medicare expenditure savings.
If a programmable shunt is used, the billing code is 62252
Obviously need a good neurologist to make the diagnosis and exclude various neurodegenerative diseases

Coin rotation test validation

2010-07-24T10:32:00.001-07:00

Hill BD et al. The Neurologist. 2010; 16: 249-253

Authors validate a longstanding easy test for fine motor processing used for decades at LSU in 86 normals. Task consists of counting number of 180 degree rotations of a quarter in ten seconds by the dominant and nondominant hands. A correction for drops is used, but not that important. Task is to rotate a quarter using thumb and fingers one and two in ten seconds with an examiner using a timer and counting. If the coin is dropped, the subject gets another ten seconds. The adjusted score is the number of rotations in ten seconds minus (0.1 x rotations x drops). Traditionally, LSU has used a cut score of ten to indicate impairment. Authors believe a cut score (for both hands) of 13 is better, with increased sensitivity and some loss of specificity.

Risk of falling in Parkinson's disease patients

2010-07-24T10:04:00.000-07:00

from Kerr et al. Neurology 2010; 75: 116=124

Authors looked at 101 independently living patients without walking aids and put various factors through a computer to predict risk of falling. The factors that increased the risk include

dyskinesias
symptomatic orthostasis
sleep disturbance
Tinetti, Berg, and TUG (timed up and go) measurements
poor peripheral sensation and knee extension strength and greater a-p sway when standing on firm surface
UPDRS total score and FOG (freezing) questionnaire
For previous nonfallers, key measurement was A-P sway on firm surface as risk for future conversion to falling
UPDRS factors that were most important were rising from chair, rapid alternating movements and leg agility

Billing pearls (Random)

2010-07-03T12:37:00.000-07:00

1. Never write "benign" positional vertigo, its "paroxysmal" positional vertigo unless you want to be downcoded.

2. Discharge day codes 99238 for less than 30 minutes, 99239 for more than 30 minutes, document time including spent at nursing station doing prescriptions, need not be continuous.

3. Critical care codes 99291, 99292 for first hour (minutes 31-74) and each additional 30 minutes, respectively. Must MANAGE some critical aspect of care and not just consult. Use different ICD9 code than the attending if you are not primary on case. Time need not be continuous, and time spent off unit eg. looking at X rays with radiologist counts, unlike floor patients. Aggregate time with partners if applicable.

4. Prolonged care codes 99356, 99357 for INPATIENTS for first hour (minutes 31-74 and each additional half hour respectively. Document reason for prolonged service, submit note to carrier, list start and end clock time required. Time spent off unit eg radiology does not count, but time spent on unit coordinating care counts.

5. Prolonged care codes 99354, 99355 are analagous to (4) above except they are for outpatients and Face to face time (start and end clock time) must be documented along with reason.

6. Modifier 25 for procedure same day as an E/M service usually EEG and EMG are exempt.

7. Documentation for high level visit: Indicate chronic illness with severe exacerbation and/or side effects such as MS exacerbation, seizure, Dilantin toxicity (if you are still using Dilantin), risk of Morbidity and mortality (INR high in stroke patient), Abrupt neuro change (TIA, seizure, AMS).

Must include in note 1) 1 new problem needing additional assessment or 2) 2 old problems inadequately controlled . Document at least a three way differential (Alzheimer's v. frontotemporal v. LBD?; or MS v. CIS v. ON due to sarcoid). Document at least 3 management options (Copaxone, Rebif, Betaseron; steroids; gabapentin: Detrol or Aggrenox v. Plavix v Asa, lipitor v. simvastatin; SQ heparin to prevent DVT's). or iv (parenteral) controlled substances.

New consults need CC, 4 facts for HPI, 1 fact each for PSF (past, family, social history), 10 point ROS (see below), 23 point Neuro SSE (see below).

8. Office followup high level requires CC, 4 facts HPI, med list, social fact, 10 point ROS (may sign and date patient form containing some of these), PLANS (labs, meds, to address problem). midlevel office visit requires CC, 4 point HPI, mention some PMH or current meds, 2 system ROS, palns to address problem (1-2 chronic problems of moderate degree, or uncertainty re risk or prognosis). Level 3, low level requires a self limited stable problem eg chronic pain needing E/M, CC, pertinent positives and negatives, and PLANS to address problem. Most documentation falls out on 3 way differential and plans.

9. ROS items to be covered in your office intake sheet come from the list: constitutional, eyes, ENZT, CV, Respiratory, GI, GU, musculoskeletal, skin and or breast, neurologic, endocrine, hematologic/lymphartic, allergic/immunologic, psychiatric. May be on a separate sheet patient fills out and checks off if MD signs and dates AND refers to it in office note. Comprehensive ROS has 10 (TEN) items out of 14.

10. Neuro single system exam requires 25 bulleted items, need to include 23. These include one of three CV elements (more may be needed for care but not for documentation). The other 22 that must be included are regular parts of neuro exam. Mandatory-- any 3 vitals (BP, HR, RR, temp, height, weight, orthostatics), general appearance, Fundoscopic exam, one of 3 cardiovascular elements (carotids, heart auscultation, peripheral vascular system), Memory (orientation, attention, recent and remote memory, language, and fund of information), CN's 2; 3,4,6; 5, 7, 8, 9, 11, 12). CN's one and ten are not required. Motor exam includes strength (4 ext), tone (4 ext with note of atrophy or abnormal movements), DTR's 4 ext's including pathologic reflexes, Coordination, Gait and station. Sensory exam-- need one element of sensation recorded.

Notes-- must document WHY you can't walk a comatose patient eg. . Constitutional signs and vital signs can be recorded by staff. Office needs to have an approved abbreviation list. Note must be legible. Templates OK, macros OK, pocket cards with elements available from AAN.

Example of a comprehensive Neuro SSE: Well developed. 120/80, HR 72, RR 16. fundi OK no bruit. MS: awake, alert, oriented x 3, dig 6 F, 3/3 objects at 5 minutes, nl naming and vocabulary. CN. VFF, EOMI, facial sensation and power normal, hears well, palate.tongue midline, SCM normal. Sens: normal PP. Motor-- nl tone/bulk/power 4 ext. FNF, gait nl, DTR's 2+ and symmetric throughout, normal.

11, Couselling and coordination of care may be used instead of documentation. Counselling involves face to face discussion with patient and/or family re tests, treatments, alternatives, prognosis, education. Coordination of care may involve interactions with other MD's or providers. Time is key. Documentation should state number of minutes spent face to face, that more than half time was spent on counselling and coordination of care, with some general idea of what was done. No history or exam is needed for documentation.

12. Be sure to document physician referring name for consults. Be sure to document MDM in detail.

sCJD mimics NCSE in ICU patients

2010-06-26T15:03:00.000-07:00

Lapergue B et al. Neurology 2010; 74:1995-1999.

10 patients with sCJD were admitted to neuro ICU with initial misdiagnosis of NCSE. Mean age 64 +/- 13, with gait ataxis (7),cognitive impairment (5), myoclonus (1), visual (5) or auditory (1) hallucinations and sudden stroke like hemiparesis (2). Disease duration was 106 days (+/- 30 days). with EEG's strongly suggesting NCSE ( see article for examples). EEG's responded to therapy with antiepileptic drugs, On reexamination, EEG's did not show rhytmic activity, but rather periodic or semiperiodic sharp wave complexes with period of .5-1.0 seconds. These were attenuated by auditory or painful stimuli. They also fluctuated with drowsiness. Importantly, there was no clinical improvement with EEG improvement. MRI showed characteristic changes in 9/10 and 14,3,3 was seen in all patients.

List: Most common 7 organisms in bacterial meningitis

2010-05-21T11:50:00.000-07:00

Streptococcus pneumoniae
Neisseria meningitided
Listeria monocytogenes
Staphylococcus aureus
Haemophilus influenza
Escheria coli
Streptococcus agalactiae

source Lin AL, Safdieh JE. The Evaluation and Management of bacterial meningitis: current practice and emerging developments. The Neurologist 2010: 16:143-151.

The Heidenhain variant of Creutzfeldt-Jakob disease

2010-05-16T17:02:00.000-07:00

From Neurology resident/fellow page
The Heidenhain variant of Creutzfeldt-Jakob disease

The Heidenhain variant of Creutzfeldt-Jakob disease presents with isolated visual

symptoms for 2-4 weeks, and these may include disturbed perception of colors or shapes,

visual hallucinations, or cortical blindness with anosognosia (Anton syndrome). The

clinical course of this variant is rapidly progressive. Diagnosis is difficult in the early

stage since the neurological examination is otherwise normal and typical EEG findings

are absent. Visual symptoms may be erroneously attributed to ophthalmologic disease,

which in some cases lead to needless ocular procedures. This is particularly important

since prion particles can be transmitted by ocular tissue. Brain MRI may show the

characteristic cortical ribbon sign with diffusion restriction in the parieto-occipital cortex.

CAPS : A treatable neurologic disorder

2010-05-14T19:44:00.000-07:00

Kitley JL, et al. Neurology 2010; 74: 1267-1270
Cryopyrin associated periodic disorder (CAPS) is a rare disorder that, untreated, will progress to amyloidosis, renal failure and death. It responds dramatically to anti interleukin 1 therapy with cankinumab. Authors summarize 13 published cases of CAPS neurologic features, including one case of their own and twelve of the literature.

Highlights
-- includes 3 previously thought to be unrelated conditions, which are the Muckle Wells syndrome, familial cold autoinflammatory syndrome (FCAS), and chronic infantile neurologic, cutaneous and articular syndrome (CINCA).

Presentation of adult patients with CAPS included
-- Headache in 12/13; migraine like in 10
-- myalgia in 9
-- hearing impairment in 7
-- papilledema in 6
--optic pallor in 2

MRIs were normal
CSF in 1 patient showed high OP and pleocytosis
FCAS presents with fever, rash, and conjunctivitis provoked by cold; is mildest
MWS is more severe with progressive SN deafness, one third developing amyloidosis, nephrotic syndrome and renal failure
CINCA presents in infancy and is most severe
Some have history of aseptic meningitis

All show episodic fever, urticarial like rash, conjunctivitis, flu like symptoms, acute phase response with anemia, high ESR and CRP, and elevated serum amyloid A.

Nosocomial bacterial meningitis pearls

2010-05-02T17:47:00.001-07:00

Van de Beek et al. NEJM 2010; 362: 146-154. Current Concepts. Review article.

1. Post craniotomy, one third of cases occur in first week, one third in second week, and one third after second week, up to "years" after craniotomy. The incidence is 0.8-1.5 %.

2. Internal ventricular catheter infection causes infection 4-17 % of time. Colonization at time of surgery is the most important cause, and most cases occur within one month.

3. External ventricular catheter shunts has an 8 % incidence of infection with a sharp rise after five days. Article suggests no reason to remove a catheter just because 5 days has elapsed.

4. CHT usually has a basilar skull fracture if infections occur. This is most common cause of recurrent meningitis.

5. Gram staining and culture are hallmarks of diagnosis and measurement of cells and diff may be falsely negative in many cases. especially ventricular catheters.

6. Post neurosurgery, a CSF lactate level of > 4 mmol/L has a sensitivity of 88 %, specificity of 98 %, PPV of 96 %, and a NPV of 94 % for bacterial meningitis. However, one review suggested many cases would be missed with this cutoff.

7. Antibiotics postop or post head injury should be vancomycin plus ceftazidine, cefepime, or meropenem. Goal should be serum trough of 15-20 for vancomycin. In intraventricular therapy, close the drain for an hour after the first dose. The trough should equal ten times the MIC of the antibiotic to sterilize the CSF.

8. External lumbar catheter infection rates have been reported between .8 and 5 percent. After LP infection rate is one in 50,000 with 80 cases per year in US.

9. Acinteobacter is more common in nosocomial infections that may be resistant. Initially may use iv meropenem, with or without intrathecal or intraventricular aminoglycoside, if resistant use colistin or polymyxin B. Colistin in one study sterilized 13/14 patients and cured those. In another study, all patients treated with colistin survived.

