Management of hepatic encephalopathy in hospital

Review Article
Leise MD, Poterucha J, Kamath PS et. al.  Management of hepatic encephalopathy in the hospital.  Mayo Clin Proc 2014; 89(2) 241-253.

Working Party for hepatic encephalopathy nomenclature:

Type A HE-- secondary to liver failure
Type B HE enteric hyperammonemia without liver disease
Type C  -- is associated with some liver disease.

Severity Grades
I-IV scale
0 normal
MHE normal exam,  nild changes visuoperceptive or psychometric tests
I Personality change, attention ddeficit, irritability, depressed state, tremor, dyscoordination
2  Changes sleep/wake cycle,letharygy , mood, behavioral/ cognitive changes; asterixus, ataxic gait, slow/slurred speech
3  Somnolence, confusion , disorientation, amnesia; muscle rigidity, nystagmus, clonus, Babinski sign, hyporeflexia
4  stupor and coma; oculocephalic reflexes, unresponsive

other scale SONIC (spectrum of neurocognitive impairment in cirrhoses)
covert HE (CHE) includes minimal HE (MHE) and grade I HE
overt HE encompasses grade II-IV. 

Also
episodic HE
persistent HE impairs day to day executive function

Epidemiology

50 percent of cirrhosis patients develop HE, and prognosis for these patients is worse even taking into account Model End Stage Liver Disease (MELD) scores.

Occurrence of OHE is approximately 22,000 per year
80 % are precipitated by an event such as GI bleed or iinfection

Most patients do not get needed maintenance care after hospital discharge

Reason for readmission is lack of education or inappropriate use of lactulose. 

Treatments- Induction therapies for episodic OHE

Nonabsorbale disaccharids-- lactulose (B galactosidofructose) and lactitol (B galactosidosorbitol) reduce ammonia by acifying colon with shift of ammonia to ammonium, shifting colonic flora from urease to nonurease producing bacterial species, and by cathartic effect.  Clinical studies are mixed/poor but its still first line in all but most sever cases.

Neomycin, metronidazole,and other antibiotics. -- neomycin is FDA approved for acute but not chronic HE to decrease gut derived bacterial derived ammonia. The evidence is weak, for OHE, and its use complicated by ototoxicity and nephrotoxicity.Possible slight benefit with metronidazole or vancomycin but each are very toxic.

Rifaximin :-- not FDA approved for episodic HE, only for secondary prevention of OHE Trials did not show substantial difference from lactitol but seemed to work faster.  RCT of rifaximin v. placebo showed benefit on composite outcome at doses of 1200-2400 mg per day for grades !-3.  May be better tolerated than lactitol.    A study of grades 3-4 with lactulose + placebo v. lactulose+ rifaximin  had more complete reversal in dual treated group (76 v. 51 %), shorter hospital stays and less ten day mortality (49 v. 24 %).

Zinc :Zinc deficiency occurs in 96 % of patients with MELD score of 12.  inc is necessary for two smmonia reduction pathways: ornithyl transcarbamylase in liver (ammonia converted to urea) and glutamine sythetase in skeletal muscle (glutamate to glutamine). One of 4 RCT's showed benefit.  Caution: zinc should be taken 2 hours before ciprofloxacin, and long term use causes copper deficiency,

L  ornithine-L aspartate : aka LOLA stimulates ammonia reduction pathways, like zinc.  Best use is in chronic HE. Has been shown to be effective, but is not available in USA

Branched chain amino acids : in cirrhosis, patients have decreased BCAA's and increased aromatic amino acids.  BCAA's are a source of glutamate which helps metabolize ammonia in skeletal muscles.  Benefits of BCAA's include better albumin synthesis, decreased insulin resistance, less hepatocellular carcinoma, and better immune function.  Studies poor quality with mixed results.  European Society for Cliical Nutrition and Metabolism recommends 1.2 g/kg / day of protein for compensated cirrhosis, and 1.5 g/kg/day for decompensated cirrhosis.  They also have grade A recommendation for standard protein supplementation for HE grade 2 or less, and BCAA for HE grades 3 and 4.

Percutaneous embolization of large portosystemic shunts :In European study , n= 37, for medically refractory patients given this, 59 % were free of HE in 100 days, 48 % in 2 years.  90 % of patients with cirrhosis improved.

