Hand stereotypies and Autism v. Rett's diagnosis

Hand stereotypies distinguish Rett syndrome from autism disorder; Goldman S, Temudo T; Movement Disorders (Jun 2012)

BACKGROUND: Rett syndrome (RTT) and autism disorder (AD) are 2 neurodevelopmental disorders of early life that share phenotypic features, one being hand stereotypies. Distinguishing RTT from AD often represents a challenge, and given their distinct long-term prognoses, this issue may have far-reaching implications. With the advances in genetic testing, the contribution of clinical manifestations in distinguishing RTT from AD has been overlooked. METHODS: A comparison of hand stereotypies in 20 children with RTT and 20 with AD was performed using detailed analyses of videotaped standardized observations. RESULTS: Striking differences are observed between RTT and AD children. In RTT, hand stereotypies are predominantly complex, continuous, localized to the body midline, and involving mouthing. Conversely, in AD children, hand stereotypies are simple, bilateral, intermittent, and often involving objects. CONCLUSIONS: These results provide important clinical signs useful to the differential diagnosis of RTT versus AD, especially when genetic testing for RTT is not an option. © 2012 Movement Disorder Society.

High dose verapamil for cluster headache and other pearls

Management of Cluster Headache; Tfelt-Hansen PC, Jensen RH; CNS Drugs (Jun 2012)

The prevalence of cluster headache is 0.1% and cluster headache is often not diagnosed or misdiagnosed as migraine or sinusitis. In cluster headache there is often a considerable diagnostic delay - an average of 7 years in a population-based survey. Cluster headache is characterized by very severe or severe orbital or periorbital pain with a duration of 15-180 minutes. The cluster headache attacks are accompanied by characteristic associated unilateral symptoms such as tearing, nasal congestion and/or rhinorrhoea, eyelid oedema, miosis and/or ptosis. In addition, there is a sense of restlessness and agitation. Patients may have up to eight attacks per day. Episodic cluster headache (ECH) occurs in clusters of weeks to months duration, whereas chronic cluster headache (CCH) attacks occur for more than 1 year without remissions. Management of cluster headache is divided into acute attack treatment and prophylactic treatment. In ECH and CCH the attacks can be treated with oxygen (12 L/min) or subcutaneous sumatriptan 6 mg. For both oxygen and sumatriptan there are two randomized, placebo-controlled trials demonstrating efficacy. In both ECH and CCH, verapamil is the prophylactic drug of choice. Verapamil 360 mg/day was found to be superior to placebo in one clinical trial. In clinical practice, daily doses of 480-720 mg are mostly used. Thus, the dose of verapamil used in cluster headache treatment may be double the dose used in cardiology, and with the higher doses the PR interval should be checked with an ECG. At the start of a cluster, transitional preventive treatment such as corticosteroids or greater occipital nerve blockade can be given. In CCH and in long-standing clusters of ECH, lithium, methysergide, topiramate, valproic acid and ergotamine tartrate can be used as add-on prophylactic treatment. In drug-resistant CCH, neuromodulation with either occipital nerve stimulation or deep brain stimulation of the hypothalamus is an alternative treatment strategy. For most cluster headache patients there are fairly good treatment options both for acute attacks and for prophylaxis. The big problem is the diagnosis of cluster headache as demonstrated by the diagnostic delay of 7 years. However, the relatively short-lasting attack of pain in one eye with typical associated symptoms should lead the family doctor to suspect cluster headache resulting in a referral to a neurologist or a headache centre with experience in the treatment of cluster headache.

tramadol and tapentadol compared

Mechanistic and functional differentiation of tapentadol and tramadol; Raffa RB, Buschmann H, Christoph T, Eichenbaum G, Englberger W, Flores CM, Hertrampf T, Kögel B, Schiene K, Straßburger W, Terlinden R, Tzschentke TM; Expert Opinion on Pharmacotherapy (Jun 2012)

 