Pharmacology minutiae of antiepileptic drugs

2010-04-18T15:43:00.001-07:00

from E Ramsey at AAN

1. Enzyme induding drugs (Phenytoin, carbamazepine and lamotrigine) cause eighty percent or more reduction of many drugs including statins, (except one), so need to way increase dose of statin. Ditto for calcium channel blockers (think nimodipine after SAH), antidepressants, erectile dysfunction drugs (all of them), and HAART therapy.

2. Carbamazepine is related to weight gain almost as much as valproate

3. Topiramate helps blood pressure and insulin sensitization needing readjustment of insulin

4. Dilantin will not be absorbed with high pH such as pepcid or protonix

5. LTG or TOP levels will increase two or three fold if you wean off an inducer like PTN due to decreased clearance

6. Warfarin metabolism with Dilantin is variable, up or down, depending on genetics.

7. Drugs that lower seizure threshold include theophylline, antihistamines, stimulants, antipsychotics, narcotics, hormones, antibiotics (PCN, metronidazole, lindane), antidepressants (SSRI, TCA's), baclofen, oral hypoglycemics, some immunosuppressants

8. CBZ induces CYP34, and ethinyl estradiol is a substrate, hence lower bc pill levels.

Saline bullets (and hypertonic saline) for increased intracranial pressure.

2010-04-10T06:22:00.000-07:00

Saline bullets are not FDA approved but rather a novel effective way to lower increased intracranial pressure acutely. The idea was proposed by Geoffrey Ling MD at a lecture based on his experience in the military. The advantage is that hypertonic saline, in this case a saline bullet, does not promote diuresis just creates a gradient that treats increased ICP. Per Dr. Ling, a saline bullet of 23 % NaCL, 30 cc, decreases ICP by 50 % and sustains the decrease for about eight hours. It needs to be given through a central line. The 23 percent saline infusion is available in every pharmacy as a basis for TPN and needs to be cannibalized from that cart since not likely to be available from pharmacy for stated purpose of controlling ICP. Once the goal is achieved Ling uses a 3 percent saline infusion at 75 cc per hour, of half NaCl and half Naacetate

Pearls CSF and alternate forms of meningitis: PCR for TB, CMV,enterovirus, VZV, toxo meningitis

2010-04-04T07:59:00.001-07:00

HSVE
1. In CSF , PCR has sens/spec of 98 and 94 % respectively, and stay positive for a long time in one third.
2. In cases of false negative, treat with acyclovir anyway for ten days if clinical suspicion is high and consider repeating LP at 48 hours.

CMV
1. PCR is 79 % sensitive, 95 % specific

toxo
1 PCR in CSF is 42 % sensitive, 100 % specific

enterovirus
1. more sensitive than viral culture

mycoplasma pn
1.need to check IgM and IgM is CSF: serum

HSVE
1. Antibody is positive at tn days in half
Tests:
immunocompetent-- initially test with PCR for HSVE, VZV, and enterovirus
immunocompromised -- add EBV and CMV PCR and HHV6 and HHV7
Consider quantitative CSF: blood esp HIV patients

TB meningitis diagnostic test pearls

2010-04-04T07:36:00.003-07:00

H/t Wendy Ziai and John Lewin Neurol Cl May 2008

1. CXR and ppd may be negative in half of cases, and typical CSF profile may not be present especially in immunosuppressed patients.

2. AFB in CSF is positive in only 30 % (maybe able to increase to 70 % with meticulous and repeated sampling), culture is only positive in 40-70 %, and may require weeks to have a result.

3. CSF adenosine deaminase (ADA) activity is a biochemical marker that may help. At a cutof of 6.97 iu/L it is fairly sensitive and specific (85 % and 88 % respectively). ADA is useful in third world countries and poorly equipped labs (Gautam et al., Nepal Med Coll, 2007).

4. Molecular nucleic acid amplification kits have sensitivity 60-83 % and specificity of 98 % and should be first line to rule out (Dinnes et al. Health Care Tech 2007)

5. PCR is fastest and most sensitive tests but is not good enough to rule out TB meningitis.

6. Measurement of interferon gamma in CSF compared with PCR is more sensitive (70 v 65 %) and has specificity of 94 %. Interferon gamma plus PCR has 80 % sensitivity.

7. In general careful bacti is as good as molecular in initially diagnosing TB meningitis although molecular stays positive longer with treatment.

8. TB is prevalent in indigent urban nonwhite populations with a high rate of HIV infection (Arch Int Med 1996). Presentation is fever, malaise, headache and personality changes, leading in 2-3 weeks to classic signs such as headache, meningismus, vomting, confusion and focal neurologic findings. Occassionally it presents like acute bacterial infefctions.

9. MRI classic triad for TB meningitis is basal meningeal enhancement, hydrocephalus, and supratentorial and brainstem infarctions; hydrocephalus can be communicating or noncommunicating.

10. Outcome scoring system is called Weisfelt system and is calculated one hour after admission based on six variables: age, heart rate, GCS, cranial neuropathies, CSF WBC, Gram stain findings.

Ventriculitis pearls and a few more meningitis pearls

2010-04-04T07:11:00.002-07:00

Ventriculitis
1. Occurs in 30 % of adult meningitis cases, 90 % of neonatal cases. Often thought of as a late occurrence in refractory meningitis but can occur as primary event also.

2. Commonly occurs with EVD or VP shunt, less commonly if EVD management protocols are strictly adhered to.

3. Hemorrhagic CSF is considered a risk factor

4. Gram positive organisms such as Staph aureus and Staph epidermidis are most common, but gram negative organisms also occur. (E coli, Klebsiella, Acinetobacter, pseudomonas species.

5. Cell index is ratio of WBC: RBC in CSF:Serum. Its used in ventriculostomy cases with IVH to consider infection. It is one normally and in ventriculitis patients without infection. In 7 patients with definite ventriculitis, index rose 3 days before diagnosis of ventriculitis and declined with antibiotic treatment (Pfauler et al. Acta Neurchir 2004)

CSF in meningitis
5. Common practice is to perform CT first, then LP, then begin therapy. These practices lead to delay in antimicrobial treatment which actually is worse for patient than risk of performing lumbar puncture. In many cases antibiotics should be given before CT because even a delay of a few hours can be catastrophic.   Aronin et al. ANn Int Med 1998.

6. Delay of LP is not needed if the following factors are not present: immunosuppression, ( to R/O toxo or lymphoma), alteration in mentation, focal deficits, seizures, pappilledema, ocular palsies, bradycardia or irregular respirations, sedation or muscle paralysis.   see Mellor DH. Arch Dis Children 1992.

7. CSF findings in bacterial meningitis WBC> 1000 (60 %) and > 100 (90%); CSF glc < 40 (50 %) but CSF : serum glc < 0.4 80 % sensitive and 98 % specific.

8. Blood cultures are positive in about 50 % of cases of bacterial meningitis, but touch preparation of the rash is positive in 70 % on Gram stain.

9. CSF lactate is not helpful in community acquired meningitis but is helpful in postop neurosurgical cases. A cutoff of 4 mmol/L lactate in CSF is superior to measuring the glucose CSF: serum ratio. 88 % sensitive, 98 % specific, ppv 96 %, npv 94 %.

10. Latex agglutination CIE is useful only for certain organisms and in patients with pretreatment of antibiotics and negative cultures.

11. C reactive protein is sensitive for bacterial meningitis in some pediatric population esp. with CSF profile c/w meningitis but negative gram stain.

12. Procalcitonin levels differentiate bacterial and virla meningitis in kids (cutoff > 5, 94 % sensitive, 100 % specific). Also in adults ( cutoff > .2 ng/mL , sensitivity and specificity 99 %) . Moreover the levels decline rapidly, within 24 hours, and may be useful to monitor the effectiveness of the treatment.   (Gendrel et al, Clin Inf Dis 1997, Viallon et al, Clin Inf Dis 1999, ibid. Crit Care 2005). PCT levels remain normal in ventriculitis and do not help in that situation.

13. Real time PCR is emerging but disadvantage include a lack of sensitivity, lack of sensitivity to antibiotics result, false negatives and contamination issues.

Infratentorial abscess after bacterial meningitis

2010-04-04T06:57:00.000-07:00

Presents with a subacute meningitis and and neck stiffness and decreased consciousness. It occurs after surgery for otitis, mastoiditis, and sinusitis. Delay in detection occurs due to CT missing the diagnosis, leading to a high mortality. MRI with DWI can differentiate this condition from reactive subdural effusion, which is important due to the risk of hydrocephalus, the need for antibiotics and sometimes surgery (should have low threshold to explore).
See van de Beek, et al. Neurology 2007, and Wong et al., AJNR 2004.

Neurocritical infection/ meningitis pearls

2010-04-03T19:30:00.007-07:00

1. Bacterial meningitis damage is half mediated by toxins, half by inflammatory response

2. Classic triad of headache, fever, and neck stiffness is NOT sensitive for meningitis. However, 90 + % of patients have 2 of the following four symptoms: ha, neck stiffness, fever and mental status changes.14 % of patients are comatose on admission, and 34 % have focal deficits. Only 30 % have nuchal rigidity. Fever is often missing in elderly, immunosuppressed and the partly treated groups. Overall fever is present in 71-77 % of cases, neck stiffness in 48 %, headache in 87-92 %, nausea and vomiting in 74 %, photophobia 57 %, seizures 5-23 %, focal signs <30 %, rash 11 %. (see van de Beck, NEJM 2006:354:44-53; Durand NEJM 1993; 321:21-28; Thomas et al, Clin Inf Dis 2002; 35:46-52). Latter article reveals Kernig's and Brudzinski's signs are NOT reliable and have a positive predictive value in the 20s and sensitivity of less than 10 percent. Older patients >60 in Dutch study had less fever and neck stiffness and more encephalopathy as a presenting sign.

In infants, signs can be subtle, bulging fontanelle and seizures is not sensitive (Klein, Pediatrics, 1986), and an LP is warranted(?controversial) in patients with first simple febrile seizure. The presentation is usually fever, lethargy, irritability, respiratory distress, jaundice, reduced food intake, vomiting and diarrhea.

Immunocompromised patients have the triad only 21 % of time, due to less immune response and greater propensity to get atypical organisms.

3. Predictors of bacterial v. viral meningitis include one of the following indicators of severity: altered consciousness, focal deficits, seizures, and shock. Non predictors include CSF glc< 2, CSF protein > 2 (Brivet et al, Intensive Care Med 2005).

4. Predictors of mortality include seizures (34 v. 7 %) and decreased level of consciousness on admission (26 v. 2 %).

5. An unusual presentation of brainstem HSVE in an immunocompromised patient included diplopia, dysarthria, and ataxia .

6. HSVE also causes radiculitis in immunocompromised (lumbosacral) and most cases of recurrent meningitis (previously called Mollaret's meningitis).

7. WNV in CNS includes movement disorders with myoclonus, postural tremor and cerebellar signs in addition to polio like features. Death can occur due to respiratory depression.

8. Presentation of cerebral abscess includes neck stiffness only in 20 % often only shows increased ICP. Seizures occur in up to 40 %. Focal specific symptoms such as aphasia occur but are variable.

9. Cranial epidural abscess presents with ha, fever, nausea and usually does not lead to neurologic complications due to neurosurgery>meningitis, with organisms often Strep, Staph and polymicrobial

10. Subdural empyema occurscausing altered level of consciousness, fever, seizures, septomthrombophlebitis, venous infarcts and more complicated course. Sources include paranasal sinuses, hematogenous spread due to emissary veins in subdural space, and postoperative extension due to epidural abscess.

11. Peripheral lab clues: amylase increased in mumps, cold agglutination titers in mycoplasma, CXR abnormal could be associated with mycoplasma, legionella or lymphocytic chorionic meningitis.

12. Cancer patients much less commonly have the triad (56 % fever, 47 % headaches, 35 % altered mental status, 14 % nuchal rigidity, 14 % completely asymptomatic, and may be related to frequency of a range of neurosurgical procedures (Safdieh, Neurology 2008).

