Monday, February 11, 2008

SCA infarction and emotional facial paresis

SCA infarct classically produces ipsilateral limb and gait ataxia, static or intention tremor, Horner's syndrome, contralateral loss of pain and temperature and decreased masseter response. Other symptoms may include deafness, impaired sweating (with Horner's) and emotional facial paresis . This derives from dorsolateral pontine pathologyThis area is distinct from the corticobulbar tract mediating voluntary facial innervation (Neuroimages, Hopf HC, Fitzek C, Marx J et al., Emotional facial paresis of pontine origin, Neurology 2000; 54: 1217).

Blogger comment-- review brainstem anatomy including lateral st tract (crossed sensory), mes tract of V (masseter r), central sympathetic tract (Horners s), lateral lemniscus (responsible for deafness), MLF

Subclavian artery dissection and triple infarction of the nervous system

Garewal M, Selhorst JB. Arch Neurol 2005; 62:1917-1919.

Background-- subclavian dissection is rare, and is usually associated with anomalies of the aortic arch, trauma or catheterization. The main clinical manifestations are chest and back pain preceding stroke, often with pain and weakness in the arm. This contrasts with vertebral artery dissection that is associated with headache and neck pain and arm pain/weakness.

In the case described, a 54 year old hypertensive developed crushing intrascapular pain and vertigo and vomiting and could not lift his arm over his head. His father had had an abdominal aortic aneurysm. He had decreased pinprick perception on his left lower jaw. He had weak deltoid, triceps, supraspinatus, and triceps. He had decreased left biceps and triceps jerks. He had dysmetria bilaterally and an ataxic gait. His radial arteries WERE SYMMETRIC!. DWI showed a left cerebellar stroke. On angio he had a subintimal thrombus in the subclavian artery. He improved over a month or two. The authors describe 3 strokes: cerebellar, spinal between C4 and C5, and multiple rootlet infarction with weak arms and denervation on EMG study.

The lit review describes a patient who developed subacute thoracic pain and bilateral arm pain.

Saturday, February 09, 2008

Natural history of vertebrobasilar dolichoectasia

Passero SG, Rossi S. Neurology 2008; 70:66-72.

There is a high degree of variability in outcome ranging from benign to malignant. Clinical expression includes compression of cranial nerves or brainstem, obstructive hydrocephalus, ischemic and hemorrhagic stroke. This study of 156 patients followed an average of 11.7 years showed that 93 patients (60 % ) had at least one event; 59 ischemic strokes, 21 hemorrhagic strokes, 31 compressive symptoms, and 2 hydorcephalus. Risk stratification was based on the severity of , diameter, height of bifurcation, nad lateral displacement of the vertebral artery. Progression of VBD was associated with a worse outcome. 43 % of patients did progress.

Detail: the maximum diameter of the BA ranged from 4.6 to 13.4 mm (mean 6.8). 86 % invlved the VA's and 45 % the anterior circulation. Strokes were more likely among patients who were hypertensive and smokes. Of the strokes, 41 % were brainstem, 29 % superficial arterial territory of PCA, 24 % thalamus, 2 % cerebellum, 66 % lacunes, 34 % large artery.

Of 56 patients who presented with ischemic stroke, 50 received antiplatelet drugs and 6 anticoagulation. 54 % had recurent ischemic strokes, and 13 % recurrent hemorrhagic strokes. 73 % of recurrent strokes happened in first five years of followup.

Treatment initially was NOT related to risk of stroke. 42 % of treated patients (n=33) and 34 % of untreated patients (n=26) had one or more ischemic strokes during followup. Death from stroke (40 % of deaths) occurred among patients who first presented with stroke.

The ten year risk of recurrent stroke among patients presenting with stroke was 56 % which compares to the Rochester experience of 29 % (Meissner and Whisnant, Stroke, 1988).

Wednesday, February 06, 2008

Aspirin for Primary prevention in women

Ridker PM, Cook NR, Lee I, et al. A randomized trial of low dose aspirin in the primary prevention of cardiovascular disease in women. NEJM 2005; 352:1293-1304. article with associated editorial by Levin RI The Puzzle of aspirin and sex NEJM 352:1366-1368.

Background: Low dose asa reduces the risk of a first MI in men, with little effect on risk of ischemic stroke. There are no similar data in women.

Article highlights: This large (39,876) trial of healthy women age 45 and older for primary prevention put them in a group of ASA 100 mg or placebo for ten years. ASA reduced the risk of stroke without affecting the risk of MI/death from cardiovascular causes, leading to a nonsignificant primary endpoint.

Editorial: the finding is the inverse in what they found in men. The author discusses that the studies were done in different decades (2 decades apart) and that the respective placebo groups had different risk profiles. The risk was 97/100000 person years in the Women's Health Study and 439 per 100,000 py's in the Physicians Health Initiiative (the male study). These were healthy women. The author reviews some of the pertinent differences in physiology by gender. Men usually have 2-3 times the number of MI's as women. Their coronary arteries are bigger and their carotid plaques "more aged." Women have 9 times the amount of stress cardiomyopathy . Their responses to drugs are different. Estrogen up-regulates prostacyclin by receptor mediated activation of cyclo-oxygenase 2. The study would seem to suggest that generally prescribing low dose aspirin to healthy women under 65 with a low risk score should be avoided. However, part of the book has yet to be written.

