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.

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