Molecular adsorbent recirculating system : aka MARS based on albumin dialysis principle.  It removes protein and albumin bound toxins such as bilirubin, bile acids, nitrous oxide and enodogenous benzodiazepines, and non protein bound ammonia.  Effect on survival is in question, but HE is improved.  It is safe and tolerated and FDA approved for HE related to decompensated liver disease.  May reduce availability of certain antibbiotics and has medical contraindications.

Secondary prophylactic maintenance strategies in HE

Lactulose  : there is solid evidence for lactulose alone, or in combination with rifaximin.  Lactulose or lactulose plus probiotics had less recurrent OHE (37 5, 45 %, and 64 % respectively). 

Rifaximin :  in rifaximin v. placebo, treated group had less recurrence and rehospitalization than placebo.  It is FDA approved for secondary prevention of HE

General approach to induction and maintenance of  first episode of HE  :

1.  Screen for precipitants of OHE including GI bleed, infection, new medications such as opiods and benzodiazepines, constipation, diarrhea, dehydration, alkalosis, hypokalemia, or hypoxemia (seen in 80 % at least one).  Then manage precipitant and use lactulose also.

2.  For nonresponders, look for other precipitants, reeval the diagnosis, make sure the patient is having 3-4 stools per day.  Could then add neomycin (FDA approved but many side effects, or rifaximin which is off label. 

3. For patients who benefit use lactulose maintenance therapy especially for Child-Turcotte-Pugh class B/C

General approach to induction and maintenance of  recurrence of HE  :

1.  Same as (1) above; check number of stools with and compliance with lactulose.  Review meds

2.  If bloating or excessive diarrhea occur with any dose of lactulose, use rifaximin instead. In breakthrough HE on lactulose, add rifaximin (preferred) or neomycin (less preferred). 

3.   If breaks through on 2 drugs above, perform contrast enhanced CT to look for large intra-abdominal portosystemic shunt, or use MRA if patient is contrast risk.  Consider a shunt embolization in CTP class A cirrhosis or low MELD score (< 12-15).  60-90 percent may remit. 

4.  If embolization is not indicated consider additional treatments such as zinc, LOLA (if available), BCAA

Treatment of Severe HE grades 3-4 :

1. ABC, look for precipitants, lactulose 15-30 cc png q 1-2 hours until 3 stools achieved.  Alternative is 300 cc lactulose in 700 cc sterile water in an enema.  , may repeat prn.  Add rifaximin .  If unresponsive, perform head CT/ EEG to check diagnosis.  If diagnosis is correct, look for shunt to embolize.; if none use BCAA, zinc and LOA

MHE: Counsel patient about risks of driving

Fwd: MRI findings in idiopathic intracranial hypertension

From: Djacobs272@aol.com
To: dhj1.neurology@minutiae.com
Sent: 5/13/2014 2:29:27 P.M. Eastern Daylight Time
Subj: MRI findings in idiopathic intracranial hypertension

1.  empty sella

2.  flattening of posterior globes

3.  distension of perioptic subarachnoid spaces

4. narrowing of transverse venous sinuses

more from Images in Neurology JAMA Neurology 2013; 70:7937-8.

5.  distended perioptic nerve sheath
6. protrusion of the papilla 
7. "strangled optic nerve appearance
8. optic disc edema and retinal layer edema

Fwd: presentations of chronic traumatic encephalopathy

 

 

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From: Djacobs272@aol.com
To: dhj1.neurology@minutiae.com
Sent: 5/13/2014 2:29:28 P.M. Eastern Daylight Time
Subj: presentations of chronic traumatic encephalopathy

 

Stern et al.  Neurology; 2013: 81:1122-1129

 

Clinical review of 36 patients, all male athletes.  They were based on autopsy studies at Boston University Center for CTAE.

 

11 patients had episodic memory impairment  and executive dysfunction (cognition group) initially, only later behavioral and mood disturbances.  Nine patients initially had depression and thirteen had initial behavior (explosivity, impulsivity, violence).  The behavior-mood group totalled 22.  Three patients were asymptomatic.

 

Age of onset of behavior / mood group was mean 51,  of cognition group, mean was 69.

 

Among football players, the most susceptible positions were runningback (21 %), linemen (48 %) and linebacker (10 %). 