Thoughts on the WASID trial

The warfarin-Aspirin Symptomatic Intracranial Disease (WASID) trial compared aspirin with warfarin and found no benefit from warfarin, but greater safety risks, leading the authors to conclude that there was no justification to use warfarin in this situation.

An editorial by Walter Koroshetz accompanying the landmark study (NEJM 2005;352:13)provides acceptance of the studies with enough included analysis of the detail to make a reasoned opinion about its limitations. Ischemic stroke, brain hemorrhage, or death from vascular causes other than stroke occurred in 22 % of patients in either group. Recurrent stroke did not differ in the two groups (.2 in ASA, .17 in warfarin groups). In WASID, 73 % of recurrent stroke occurred in the index vessel.

Problems: 1) ASA dose of 1250 per day is nonstandard 2) the target INR of 2-3 was reached only about 63 % of the time and 3) 28 % of patients dropped out of the warfarin group. The rate of stroke related to IN mattered. It was 25 per 100 patient years with a subtherapeutic INR, 5.0 per 100 patient years with a therapeutic INR. Koroshetz notes that the "data suggest that anticoagulation within the therapeutic range is associated with a striking reduction in the risk of cerebrovacular and cadiovascular events." The problem, is achieving anticoagulation within the therapeutic range, either in a trial or in clinical practice. Koroshetz further notes that "the WASID data do not necessarily suggest that all patients with symptomatic intracranial stenosis should be treated with aspirin during all phases of their disease and be left to face a 22 % two year risk of ischemic stroke, brain hemorrhage or death from vascular causes other than stroke that the WASID trials predicts." There is a very high risk period right after enrollment, due to recurrent stroke, and Koroshetz suggests using Lovenox followed by anticoagulation rather than just warfarin.

Blogger comment: Recall that in most clinical trials of ASA (not for intracranial stenosis) the NTT for saving one person from a stroke is very high,, ranging from 79 to 129 in various aspirin trials, with the NTT for Plavix around 50 and for Aggrenox around 37. So for a disease with a 1/5 risk of stroke, aspirin may be better/safer than warfarin but still is not that good. So, a treatment, any treatment, that can improve those odds in a high risk group is desperately needed. If a new drug came forth that anticoagulated and could be kept in range reliably (unlike warfarin , which WASID proved can't be) another clinical trial for intrancranial stenosis would be indicated.

One last note-- it shold be noted that some of the initiators of the WASID and WARRS trials are Bostonians who have historically been dedicated warfarin users. These neurologists deserve our credit for designing and properly critiquing the studies here.

Statin therapy in stroke prevention: a metaanalysis involving 121,000 patients

O"Regan C, Wu P, Arora P, et al. Am J Med 2008; 121:24-33.

High points: the pooled relative risk of statin therapy for all cause mortality was 0.88 (95% CI .79-.91). Each unit increase in LDL results in a .3% increased RR of death. ONLY ONE TRIAL WAS FOR SECONDARY PREVENTION.

Details: RR of statin patients in all pooled trials, for cardiovascular death, .81, for nonhemorrhagic cerebrovscular death, .81, hemorrhagic stroke , 0.94, and fatal strokes .99. Be cautious of hemorrhagic strokes.

Sunday, February 03, 2008

Minocycline treatment for acute stroke

Lampl Y, Boaz M, Gilad R.Minocycline treatment in acute stroke. An open label, evaluator blinded study.

Patients received 200 mg minocycline orally for five days after stroke, and NIHSS was used. 152 patients were studied (74 received minocycline, 77 placebo). NIHSS and mRS were lower and BI higher in treated group. Deaths, MI, recurrent strokes, and hemorrhagic stroke transformations were no affected.

Study was based on "clear" neuroprotective effect seen in animal models of MS, PD, HD, and ALS. Pyramidal cell survival improved from 10 to 77 % due to "complete prevention of microglia ischemia induced activation." Minocycline prevents infarct volume expansion, inhibits IL 1B converting enzyme, cycklooxygenase 2, PGE 2 expression. Proposals suggests its antiinflammatory, reduces microglial activation, matrix metalloproteinase activation, nitric acid production, and inhibition of apoptosis. In spinal cord its an NMDA antagonist, and prevents activated caspace 3 formation.

Blogger note: The large multicenter phase III trial of minocycline in ALS reported that ALS was HARMED BY minocycline, details at the link below:
http://strokenotes.blogspot.com/2008/02/minocycline-treatment-for-acute-stroke.html

Friday, February 01, 2008

Predictors of stroke among patients with AF

1. Prior stroke/TIA is highest risk and confers > 5 % per year risk (6-9% per year)
2. Diabetes confers 2-3.5% risk
3. Age > 75 1.5-3 % per year
4. History of HTN 1.5-3 % per year

Source
Strokse Risk in AF Working Group. Independent predictors of stroke in patients with AF: A systematic review. Neurology 2007; 69:546-554.