Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL).

A 44-year-old Caucasian man presented with seizures and cognitive impairment. He had marked retinal drusen, and MR brain scan showed features of cerebral small vessel disease; he was diagnosed with a leukoencephalopathy of uncertain cause. He died at the age of 46 years and postmortem brain examination showed widespread small vessel changes described as a vasculopathy of unknown cause. Seven years postmortem, whole-genome sequencing identified a homozygous nonsense HTRA1 mutation (p.Arg302Ter), giving a retrospective diagnosis of cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy.

Encephalopathy in a Large Cohort of British Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy Patients.

Background and Purpose- Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common monogenic form of stroke usually presenting with migraine with aura, lacunar infarcts, and cognitive impairment. Acute encephalopathy is a less recognized presentation of the disease. Methods- Data collected prospectively from 340 consecutively recruited symptomatic patients with diagnosis of CADASIL seen in a British National CADASIL clinic was retrospectively reviewed and original clinical records and imaging obtained. An encephalopathic event was defined as an acute event of an altered state of consciousness in a patient with CADASIL, manifesting with signs of brain dysfunction, which warranted hospital admission in the absence of any other cause. Clinical characteristics, risk factors, and outcome of encephalopathic presentations were studied. Results- A total of 35 of 340 (10.3%) participants had a history of 50 encephalopathic events which was the first hospital presentation of CADASIL in 33 (94.3%) patients. Most commonly reported features during episodes were visual hallucinations (44%), seizures (22%), and focal neurological deficits (60%).Complete recovery within 3 months was reported in 48(96%) episodes. In 62% of episodes, there was a history of migraine or migraine aura directly preceding the encephalopathy. In 2 out of 15 cases where magnetic resonance imaging during episodes was available, unilateral focal cortical swelling was seen. A past history of migraine was independently associated with encephalopathy (odds ratio=12.3 [95% CI, 1.6-93.7]; P=0.015). Conclusions- In up to 10% of CADASIL patients, a reversible encephalopathy is the first presentation leading to diagnosis. The strong association with migraine suggests a shared pathogenesis. Focal cortical swelling may be seen on magnetic resonance imaging during the acute episode.

Recent advances in the management of symptomatic vertebral artery stenosis.

PURPOSE OF REVIEW: Vertebrobasilar stenosis accounts for 20% of posterior circulation strokes and is associated with high risk of early stroke recurrence. We review data from randomized controlled trials examining whether stenting may reduce this risk, including the recently published Vertebral Artery Ischaemia Stenting Trial (VIST). RECENT FINDINGS: VIST and VAST (Vertebral Artery Stenting Trial), having recruited both intracranial and extracranial vertebral stenosis and showed a low rate of perioperative stroke for extracranial (0 and 2%, respectively), but a higher rate for intracranial stenosis (15 and 22%, respectively). In VIST, the primary endpoint of stroke occurred in five patients in the stent group vs. 12 in the medical group (hazard ratio 0.40; 95% confidence interval 0.14-1.13, P = 0.08), although when days from last symptoms were adjusted for, the hazard ratio was 0.34 (95% confidence interval 0.12-0.98; P = 0.046). SAMMPRIS (Stenting and Aggressive Medical Management for the Prevention of Recurrent Stroke in Intracranial Stenosis) recruited only intracranial vertebral stenosis and showed a better outcome with intensive medical therapy than stenting. SUMMARY: Stenting of extracranial stenosis can be performed with a low operative risk. VIST suggests it may reduce longer term stroke risk, but this needs confirming in larger trials. For intracranial stenosis, due to a higher operative risk, current evidence favours medical treatment. SAMMPRIS have emphasized the need for intensive medical therapy whether or not stenting is performed.