Tuesday, March 25, 2008

Fasting causes stroke


Saadatnia M et al. showed an fourfold increase in cerebral venous sinus thrombosis during Ramadan, a month during which Muslims fast. P02.007 AAN book 2008.

Misdiagnosis of Fabry disease

Po1.145 AAN book 2008 first author L Marchesoni. Argentina.

Fabry's disease is an x linked recessive lysosomal storage disease due to deficient alpha galactosidase A. Untreated males usually die by the end of the sixth decade. The initial presentation is usually acroparesthesias, not relieved by rubbing, but prevented with acetophenacetin and ingestion of large amounts of liquids. Subsequently, abdominal pain, angiokeratomas and anhidrosis occur. Most are diagnosed after 15 years or more. Misdiagnoses included cryptogenic/psychogenic pain, RF, flatfoot, gout, food intoxication, cholecystitis, "glandular block", petechiae, vascular fragility, and others. Angiokeratomas are seen first around the umbilicus, and on the extensor surfaces of the elbows and knees, and in body creases including the hips and the genital areas. Opthalmic signs include whirl like feathery opacities, dust like haziness on cornea, dilated and tortuous corneal vessels, and corneal dystrophy on slit lamp that does not affect vision(cornea vittilicata). The opthalmic abnormality is present in nearly 90 % including female carriers who can thus be diagnosed by slit lamp exam.

Features can include tinnitus and deafness, although that is not in many textbooks (Lou Caplan); also vertigo. Other features are heat intolerance, inability to sweat, with the skin turning beet red on heat exposure. Other factors are postprandial abdominal cramping, and diverticula that can rupture. Left ventricular hypertrophy is seen as is small fiber neuropathy with decreased TEMPERATURE sensation. A recent case was reported of a patient presenting with a mimic of TGA (The Neurologist 2012; 18:413-4).

Strokes occur in posterior circulation  , large and small arteries.

Pathologically, thickened walls in smaller arterioles is noted and in the brain, a double refractile material is seen. Cardiac and renal disease predominate, and many strokes are subclinical. Treatment must begin very early. Misdiagnosis of MS is common especially with brainstem strokes. CRAO, optic atrophy, loss of nasal field, third nerve palsy, lateral medullary syndrome, TMB are all reported, as are various lacunar syndromes. Cardiac evaluation shows hypertrophic cardiomyopathy and MVP in more than half. Renal failure is due to the deposition of lipid in glomeruli and tubules.  Proteinuria is a feature.  Lymphedema is seen . Basilar artery is described as pathologically enlarged and at times dolichoectatic.

The gene for alpha galactosidase a is Xq22.1, and different mutations are known. Female heterozygotes still have early stroke and can have heart and kidney disease and elevated ceramide trihexoside in urine. Treatment is biochemical Fabrazyme made by Genzyme (see pubmed how to do). CBZ, PTN, ASA ticlid, Vit E can be used for various symptoms/problems.

Additional material:
Testai FD, Gorelick PB.  Inherited metabolic disorders and stroke part I:  Fabry disease and mitochondrial myopathy, encephalopathy, lactic acidosis and stroke like episodes.  Arch Neurol; 2010: 67: 19-24.

More than 400 mutations of the alpha gal gene are identified, most being missense or nonsense substitutions.  Absent family history does not rule out the diagnosis.  The incidence is 1: 117,000 births and 1: 40,000 men.  However, in cryptogenic stroke in the young, FD is responsible for 1.2 % (of age less than 55).  Inn the database, women have more strokes than men, 2:1 with mean age 43 for women, and 28 for men.  Basilar artery diameter is said to be a sensitive measure of FD (Neurology 2009). 

Due to skewed organ specific X chromosome inactivation (nonrandom lionization), women may have atypical organ specific presentation, leading to challenges in diagnosis.  These may include cardiac, renal and cerebrovascular manifestations.  Diagnosis is made by alpha gal activity in leukocytes or plasma, but in women, gene sequencing and linkage studies may be needed, due to heterozygosity.

Acroparesthesias are associated with accumulation glycosphingolipids  in DRG and Nerve conductions and EMG's are negative.

Measurement of leukocyte GAL activity is 100 percent sensitive in males but only five percent in women

MRI shows T2 hyperintense signal in frontal and parietal white matter and T1 hyperintensity in pulvinar as well as dolichoectasia.  Treatment decreased LV mass and pain but unknown if it helps stroke.

The varicella zoster virus vasculopathies: clinical, CSF, imaging and virologic features


Nagel MA, Cohrs RJ, Mahalingam R et al. Neurology 2008; 70:853-860.