13. Novel lab tests to help diagnose bacterial meningitis include: CSF lactate> 4.2 (nonspecific and only sensitive in acute setting), CRP (normal level has high negative predictive value) and serum procalcitonin level (newest marker) (see Tunkel Clin Inf Dis 2004; Sormunen, J Ped 1999; Viallon et al, Clin Inf Dis 1999 and others).

14. Third generation cephalosporins sterilize the CSF within 2 hours in all patients; in one third by one hour. Latex agglutination and PCR techniques are useful in these situations.

Blast TBI and other TBI pearls

2010-04-03T18:56:00.000-07:00

1. Battlefield injury without breach of cranium thought to have different pathology than standard CHT or penetrating injury. Its due to a concussive pressure wave.

2. Battle armor and helmets, and medical care on the scene have reduced the kill wounded ration to less than 1:10, v 1:4 in WWII.

3. Secondary injury factors are the focus of treatment.

4. Mild , moderate and severe TBI is defined by GCS. Mild is 13 or above, moderate is 8-13, and severe is < 8.

5. Second impact syndrome has a high mortality, up to 50 % but the mechanism is not well understood

6. Early mgmt recommendations include avoiding hypotension and hypooxygenation in addition to ABC.

7. The role of hemicraniectomy is being studied in the RESCUE trial

8. Indications for ICP monitoring include abnormal CT scan, hypotension (SBP < 90), or age > 40.

9. Hypertonic saline boluses may be as effective as mannitol. Give through a central line. 2-3 % hypertonic saline through a peripheral line is given half NACL, half Na acetate.

10. Pseudoaneurysms and vasospasm are very common.

status epilepticus pearls

2010-04-03T18:29:00.000-07:00

1, Among patients with convulsive SE that stops, 14 % have ongoing subclinical status and 48 % have ongoing intermittent seizures (DeLorenzo et al., Epilepsia 1998)

2. Risk factors for increased mortality in SE include higher age, intubated, length of time till treated

3. Fever contributes to cerebellar injury, and neuromuscular blockade prevents (Meldrum 1973 Arch Neurol)

4. Among eleven patients with SE who died acutely, 8 had contraction band necrosis of cardiac muscle, and died due to initial catechol release Manno et al. Ann Neurol 2005)

5. Neuron specific enolase (NSE) is unvestigated as a marker for neuronal injury in prolonged SE

6. The VA cooperative study (Treiman et al, NEJM, 1998) looked at overt status and found the efficacy of each of the following regimens in stopping SE: lorazepam, 65 %, phenobarbital 58 %, diazepam plus phenytoin, 56 % ,and phenytoin alone 44 %. Subjects who failed the first drug responded to the second drug (7 %) and the third drug (2.3 %) at a low rate. The only significant difference statistically was between lorazepam and phenytoin.

7. Inttravenous valproate may be as good or better than phenytoin or fos-phenytoin ( Aggarwal et al, Seizure, 2007) both as a first line and second line agent (Misra Neurology 2006). If used with phenytoin, it may increase the free level of the drug, paradoxically causing increased seizure. Antibiotics such as merepenem and amikacin may cause a dramatic fall off in the blood level of valproate, possibly due to increased renal excretion. Beware of other p450 metabolized medications. Valproate is a broad spectrum antiepileptic drug, with action against all seizure types including postanoxic myoclonus, and does not sedate or cause hypotension. Therefore it may be DOC in patients with a DNR order. Dose is 25 mg.kg

8. Initial dose of thiopental in ICU setting is 2-4 mg/kg bolus, then 3-5 mg/kg/hour. Pentobarb has slower onset and offset than thiopental and should be dosed initially at 5 mg/kg with repeated boluses of same until seizures stop, with initial maintenance at 25-50 mg/minute, titrated to burst suppression. Half life is over 34 hours. Midazolam initial dose is .2 mg/kg, repeated every five minutes up to 2 mg/kg until seizures stop, with a continuous dose range of 0.05 - 2.9 mg/kg/hour.

9. Propofol has rapid onset and rapid clearing. Dose is bolus of 1-2 mg/kg, then a continuous infusion of 1-15 mg/kg/hr with a maximum dose of 5 mg/kg/hr if maintained for days. Beware of "propofol infusion syndrome" of metabolic acidosis, cardiac failure, rhabdomyolysis, hypotension, and death.Risk factors are prolonged doses (> 48 hours), high doses (>5 mg/kg/hr), head injury, lean body mass, and concurrent use of catechols or steroids. Concurrent clonazepam may also help prevent PIS (Rosetti et al, Epilepsia 2004).

10. Intravenous levitiracetam is useful in benzo refractory partial seizures, usually stopping it without causing severe AE's (Knake et al. JNNP 2008).

11. Ellis looked at patients with grade 3 or 4 hepatic encephalopathy, and found of 42 total patients split between prophylactic AED and controls, subclinical status was common among the control group (45 %) but not in the treated group with (15 %). At autopsy the control group had more brain edema (Ellis et al, Hepatology 2000). This constitutes an argument for continuous EEG monitoring.

12. In renal patients, AED's are divided into the dialyzable and the nondialyzable. Highly bound drugs (PTN, VPA, CBZ) are not dialyzed significantly. Moderate protein binding eg LTG (lamotrigine) may need pre and post dialysis levels. AED's THAT REQUIRE REPLACEMENT AFTER DIALYSIS ARE GBN, PREGABALIN, ETHOSUXIMIDE, LEVITIRACETAM, PHENOBARBITAL AND TOPIRIMATE. The serum concentrations of these can decrease 50 % after dialysis

13. Among posttransplant patients, many seizures occur, and many are nonconvulsive. In liver transplant, the incidence may be as high as one third, slightly less in pancreatic, much less with other organs. Day 4-6 post transplant is highest occurrence. Most patients do not have prior seizures. Short term AED's are indicated.

Medications that reduce seizure threshold

2010-04-03T17:41:00.000-07:00

from Neurologic Clinics 2008

Antidepressants esp. buproprion and maprotilene
antipsychotics especially phenothiazines and clozapine
Lithium
baclofen
AED withdrawal
super high phenytoin levels
theophylline
Analgesics esp. meperidine-demerol, fentanyl and tramadol
opiod withdrawal
benzodiazepine withdrawal
barbiturate withdrawal
antibiotics-- beta lactams (cefezolin), carbapenems (imipenem), quinolones, isoniazid (treat with B6), metronidazole
antiarythmics-- lidocaine, digoxin, mexelitine
radiographic contrast dyes
immunomodulators-- cyclosporine, tacrolimus, interferons
chemotherapeutic drugs-- alkylating agents such as chlorambucil and busulfan
an

Concussion pearls

2010-03-30T15:03:00.000-07:00

1. See prior posts on sideline assessment and Vienna return to work
2. Younger athletes (high school) take longer to recover from concussions than college or NFL players on neuropsychologic testing and should be kept out longer accordingly.
3. the role of multiple concussions in a single season or time between concussions is unclear but under investigation
4. Clinical head injury in football is strongly related to translational forces. Rotational forces follow translational forces. These forces are highest with helmet to helmet hits and backward falls onto ground
5. Head down strike increases the mass of the striking player 67 % due to alignment of the torso, and thereby increases the severity of concussion accordingly.
6. Thicker larger and lighter helmets improve the function of prevention and decrease concussion severity
7. Clinically differentiate early (temporal) injury involving dizziness and later (>40 msec) injuyr involving fornix and midbrain that is more likely associated with memory loss.
8. The notion of grading concussion the day of the injury may be in error as late cognitive changes are far more important in predicting delayed recovery

Concussion: University of Pittsburgh sideline mental status examination card

2010-03-30T14:40:00.001-07:00

Orientation questions
What stadium is this?
   What city is this?
   Who is opposing team ?
What month is it?
           What day is it?

Post-traumatic amnesia
Remember three words: girl , dog and green (ask player to repeat them)

Retrograde amnesia
   Ask "What happened in prior half"
   "What happened before you were hit"
"What was the score before the hit"
"Do you remember the hit"

Concentration
          ask the player to say the days of the week backwards, starting from today
ask the player to say the following numbers backwards: 63, 419

Memory
ask the player to recall the three words given earlier

Vienna conference return to play recommendations1.   Remove from game if any signs of concussion- any items missed on sideline exam
2. No return to play in current game
3. Medical evaluation after injury a. rule out serious focal injury b. neuropsychologic evaluation
4. Stepwise return to play    a. rest till asymptomatic      b.   light aerobic      c. sport specific training     d. noncontact practice      e. full contact practice     f. return to play

Concussion- player complaint and observer notation

2010-03-30T14:31:00.000-07:00

from Mark Lovell University of Pittsburgh signs and symptoms of concussion

Signs observed by staff                          player complaint

Appears dazed or stunned                     headache

Is confused about assignment nausea

Forgets plays balance problem or dizziness

Unsure of game/score opponent double or fuzzy/blurry vision

Moves clumsily    sensitive to light or noise

answers questions slowly sluggish/slowed down

loses consciousness    "foggy" or "groggy"

behavior/personality change    concentration or memory problem

retrograde amnesia    later sleep problem

anterograde amnesia    fatigue

orbital pseudotumor due to thyroid opthalmopathy v, myositis

2010-03-28T10:24:00.000-07:00

Differential points: left image, from internet, shows medial rectus hypertrophy which (along with inferior rectus) is characteristic of thyroidopthalmopathy. This condition is also tendon sparing. Right image is orbital pseudotumor which in this case affects lateral rectus and tendon. The condition on right can be secondary to a number of different conditions including RA, orbital tumor, Crohn's disease, and others.

AAN quick hits 2010 novel uses of medication

2010-03-28T09:18:00.000-07:00

pseudoatrophy MRI in MS helped with lamotrigine

cerebellar ataxia benefitted with varenicycline

frataxin level in FA helped with single dose erythropoetin

cell death in SCA type 3 (Machado-Joseph disease) helped by Lithium

improved ataxia and tremulousness with levodopa treatment for Angelman's disease

improved hypoxic damage with SSRI's in medically refractory partial epilepsy

CIS conversion to CDMS reduced by atorvastatin 80 mg

SUNCT/SUNA response to occipital nerve stimulator

CLIPPERS syndrome

2010-03-28T08:31:00.000-07:00

Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids. Clippers. (Mayo Clinic) AAN 2010 P02:182. Eight patients had a distinctive clinical and radiological CNS disease with treatment. Presentation was episodic diplopia or facial paresthesias with subsequent progressive ataxia, diplopia, dysarthria and paresis responsive to high dose steroids. MRi showed gado enhanced peppering of pons extending into the medulla. Weaning steroids always led to worsening. Neuropath showed perivascular T lymphocytic infiltration without evidence of granulomas, lymphoma or vasculitis.

2 type disproportionate anterocollis in Parkinson syndromes

2010-03-28T06:57:00.000-07:00

Neurology 2020 AAN PO1.274 Clinical subtypes of disproportionate anterocollis in parkinsonian syndromes Revuelta G, Factor S.

Myopathic subtype-- neck extensor weakness and limited range of motion, neck extensor myopathy on EMG,

dystonic subtype-- no weakness, full range of motion, laterocollis/torticollis and hypertrophy.

Other Mitochondria disease: MNGIE

2010-02-21T06:46:00.000-08:00

MNGIE- aut rec, presents with abdominal pain, malabsorption and weight loss. Peripheral neuropathy and leukodystrophy occur.Serum lactate is almost invariably high. Elevated thymidine is seen, and WBC shows decreased thymidine phosphorylase (buffy coat??).

Clinical presentations of mitochondrial cytopathies MELAS , MERRF and LHON

2010-02-21T06:40:00.000-08:00

Melas- hypoacusis, ataxia, dementia, opthalmoplegia, encephalopathy, stroke like syndromes, exercise intolerance, proximal myopathy, type 2 diabetes. Due to point mutation, can occur at most ages and mimic multiplle sclerosis with progressive or remitting and relapsing presentations

MERRF isolated myoclonic epilepsy with or without ataxia, myopathy, peripheral neuropathy, and multiple lipomas in head region. Neuropsychiatric manifestations including OCD, depression, psychosis and type two diabetes are common. Any age of presentation to mid 40s. Progressive decline

LHON- painless, rapidly progressive vision loss with centrocecal scotoma in teenagers or young adults with male predominance (65-35). Can mimic MS.