Introduction: Many opioid analgesics share common structural elements; however, minor differences in structure can result in major differences in pharmacological activity, pharmacokinetic profile, and clinical efficacy and tolerability. Areas covered: This review compares and contrasts the chemistry, pharmacodynamics, pharmacokinetics, and CNS 'functional activity' of tapentadol and tramadol, responsible for their individual clinical utilities. Expert opinion: The distinct properties of tapentadol and tramadol generate different CNS functional activities, making each drug the prototype of different classes of opioid/nonopioid analgesics. Tramadol's analgesia derives from relatively weak µ-opioid receptor (MOR) agonism, plus norepinephrine and serotonin reuptake inhibition, provided collectively by the enantiomers of the parent drug and a metabolite that is a stronger MOR agonist, but has lower CNS penetration. Tapentadol's MOR agonist activity is several-fold greater than tramadol's, with prominent norepinephrine reuptake inhibition and minimal serotonin effect. Accordingly, tramadol is well-suited for pain conditions for which a strong opioid component is not needed-and it has the benefit of a low abuse potential; whereas tapentadol, a schedule-II controlled substance, is well-suited for pain conditions requiring a strong opioid component-and it has the benefit of greater gastrointestinal tolerability compared to classical strong opioids. Both drugs offer distinct and complementary clinical options.

Spontaneous abscess think and look for HHT

Polymicrobial brain abscess in hereditary haemorrhagic telangiectasia (Osler's disease)]; Polak P, Snopkova S, Husa P; Deutsche Medizinische Wochenschrift 137 (33), 1635-8 (Aug 2012)

History and admission findings: A 38-year-old woman who suffered from migraine was admitted because of severe, worsening headache for 24 hours (dissimilar to the previous migraine attacks), with impaired vision and weakness of the right arm. Mild hemiparesis and expressive aphasia indicated an intracranial tumor.Investigations: Cranial computed tomography revealed a focal lesion with a diameter of 2.5 cm in the left frontoparietal lobe, with signs of intracranial hypertension, indicating cerebral metastasis or an abscess. Magnetic resonance imaging confirmed the diagnosis of a brain abscess.Treatment and course: An urgent craniotomy was performed and the abscess was evacuated. An empirical antibiotic combination with chloramphenicole and metronidazole (switched to cefotaxime because of thrombocytopenia) was initiated. Cultivation of pus revealed Streptococcus constellatus, Aggregatibacter aphrophilus and Fusobacterium spp. Within the first two weeks of treatment progession of the abscess was noted, therefore a second craniotomy with debridement was performed. An elective CT-angio scan revealed several arteriovenous malformations in the caudal segments of both lungs which were embolized without complications. Only retrospectively, cutaneous teleangiectasias were recognized. At present, the patient and her direct relatives are submitted to genetical screening for Osler's disease.Conclusion: In patients with brain abscesses of unknown origin and with a history of repeated epistaxis and/or gastrointestinal bleeding, Osler's disease (hereditary hemorrhagic telangiectasia) should be considered and pulmonary arteriovenous malformations excluded. Physicians should search for cutaneous or mucous teleangiectasias. Family screening and long-term follow-up according to international guidelines is recommended.

Comment  Another reminder of historical questions to ask about when examining a patient with brain abscess.

Omega-3 fa's for protection against paclitaxel induced PN

Omega-3 fatty acids are protective against paclitaxel-induced peripheral neuropathy: A randomized double-blind placebo controlled trial; Ghoreishi Z, Esfahani A, Djazayeri A, Djalali M, Golestan B, Ayromlou H, Hashemzade S, Asghari Jafarabadi M, Montazeri V, Keshavarz SA; BMC Cancer 12 (1), 355 (Aug 2012)