 

Ten subjects were diagnosed as dementia: 10 with AD, 4 with "dementia pugilistica" or "football related" and 2 unspecified.  All 10 had stage 4 CTAE.  Seven were from the cognitive group, 2 from mood group, and 1 from behavior group. From diagnosis to death was mean 8 years. 

 

Mean age of onset was 57.7 years, mean age of dememntia diagnosis was 72.6 years .  4 had a history of falls, 1 of tremor.  All 10 had memory/executive dysfunction, 7 had language deficits, 2 had visuospatial deficits, 6 were described as having a "short fuse."  Mood group had 2 with predominant sadness and 2 with anxiety, 

 

ApoE$  homozygotes occurred more frequently than in population. 

Fwd: Secondary causes of pseudotumor cerebri syndrome

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From: Djacobs272@aol.com
To: dhj1.neurology@blogger.com
Sent: 5/13/2014 2:29:28 P.M. Eastern Daylight Time
Subj: Secondary causes of pseudotumore cerebri syndrome

(from Neurology, 2013; 81:1159-1165

cerebrovenous abnormalities:

cerebral venous thrombosis (CVT)

bilateral jugular thrombosis or surgical ligation

middle ear or mastoid infection

increased right heart pressure

superior vena cava syndrome

AV fistulas

hypercoagulable states

Medications and exposures:

Antibiotics: tetracycline, minocycline, doxycycline, nalidixic acid, sulfa drugs

Vitamin A and retinoids

hypervitaminosis A, isotretinoin, all trans retinoic acid for PML, excessive liver ingestion

Hormones:  HGH, thyroxine (in children), leuprorelin acetate, levonorgestrel (Norplant), anabolic steroids

Withdrawal from chronic corticosteroids

Lithium

chlordecone

Medical conditions

Endocrine:  Addisons, hypoparathyroidism

hypercapnia-- sleep apnea, Pickwickian syndrome

Anemia

Renal failure

Turner syndrome

Down syndrome

Fwd: Diagnostic criteria for pseudotumore cerebri

 

 

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From: Djacobs272@aol.com
To: dhj1.neurology@blogger.com
Sent: 5/13/2014 2:29:29 P.M. Eastern Daylight Time
Subj: Diagnostic criteria for pseudotumore cerebri

 

Neurology 2013; 81:1161

 

A.  Required

       1.  Papilledema

       2.  normal neuro exam except cranial neuropathy eg abducens palsy

       3.  Neuroimaging-- normal MRI with and without contrast

       4.  Normal CSF composition

       5.  Elevated CSF opening pressure:  , > 250 in adults > 280 in clhildren

 

Diagnosis of pseudotumor cerebri syndrome without papilledema

       1.  If 2-5 above are satisfied and in addition unilateral or bilateral  VI n palsy

        2.  Absent papilledema/ VI n palsy, diagnosis is suggested but not made with 3/4 imaging criteria met:  empty sella, flattened posterior globe, distended perioptic subarachnoid space with or without tortuous optic nerve, and transverse sinus stenosis.

 

Under research:  findings of narrowed Meckel's cave and cavernous sinuses on MRI and widened foramen ovale on CT

 

Uncommon manifestations:  facial paresis, hemifacial spasm, radicular pain, rhinorrhea, otorrhea, III n , IV n and general oculoparesis.

 

Less specific symptoms of:  headache, transient visual obscurations, pulse synchronous tinnitus, binocular diplopia, neck shoulder and back pain

Uveomeningeal syndromes: ABRA (Amyloid beta related angiitis )

Neurology 2013; 81: 1796-7

ABRA is a subtype of PCNSV (primary CNS vasculitis) with a beta pathology, found in about 18 % of biopsies showing vasculitis.  PNSV has an incidence of about 2.4 per million. Presentation is cognitive impairment, +/- seizures, focal deficits, hallucinations, multifocal or confluent T2 white matter confluence and cortical microbleeds. Often CSF protein is elevated and there is a leukocytosis.  This reported case had uveomeningeal findings clinically and on MRI. 

Diagnosis by biopsy aND MAY BE AUTOIMMUNE AND RESPOND TO IMMUNOTHERAPY IN THIS CASE PREDNISONE 60/ DAY AND CELLCEPT  1500 BID RESULTED IN IMPROVEMENT

SEPARATE ARTICLE
Neurology 2013; 81: 1596-1603

ABRA characteristics of patients:  Authors from Mayo compared  78 patients, 40 with CAA (no inflammation) and 28 with granulomatous vasculitis (ABRA) , 10 with CAA related inflammation, and 118 matched patients with PCNSV with AB seen over 25 years. 

