Friday, April 04, 2014

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. 


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). 

Monday, January 20, 2014

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) ,

Tuesday, December 24, 2013

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
      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

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

carnitine deficiency
myotonic dystrophy
congenital myopathy
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.

Tuesday, October 01, 2013

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). 


Friday, April 12, 2013

Papilledema and obstructive sleep apnea syndrome.



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


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.


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.


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.

Monday, April 08, 2013

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