ABSTRACT: BACKGROUND: Axonal sensory peripheral neuropathy is the major dose-limiting side effect of paclitaxel.Omega-3 fatty acids have beneficial effects on neurological disorders from their effects on neurons cells and inhibition of the formation of proinflammatory cytokines involved in peripheral neuropathy. METHODS: This study was a randomized double blind placebo controlled trial to investigate the efficacy of omega-3 fatty acids in reducing incidence and severity of paclitaxel-induced peripheral neuropathy (PIPN). Eligible patients with breast cancer randomly assigned to take omega-3 fatty acid pearls, 640 mg t.i.d during chemotherapy with paclitaxel and one month after the end of the treatment or placebo. Clinical and electrophysiological studies were performed before the onset of chemotherapy and one month after cessation of therapy to evaluate PIPN based on"reduced Total Neuropathy Score". RESULTS: Twenty one patients (70 %) of the group taking omega-3 fatty acid supplement (n = 30) did not develop PN while it was 40.7 %( 11 patients) in the placebo group(n = 27). A significant difference was seen in PN incidence (OR = 0.3, .95 % CI = (0.10-0.88), p = 0.029). There was a non-significant trend for differences of PIPN severity between the two study groups but the frequencies of PN in all scoring categories were higher in the placebo group (0.95 % CI = ([MINUS SIGN]2.06 -0.02), p = 0.054). CONCLUSIONS: Omega-3 fatty acids may be an efficient neuroprotective agent for prophylaxis against PIPN. Patients with breast cancer have a longer disease free survival rate with the aid of therapeutical agents. Finding a way to solve the disabling effects of PIPN would significantly improve the patients' quality of life.Trial registrationThis trial was registered at ClinicalTrials.gov (NCT01049295).

Comment-- a disease in need of a prevention and cure!

More on overutilization of TA biopsy

Temporal Artery Biopsy is not Required in all Cases of Suspected Giant Cell Arteritis; Quinn EM, Kearney DE, Kelly J, Keohane C, Redmond HP; Annals of Vascular Surgery (Jan 2012)

 

BACKGROUND: Temporal artery biopsy (TAB) is performed during the diagnostic workup for giant cell arteritis (GCA), a vasculitis with the potential to cause irreversible blindness or stroke. However, treatment is often started on clinical grounds, and TAB result frequently does not influence patient management. The aim of this study was to assess the need for TAB in cases of suspected GCA. METHODS: We performed a retrospective review of 185 TABs performed in our institution from 1990 to 2010. Patients were identified through the Hospital In-Patient Enquiry database and theater records. Clinical findings, erythrocyte sedimentation rate, steroid treatment preoperatively, American College of Rheumatology (ACR) criteria for GCA score, biopsy result, and follow-up were recorded. RESULTS: Fifty-eight (31.4%) biopsies were positive for GCA. Presence of jaw claudication (P = 0.001), abnormal fundoscopy (P = 0.001), and raised erythrocyte sedimentation rate (P = 0.001) were significantly associated with GCA. The strongest association with positive biopsy was seen with the prebiopsy ACR score (P<0.001). Twenty-four (13.7%) patients had undergone biopsy, despite no potential for meeting ACR criteria preoperatively. None of these were positive. Overall, 29 (16.4%) patients had management altered by TAB result. CONCLUSIONS: Our results confirm that TAB does not affect management in the majority of patients with suspected GCA. We conclude that TAB has benefit only for patients who score 2 or 3 on the ACR criteria for GCA without biopsy.

 

Comment-- TA biopsy, along with brain biopsy and muscle biopsy is overutilized and requires expert analysis before being ordered.

Paroxetine and venlafaxine for depression in Parkinson's disease

A randomized, double-blind, placebo-controlled trial of antidepressants in Parkinson disease; Richard IH, McDermott MP, Kurlan R, Lyness JM, Como PG, Pearson N, Factor SA, Juncos J, Serrano Ramos C, Brodsky M, Manning C, Marsh L, Shulman L, Fernandez HH, Black KJ, Panisset M, Christine CW, Jiang W, Singer C, Horn S, Pfeiffer R, Rottenberg D, Slevin J, Elmer L, Press D, Hyson HC, McDonald W, For the SAD-PD Study Group; Neurology 78 (16), 1229-1236 (Apr 2012)

 