Mitchondrial cytopathies

2010-02-21T06:33:00.000-08:00

visit http://www.mitomap.org/ for detailed information on cytopathies

Leigh disease (Complex 1>complex 2,3) aut rec
Succinate dehydrogenase gene (SDHB c and D) paraganglioma and pheochromocytoma, aut dom
polymerase gamma (POLG) mutations-- Alpers syndrome (hepatoencephalomyopathy), CPEO, spinocerebellar ataxia, sensory ataxia neuropathy with dysarthria and opthalmoplegia (SANDO),
ECGF1 (thymidine phosphorylase)- MNGIE

GI differential
liver involvement- Alpers syndrome
irritable bowel, intestinal pseudoobstruction--MELAS
severe GI dysfunction--MNGIE

Neuropathy-- MNGIE, SANDO

Historical points to ask about: deafness, short stature, early cardiac death in family, muscle discomfort or exercise intolerance, early onset DM.
Barth syndrome-- deafness and dystonia

Diagnostic tests
elevated lactate-- 60 percent sensitive, not completely specific
lactate/pyruvate ratio in CSF- may differentiate pyruvate dehydrogenase deficiency from primary mit. cytopathy
plasma amino acids- elevated alanine may be seen
elevated CPK- may be seen in myopathy, not specific
alpha feto protein- may be seen in Alpers' syndrome early along with increased GGTPand others
thymidine levels-- high in MNGIE
urine organic acids-- high levels of ethylmalonic acid prompts ETHE1 gene for encephalopathy
high 3 methyl glutaconic acid prompts look for tafazzin mutation for Barth syndrome
folate, B12, vitamin E- may be low in percentage coincidentally or secondarily

MRI- high T2 signal in putamen leading to striatal necrosis characterizes Leigh disease
occipital stroke-- consider MELAS

Cerebral palsy for adult neurologists: pearls

2010-02-20T14:40:00.000-08:00

1. Gross Motor Functional Classification System is most widely used

Level I Ambulatory in all settings
Level II Walks without aids but has limitations in community settings
Level III Walks with aids
Level IV Requires wheelchair or adult assistance
Level V Fully dependent for mobility

Of all CP patients, 40 % are level I, and 66 % are levels 1-3 (ie. ambulatory)

2. O CP patients, approximately one third will have spastic quadriplegia, one third spastic hemiplegia, one fifth spastic diplegia, and the rest either dyskinetic or ataxic-hypotonic CP. It is rare for CP patients with spastic hemiplegia or spastic diplegia to be nonambulatory, but 75% of spastic quadriplegia patients are not ambulatory. Those same patients are much more likely to suffer comorbidities such as epilepsy.

3. Genetic defects such as DCX and LISI can be sought, and coagulation pathway abnormalities (Leiden mutation eg.) among those suffering from placental thrombosis.

Care of hydrocephalus in adults pearls

2010-02-20T14:12:00.000-08:00

1. Hydrocephalus may be decreasing. Reasons may include higher threshold for surgery (artefact of practice) increased folate in pregnancy causing less myelomeningocoele.

2. Unchanged CT scan does not exclude obstruction

3. ETV or endoscopic third ventriculostomy is a more recent alternative to shunting in a highly select group of patients. The procedure is more prone to immediate catastrophe, but less to long term infection, although obstruction can occur years later (as it can with any shunting procedure). ETV may be best for older children with obstructive hydrocephalus or aqueductal stenosis.

4. A top down approach to assessing meningocoele would sequentially assess hydrocephalus, Chiari malformation, syringobulbia.syringomyelia, tethered cord.

Diagnostic criteria for FXTAS (fragile x associated tremor ataxia syndrome)

2010-02-20T13:53:00.000-08:00

Molecular-- CGG repeat 55-200
Clinical
   Major intention tremor, cerebellar ataxia
   Minor Parkinsonism, moderate to severe short term memory loss, executive function deficit
Radiologic
   Major white matter lesions in middle cerebellar peduncles (MCP sign)
   Minor lesions in cerebral white matter, moderate to severe brain atrophy

Diagnostic categories

Definite-- one major clinical, and one major radiologic, or present inclusions at autopsy
Probable-- two major clinical, or one minor clinical and one major radiologic
Possible-- one major clinical and one minor radiologic

Dystrophinopathies in adults: pearls

2010-02-20T13:26:00.002-08:00

See also http://emgnotes.blogspot.com/2010/01/dystrophinopathy-clinical-diagnostic.html and here are ten more pearls

1. Many DMD patients now live into 30s and 40s as do carriers or those with BMD. DMD frequency is about 1:3500 whereas BMD is 1:15,000 to 1:35,000.

2. Dystrophinopathy should be suspected in a child or adult with the following clinical signs/symptoms: progressive skeletal muscle weakness, increased CPK, intellectual impairment, myalgias, or cardiomyopathy.

3. BMD patients by convention ambulate after 16. In 40 + year olds, isolated quad weakness can be confused with IBM. EKG findings are similar to DMD (arrythmias or decreased EF requiring Ace inhibitors). Chronic respiratory insufficiency can be associated with right heart failure.

4. Minimally symptomatic BMD with exertional intolerance, myalgia, myoglobinuria, or elevated CK diagnostic yield increases with subtle signs such as clumsy as child, toe walking, positive family history, calf or tongue hypertrophy, or myopathic units on EMG.

5. All patients regardless of symptoms should have periodic pulmonary function testing, EKG, and echocardiography.

6. Vaccinations including pneumococcal and influenza are recommended with low threshold for treating potential infections with antibiotics.

7. Anesthetic risks mandate patients wear a med alert bracelet. These risks are minimized with nondepolarizing muscle relaxants.

8. Bowel program plus suction continuous via gj tube reduces abdominal pain. Restricted jaw opening can mandate placement of a tube.

9. Consider seated position or other creative safety measures during surgery if possible and if indicated.

10. PT with range of motion and stretching exercises are hallmark.

Autosomal dominant ataxias with known causation

2010-02-14T09:54:00.000-08:00

Most common types are SCA I,II, III, VI which comprise > 50 % cases in USA. * indicates caused by polyglutamine CAG repeat expansion

SCA I--*-- begins as gait disorder, progresses to four extremity ataxia with dysarthria leaving patient wheelchair bound within 15-20 years.There is phenotypic variability and anticipation (genetically). Clinically there is involvement of cerebellum with neuronal dropout of Purkinje cell layer and clinical involvement of the brainstem. No supratentotial involvement. Not as common as type II but well worked out molecularly,

SCA II--*--characterized by ataxia, dysarthria, slow saccades and neuropathy. Originally Cuban description. Very common worldwide, especially in India. Slow saccades are not pathognomonic, they also are seen in SCA I and III. Dementia, areflexia, myokymia also are seen. Gene expansion includes cytoplasmic protein ataxin, function of which is unknown. Anticipation is marked, and disease may present in one generation in old age, in the next much earlier. Number of repeats are 35-77 , with 32-34 "zone of reduced penetrance."

SCA III--*--Very common, is aka Machado-Joseph disease. Presents with ataxia, eye movement abnormalities (bulging eyes, opthalmoparesis, staring eyes), speech and swallowing abnormalities. Pathologic abnormalities include cerebellar afferent and efferents, pontine and dentate nuclei, substantia nigra, subthalamic, GP, cranial motor nuclei and anterior horn cells. Ataxin 3 gene is at fault. Repeats: normal 12-42, high is 52-84. Early onset rigidity and dystonia (largest expansions), middle onset adult ataxia, late onset neuropathy (smallest expansions). A few patients have Parkinson's that is dopamine responsive and even fewer have RLS. Peripheral involvement is especially variable. MRI shows range from fourth ventricle enlargement to severe olive sparing spino pontine cerebellar atrophy.

SCA-- V-- "Lincoln family ataxia"--slowly progressive dominant ataxia found in grandparents of Lincoln. SPTBN2 gene ecoding B III spectrin is at fault.

SCA VI --*-- milder disease, pure cerebellar associated with normal lifespan. Presentation is gaze evoked nystagmus, dysarthria, onset at age 50 or so, impaired vibratory and position sense.Its fairly common in Japan and in Germany. Caused by expansion/repeat in voltage dependent calcium channel,same gene that causes episodic ataxia type 2 and familial hemiplegic migraine. However, mutations in these conditions in the same gene are different mutations.

SCA 7--*-- cerebellar brainstem disease associated with retinal degeneration and blindness. It has striking instability of transmission especially with paternal transmission, with cases in utero and in childhood.

SCA 8--*-- classical presentation of disease with gait and limb ataxia, swallowing speech and eye movement abnormalities. Most have progressive ataxia.

SCA 10 --*-- Mexicans with cerebellar symptoms and seizures. Extremely large expansion is found in SCA 10 gene. Ashizawa.

SCA 11--*-- 2 British families reported with benign gait and limb ataxia. TTBK2 gene.

SCA 12 --*--PP2R2 gene with dominant ataxia presenting with upper extremity tremor, progressing to head tremor, bradykinesia, abnormal eye movements. Onset 8-55 years.

SCA 13 --*-- dominant ataxia, may present in childhood with MR, dysarthria, nystagmus, +/- hyperreflexia. Due to KCNC3 gene mutation in voltage gated K channel subunit.

SCA 14 --not repeat--slowly progressive ataxia with dysarthria in early adulthood. May be pure cerebellar or accompanied by myokymia, hyperreflexia, axial myoclonus, dystonia and vibratory sense loss.

SCA 15-16-- allelic (ie same allele) disorder occurring in Austrailian and Japanese families, slowly progressive pure cerebellar disorder. Dysarthria, horizontal gaze evoked nystagmus, sometimes head tremor. Disease is due to deletions in IPTR gene

SCA 17 --*--Widespread cerebral/cerebellar dysfunction, rare in US, more common in Japan. Presents with gait and limb ataxia, psychiatric dysfunction, EPS, seizures, may resemble Huntington;s disease. MRI shows widespread cerebral and cerebellar dysfunction. Onset in mid to young adulthood.

SCA 26 -- Norwegian pure cerebellar ataxia that maps closely to gene affecting Cayman ataxia and SCA 6 with Purkinje cell degeneration.

SCA 27-- Dutch disease manifests with hand tremor in childhood.

DRPLA-- *-- progressive ataxia, choreoathetosis, dementia, seizures, myoclonus, and dystonia. Before age 20 there are almost always seizures and a progressive myoclonic seizure like presentation. Older patients get ataxia with choreoathetosis and dementia. More common in Japan, but Haw River phenotype is an African American family in the Carolinas with seizures and cerebral calcifications.

episodic ataxias--EA1 and EA2 are due to mutations in K and Ca channel genes. EA1-- patients ahve minutes of ataxia due to stress, exercise or change in posture. Patients also may have myokymia. KCNA1 gene. EA2 has ataxia that lasts days , precipitated by stress, exercise or fatigue and is due to mutation of same gene as SCA 6 (CACNA1A4 gene). Acetozolamide may help. Other EA's with prominent vertigo also are described.

Friedrich's ataxia, FARR, LOFA, VLOFA

2010-02-14T07:38:00.001-08:00

Friedrich's ataxia (AR) is subclassified into classical (75%), FARR (FA with retained reflexes, adult onset), LOFA (late onset FA) and VLOFA (very late onset FA).
In FA, pathology involves spinocerebellar tracts, lateral corticospinal tracts, posterior columns but NOT cerebellum. Clinical features include a. progressive gait ataxia and scoliosis b. gait worse in darkness (posterior column involvement) and worsening during puberty c. dysarthria and hand incoordination d. areflexia e. extensor plantars. Associated features may include e. optic nerve atrophy (25%), f. SN hearing loss (10%) g. optic flutter or square wave jerks but not opthalmoplegia h. hypertrophic cardiomyoapthy (90%) i. pes cavus j. diabetes mellitus in 15 % 15 years after onset j. wheelchair bound after 15 years k. Death 30-70.
In FARR, LOFA, VLOFA, sporadic ataxia occurs without cardiomyopathy. Spasticity occurs, areflexia does not. Again normal cerebellum. Sporadic ataxia patients may warrant gene testing for frataxin. Affected patients usually have 2 affected alleles, carriers have one. Rarely, sequencing of second allele for FXN is needed to find a point mutation (compound heterozygosity).

