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

Billing pearls (Random)

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.  This is appropriate for er tpa administration.

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

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

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

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

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

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

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.

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

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

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.