ABRA patients were older, had more altered cognition, seizures and spells, gado positive leptomeninges, ICH, and higher CSF protein.  Response to treatment was similar.

CTM v MRI for orthostatic headache with CSF leak

Neurology 2013; 81: 1789-92. 

Authors did MRI's on 12 patients with CTM proven leaks ("gold standard" test).  11/12 had positive MRI of spine with extradural fluid collections (highly sensitive) and 6/12 having spinal dural enhancement (less sensitive).  The dura is seen as a pencil line on sagittal T1 because its displaced by fluid in the dorsal epidural space.  Other signs to be expected are brain sag, pachymeningeal enhancement, posterior fossa crowding and cerebellar tonsillar descent.

Hemosiderin deposition in brain as footprint of high altitude cerebral edema (HACE)

Neurology 2013; 81: 1776-9.

Idea- hemosiderin does not go away so patients who experience HACE have hemosiderin seen in corpus callosum-- specifically splenium-- months or years after initial injury.  37 mountaineers were studied, 8 of whom had had HACE, 11 acute mountain sickness, and 8 high clims without injury.  Unequivocal microhemorrhages were seen in 8 subjects and equivocal ones in 2 others, 1-35 months after climb.  Severe cases had microhemorrhages outside the splenium. 

Recall that HACE is vasogenic edema that is often fatal within 24-48 hours due to brain herniation.  Authors concluded that the sign of the microhemorrhages in the spleium is very specific  and the severity of the disease correlates with the severity of the microhemorrhages. 

Authors further hypothesize that microhemorrhages are a specific finding due to hypoxic insult of the blood brain barrier due to a hydrostatic leak with extravasation of red blood cells, much as occurs in lungs in patients with high altitude pulmonary edema *HAPE). 

Metformin induced B12 deficiency

Arch Int Med 2006 166: 1975-9

Retrospective study found B12 deficiency correlated with dose and duration of metformin therapy.  B12 deficit defined as less than 150.  N was 155 patients.  Mechanism is inhibition of calcium dependent ileal absorption of B12-intrinsic factor,  which calcium supplementation can reverse. 

Along with acid inhibitors (PPI's H2 blockers, metformin is most common cause of B12 deficiency.  Odds ratio is 2.88 for each i gram increment and 2.39 for use > 3 years. 

In one study 6 percent of cases of B12 deficiency had associated metformin use (Br M J 1971) ,

Statin myopathy pearls

1. Occurs in fifteen percent of those receiving statins

3.  Risk factors for include: 
      higher dose statin
      statin myopathy in a first degree relative
      older age
      female
      small build
      concurrent systemic disease (renal, hepatic, or diabetes)
      multiple medications including fibrates, nitrates and cyt P450 metabolized drugs
genetic polymorphisms may exist

4.  Time course of onset usually one month but may be delayed years

5.  Presentation:  weak, high CK, irritability on EMG

6.  Co Q depletion may play a role, but studies have not shown CoQ is helpful

7.  Immune mediated myopathies can follow withdrawal of statin.

8.  fibrates, nitrates and ezetimibe also can cause myopathy

Head drop in neurologic disease: differential and pearls

Clinical: typically occurs in women over age 65
neck extensor weakness is usually subacute and associated with proximal arm weakness

EMG abnormal (myopathic or denervating) in cervical or thoracic paraspinal muscles but normal in limb muscles

Immunomodulators don't affect prognosis

differential:
polymyositis
ALS  (usually not isolated finding)
MG   ( three percent have headdrop as initial presentation)

 IBM
CIDP
carnitine deficiency
FSH
myotonic dystrophy
congenital myopathy
hpt
Parkinson's disease

Briemberg-Use of MRI-- in MG signal from paraspinals is normal, in isolated myopathy of neck muscles there is edema seen.The MG would be seronegative myasthenia gravis.