Neurosarcoidosis pearls diagnosis

2010-02-06T07:02:00.001-08:00

1. Percent with cranial neuropathy-- 50-75 (most common VII, second II, all can be affected)

2. Percent with parenchymal brain lesions-50

3. Other manifestations - cognitive 20, meningeal 10-20, PN 15, seizures 5-10, spinal 5-10, myopathy 1.4-2.3

4. Neuroendocrine presentations may include polydipsia, polyuria, panhypopituitarism, or massive obesity if sarcoid invades satiety center of hypothalamus

5. Neuropathy can be virtually any type

6. Myopathy can be acute, chronic or nodular and is usually subclinical. In contrast to steroid myopathy (the rule-out diagnosis often), sarcoid myopathy may have palpable nodules, contractures, cramps, elevated CPK, and fibrillation potentials and positive sharp waves on EMG. Both steroid and sarcoid myopathy will have myopathic potentials.

7. Contrast enhanced MRI to look for meningeal involvement is extremely important, but is not specific.

8. Whole body PET imaging is better than Gallium and can be used to look for lymph nodes suitable for biopsy for diagnosis, but is not specific

9. CSF is normal in one third,but can show high protein, lymphocytosis, low glucose. OCB's , high IgG index

10. CSF ACE levels are insensitive (24-55 %) but fairly specific (93%) for CNS sarcoid

11. Heerfordt's syndrome consists of facial palsy, parotid enlargement, uveitis and fever and is considered so typical that tissue biopsy is not required

Persistent genital arousal syndrome: neurology of and comparison to epileptic orgasms

2010-01-29T11:58:00.002-08:00

This post details a neurologic basis to persistent genital arousal syndrome (PGAS). The condition is characterised by unwanted repeated multiple daily episodes of sexual arousal, that often leads to dozens or hundreds of orgasms daily, relieved with masturbation briefly before recurring. It can be lifelong, occur during pregnancy, or in the postmenopausal state. Precipitating factors include pudendal nerve injury, and antidepressant drugs including trazodone. A strong association with restless legs syndrome and overactive bladder has been noted. Treatments that were successful in many patients include clonazepam, tramadol, pelvic floor massage focusing on the pudendal nerve, varenicycline,and pudendal nerve blocks.

This condition can be differentiated from orgasmic seizures, which itself needs to be divided into different entities. Orgasms as an aura of a seizure can occur usually due to right hippocampal, but occassionally left hippocampal or left parietal epilepsy. Reflex epilepsy after orgasm also occurs again usually after right temporal but occassionally left frontal seizures and in one case report reflected the manifestations of complete heart block, cured with a pacemaker. Reflex epilepsy occurring as orgasmic aura has been reported after toothbrushing in one Taiwanese patient.

see pub med for references

Antiepileptic drugs and peripheral neuropathy

2010-01-26T06:20:00.001-08:00

Effects of the antiepileptic drugs on peripheral nerve function; Boylu E, Domaç FM, Misirli H, Senol MG, Saraçoglu M; Acta Neurologica Scandinavica 121 (1), 7-10 (Jan 2010)

Upshot-- carbamazepine, but not valproate, oxcarbazepine and topirimate, affect nerve conduction studies among chronic takers.

Clinical pearls in diagnosis of vestibular disorders

2010-01-24T17:50:00.000-08:00

1. Look for nystagmus with and without fixation. To achieve latter, either examine in a darkened room with Frenzel glasses or use opthalmoscope in one eye and cover the other.

2. Nystagmus can be assessed with holding eyes 30 degrees from midline in 4 positions (L-R-U-D) each for 20 seconds. Further out, and nystagmus is expected. Use a chart to score.

3. Nystagmus through eyelids can be confused with lid twitch.

4. Features of central nystagmus that differ from peripheral include pure vertical, horizontal or rotatory rather than combined; no effect of fixation; may change direction; central abnormality may affect pursuit or OKN. In central nystagmus, there may be a null zone near center after which nystagmus changes direction when eyes look in opposite direction.

5. Head thust sign is a simple test at bedside, of horizontal component. Move head rapidly a short distance horizontally in one direction and then other. Eyes should at start be ten degrees from primary position so that after the thrust they will be near primary position. Patient fixates on examiner's nose. If there is a catch up saccade in one direction but not the other, that is evidence of a peripheral lesion on that side. The absence of a head thrust sign suggests a central etiology.

6. Patients with peripheral lesions veer towards the side of the lesion when up. Patients with central lesions often cannot stand. Patients with central lesions are more likely to have dysarthria, numbness or weakness.

7. Viral labyrinthitis needs to be diagnosed after ruling out other entities. Bacterial usually has associated mastoiditis that is identified on CT scans of the temporal bone. Usually auditory and vestibular function both are affected with bacterial infection.

8. Recurrent episodes that become bilateral and lead to deafness within months are associated with syphilis.

9. Perilymh fistula often presents abruptly after a precipitating event, such as head trauma, barotrauma, strain while lifting, or sneezing. It is very common among patients who have undergone stapedectomy for otosclerosis. Patients with fluctuating symptoms or positive fistula test need to undergo surgery.

10. Very important: the Dix Hallpike test can be positive in central vertigo cases, including tumors, but features are different. Central variety fails to attenuate with repeated tests, may last longer than 30 seconds, and may have fast phase downward to cheek (as opposed to peripheral which is to bottom ear and forehead).

Classical Babinski-like signs

2010-01-24T15:06:00.000-08:00

Extensor toe signs
Babinski response- extension of big toe, fanning of small toes with stroking plantar surface
Chaddock response- same response except stimulation is of lateral foot from lateral malleolus
Gordon leg sign-- same with stimulation of squeezing leg muscle
Oppenheim's sign-- same result with downward stroking of tibia and tibialis anterior muscle
Gonda's reflex--upward movement of big toe by moving another toe down and releasing with snap
Shaefer's sign-- Babinski response by squeezing Achilles' reflex

Non extensor toe long tract signs
Rossolimo's sign-- same response with striking or tapping the ball of the foot
Mendel-Bechterew sign- flexion of 4 outer toes by striking dorsum of foot
Hoffman's sign-- Clawing of the thumb and all fingers by flicking distal phalanx of index finger
Gordon's finger sign-- flexion of fingers or thumb/index finger with pressure over pisiform bone
Chaddock's wrist sign- wrist flexion, extension & fanning of fingers with stimulation of ulnar side of hand
Hirschberg's sign- adduction and internal rotation while stroking the inner border of foot
Ankle clonus-- may be normal if unsustained
Patellar clonus (trepidation sign)-- lifting relaxed knee suddenly looking for increased tone

Other pathologic signs
Beevor's sign-- with lesion at T10, the patient tenses abdominal muscles and ombilicus moves upwa rds, doe to paralyzed
Mass reflex of Riddoch-sudden emptying of bowel and bladder, flexion of lower limbs and sweating. Its released pathologically by severing spinal cord and striking skin below

Classical abnormal gaits

2010-01-24T14:41:00.000-08:00

Tabetic (ataxic) gait
Hemiplegic gait
Steppage gait
Scissors gait
Drunken or ataxic gait
Waddling or clumsy gait
Festinating gait
Hysterical gait
astasia - abasia

metoprolol : no effect on QOL in recurrent syncope

2010-01-24T09:26:00.001-08:00

Effect of metoprolol on quality of life in the prevention of syncope trial; Sheldon RS, Amuah JE, Connolly SJ, Rose S, Morillo CA, Talajic M, Kus T, Fouad-Tarazi F, Klingenheben T, Krahn AD, Koshman ML, Ritchie D; Journal of Cardiovascular Electrophysiology 20 (10), 1083-8 (Oct 2009)

INTRODUCTION: Vasovagal syncope is common, often recurrent, and reduces quality of life. No therapies have proven useful to improve quality of life in adequately designed randomized clinical trials. Beta-blockers have mixed evidence for effectiveness in preventing syncope. METHODS: The Prevention of Syncope Trial was a randomized, placebo-controlled, double-blind, multinational, clinical trial that tested the hypothesis that metoprolol improves quality of life in adult patients with vasovagal syncope in a 1-year observation period. Randomization was stratified in strata of patients<42 and>or =42 years old. The quality of life questionnaires Short Form-36 (SF-36) and Euroqol EQ-5D were completed at baseline and after 6 and 12 months of treatment by 204, 132, and 121 patients, respectively. RESULTS: There were 208 patients, mean age 42 +/- 18, of whom 134 (64%) were females. All had positive tilt tests. There was no improvement in quality of life during the trial in the entire group or in either treatment arm. Patients in the metoprolol treatment arm did not have improved quality of life compared to the patients in the placebo arm using either the SF-36 or EQ5D after either 6 or 12 months. Finally, there was no improvement in quality of life associated with metoprolol use in patients either<42 or>or =42 years of age. CONCLUSION: Metoprolol does not improve quality of life in patients with recurrent vasovagal syncope and a positive tilt test.

ED treatment of migraines: i-v prochlorperazine plus Benadryl beats sumatriptan

2010-01-24T09:24:00.001-08:00

A Prospective, Randomized Trial of Intravenous Prochlorperazine Versus Subcutaneous Sumatriptan in Acute Migraine Therapy in the Emergency Department; Gutierrez FJ, Rieg TS, Moore TS, Gendron RT, Kostic MA; Annals of Emergency Medicine (Dec 2009)

STUDY OBJECTIVE: Intravenous (IV) prochlorperazine with diphenhydramine is superior to subcutaneous sumatriptan in the treatment of migraine patients presenting to the emergency department (ED). METHODS: In this randomized, double-blind, placebo-controlled trial, after providing written informed consent, patients presenting to the ED with a chief complaint of migraine received a 500-mL bolus of IV saline solution and either 10 mg prochlorperazine with 12.5 mg diphenhydramine IV plus saline solution placebo subcutaneously or saline solution placebo IV plus 6 mg sumatriptan subcutaneously. Pain intensity was assessed with 100-mm visual analog scales (visual analog scale at baseline and every 20 minutes for 80 minutes). The primary outcome was change in pain intensity from baseline to 80 minutes or time of ED discharge if subjects remained in the ED for fewer than 80 minutes after treatment. Sedation and nausea were assessed every 20 minutes with visual analog scale scales, and subjects were contacted within 72 hours to assess headache recurrence. RESULTS: Sixty-eight subjects entered the trial, with complete data for 66 subjects. Baseline pain scores were similar for the prochlorperazine/diphenhydramine and sumatriptan groups (76 versus 71 mm). Mean reductions in pain intensity at 80 minutes or time of ED discharge were 73 mm for the prochlorperazine/diphenhydramine group and 50 mm for those receiving sumatriptan (mean difference 23 mm; 95% confidence interval 11 to 36 mm). Sedation, nausea, and headache recurrence rates were similar. CONCLUSION: IV prochlorperazine with diphenhydramine is superior to subcutaneous sumatriptan in the treatment of migraine.

seroquel for refractory migrained pilot study

2010-01-24T09:20:00.001-08:00

An Open Pilot Study Assessing the Benefits of Quetiapine for the Prevention of Migraine Refractory to the Combination of Atenolol, Nortriptyline, and Flunarizine; Krymchantowski AV, Jevoux C, Moreira PF; Pain Medicine (Dec 2009)

Background. Migraine is a prevalent neurological disorder. Although prevention is the core of treatment for most, some patients are refractory to standard therapies. Accordingly, the aim of this study was to evaluate the use of Quetiapine (QTP) in the preventive treatment of refractory migraine, defined as previous unresponsiveness to the combination of atenolol, nortriptyline, and flunarizine. Methods. Thirty-four consecutive patients (30 women and 4 men) with migraine (ICHD-II), fewer than 15 days of headache per month, and not overusing symptomatic medications were studied. All participants had failed to the combination of atenolol (60 mg/day), nortriptyline (25 mg/day), and flunarizine (3 mg/day). Failure was defined as<50% reduction in attack frequency after 10 weeks of treatment. After other medications were discontinued, QTP was initiated at a single daily dose of 25 mg, and then titrated to 75 mg. After 10 weeks, headache frequency, consumption of rescue medications, and adverse events were analyzed. Results. Twenty-nine patients completed the study. Three patients withdrew and two were lost to follow-up. Among those who completed, 22 (75.9%; 64.7% of the intention-to-treat population) had greater than 50% headache reduction. The mean frequency of migraine days decreased from 10.2 to 6.2 per month. Use of rescue medications decreased from 2.3 to 1.2 days/week. Adverse events were reported by nine (31%) patients. Conclusions. Although limited by the open design, this study provides pilot data to support the use of QTP in the preventive treatment of refractory migraine. Controlled studies are necessary to confirm these observations.