OBJECTIVE: To evaluate the efficacy and safety of a selective serotonin reuptake inhibitor (SSRI) and a serotonin and norepinephrine reuptake inhibitor (SNRI) in the treatment of depression in Parkinson disease (PD). METHODS: A total of 115 subjects with PD were enrolled at 20 sites. Subjects were randomized to receive an SSRI (paroxetine; n = 42), an SNRI (venlafaxine extended release [XR]; n = 34), or placebo (n = 39). Subjects met DSM-IV criteria for a depressive disorder, or operationally defined subsyndromal depression, and scored>12 on the first 17 items of the Hamilton Rating Scale for Depression (HAM-D). Subjects were followed for 12 weeks (6-week dosage adjustment, 6-week maintenance). Maximum daily dosages were 40 mg for paroxetine and 225 mg for venlafaxine XR. The primary outcome measure was change in the HAM-D score from baseline to week 12. RESULTS: Treatment effects (relative to placebo), expressed as mean 12-week reductions in HAM-D score, were 6.2 points (97.5% confidence interval [CI] 2.2 to 10.3, p = 0.0007) in the paroxetine group and 4.2 points (97.5% CI 0.1 to 8.4, p = 0.02) in the venlafaxine XR group. No treatment effects were seen on motor function. CONCLUSIONS: Both paroxetine and venlafaxine XR significantly improved depression in subjects with PD. Both medications were generally safe and well tolerated and did not worsen motor function. Classification of Evidence: This study provides Class I evidence that paroxetine and venlafaxine XR are effective in treating depression in patients with PD.

382 Stars

VISUAL SNOW SYNDROME

Presented by Christopher Schankin Ph D at UCSD Headache center

 

More than half of patients with "visual snow" have migraine, and almost all have other symptoms in eyes including floaters (73 %), persistent visual images (63 %), difficulty seeing at night (58 %) tiny objects moving on blue sky (57 %), light sensistivity (54 %), trails behind moving images (48 %), bright flashes (44 %), colored swirls , clouds, or waves when their eyes were closed (41 %). 

cataplexy clips on CNN

http://www.youtube.com/watch?v=ALVqaKQ5MWY&feature=related

a little long  / basic but there are lots clips of cataplexy, overt and subtle

nv

CLIPPERS syndrome

Core features of CLIPPERS (an MS mimic)

Clinical-- subacute progressive ataxia and dysarthria.  May in some cases have other brainstem features or cognitive symptoms.  These include facial paresthesias, diplopia, dysgeusia and myelopathy. 

MRI- 1.  numerous nodular or punctate enhancing lesions bilaterally in at least 2 of 3: pons, cerebellum, brachium pontis  2.  Individual lesions are small but may coalesce to form larger lesions (mass effect has never been reported)  3.  Lesions may occur in spinal cord, basal ganglia nad cerebral white matter but should be less dense the further from the pons  4.  Absent features: restricted diffusion on DWI, marked hyperintensity on T2, abnormal cerebral angiogram

Corticosteroid responsiveness-- prompt and significant clinical and radiographic response to steroids-- with relapse when steroids are withdrawn or fell below 20 mg po daily.  Uncertain:  elevated IgE in some patients is reported as are oligoclonal bands.

Histopathology--- a. white matter perivascular lymphohistiocytic infiltrate with or without parenchymal extension   b.  infiltrate contains predominant CD+ and CD4+ lymphocytes  c.  absent monoclonal or atypical lymphocyte population , necrotizing giant cells or granulomas, or histologic features of vasculitis such as destruction of vessel wall, fibronoid necrosis, leukocytoclasia, fibrin thrombi. 

Exclusion of mimicking diseases including sarcoid, neuro-Behcet's, vasculitis and lymphoma, glioma, histiocytosis, multiple sclerosis, autoimmmune disorders, Bickerstaff's encephalitis. 