Dx of neurologic emergencies in pregnancy/postpartum

Edlow JA, Caplan LR, Obrien K, Tibbles CD. Diagnosis of acute neurological emergencies in pregnant and post-partum women.  Lancet Neurology 2013; 12: 175-185

This is a review article that is nicely written.  I am blogging some of the minutiae of the article, not necessarily the major points, that might escape otherwise.  Here are a few pearls from the article:

1.  There is 8-39 % overlap between PRES and RCVS of patients with both conditions.

2.  Suspicious for preeclampsia:  bilateral throbbing headaches with blurring and scintillating scotomata. Before ecampsia occurs with seizures, preceding symptoms may include frontal or occipital headache, blurring, photophobia, RUQ or epigastric pain, and altered mental status.  90 % occur at or after 28 weeks, and a third after delivery. 

3.  Differential of thunderclap headaches:  subarachnoid hemorrhage, PRES, RCVS, and extracranial arterial dissections. 

4.  HELLP syndrome stands for hemolysis, elevated liver function tests, low platelets.  However, TTP also can present with low platelets.  TTP is treated with plasma exchange, HELLP with magnesium and delivery of fetus. 

5.  In PRES seizures occur at onset, in CVT they occur somewhat later in course, usually after headache is established.

6.  More than 75 % of CVT cases in this group are postpartun, not during pregnancy.

7.  RCVS is associated also (in addition to postpartum state) with "vasoactive substances" including SSRIs, cocaine, phenylpropanolamine, blood products, catechol secreting tumors, and dissections.  RECURRING DAILY THUNDERCLAP HEADACHES AFTER A SINGLE THUNDERCLAP HEADACHE OVER SEVERAL WEEKS ARE NEARLY PATHOGNOMONIC.  Vomiting, confusion photophobia, and blurring are common.  Seizures almost always follow the headache. 

8.  Rare:  Air embolism: with PFO.  Associated agitation, confusion, seizures and encephalopathy in context of CV or respiratory collapse during or after labor.  Nearly any focal neurologic or generalized neuro symptoms can occur.  Two signs that are pathognomonic include air in retinal veins and mill wheel cardiac murmur. 

9.  Choriocarcinoma metastasizes to the brain in 20 percent of cases. 

10. Wernicke's encephalopathy can complicate hyperemesis gravidarum.  Eye movement problems are almost always present and is frequently a metablolic acidosis.

11.  TTP pentad is:  thrombocytopenia, microangiopathic hemolytic anemia,  fever, neurologic and renal dysfunction. 

12.  There are three differtiable pituitary disorders:  adenoma with apoplexy-- hemorrhage or infarct into the gland (headache, visual loss, opthalmoplegia and decreased consciousness);  Sheehan's syndrome ( hypopituitarism indolently presenting weeks to months after severe postpartum hemorrhage), and lymphocytic hypophysitis (headache and visual symptoms that present acutely). 

 

Chair for paraplegic

http://www.wimp.com/newdevice/

Papilledema and obstructive sleep apnea syndrome.

Purvin VA, Kawasaki A, Yee RD.

 Abstract

OBJECTIVES:

To characterize the pathogenesis and clinical features of optic disc edema associated with obstructive sleep apnea syndrome (SAS).

METHODS:

A series of 4 patients with SAS and papilledema (PE) underwent complete neuro-ophthalmologic evaluation and lumbar puncture. In 1 patient, continuous 24-hour intracranial pressure (ICP) monitoring was also performed.

RESULTS:

All 4 patients had bilateral PE that was asymmetric in 2. Three patients had optic nerve dysfunction, asymmetric in 1, unilateral in 2. Daytime cerebrospinal fluid pressure measurements were within normal range. Nocturnal monitoring performed in one patient, however, demonstrated repeated episodes of marked ICP elevation associated with apnea and arterial oxygen desaturation.

CONCLUSIONS:

We propose that PE in SAS is due to episodic nocturnal hypoxemia and hypercarbia resulting in increased ICP secondary to cerebral vasodilation. In these individuals, intermittent ICP elevation is sufficient to cause persistent disc edema. These patients may be at increased risk for developing visual loss secondary to PE compared with patients with obesity-related pseudotumor cerebri because of associated hypoxemia. The diagnosis of SAS PE may not be appreciated because daytime cerebrospinal fluid pressure measurements are normal and because patients tend to present with visual loss rather than with symptoms of increased ICP.