Kearn's Sayre syndrome

2010-01-22T13:59:00.001-08:00

Rowland's diagnostic criteria

Obligate triad

1) Onset before 20

2) Progressive external opthalmoplegia

3) Pigmentary retinopathy

plus at least one of: CSF protein>100, ataxia, cardiac conduction block

websites for genetic information

2010-01-17T08:11:00.000-08:00

http://www.geneclinics.org/

http://www.neuromuscular.wustl.edu/

http://www.pdgene.org/

Neurotoxicology: sources of lead in adults

2010-01-14T06:52:00.002-08:00

Lead poisoning occurs due to inhaling inorganic lead salts and fumes in processes involving remelting of lead. These include painting, printing, pottery glazing, lead smelting, welding and storage battery manufacturing. Other cases have occurred in miners, foundry and garage workers especially those who soldered radiators. Aruvedic herbal remedy for arthritis is described. Moonshine whiskey was very common in one series. The presentation is colic, anemia and peripheral neuropathy. It responds somewhat to calcium salts but not morphine (colic). Organic lead poisoning occurs in those who clean gasoline storage containers with insomnia, hallucinations, delusions and irritability. Hematologic changes are not found, and its usually reversible.

Stiff man syndrome (stiff person syndrome) Pearls

2010-01-14T06:28:00.003-08:00

1. Insidious onset, then robotic appearance to walking and exaggerated lumbar lordosis in middle aged. Attempted passive movement causes a unique rock like immobility.

2. Trismus does not occur, and eye movements are not affected. Noise may precipitate an attack. Reflexes are normal, and lumbar spine is stiff on exam.

3. "Stiff limb" in one leg, spreading to other, has same antibodies (anti GAD) is similar to lcoalized tetanus.

4. EMG is normal and spasms disappear during sleep and anesthesia, differentiating from myokymia and Isaac's syndrome.

5. Rare paraneoplastic form usually accompanies breast cancer with antibodies to amphiphysin or gephyrin (proteins related to synaptic GABA receptors) and may be accompanied by opsoclonus or encephalopathy.

6. Differential diagnosis includes tetanus, Isaac's syndrome and myoclonic spinal neuronitis.

7. An infantile form starts at age 2 months and disappears by age 2.

Lysosomal storage diseases in adults

2010-01-10T15:16:00.004-08:00

1. Of 45 or so diseases, all are autosomal recessive except the 3 that are X linked, namely Hunter's disease (mucopolysaccharadosis type II), Fabry's, and X linked myopathy with cardiomyopathy (lysosomal associated membrane protein 2, or LAMP 2).

2. GM2 can resemble Friedrich's ataxia, but unlike Friedrich's has hyperreflexia, episodic psychosis, and absent cardiomyopathy and scoliosis which should give away the diagnosis.

3. Dementia is common, and is a presenting feature of Kuf's disease type M and adult onset MLD. Dementia is most common presenting feature of adult onset mannosidosis, fucosidosis, aspartylglucosaminuria, Niemann Pick type c (along with vertical gaze palsy, dystonia, and dysarthria)

4. Progressive myoclonic epilepsy occurs in Kufs disease type A with spike wave on EEG and photosensitivity at low flash frequencies (see Berkovic 1988 Brain for review article). Type B is characterized by dementia, ataxia, EPS and facial dyskinesias. Sialodosis type I aka cherry red spot myoclonus has treatment resistant epilepsy with macular cherry red spot and abnormal neuraminidase in skin fibroblasts.

5. Late onset myopathy occurs in Pompe's disease, with high CPK, accumulated glycogen in vesicles, and deficient alpha glucosidase which is hard to measure. Danon disease is X linked recessive and has hypertrophic cardiomyopathy and muscle weakness, and muscle biopsy shows autophagic vacuoles with glycogen. Its due to LAMP 2 deficiency. There is mild MR and usually, death before 30.

Managing adults with hydrocephalus : pearls

2010-01-09T08:52:00.005-08:00

This post assumes patients who received a shunt as a child has problems as an adult

1. Signs of shunt malfunction/ increased ICP. On PE look for VI n palsy, papilledema, +/- reliability of shunt pump test

2. On history consider HA worse in AM or with recumbency, associated vomiting with relief, and diplopia suggest raised intracranial pressure. If HA is worse when up, consider low pressure headache

3. On imaging, assess all 4 ventricles independently, look for periventricular edema, edema around proximal shunt tip, loss of cerebral sulcal pattern near vertex, or loss of CSF spaces in basal cistern and Sylvian fissure. ALWAYS compare to prior scan closely.

4. ETV or endoscopic third ventriculostomy is used in some patients especially with third ventricular obstructions. ETV has a risk of catastrophe, a higher risk of immediate failure, a lower risk of long term failure but still can obstruct years later (unlike most standard shunts). ETV has the compelling advantage of a lower infection risk.

5. Patients with myelomeningocoele should be evaluated in a top down manner: shunt obstruction, Chiari malformation, syringomyelia/syringobulbia, and tethered cord. Often neurosurgeons will want to surgically manage the shunt to make sure it is working before embarking on other issues in these cases. An example case in Continuum was a patient who had presented with hand weakness and syringomyelia, but who had massively dilated ventricles and whose primary problem was in fact the shunt dysfunction.

Fragile X tremor ataxia syndrome (FXTAS)

2010-01-07T17:26:00.003-08:00

FXTAS is due to premutation, and an excess amount of FRMP protein (50-200 repeats). Not all carriers develop FXTAS. Features include

1. usually presents with intention or action tremor with handwriting or using utensils

2. above is followed by ataxia with falls and unstable gait
above occurs in male carriers at a rate of 17% by 50's, 38 % by 60's, 47 % by 70's and 75 % by 80's. Women have less FXTAS with 8 % of those with premutation affected.

Other neurologic features
1. painful neuropathy

2. autonomic dusfunction (erectile dysfunction, hypertension, OH, urinary urgency and frequency, and incontinence. Girls develop premature ovarian insufficiency or POI.

3. White matter abnormalities (increased T2 intensity)especially bilateral cerebellar peduncles but elsewhere in deep white matter(seen in 60 % males, 13 % of females)

4. Executive dysfunction, short term memory loss, disinhibition and dementia

5. Unique eosinophilic intranuclear inclusions in neurons and astrocytes especially in the hippocampus and in the limbic system that are tau negative. They also occur in the PNS including the pericardiac and mesenteric ganglia and Leydig cells of testes.

6. Testosterone deficiency

7. Anxiety, social phobia and depression

8. Women with FXTAS : 43 % have fibromyalgia and 50 % have thyroid disease usually hypothyroidism

9. 2-3 per 100 develop multiple sclerosis and some develop Alzheimers

Treatment: SSRI's for anxiety, lithium for depression

Fragile X syndrome (FXS) clinical features

2010-01-07T17:16:00.004-08:00

1. long face
2. prominent long ear pinnae
3. high arched palate
4. mitral valve prolapse
5. dilated aortic arch
6. flat feet
7. hyperextensible finger joints in childhood
8. macroorchidism (testicular volume greater than 30 cc in adulthood)
9. soft or velvet like skin.
10. Daughters can receive premutation only, sons cannot receive gene from their father
11. Single palmar crease

rare problems-- elasticity leads to increased hernias, and dilation of ureteric root leads to hydronephrosis.

Neuropsych
1. hyperarousal to stimuli with increased sympathetic response
2. Agression, anxiety
3. Concrete thinking
4. Dramatic decline of cognition in middle or later life, due to FRMP regulating amyloid precursor protein (APP) leading to coexisting Alzheimer's disease
5. Men typically are not sexually active and do not marry (not invariable)

Morvan syndrome aka "Choree Fibrillaire"

2009-12-24T17:30:00.002-08:00

Four cardinal features of Morvan syndrome are

1. Neuromyotonia or myokymia

2. Dysautonomia (esp hyperhidrosis, hypersalivation, labile hypertension). Weight loss is common.

3. Severe insomnia

4. Fluctuating encephalopathy with vivid hallucinations

Other notes-- MRI and random eeg is often normal. Patients are usually young males, EMG and PSG are not normal, and VGKC's are often present. Differential includes FFI, CJD, rabies virus, and Lewy body disease. The key clinical finding that differentiates is the dysautonomia and neuromyotonia. Often is fatal, but Ligouri et al. reversed one case with plasma exchange.

Ligouri R, Vincent A, Clover L, et al. Morvan's syndrome. Peripheral and central nervous system and cardiac involvement with antibodies to voltage gated potassium channels. Brain 124: 2417, 2001.

Note-- there is a second "Morvan's disease" that refers to atrophic changes in bone, skin, muscles of hand in syringomyelia.

Clinical spectrum of disease of VGKC

2009-12-24T16:19:00.002-08:00

Voltage gated calcium channels are seen in a variety of neurologic diseases. They include

1. Autoimmune neuromyotonia (formerly Isaac's syndrome)
2. Morvan's syndrome (encephalopathy and myotonia). Augustus Morvan (1870) "la choree fibrillaire." see separate post on Morvan's in this blog
3. Encephalopathy without neuromuscular excitability--clinical syndrome consists of a) clinically indistinguishable from paraneoplastic limbic encephalitis (PLE) b) subacute cognitive impairment with behavioral changes and temporal lobe seizures c) FLAIR and T2 changes in mesial temporal lobes on MRI d) temporal lobe eeg abnormalities e) association with hyponatremia f) male predominance g) dramatic response to IVIG or steroids
4. Are occassional cases with associated cancer, especially lung and thymus carcinoma, but these are typically associated with "other" paraneoplastic markers and symptoms and are minority
5. A similar presentation and responsiveness to treatment occurs in VGKC negative patients who have anti hippocampal neuropil antibodies.

Coccidiodal meningitis and brain abscesses: analysis of 71 cases at a referral

2009-12-07T10:05:00.001-08:00

Drake KW, Adam RD. Neurology 2009; 73:1780-1786

Most patients present with headache only (77%) while 23 % had nuchal rigidity, 39 % had mental status changes, and one third focal signs especially gait disturbance or ataxia, may be due to hydrocephalus. Risk factors are HIV/chronic steroids but not diabetes. Also, liver failure, hem/lymph malignancies, and ESRD. Increased risk for males (2:1), Hispanic, black and Asian patients in endemic areas (black patients have 6:1 risk). CSF had mononuclear pleocytosis, 69 % had abnormally low glucose, occasionally high protein or eosinophils. CSF antibody/culture often negative on presentation (50 %), but in those patients, serum antibody test is usually positive. Also CSF cultures or brain biopsy occasionally used for diagnosis. Imaging may show basilar meningitis or hydrocephalus and vasculitic infarcts. Many patients had antecedent illnesses, including respiratory, that may or may not have been diagnosed as coccidio or occasionally osteomyelitis, lymphadenitis, skin lesions, and soft tissue masses. Treatment is with azoles, esp. fluconazole which has supplanted amphotericin and others. Relapse can occur years or even decades later if azole therapy is stopped. Shunts are frequently needed for treatment of hydrocephalus. Prognosis is now good for those compliant with therapy.