Stark and related laws resources

What Neurologists need to know about the Stark Law,

http://www.aan.com/globals/axon/assets/6532.pdf

Steroids Help Unfreeze Bell's Palsy

 Early treatment with the corticosteroid prednisolone appeared to significantly reduce mild to moderate sequelae in Bell's palsy as judged by two scoring systems, according to results from a large Scandinavian trial.
As measured by the Sunnybrook scoring system, among more than 800 patients randomized to 1 of 4 treatment groups, those who received prednisolone had a significant reduction in mild to moderate impaired facial function at 12 months (P<0.001) compared with those who did not receive the steroid, Thomas Berg, MD, PhD, of Oslo University Hospital Rikshospitalet in Norway, and colleagues reported.
The difference between patients who received prednisolone and those did not in two House-Brackmann gradings levels was also significant (P<0.001 and P=0.01, respectively), Berg and co-authors wrote in the May issue of the Archives of Otolaryngology – Head & Neck Surgery.
Two of the treatment groups also received the antiviral valacyclovir (Valtrex), but no significant differences were found in those groups, they added.
The cause of Bell's palsy, which damages the facial cranial nerve and affects up to 40,000 Americans, is unknown.
One theory is that reactivation of a latent herpes simplex virus may cause inflammation and injury to the facial nerve, Berg and his co-authors noted, adding that treatment has been based on this theory.
About 70% of Bell's palsy patients recover completely within 6 months without any treatment, the authors noted. The remaining 30% have varying degrees of sequelae with functional, psychosocial, and aesthetic disturbances.
And despite some data that prednisolone improved complete recovery rates, large controlled studies on the effect of corticosteroids (and any additive effect of antivirals) were lacking.
To help correct this information deficit, the researchers recruited 829 patients (341 women and 488 men) over a 5-year period. They ranged in age from 18 to 75 and were enrolled at 17 public referral centers involved in the Swedish and Finnish Scandinavian Bell's Palsy Study, a prospective, randomized, double-blind, placebo-controlled, multicenter trial.
The patients were randomized within 72 hours in a factorial fashion to placebo plus placebo (n=206); prednisolone, 60 mg/d for 5 days, with the dosage then tapered for 5 days, plus placebo (n=210); valacyclovir hydrochloride, 1,000 mg 3 times daily for 7 days, plus placebo (n=207); or prednisolone plus valacyclovir (n=206).
The researchers then evaluated facial functioning at 12 months, using two separate grading systems -- Sunnybrook and House-Brackmann.
The Sunnybrook system, considered the more sensitive of the two, evaluates resting symmetry, degree of voluntary movement, and synkinesis to form a composite score, for which 0 indicates complete paralysis and 100, normal function.
The House-Brackmann system consists of a 6-grade scale (I to VI), in which I indicates normal function and VI, complete paralysis.
Follow-up visits were between days 11 to 17 and at 1, 2, 3, 6, and 12 months after randomization. If the recovery was complete (defined as a Sunnybrook score of 100) at 2 or 3 months, the next follow-up was at 12 months. Patients were grouped according to severity of sequelae by both scoring systems at 12 months.
In 184 of the 829 patients, the Sunnybrook score was less than 90 at 12 months; 71 had been treated with prednisolone and 113 had not (P<0.001).
In 98 patients, the Sunnybrook score was less than 70; 33 had received prednisolone and 65 had not (P<0.001), Berg and colleagues wrote.
The difference between patients who received prednisolone and who did not in House-Brackmann gradings higher than I and higher than II was also significant (P<0.001 and P=0.01, respectively).
No significant difference was found between patients who received prednisolone and those who did not in Sunnybrook scores less than 50 (P=0.10) or House-Brackmann grades higher than III (P=0.80).
Synkinesis was assessed with the Sunnybrook score in 743 patients. Among those, 96 patients had a synkinesis score more than 2, of whom 33 had received prednisolone and 63 had not (P=0.001). There were 60 patients who had a synkinesis score more than 4, of whom 22 had received prednisolone and 38 had not (P=.005).
The authors cited several limitations to their study.
"Subgroup analyses led to a reduction of patients in the analysis groups, which makes statistical comparisons more hazardous" they wrote. Nor did they "make the distinction between incomplete and complete palsy at baseline," but analyzed the median baseline scoring levels, which were found to be similar in the different treatment groups.
The investigators concluded that while "treatment with prednisolone significantly reduced mild and moderate sequelae in Bell's palsy at 12 months, prednisolone did not reduce the number of patients with severe sequelae," and valacyclovir had no effect.

Low pressure headaches - pearls

1.  aka SIH, or spontaneous intracranial hypotension/ spontaenous CSF leak

2.  Diagnostic criteria (journal Headache, 2011) :  a. orthostatic headache  b.  no recent dural puncture  c. not attributable to another disorder  and d.  at least one of the following: (1) low OP < 60 mm H20  (2) sustained improvement after epidural blood patches   (3) demonstrated active leak  (4) cranial MRI showing brain sagging or pachymeningeal enhancement

3.  Clinical pearl:  MRI without contrast can lead to false diagnosis of Chiari malformation and repair of which will not help.