Common pitfalls in management IIH

Management Errors:
missing venous sinus thrombosis
failure to address other secondary causes (e.g., anemia, hypoxia)
relying on optic disc appearance without monitoring visual fields
being too slow to proceed to surgical intervention

Papilledema pearls

 

1. Cotton wool spots OFF disk may suggest hypertensive syndrome

 

2.  Hemorrhages off disc suggest central retinal vein occlusion

 

3.  New onset pulsatile tinnitus is significant finding indicating need to look for increased ICP, as well as transient obscurations, graying of vision for twenty seconds, with postural change and headache.  Field before acuity is affected, disc edema usually affected.

 

4.  MRI findings  may include disc enhancement, occassionally, enhanced perioptic space (40 %), flattening of posterior globe (80 %), empty sella  Get MRI/MRV

 

5.  Check blood pressure

 

6.  Blood:  CBC, electrolytes for Addison's, Ca for HPT, ANA for lupus that is it..  Lumbar puncture always.

 

7.  Must check visual fields  since acuity is preserved. That is affected early.

 

8.  Protect optic nerve function and appearance: the two goals of management of pappilledema, not normal pressure, that is not a goal.

 

9.  Therapy:  diamox 500 bid to start, add Lasix 40  mg q am with Kcl 20 meq.

 

10. Fenestration protects eye, but does not lower headache or pressure.  Consider fenestrating patients with progressive visual loss, severe loss early, patients with severe papilledema at risk for hypotension (dialysis) or patients unable to comply with monitoring vision.  Shunt is a better treatment for headache of IIH.

 

 

h't Valerie Purvin AAN 2013

Causes of pappilledema (bilateral) with good optic nerve function

 

increased intracranial pressure

 

malignant hypertension

 

toxins (amiodarone,cyclosporine)

 

sleep apnea syndrome

 

uveitis, eg. sarcoidosis

 

 

Fwd: Neurological complications of influenza

Neurological complications of influenza

Tsai JP, Baker AJ.  Neurocritical Care 18:2013; 118-130 (review article)

There are five types of encephalopathy, two benign and three malignant.  Typically they occur a mean of two weeks post influenza, and are not associated with CNS inflammation.  They include:

1)  MERS (mild encephalopathy with reversible splenial lesion)-   influenza symptoms, then prodrome of decreased level of consciousness, seizures, CSF pleocytosis, EEG abnormal, often within 103 days, and total resolution within one month with or without therapy.  Agents include infl A and B, Legionella, Staph and Strep species,  and E Coli.  Splenial lesion is thought to represent intramyelinc edema with fiber separation.

2)  HSES (hemorrhagic shock and encephalopathy syndrome (peds only)) shock, seizures, coma, DIC, diarrhea, drop HB/platelets, elevated LFT's, renal dysfunction, acidoses, negative blood and CSF cultures.  "Definite" all 9 criteria are met, "probably" is 7-8 criteria met.  Originally defined by Levin et al, 1982.  Biphasic course with improvement then deterioration may occur.  Abnormal EEG, diffuse cerebral edema, hemorrhagic necrosis occur.  Morbidity  plusmortality may > 90 percent.

3) ANE-- Acute necrotizing encephalopathy (pediatric and adults)-- most common complication of influenza.  Course is fever, URI prodrome, then rapid and severe decline in consciousness often with seizures at onset and within 1-3 days of onset of systemic symptoms.  CSF shows mild pleocytosis, limited utility.  MRI shows severe symmetric, diffusion restricting lesions in both thalami, rostral midbrain tegmentum, putamena, periventricular white matter and cerebellar hemispheres.  Decreased flow without stenosis or emboli is seen in thalamaperforators, SCA's , and deep internal and great cerebral veins.  Early steroid therapy aids survival among patients without brainstem lesions. 

4)  (AESD) Acute encephalopathy with seizures and late restricted diffusion-- predominantly a pediatric diagnosis with variable features and prognosis and several eponyms

Pearls on carotid cavernous fistulas

from Wijdicks text on acute neurology

1.  Associations--
      remote trauma
      post transsphenoidal surgery
      post ethmoidal surgery
     post carotid surgery
     Ehlers Danlos syndrome
     pregnancy

2.  Visual loss is due to increased intraocular pressure or reverse of flow or thrombus in superior opthalmic vein (SOV).  Balloon or coil occlusion has been reported (sometimes) to reverse blindness