Idiopathic intracranial hypertension in men

2009-11-29T11:28:00.001-08:00

NEUROLOGY 2009;72:304-309

66 men out of 721 consecutive patients were studied. The takeaways are that men

1. Men were less likely to have HA (55 v. 75 %) but more likely to have visual disturbance. Acuity and fields were worse and men had about twice the risk of having permanent visual sequelae.

2. Men were more likely to have sleep apnea (24 v. 4%)

3. Tinnitus was less common in men (20 v. 38 %)

Refsum like disorder in a Norwegian cosanguineous family

2009-11-29T10:54:00.001-08:00

T. Fiskerstrand, MD, PhD, P. Knappskog, PhD, J. Majewski, PhD, R. J. Wanders, PhD, H. Boman, MD, PhD and L. A. Bindoff, MD, PhD . A novel Refsum-like disorder that maps to chromosome 20. NEUROLOGY 2009;72:20-27

This slowly progressive disorder starts in childhoodwith signs of peripheral neuropathy (pes cavus, tendoachillescontracture). Hearing loss and cataract become evident in thethird decade. Subsequently, patients develop a disorder of gaitdue to the combination of ataxia and spasticity, and a pigmentretinopathy. While the clinical picture is reminiscent of Refsumdisease, affected individuals have normal phytanic and pristanicacid levels in plasma, as well as normal enzymatic activityfor -oxidation. We mapped the disease to a 15.96 Mb region onchromosome 20 (20p11.21-q12), containing approximately 200 genes(maximum lod score = 6.3).

Politics of health care reform in NEJM distort reality

2009-11-28T06:35:00.005-08:00

The October 29, 2009 issue of the New England Journal of Medicine contains four separate articles on health care issues which, if taken in their entirety, represent the absurdity to which the health care debates in the United States have gone.

The first article-- the best of the four-- describes how much FDA information never reaches clinicians (1). Clinicians and the public rely on the Food and Drug Administration (FDA) for drug and product approvals and denials, and for disseminating accurate information about drugs in their product inserts. I learned that the lengthy, often poorly written and weakly summarized debates about drugs are posted publicly at www.accessdata.fda.gov/scripts/cder/drugsatfda/. The authors cited glaring examples of critical information that somehow was not included in the product labels. Zometa (zoledronic acid, Novartis), used to treat hypercalcemia of malignancy, at the 8 mg dose, caused more renal toxicity and death than the 4 mg dose and was no more effective. Nonetheless, the labelling suggested using the higher dosage "in refractory cases." The product label did not mention increased mortality at the higher dose.

Lunesta (eszopiclone, Sepracor), sold 800 million dollars last year with the help of a direct to consumers marketing campaign. Yet the efficacy data, buried on page 306 of 403, shows patients slept 15 minutes earlier and 37 minutes longer than placebo, with no clinically meaningful improvement in next day alertness or functioning. Similarly, Rozerem (ramelteon), another approved sleep drug, caused younger adults to fall asleep 14 minutes earlier, and older ones 7 minutes earlier, with no improvement on subjective assessments of sleep quality.

The very next article details ways the same government can "further" improve health care. Victor Fuchs (2). advocates incremental rather than radical health care reform. The first of his four proposed reforms is to eliminate employer based health care coverage tax exemptions. The purpose is to raise 200 billion dollars in new revenues, that is taxes, to make the tax system "fairer" since the tax benefit is a regressive tax. He alleges it benefits the wealthy. (Wait a minute-- my practice employs 15 people, who have relatively low incomes and have the same insurance I have. A biller who had breast cancer last year would never have gotten treatment without our comprehensive health insurance). This would allow the creation of insurance exchanges, the second idea, that would, using Fuchs' words, be not as "generous" to "consumers" (actually, sick patients) as the private plans they replace. Supposedly, these exchanges would decrease "broker" costs.

The third, chilling suggestion of Fuchs is the appointment of an "expert" commission to devise changes to the ways Medicare reimburses providers. Fuchs cites "special interests" as blocking the "public good," as a charged way to rally the troops. Again, citing my own practice, with 50 % overhead, a 10 % payment cut equals a 20 % loss of income. Could it be, that by going after providers who have already been sucked dry, Fuchs will drive people out of practice, resulting in fewer providers, thereby raising the cost of care? Fuchs' final idea is an office for technology assessment that would be "quasi-independent." Of whom, I might ask.

The third article-- the last to be reviewed here- describes implementing evidence based medicine in Washington state (3). The state has total authority, except where prohibited by federal statute, to use evidence based methods to assess drugs, devices, surgical procedures, diagnostic tests, imaging procedures, and medical equipment. The author decries the political "pressure" wrought by patients who testify that the benefitted from a technology the state wants to eliminate. Obscenely, the same authors equate pharmaceutical direct to patient marketing with physician "autonomy" and "financial incentive" in ordering tests.
The authors note the "challenges" of this policy, citing the example that thymectomy of myasthenia gravis, used since 1912, has never undergone a rigorous trial. This author will note a few more nonevidence based treatments: penicillin for infection, appendectomy for appendicitis, and burr holes for subdural hematomas of the brain. Are these procedures necessary? Shall the government be in a position to decide? May I be so impudent to suggest satisfaction surveys be returned for all cases of physician assisted suicide?

The assumption of evidence based medicine is that care from one can be generalized to another and is equivalent to another. Evidence is important, and can help us learn how to be better doctors. But, evidence is not the be all and end all. Sometimes doctors have to take the controls from the nurse practitioners and PhD's and make decisions that are in the best interests of the patient. The reasons may not be obvious to the lay public but may be based on sound understanding of pathophysiology. Experience and judgment, absent from these vacuous bureaucratic declarations, still are what most patients seek.

1. Schwartz LM, Woloshin S. Lost in transmission: FDA drug information that never reaches clinicians. N Engl J Med 2009; 361:1717-1720.

2. Fuchs VR. Four health care reforms for 2009. N Engl. J Med 2009; 361: 1720-1722.

3. Franklin GM, Budenholzer BR. Implementing evidence based health policy in Washington State. N Engl J Med 2009; 361:1722-1725.

Idiopathic recurring stupor & narcolepsy automatisms

2009-11-27T06:03:00.002-08:00

Several sleep related conditions may mimic and be misdiagnosed as seizures. 80 % of narcoleptics have automatic behavior during sleep. The individual appears awake but is without full awareness. Behavior may be inappropriate and resemble a fugue state.

Idiopathic recurring stupor was described in 1990. The stupors may occur a few times weekly to a few times annually, and last from hours to days. All cases show a widely distributed nonreactive 13-18 hz activity. Flumazeni, a benzodiazepine antagonist, quickly but temporariy reverses the stupor and eeg findings. The culprit is thought to be endogenous benzodiazepines called "enzopines" that act on the GABA A receptor for benzodiazepines. These ligands may alsobe important in learning, memory, hepatic encephalopathy, and panic attacks. CSF enxopine-4 levels are more than 100x higher than in control subjects.

The Larynx for Neurologists

2009-11-26T19:47:00.003-08:00

Meyer TK. The Neurologist 2009; 15:313-318. Also points from Rosenfield DB,and Viswanath NS. Neurolaryngology.in Evans R. Diagnostic Testing in Neurology Philadelpia, Saunders, 1999, pp. 223-229.

Larynx functions: phonation, deglutition, airway protection, control of respiration. Laryngeal closure also allows increased abdominal pressure for defection, parturition and stabilization of thorax for heavy lifting.Humans have a lower larynx than grazing animals,helping phonation but more precarious for airway control.

Diseases
Parkinson's disease-- vocal folds are atrophied and bowed with incomplete closure. Patients perceive their own hypophonic speech as of adequate loudness. Voice is also due to bradykinetic efforts from inadequate bellows mechanism (diaphragm and chest wall). Treatment includes bilateral bulking injections to vocal cords to facilitate glottal closure which can be temporary or permanent. Lee Silverman voice technique also helps.

Vocal Cord paralysis. Patient has weak breathy wet voice. It usually occurs due to tumor or surgery. If one vocal cord does not close, can do implant medialization, which will improve voicing and cough in all, and speech in 70 %.

Spasmodic dysphonia-- is a focal dystonia of 2 types. Adductor s.d. is characerized by harsh strangled quality with voice breaks. Abductor s.d is characterized by sustained breathiness with breathy voice breaks. The dystonia is task specific, eg. with breathing, sparing other functions such as swallowing. SD is female predominant with 73 % ADSD, 17% ABSD. Its associated with essential tremor in 30 % and other dystonias in 14 %. Botox is best treatmentfor both types, although the procedure is different for each.

Historical points in dysphonia. Getting stuck,shaking, or improving with alcoholsuggests ET. Trauma can cause dislocated arytenoid cartilage. Pain indicates focal pathology or GERD. Abrupt onset maybe psychogenic. Fluctuations may represent myasthenia.

Signs--

some physical exam tests for conversion disorder

2009-11-26T18:53:00.002-08:00

1. Pseudoptosis v. real ptosis. In pseudoptosis, the orbicularis eyebrow brings the eyebrow down. In real ptosis, the frontalis brings the eyebrow up.

2 Hysterical dysphonia. The vocal cords are normal during larygoscopy, cough is normal, articulation in whisper is normal.

3. Monrad Krohn's cough test for hysterical monoparesis. Stands behind patient, grab both lattismus dorsi,ask patient to cough, lats contract prove integrity of brachial plexus.

4. Double crossed arm pull test for hysterical monoparesis. Grab patient's wrists which are crossed across his chest and tell him, "when I say now, pull back as hard as you can." He may pull both sides.

5. "Make a fist " test for psychogenic wrist drop. Wrist elevates with a fist (functional position) or with holding a pencil in posiition.

6. Reversed hands test for functional monoparesis. Interlock hands, ask patient to move finger pointed to.

7. Backward displacement test for psychogenic foot drop. Push patient backwards and see anterior tib dorsiflexors spring into action.

8. Hoover test.One hand under each heel. Ask patient to raise the good leg, and the other one will inadvertently push down in functional patient. If ask patient to push down with both legs, if organically paralyzed he won't if hysterical he might.

9.Raimiste's leg abduction/adduction test for hysterical weakness. Similar to Hoover test for abduction and adduction of legs.

10. Psychogenic visual field deficit with tubular vision, same deficit for near and far Similar, spiral visual field defect may occur with smalllr field with each trial.

Provocative sensory tests pearls

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1. Demyer advocates performing position sense tests with the fourth rather than the first digit for greater sensitivity.

2. Pallanesthesia refers to vibratory testing.

3. The directional scratch test on the dorsum of the palm and leg may be superior to other tests of vibratory or position sense (Hankey and Edis, JNNP, 1989). Scratch a line across 2 cm and ask patient if scratch was up or down. If unable to perform accurately (ie, 100 %), repeat with distance systematically increased to make the test quantitative.

4. Two point discrimation with a paper clip can be done touching the patient with one or both ends of the paper clip and asking if patient got one or more than touch. Thresholds for normal two point discrimination in patients more than 7 years old, 2-4 mm on fingertips, 4-6 mm on dorsum of fingers, 8-12 mm on palms, 20-30 mm on dorsum of hands,

Circadian rhythm disorders-- P Zee

2009-11-25T19:47:00.004-08:00

AAN talk stuff 2009

1. Keeping time can be regulated at a genetic molecular level with clock genes. This affects both ASPD and DSPD.
2. SCN sends a signal to pineal, which feedbacks to SCN altering circadian rhythms. The main influences on are light, melatonin, and physical activity.
3. Advanced or delayed circadian rhythm disorders occur. Assess with: 7 day eveningness/morningness questionnnaire, sleep diary, actigraphy, core body temperature, melatonin level (24 hour or sleep onset DLMO, clinically available, from saliva) or PSG- ambulatory .
4. Advanced and delayed sleep phase disorder. Rectal body temp usually nadirs 4-6 am, so someone who nadirs at 11 am (college kid?) has a delayed circ disorder. Same patient, melatonin spikes at 1 am whereas for most of us it happens at 9 pm. DSPS has higher rate of BPAD

jet lag pier.acponline.org googlejetlag calculator

east ward trouble falling asleep
west ward trouble staying asleep.

if lags going to Europe, avoid bright light in AM. Speeds up realignment.Needs a week to realign otherwise. Going back west, use melatonin at bedtime at destination.

