Evolution of intracranial atherosclerotic disease under modern medical therapy.

OBJECTIVE: Understanding how symptomatic intracranial atherosclerotic disease (ICAD) evolves with current medical therapy may inform secondary stroke prevention. METHODS: In a prospective academic-initiated study, we recruited 50 patients (mean age = 63.4 ± 9.0 years) with acute strokes attributed to high-grade (≥70%) intracranial atherosclerotic stenosis for 3-dimensional rotational angiograms before and after intensive medical therapy for 12 months. Treatment targets included low-density lipoprotein ≤ 70mg/dl, glycosylated hemoglobin (HbA1c) ≤ 6.5%, and systolic blood pressure ≤ 140 mmHg. We analyzed infarct topography and monitored microembolic signal in recurrent strokes. The reference group was a published cohort of 143 ICAD patients. RESULTS: Overall, the stenoses regressed from 79% at baseline (interquartile range [IQR] = 71-87%) to 63% (IQR = 54-74%) in 1 year (p < 0.001). Specifically, the qualifying lesions (n = 49) regressed (stenosis reduced >10%) in 24 patients (49%), remained quiescent (stenosis same or ±10%) in 21 patients (43%), and progressed (stenosis increased >10%) in 4 patients (8%). There was no difference in intensity of risk factor control between groups of diverging clinical or angiographic outcomes. Higher HbA1c at baseline predicted plaque regression at 1 year (odds ratio = 4.4, 95% confidence interval = 1.4-14.5, p = 0.006). Among the 6 patients with recurrent strokes pertaining to the qualifying stenosis, 5 patients had solitary or rosarylike acute infarcts along the internal or anterior border zones, and 2 patients showed microembolic signals in transcranial Doppler ultrasound. INTERPRETATION: A majority of symptomatic high-grade intracranial plaques had regressed or remained quiescent by 12 months under intensive medical therapy. Artery-to-artery thromboembolism with impaired washout at border zones was a common mechanism in stroke recurrence.

Prognosticating acute symptomatic seizures using two different seizure outcomes.

PURPOSE: This study examined the profiles and prognosis of first acute symptomatic seizure (ASS). Because seizure recurrences may occur in the setting of a persisting or reemerging acute symptomatic cause or in the setting of an unprovoked seizure, we documented the prognosis of ASS in terms of acute symptomatic seizure (AS) or unprovoked seizure (US) recurrence. METHODS: We conducted a prospective study of patients with suspected seizures between April 2004 and December 2005. Patients were classified according to medical history taking, routine clinical evaluation, and expert adjudication, and they were followed for a minimum of 2 years or until death. The Kaplan-Meier method and univariate/multivariate statistical analysis were used to determine prognosis. RESULTS: One hundred five patients with first-ever ASS were identified. For many, first ASS was associated with status epilepticus (29.5%), multiple-onset (>1 seizure within 24 h on day of presentation) (35.2%), and multiple etiologies (22.9%), with a mortality of 30% at 2 years (Kaplan-Meier method). Using AS as outcome, the risk of recurrence following an ASS was 32% at 2 years [mean time to recurrence 20.5 days with epileptiform electroencephalography (EEG) being an independent predictor; p = 0.005, odds ratio (OR) 16, 95% confidence interval (CI) 4.09-62.7]. Using US as outcome, the risk of recurrence following an ASS was 12% at 2 years. DISCUSSION: Although ASS did not associate with a high rate of US recurrence, we demonstrated that ASS was often followed by another AS. This may have implication for short- to medium-term antiepileptic agent therapy, especially when the acute symptomatic cause takes a long time to treat, is prone to reemergence, or is irreversible.

Headache in patients with epilepsy: a prospective incidence study.

High prevalence of headache has been reported in patients with refractory epilepsy in cross-sectional surveys based on retrospective recall. We conducted a prospective study to document the incidence of headache over a 3-month observation period in a cohort of 227 adult patients with less refractory epilepsy. The mean seizure frequency was 2.46 per month. Fifty (22%) patients reported to have had at least one headache episode, 45 (19.8%) had interictal headache, 11 (4.8%) had periictal headache, and 5 (2.2%) had both interictal and periictal headache. Forty-nine percent of the patients with headache took over-the-counter analgesics as acute treatment. The headache was rated to have made very severe or substantial impact on their lives by 34% of patients. A formal headache diagnosis was not made in any of the patients prior to the survey. Although the incidence of headache in epilepsy patients appeared to be low, it was underdiagnosed and associated with substantial negative impact.

Association between HLA-B*1502 allele and antiepileptic drug-induced cutaneous reactions in Han Chinese.

A previous study conducted in Taiwan found a 100% association between HLA-B*1502 allele and carbamazepine-induced Stevens-Johnson syndrome (SJS) in Han Chinese subjects, with an extremely high odds ratio compared with carbamazepine-tolerant subjects (odds ratio = 2,504). We examined this association in 24 Hong Kong Han Chinese subjects who had cutaneous adverse reactions induced by different antiepileptic drugs (AEDs). They were matched with 48 AED-tolerant controls. HLA-B*1502 was associated with severe cutaneous reactions (SCR) induced by AEDs, which included carbamazepine, phenytoin, and lamotrigine (p = 0.001, odds ratio = 17.6), but was not associated with maculopapular exanthema (MPE) (p = 0.32). Further studies in larger samples of ethnically matched subjects should be conducted to confirm the findings. Identification of genetic polymorphisms predisposing to development of AED-induced SCR offers the possibility of avoiding these high-risk drugs in genetically susceptible individuals.