4.  Headaches can be frontal/occipital/holocephalic/ cervical interscapular/ nonorthostatic or lingering nonorthostatic before or after orthostatic/ thunderclap headache/ cough headache/ second half of the day headache/ acephalgic forms

5. May require multiple blood patches to fix

History and physical exam pearls of TA biopsy

Headache pearls
1.  Headache can be ANY phenotype, mimic cluster, icepick HA, stabbing headache or other
2. may be dull and boring with lancinating pain, and associated scalp tenderness
3.  Worse with cool temperature
4. May be intermittent
5.  High dose steroids, TA biopsy and vision loss may all improve headache pain

TA exam pearls
1.  Beading
2.  Prominence
3.  Tenderness
4. Pulselessness
5. Erythema over artery

Clinical associated findings/pearls
1.  Fever
2.  Asthenia
3. Arthralgias/synovitis
4. myalgias
5.  weight loss
6.  cough
7.  mental status changes-delusions, depression, memory impairments, dementia

Ischemic complications
1.  jaw claudication
2.  Scalp necrosis
3.   tongue necrosis
4.  sore throat
5.  hoarseness
6.  stroke or TIA
7.  Angina or MI
8.  Upper limb claudication or pain

temporal arteritis pearls

CTA or MRA for evidence of large vessel involvement

PET for evidence of aortic inflammation

ESR is <50 in 10 % and< 40 in 5.8 %, CRP more sensitive

Other labs- anemia, increased Platelets,fibrinogen and alk phos occur

some use aspirin

65 % have visual obscurations before permanent visual loss, on average 8.5 days before

Contralateral eye may be affected, average, 5 days after first eye has visual loss.

lack of relief with prednisone is a sign of wrong diagnosis


1990 criteria require 3/5: 
new onset headache or new type of headache
age > 50
TA tender orpulseless, unrelated to atherosclerosis
WSR> 50
Abnormal biopsy with inflammation and multinucleate giant cells

Temporal arteritis biopsy formula

Younge BR et al.   Mayo Clinic Proceedings 2004 79; 483-91

Formula for positive TA biopsy
Value= (-240) + 48 (headache) + 108 (jaw claudication)+ 56 (scalp tenderness) + 1(ESR in mm/hr) + 70 (ischemic optic neuropathy) + 1 (age in years)

if symptom is not present, give zero for that element
<-110  low risk
-110 to 70  intermediate risk
>70   high risk

Pearls about hypothermia

Blondin and Greer.  The Neurologist 2011; 17:241-248.
1. Beware of accumulation of midazolam, propofol, and fentanyl during hypothermia

2. Traditional statement about prognosis with no motor signs (pupil, corneal, posturing) does not apply to hypothermia, as some survivors with good prognosis who were treated with hypothermia had no responses till day 6. The presence of a motor response at day 3 suggests a good outcome.Absent motor response does not predict a poor outcome.

3. Absent brainsten reflexes at day 3 is predictive of poor response but is not absolute.

4.  SEP responses disappear below 30 degrees centigrade. At 32-34 degrees, they should be prolonged but present

5.  EEG:  small studies; alpha coma, and burst suppression patients did not regain consciousness, and refractory status epilepticus patients did not regain consciousness. All patients with initially continuous EEG did regain consciousness, and among those with flat eeg's only those that evolved to a continuous pattern regained consciousness.

6.  Myoclonus is not predictive uniformly of a bad prognosis.It may be due to weaning neuromuscular blockade, to seizures, or metabolic status.

7.  Neuron specific enolase (NSE) is important in coma, but there is no reliable cutoff number among patients treated with hypothermia.  Otherwise, rising NSE between 24-48 hours is important.

8.  MRI ADC abnormalities >  10 % of brain volume 2 or more days out invariably had a bad prognosis.

Clinical findings that do not negate Brain death

diabetes insipidus
organ failure
sweating and tachycardia
simple and complex repetitive and spontaneous movements
bilateral finger tremor
cyclic pupillary dilatation and constriction
repetitive leg movements
myokymia of face
eyelid opening
undulating toe reflex
autocycling respirations that are really ventilator driven
(above since 1995)

cremasteric, plantar, abdominal reflexes
triple flexion response
deep tendon reflexes
respiratory like reflex
Lazarus sign
limb movements besides posturing
(above pre 1995)

cf Scripko and Greer  The Neurologist 2011;17:237-240

AED selection for patients taking antiretrovirals

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

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

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

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. 