Other quick hits
REM sleep centers include pons -- perilocus cereleus for atonia, and vestibular nuclei for generation of REM and basal forebrain also plays a role as do other areas.

Sleep pearls, neuromuscular diseases other than ALS

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1. For SMA, do PSG if FVC is less than 65 %. This is due to kyphoscoliosis and disphragmatic weakness. Treatment prolongs life length. The have CSA and OSA. Annual screening should be done to growth .

2. Facial issues challenge including short chins and disproportionate midfacial growth causes significant mask leak, and overwhelming constipation causes significant aerophagia.

Duchenne's MD

1. When DMD becomes nonambulatory and scoliosis sets in, sleep problems escalate rapidly. Sleep physicians should by policy statement, be part of team at time of diagnosis, so families understand dyspnea related problems. When they are in wheelchair, they should have annual PSG's.

2. They have problems with dream sleep.

3. An old study showed NIV early in Duchenne's leads to worse outcomes. The data may be different in the steroid age.

Myotonic dystrophy, DM1 subtype.

1. CTG repeats increase over generations and leads to EDS without strict correlation to muscle issues. Hypersomnia has primary central reasons.

2. Sleep fragmentation with short REM latency, decreased Rem abouts and feel tired.

3. MSLT's resemble narcolepsy. Not narcolepsy, since no hypnagogic hallucinations, cataplexy, and no abnormal hypocretin abnormalities.

4. Abnormal cortisol and thyroid rhythms and dropout neurons in raphe nucleus.

5. RCT's with modafinil have not been completed but treat with stimulants not just sleep disordered breathing

Postpolio syndrome

Worsening fatigue, severe and incapacitating is the first and prime symptom in PPS. Its due to multiple problems. Menopause is very important. RLS is very common. Fasciulations are commonly seen in PSG's Inflammation, esp. IL6 , but may not be related to sleep homeostatic mechanisms.

Prior to sending to sleep lab, check a NIF and FVC, and can start NIV without sleep lab referral.

Spinal cord injuries

1. Sleep problems include pain, spasms, trouble breathing.

2. Higher injury leads to OSA, 48 % with increased neck thickness with unopposed parasympathetic stimulation and head position with changes over time.

3. Use of meds such as baclofen worsen things

4. Involvement of SCG at C3 affects melatonin.

Pearls on sleep disorders in ALS

2009-11-25T18:15:00.000-08:00

1. In ALS starting NIV at 70 % predicted FVC preserves life longer than if begun at 50 %. (life extension of 2.7 vs. 1.8 yrs)

2. In ALS CSA and OSA occur early, but OSA drops out, and thoracoabdominal paradox occurs in 30 % and is difficult to test with PSG.

3. Testing should use multiple modalities including nocturnal O2 sats, supine FVC, NIF not necessarily PSG. pCO2 more than 45 may be enough.

4. Bulbar disease especially with FTD is a major risk for nonuse of NIV

5. Siallorrhea can be treated with benadryl or elavil which also helps sleep and does not mandate non use of NIV

6. Sleep labs are not set up for ALS patients for many reasons -- lack of facilities for lifts, caregivers, et al.

7. Classic bilevel devices for central apneas don't account for short shallow breathing in ALS. Newer pressure control devices that guarantee a longer inspiratory time with a targeted tidal volume are much better. Need a tidal volume of 8cc/kg IBW. This used to be achieved by classic ventilator with a mask.

8. Inappropriate devices such as servo ventilation devices (designed for Cheynes-Stoke breathing) decreased minute ventilation and is not good for ALS. Autotitrating bilevel devices are designed for use in OSA and are not good in ALS.

9. Ease of breathing comes from frictional work, with expansion of chest wall, and elastic work, with expansion of lung itself. Lower breaths per minute maximizes elastic work, higher bpm maximizes frictional work, with combined benefit somewhere in the middle with 20 or so bpm.

10.F/ Vt (respiratory rate /tidal volume) is a useful surrogate marker for wob, or work of breathing. If its less than 33, work of breathing should be OK. Note that Vt (wob) is proportional to (I-E)/R*T, where (I-E), or the difference between IPAP and EPAP is pressure support, and R is resistance (which may be increased by kyphoscoliosis eg.) and T is inspiratory time, which turns out to very important in these patients.SLOW deep breathing may be easiest factor to manipulate in these patients.

11. Settings that are important: slow rise time of ventilation in bulbar disease (fast rise time in diaphragmatic disease), inspiratory time of .8 to 1.4 seconds, trigger and cycle adjustments to improved comfort, and tubing sleeve for increased humidity.

Pearls on melatonin and sleep timing Moore

2009-11-25T17:44:00.002-08:00

from AAN meeting talks

1. Proposes wakefulness is divided into waking and "default" resting mode with absolutely reliable activation of certain parts of brain during default wakefulness. We do not know what activates the :"default network"

2. Circadian timing is regulated by suprachiasmatic nucleus which inhibits sleep,without which you get random sleep patterns.

3. Retinohypothalamic tract from retina from specific ganglion cells in the photoreceptors that entrain circadian rhythims. They go to SCN via old photopigment called melanopsin with glutamate.

4. VLPO or homestatic drive inhibits ARAS by accumulating NREM sleep via accumulating substances, adenosine and others.

5. So circadian and homestatic drive mechanisms both act on activating activity and regulate sleep.

Presentations of adult onset leukodystrophy

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Costello DJ et al. The Neurologist 2009;15:319-328
ALD kids get spastic paraparesis with detrusor instability. Defect is VLFA's ABCD1 mutation. MRI lesion is leukodystrophy starting posteriorly, may enhance partially and be confused with inflammatory disease. Adults may present with neuropsychiatric disease, followed by spasticity, ataxia, seizures, and death. Two thirds of female carriers also develop some sort of progressive myelopathic picture. They may have more pain and be misdiagnosed as having MS or fibromyalgia. Adult cerebral (AC-ALD) is more fulminant than X-ALD.

MLD is aut rec. Presentations in younger patients include disturbed gait, ataxia, quadriplegia, optic atrophy, and peripheral neuropathy, to decerebrate rigidity. In adults, presentation is often neuropsychiatric with misdiagnosis of schizophrenia, or even normal, with neuropscyh testing especially showing problems with visuospatial construction. There are dramatic elevated sulfatides due to arylsulfatase deficiency.

In Krabbe disease, beta galactocerberosidase occurs, is characterized by , in adult form, various motor presentations with progressive cognitive decline, seizures, cortical blindness with 20 % having uniform slowing of nerve conduction studies. Substrate (galactosylceramide) levels are increased but only mildly, but within oligodendrocyte, there are 100 fold increases in psychosine which is cytotoxic and selectively damages oligodendrocytes. Its been described up to age 84. Get posterior predominant involvement, no enhancement.

In Vanishing White matter disease, adult onset, there is cognitive involvement, pseudobulbar palsy, spastic paraparesis, with an important association with ovarian failure, "ovarioleukodystrophy." Its caused by mutations in e1f2b, affects ribosomes and proteins, causes cystic degeneration and rarefaction of the white matter. Clinical features not completely understood, probably is more common than thought.

Alexander disease-- due to mutation in GFAP, causes Rosenthal fibers. Get bulbar and pseudobulbar palsy with white matter abnormalities starting in front.

Canavan disease-- increased NAA in urine, Spectroscopy is good to diagnose this.

Hereditary diffuse leukoencephalopathy with spheroids is almost exclusively diagnosed in adults. Present with deteriorated behavior and personality and seizures. Diagnosis is by tissue.

Pelizaeus Merzbacher is X linked but like ALD carrier females have a forme of disease. Tremor, ataxia, dementia, and progressive spastic paraplegia occur. Mutation on PLP 1 on X q 22 occur. Classic hypomyelinated CNS disorder.

Recessive hypomyelinating leukoencephalopathy (RHL) =PM like disease is a hypomyelinating disease.

others see text, also for Rx

Emerging neuro infections: CHIK, Hendra & Nipah viruses

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Ibid (Tyler KT in Arch Neurol 2009)

CHIK virus
infection due to enhanced vector competence. Spread by mosquitoes to humans, togavirus. Abrupt onset fever, joint swelling, myalgia, headache, back pain, and rash. Diagnosis is by CDC IgM and IgG. Rare neurologic cases include encephalitic infections of newborns and elderly.
Other presentations include encephalomyelitis, myeloradiculitis, acute flaccid paralysis (GBS like), encephalopathy and seizures. A mutation in viral envelope dramatically changed infectivity. Endemic travellers to new areas cause infections

Nipah and Hendra viruses.
classification is henipavirus of paramyxovirus. In Australia it first was identified as a highly infectious disease of horses and close human contacts/handlers. Aseptic meningitis and encephalitis occurred in Hendra, a location in Australia.

Nipah virus, closely related, occurred in pig farms in Singapore and Malaysia in 1998. Encephalitis and pneumonitis were common, with a 40 % mortality. The incubation perido was two weeks, with a 3-4 day prodrome. Mortality was 73 %. MRI usually showed multiple small subcortical lesions on T2 and FLAIR images without edema. PEARL- relapsing and delayed onset disease can occur. in 3 % or so average 8 months after first event, with an acute onset the second time. There was an associated systemic vasculitis with thrombosis and parenchymal necrosis in the CNS. Syncytial multinucleated endothelial cells are pathognomomic and occurred in 25 %. A subsequent outbreak in Bangladesh was not associated with pig farms and was shown to be associated with flying foxes and fruit bats with spread through urine of latter. Human to human transmission occurred, including between patients and health care workers.

Monkeypox virus causing neurologic human infection

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Tyler KL. Emerging viral infections of the CNS. Part II. Arch Neurol 2009; 66: 1065-74.
Due to exotic pet (mammal ) trade from Africa including Gambian pouched rats, dormouse, and rope squirrels, spread to prairie dogs in the US to humans.

Most common symptoms, 50 percent or more have rash, fever, chills, adenopathy, myalgias, sweats and cough. Rash follows several days later and typically is maculopapular, proceeding through stages with papules, vesicles, and pustules. The rash is centifugal and involves the hands or feet in 80 %, legs or feet in 65 %, head in 6 %, and resembles chicken pox. Unlike chicken pox (and like syphilis and ricketsial infection) there is lymphadenopathy and involvement of the palms of the hands and soles of the feet. Diagnosis is with skin biopsy, PCR, and ELISA.

One six year old developed encephalitis. Diagnosis was made by serum IgM and IgG and CSF IgM, with negative PCR.

rituxan and MG details

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Rituximab for myasthenia gravis developing after bone marrow transplant

Neurology - Volume 55, Issue 7 (October 2000) Rituximab was administered at a dose of 260 mg/m² iv every 7 days for 4 weeks. 6-Methylprednisolone and pyridostigmine were initially maintained at the pre-rituximab dosage of 0.5 mg/kg daily and 4 mg/kg daily. During and after treatment with rituximab the patient was monitored (figure) for muscular strength and performance status using Karnofsky's scale, ARAb titer every other week using a radio receptor assay (Alifax, Hamburg, Germany; cat. no. RE21023/21), CD 20+ lymphocytes (monthly count), serum Ig level, and 6-methylprednisolone and pyridostigmine dose. Rituximab was well tolerated and no complications or toxic effects were registered in the following 5 months of observation. From the fourth week on the performance status improved and ARAb titer decreased. 6-Methylprednisolone and pyridostigmine dosage were gradually tapered to 0.2 mg/kg daily and 3 mg/kg daily at the sixth month of observation, with a performance status of 80 and a substantial reduction of corticosteroid-related symptoms and signs. After treatment with rituximab we observed no changes in serum Ig level; we documented a substantial and prolonged reduction of CD 20+ lymphocyte count (0.2 × 10⁹ /L pre-rituximab, 0.07 × 10⁹ /L and 0.04 × 10⁹ /L 1 and 5 months after the fourth rituximab infusion).