3.  On angiography, immediate opacification of carotid sinus is seen after carotid injection.

4.Clinical findings include III n palsy, lid swelling, tortuous veins, dis edema and visual loss.

tests to consider in patients with encephalitis

serology- HIV, EBV, acute and convalescent phases St Louis encephalitis, eastern equine encephalitis, LaCrosse and West Nile viruses; acute and convalescent phase serum titers of myc. pneum, ricketsii ricketsiae, ehrlichia chaffensis, anaplasma phagocytophilum; rpr and fta;  lyme (ELISA and Western blot), IgG for toxoplasma; serum cryptococcal antigen; complement fixing or immunodiffusion antibodies for coccidio species

blood cultures;

Respiratory secretions pcr for myc. pneum;

CSF cultures;  IgM for St Louis, West Nile and VZV; vdrl and fta, IgG index, lyme (elisa and Western blot), CSF cryptococcal antigen; CSF histoplasma antigen;  complement fixing or immunodiffusion antibodies for coccidio species

CSF pcr's for HSVE I and II, enteroviruses, VZV, EBV, ehrlichia and anaplasma species, myco. pneum.

blood smears for morulae

culture respiratory secretions,nasopharyx, throat and stool

skin culture of rash if present for HSV and VZV

urine -- histoplasma antigen

Signs indicating causes in confused febrile patients

from  Wijdicks, The practice of emergency and critical care neurology.

Rash-- ricketsiae, aspergillus, vasculitis

petechiae-- TTP, meningococcemia, endocarditis, drug eruption, leukemia

splenomegaly-- toxo, TB, sepsis, HIV, lymphoma

pulmonary infiltrates-- legionella, fungi, TB, mycoplasma, pneumonia, tick borne, Q fever

Meningococcal meningitis and corticosteroids

Brust JCM.  Meningococcal meningitis, dexamethasone and Class III evidence(editorial) Neurology 2012; 79: 1528-9.

The most recent Cochran review shows a benefit of adjunctive dexamthasone to mortality in Streptococcalbut not N meningitidis meningitis with benefits to adults and children in high but not low income countries ( See Brouwer MC et al, 2010).  Significantly, however, dexamethasone does no harm.  Recommendation is .6 mg/kg.day for four days.  It should be given prior to or with the first dose of antibiotic before lysis occurs.  In practice, steroids rarely are stopped when Neiss men is identified as the organism, but that does not harm the patient.

Postural tachycardia syndrome (POTS)

A heterogenous and multifactorial disorder.

Benarroach EE, Mayo Clin Proc 2012; 87:(12) 1214-1225.

A recent review article by the amazing Eduardo Benarroch. 

Definition POTS:  (IN ADULTS) HR increase of 30 bpm within 10 minutes of standing or head up tilt (HUT) without orthostatic hypotension.  Definition may be inadequate for yong teens or those with low resting HR.  Lesser degrees of abnormality is called "orthostatic intolerance."

Symptoms: of cerebral hypoperfuson and (reflex) sympathetic hyperactivity relieved by incumbency.  They include, light headedness, blurred vision, cognitive difficulty, generalized weakness (for hypoperfusion) and palpitations, chest pain, tremulousness (for sympathetic part).   One third have secondary vasovagal syncope with typical exacerbating factors (heat exposure, heavy meals, exertion, prolonged incumbency, menses and certain drugs).

Demography:  females have more (4.5:1), age usually 15-25, half have preceding viral illness and 25 % have a positive family history of.Deconditioning, psychological factors are important and autonomic defined abnormalities are relatively uncommon. 

Pearls:
1.  "Neuropathic" POTS is a subtype with LE sympathetic denervation with loss of sweating, quantitative sudomotor testing, impaired NE release in LE's in response to orthostatic stress. Its probably due to inpaired vasoconstriction and venous pooling in legs. They are also the high flow subtype in blood flow testing of legs. 14 % have ganglionic acetylecholine receptor antibody, hence may be autoimmune/

2.  Hyperadrenergic POTS-- 30-40 % have high NE levels (>600 pg/mL), HTN during HUT, tachycardia, HTN and hyperhidrosis episodes triggered by orthostasis OR emotional stimuli/physical activity.  This is low volume group with supine vasoconstiction, supine tachycardia, pale and cold skins.  Hyperadrenergic state due to norepinephrine transporter (NET) blockade by drugs (TCA's. methylphenidate and related stimulants and others) or secondary to mast cell disorders.  Consider hyperthyroidism or pheochromocytoma in these patients. 