Review article of 30 patients, the first large review in about 30 years, busts some myths about VZV stroke. Among them:

1. Rash occurred in only 63 %, often many months prior to the stroke (mean 4 months)
2. CSF pleocytosis occurred in only 67 %
3. Angiography was abnormal in only 70 %
4. Large arteries were involved with small arteries (50%) or small arteries were involved alone (37% ) whereas large arteries alone occurred in only 13 %.
5. VZV DNA was found in only 30 %
6. The best lab test, by far, was CSF anti VZV IgG antibody with reduced IgG index (serum : CSF) confirmed intrathecal synthesis. The only 2 negative cases out of 30 were children who developed vasculopathy after chickenpox.
7. Case series was not large enough to determine optimal treatment (acyclovir v. acyclovir + steroids); however, some cases relapsed and then improved when either acyclovir course was extended or steroids were addded to acyclovir. Overall in the small series, 2/3 improved with acyclovir alone, and 3/4 with acyclovir + steroids.
8. 11 patients out of 30 were immunocompromised (2 AIDS, 3 HIV +, 2 leukemia, 1 CREST s, 1 lymphoma, 1 low CD4 count, and 1 treatment for RA/SLE).
9

PRoFESS Trial


Diener HC , Sacco R, Yusud S et al. Rationale, design and baseline data of a randomized, double blind controlled trial comparing two antithromobotic regiments (a fixed dose combinations of ER dipyridamole and plus ASA with clopidogrel) and telmisartan versus placebo in patients with strokes: the prevention regiment for effectively avoiding second strokes trial. Cereebrovasc Dis 2007; 23:368-380.

Blogger comment: The authors were obviously science and not English majors, and the lower case "O" is annoying. In sum this study compares aggrenox against plavix, and makes a side study of telmisartan.

There are 695 sites from 35 countries, involving patients over 50 with stroke within 120 days, with recurrent stroke as the primary outcome in a time to event analysis. The secondary outcome measure is the composite of stroke, MI or vascular death. The main study is non-inferiority, then superiority and the side study assesses suuperiority over placebo. Over 20,000 patients are randomized. The mean age was 66, 2:1 male, large and small vessel strokes are included. The deisgn is 2 x 2 factorial design.

The expected event rate in the clopidogrel group was 5.25 % per year, necessitating 15,500 subjects but the number was increased when the event rate turned out to be lower.

COL4A1 mutations and stroke


Vahedi et al. Neurology 2007; 69: 1564-8
and editorial
Meschia JF and Rosand J. Fragile vessels handle with care Neurology 2007; 69: 1560-1561

COL4A1 gives the brain resistance to minor head trauma. It encodes the gene for collagen alpha 1. Human conditions linked to a mutation include autosomal dominant porencephaly, retinal arteriolar tortuosities, and traumatic or antithrombotic associated symptomatic cerebral hemorrhages and otherwise undetected microhemorrhages on MRI. MRI can also show diffuse leukoencephalopathy and enlarged perivascular spaces. The report by Vahedi includes a patient who died of subarachnoid hemorrhage and another who died at age 40 of anticoagulation associated hemorrhage.

The editorial authors compare the condition to CADASIL insofar as many different mutations can cause the condition. The theme of trauma or injuries to vessels as triggers to hemorrhage recurs. Treatment of affected patients may including withholding antithrombotics or anticoagulants, avoiding contact sports, genetic screening in pregnancy, and of family members (including asking specifically about congenital hemiplegia rather than "porencephaly"), periodic screening with MRI's, further evaluating tortuous vessels seen on funduscopy and others.

Monday, March 24, 2008

Imaging Pearl for cerebral venous sinus thrombosis


Courtesy of David Lee Gordon, Chairman Oklahoma (the neurology department not the musical)

Look at the parenchymal MRI (not MRV) images, particularly the T1noncontrast sagittal images. If the noncontrast T1 sagittal images shownormal (hypointense = black) flow void in the left transverse sinus andlack of flow void (hyperintense = white) in the right transverse sinus,you have your answer without a venogram.The left transverse sinus is commonly hypoplastic, not the right (sinceuually the right transverse sinus drains the larger superior sagittalsinus and the left transverse sinus drains the smaller straight sinusand the confluence is usually not a confluence at all). Also a temporalhemorrhage is precisely what I would expect from an ipsilateraltransverse sinus thrombosis. If the patient does indeed have CVT,anticoagulation often leads to improve despite the presence ofhemorrhage.