#25: Unusual symptoms and syndromes in multiple sclerosis
This is a Continuum article that describes lots of bizarre symptoms such as:
- Pulfrich phenomenon: due to differences in light perception between eyes, moving objects appear to travel in an elliptical orbit instead of a straight line. Most notably, this causes the sensation while driving that cars are swerving in one’s direction. Occurs after optic neuritis or other unilateral eye issues.
- Uthoff phenomen: blurry vision with exercise or other stressors, due to impaired conduction at higher body temperatures.
- Paroxysmal neurologic events like paresthesias or tonic spasms: positive symptoms thought to be caused by spontaneous impulses generated around a plaque, that propagate away from the area of demyelination.
- Hypothermia from anterior hypothalamic lesions, that seems to respond to IV thiamine
#24: Seasonal variation of relapse rate in multiple sclerosis is latitude dependent
- This study looked at data from an online MS registry (MSBase); 9811 patients at 55 centers had relapses within the start of the observation period
- There was an annual pattern to relapse onset: they were most common in spring, and least common in fall. Less time elapsed between the winter nadir of solar radiation and the spring peak of relapses at higher latitudes
- The article speculates this is because residents of more northern latitudes have lower reserves of vitamin D, but it also points out that some respiratory viruses follow this pattern as well
Still unclear, I guess, but this is good support there is a seasonal effect.
#23: Malignant middle cerebral artery infarction: pathophysiology, diagnosis and management
- Space occupying edema is the most common cause of early mortality in stroke; edema peaks at days 2-4
- “Malignant MCA syndrome” really just refers to a big MCA stroke that swells a lot
- Mechanism of cytotoxic edema is ischemia causing lack of oxygen and glucose, which leads to failure of the sodium/potassium ATPase; this results in sodium rushing in, osmotically drawing water in along with it, so the cell swells and dies
- Vasogenic edema is caused by breakdown of the blood-brain barrier post stroke, the mechanism for which is not fully understood; proteins and ions leak out of the blood into the extracellular space
- Radiographical predictors of poor outcome include more than 50% involvement of MCA territory, and pineal gland displacement
- The article talks about 3 trials for decompressive surgery: DECIMAL and HAMLET showed improved survival but not improved mRS; DESTINY was stopped early
#22: Long-term mortality after stroke among adults aged 18 to 50 years
Reason for study: 10% of strokes are in adults younger than 50. What do we know about their natural history?
Study design: prospective study that followed a cohort of 959 consecutive patients aged 18-50 who presented with their first lifetime TIA, ischemic stroke or ICH to an academic medical center in the Netherlands. Patients were excluded for hemorrhage secondary to trauma, SAH or aneurysmal ICH, tumor, or venous sinus thrombosis. Primary outcome was all cause mortality compared to expected mortality based on the entire Dutch population.
- 30 day mortality was 0.4% for TIA, 3.6% for ischemic stroke, 22% for ICH
- Mortality was higher than expected mortality across the board. Mortality for TIA was 2.5% at five years, 9.2% at 10, and 24.9% at 20. For the same time points, mortality after ischemic stroke was 5.8%/12.4%/26.8%; for ICH, 6.1%/10.3%/13.7%
- 55% of deaths after ischemic stroke was due to vascular causes
Long term mortality wasn’t that much higher for stoke vs TIA, so it’s good that we essentially treat them the same. One of my attendings says that it’s good to admit people to the hospital even for a TIA with a low ABCD2 score, since it scares them into understanding it’s a big deal–and data like this supports that.
#21: Management of asymptomatic internal carotid artery stenosis
- This article is a JAMA Grand Rounds that tries to answer the scenario in which a PCP hears a carotid bruit in an elderly patient, and ultrasound confirms high grade stenosis–should they be referred for intervention, or stick to medical therapy alone?
- Spoiler: the evidence isn’t great.
- 10-15% of strokes in the US are associated with ICA stenosis (symptomatic or asymptomatic)
- 7-9% of patients older than 75 have asymptomatic ICA stenosis
- The natural history of carotid disease has changed: in the 1980s, the stroke risk was 3% per year for >80% stenosis, 5%/yr for >90% stenosis, but these rates have significantly declined over the years
- Statins are a magic drug: in patients with CAD or diabetes, simvastatin 40mg daily was associated with a 25% reduction in stroke risk; in patients with diabetes and additional risk factors, atorvastatin 10mg decreased stroke risk by 48% compared with placebo
- Two older trials supported CEA (ACAS and ACST), but achieving similar results requires a perioperative risk of <3%, which is hard to achieve in the community
- CREST evaluated stenting vs CEA in 2502 patients, including both symptomatic and asymptomatic patients, and found no difference, but stenting hasn’t become standard of care
- The primary cause of mortality in patients with asymptomatic ICA stenosis is cardiac: having a carotid bruit increases your risk of heart attack by three, to 5% per year
…and we’re back! Sorry guys–I don’t even have a good excuse for falling off my articles bandwagon. (I may have gotten sucked into rereading The Mists of Avalon, which is excellent but also 900 pages so consumed most of my reading bandwidth. Whoops.)
Here are a few more stroke articles. First, is subclinical AF an important cause of cryptogenic stroke?
#20: Subclinical atrial fibrillation and the risk of stroke (the ASSERT trial)
- 15% of strokes are due to documented atrial fibrillation, but 25% have no obvious cause–are these caused by undocumented AF?
- The ASSERT study recruited 2580 patients who were older than 65, had hypertension, and needed a pacer or ICD
- None of the participants were on anticoagulation at the start of the study, but 61% were on aspirin
- The devices were interrogated at 3 months. 261 patients (10%) had at least one episode of subclinical atrial tachycardia, defined as an atrial rate over 190 for at least 6 minutes. 7 patients developed clinical AF during this window.
- Of the patients with subclinical AF during the 3 month study period, the median number of episodes was only 2, and the median time to detection was 36 days! So even a 28 day Holter monitor likely misses a lot of these patients.
- Of the 261 patients with subclinical AF, 11 (1.69%/yr) had an ischemic stroke or systemic embolism during the follow up period, vs 0.69% /yr in the group without; the hazard ratio was 1.76
- During the 2.5 year follow up, 633 participants (34.7%) developed subclinical AF, vs only 15.7% developed clinical AF
So, I guess the conclusion is that subclinical AF is, really, a stroke risk factor. But honestly my takeaway is that if have high blood pressure and *need a pacer* and you’re an AARP member, you will have AF if you don’t already. This is not so exciting. I want to see the same study with a loop recorder or something in patients with cryptogenic stroke. Also, the paper points this out, but just because it increases stroke risk, we don’t know if anticoagulation helps these people.
#19: Anticoagulation versus placebo for heart failure in sinus rhythm
- This one’s a Cochrane review. Actually the 2012 version, because it’s what I had sitting around, but I notice that the 2014 version still only includes the same two studies. (Probably because WARCEF was the big new one, but it’s not placebo based.)
- So they did this whole search, found 1200 articles, but there were only 5 studies that met their search criteria: WASH (2004), HELAS (2006), and 3 studies from the fifties (!) that weren’t quite up to snuff by modern methodological standards and were excluded.
- There is a lot of discussion of different bias types, but the takeaway is that combining the two studies showed no benefit to anticoagulation vs anything.
I believe them, but these reviews are…not that exciting to read fully? Like maybe I should just skim to the conclusions? Is it just me?