3.  Hypovolemic POTS (28 %).  May be due to low renin/aldosterone secretion or to inappropriately high ACE-2 activity.  May be related to primary GI disorder of N/V/D. 

4. Comorbidities:  Visceral pain and dysmotility, CFS, FM, sleep disorders, myofascial pain, Ehler Danlos syndrome especially type III with variations in tenascin X.  May be related to early onset of chronic pain, with anxiety and sensory amplification state.  Headache with or without CSF leak.

Cogan syndrome: analysis of reported neurologic manifestations

Antonios N, Silliman S.  The Neurologist 2012; 18:55-62

 

This is a review paper/,eta-analysis of all reported cased.  Cogan syndrome, or  non-syphilitic ocular keratitis and vestibuloauditory dysfunction, is diagnosed clinically not by any test, except to exclude other conditions.  353 cases were reviewed. 

 

Hearing loss, usually high tone SN hearing loss, may start unilaterally but almost always becomes bilateral and is followed by dizziness or vertigo (90 %), nausea and vomiting, and may mimic Meniere's syndrome.  It has a fluctuating and progressive course and can recur after as much as 13 years.  Interstitial keratitis occurs in 77 %, often as the second major symptom complex, often starting with scleral redness, photophobia, eye pain, decreased acuity, due to corneal clouding and may be fluctuating from day to day.  Less common symptoms iclude iritis,uveitis, cataracts, scleritis, conjunctivitis and others.Slit lamp shows corneal stromal scarring and neovascularization. 

 

Systemic symptoms that may occur include fever, rash, lymphadenopathy, arthritis, polychondritis, aortitis, and others.

 

Vestibulocohlear/ocular diseases that can be excluded include Susac's syndrome, GCA, lupus, relapsing polychondritis, Churg-Strauss and Behcet's.   Hearing loss is usually permanent and occurs in first three years,  Topical steroids can be used to preserve vision and topical atropine to reduce eye pain.

 

Neurological involvement (not counting above symptoms) occur in 29 % and include CNS such as stroke, encephalitis, aseptic meningitis, myelopathy, cerebral venous thrombosis and optic nerve disorders.  PNS symptoms are just as common and include cranial neuropathy , especially facial paresis, mononeuropathy, peripheral neuropathy and myopathy. 

 

Authors analyze reports and doubt trueness of reports of ischemic stroke of CVST although acknowledge most of the rest of the above.  Pathology may show arteritic changes.  Treatment with 1 mg/kg prednisone is helpful.

Erythropoetin asneuroprotective in heart surgery

Importance of erythropoietin in brain protection after cardiac surgery: a pilot study; Lakic N, Surlan K, Jerin A, Meglic B, Curk N, Bunc M; Heart Surgery Forum 13 (3), E185-9 (Jun 2010)

BACKGROUND: Neurologic complications after cardiac operations present an important medical problem, as well as a financial burden. They increase the morbidity and hospital stays of patients who have otherwise undergone successful heart operations. The current protocols for perioperative brain protection against ischemic events are not optimal. Because of its different pleiotropic mechanisms of action, recombinant human erythropoietin might provide neuroprotection. METHODS: In this study, we included 20 patients who were older than 18 years and required surgical revascularization of the heart with the use of the heart-lung machine. Ten patients received 3 consecutive intravenous doses (24,000 IU) of recombinant human erythropoietin (rHuEpo). Neurologic and magnetic resonance imaging (MRI) examinations were done before and in the first 5 days after surgery. RESULTS: The erythropoietin-treated and control groups were comparable with respect to study protocol outcomes: number of coronary artery bypass grafts (3.3 and 3.2 grafts/patient, respectively), operative time (4.12 and 4.6 hours), and transfusion volume per patient (708 and 674 mL). The groups were also comparable with respect to blood pressure values at all stages of the operation. MRI scans revealed that 4 of 10 patients from the control group had fresh ischemic brain lesions after open heart surgery. None of the patients in the erythropoietin-treated group had fresh ischemic brain lesions. CONCLUSION: Although the number of patients was small, the results regarding brain protection with rHuEpo are encouraging. rHuEpo is a promising neuroprotective agent.

25

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