33

Ketamine: to induce coma in cases of brain injury?

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

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)

 

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

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

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

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

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

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

 

h/t NOVEL

 

neurodoc

Flail arm and flail leg variants of ALS

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

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

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

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

 

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

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

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

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

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

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 utility of seropositive voltage gated calcium chanell complex antibody

Jammoul A, Shayya L, Mente K et al.  Neurology Clinical Practice  2016; 6:409-418.

Authors differentiate "classic" group with limbic encephalitis or neuromyotonia (9.6% of total) and note the others had a panoply of diagnoses that were nonclassic.  The classic group was more likely to have high titers of ab, but there was overlap.  91 % of lcassic and 21 % of nonclassic had levels > 0.25 nM.  75 % of patietns in high level ab group had autoimmune disorders, and 75 % of patients with low level titers did not.  26 % of patients had a remote malignancy (active, remote, solid or hematologic) but not ab titer difference was noted among the groups . 

Conclusions:  1.  High VGKC ab levels are found in patients with classic and other autoimmune disorderes,  Low level ab titers are seen in nonspecific and mostly nonautoimmune disorders

2.  The presence of VGKC antibodies rather than the level may serve as a marker of malignancy

Notes this is bad on a chart review of 6,032 patients who underwent evaluation . 

The nonclassic group includes PNS and CNS diorders including neuropathy, dementia, ALS, CJD.  Some patietns had nonspecific symptoms such as stutering speech, nausea and vomting and orthostasis without diagnosis of neurologic disease. 

Cancers were oftendiagnosed due towhole body CT/PET; 2 patietns had previously unknown cancer (Ovarian and lung).  Cancer occurred more commonly in those over age 45.  Many cases of ab finding were remote by over ten years from actual tumor.

Clinical spectrum of voltage gated potassium channel (VGKC) autoimmunity

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
7. FACIAL BRACHIAL DYSTONIC SEIZURE

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

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

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

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

 

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

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

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

 

neurodoc

MGUS Pearls

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.  Presentation is progressive distal weakness, paresthesias, and numbness more often than CIDP like.  Weakness if usually in ankles most severely.  Patients are wheelchair bound within a year.  There is 40 % mortality at five years.  EMG shows demyelination with secondary axonal loss. Conduction block is rare. 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.  Misdiagnosed early as CIDP.  Diagnosis of: demyelinating PN, monoclonal gammopathy and one of the three:  osteosclerotic myeloma, Castleman's disease or increased VEGF.  Also must have one or more of following:  organomegaly, endocrine dysfunction, edema , skin changes (hypertrichosis or hyperpigmentation), papilledema, thrombocytosis, polycythemia). 

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.  DADS M polyneuropathy may be misdiagnosed as CIDP but respond more poorly to treatment regimens used for CIDP.

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

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:

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

Gait criteria:  At least two of the following

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

Cognition (at least two of following)

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

Urinary symptoms: one of following

 

1. Episodic urinary incontinence not attributable to other causes
2. Persistent urinary incontinence
3. Fecal and urinary incontinence

OR  One of following

1. Urinary urgency
2. Urinary frequency- 6 or more voids in 12 hour period
3. 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:

1. Rely on family assessment as much as what patient says about gait assessment
2. Levodopa trial occassionally needed to sort out festination
3. 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
4. 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
5. 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
6. Urinary incontinence may be described as urinating just before reaching the toilet
7. 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)
8. Atypical presentations in young may include headache, and poor job performance rather than memory loss.
9. 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
10. Thinned /  distended callosum may predict shunt responsiveness, may be seen as "bowing" on sagittal views
11. 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.
12. Behaviorally and by fMRI, increased Stroop testing and finger tapping correlates with SMA functional activity
13. 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 %. 
14. ELD (extended lumbar drainage x 3 days) if no response, very few patients will benefit from surgery.
15. 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. 
16. If a programmable shunt is used, the billing code is 62252
17. Obviously need a good neurologist to make the diagnosis and exclude various neurodegenerative diseases

Coin rotation test validation

 

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

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