Tolerability of clobazam as add-on therapy in patients aged 50 years and older with drug-resistant epilepsy.

OBJECTIVE: To evaluate the tolerability of clobazam in patients with drug-resistant epilepsy aged 50 years and older. METHODS: We performed a single center, retrospective chart review of patients at least 50 years of age with drug resistant epilepsy of any type who started clobazam as an add on therapy. Retention rate, safety, and tolerability at 6 and 12 months and last follow-up, and the discontinuation rate due to side effects were analyzed. RESULTS: A total of 26 patients met inclusion criteria. Mean age was 62 ± 7.1 years, and 69.2% of patients were female. The mean baseline seizure frequency before initiation of clobazam was 2 (range 1-30) seizures per month. The mean total daily dose of clobazam administered was 13 (range 5 to 30) mg/day. At the 12-month follow-up visit after clobazam initiation, 40% of patients were seizure-free and an additional 45% of patients had > 50% reduction in seizure frequency. The mean seizure frequency at 12-month follow-up was 1.5 (range 0-24) seizures per month. The mean total dose of clobazam at 12-month follow-up was 14.25 (range 5 to 25) mg/day. The mean duration of clobazam at last follow was 55.2 ± 27.02 (mean ± SD months) and 18 (69.2%) patients remained on clobazam. Twenty out of 26 (76.9%) patients reported at least one side effect and 6/26 (23%) discontinued the medication within a month of initiation. At last follow-up, 40% remained seizure free on stable dosing. CONCLUSION: Clobazam can be a safe and tolerable, add-on treatment older adults with drug-resistant epilepsy. Those who responded tolerated the medication well. Discontinuation due to side effects occurred soon after initiation of therapy.

A quantitative method for evaluating cortical responses to electrical stimulation.

BACKGROUND: Electrical stimulation of the cortex using subdurally implanted electrodes can causally reveal structural connectivity by eliciting cortico-cortical evoked potentials (CCEPs). While many studies have demonstrated the potential value of CCEPs, the methods to evaluate them were often relatively subjective, did not consider potential artifacts, and did not lend themselves to systematic scientific investigations. NEW METHOD: We developed an automated and quantitative method called SIGNI (Stimulation-Induced Gamma-based Network Identification) to evaluate cortical population-level responses to electrical stimulation that minimizes the impact of electrical artifacts. We applied SIGNI to electrocorticographic (ECoG) data from eight human subjects who were implanted with a total of 978 subdural electrodes. Across the eight subjects, we delivered 92 trains of approximately 200 discrete electrical stimuli each (amplitude 4-15 mA) to a total of 64 electrode pairs. RESULTS: We verified SIGNI's efficacy by demonstrating a relationship between the magnitude of evoked cortical activity and stimulation amplitude, as well as between the latency of evoked cortical activity and the distance from the stimulated locations. CONCLUSIONS: SIGNI reveals the timing and amplitude of cortical responses to electrical stimulation as well as the structural connectivity supporting these responses. With these properties, it enables exploration of new and important questions about the neurophysiology of cortical communication and may also be useful for pre-surgical planning.

A case of paraneoplastic neuromyelitis optica associated with small cell lung carcinoma.

Neuromyelitis optic spectrum disorders are demyelinating conditions that are typically idiopathic, though various case reports have demonstrated an association with malignancy. We present the case of a 64year old woman with NMOSD in the setting of small cell lung cancer. She had longitudinally extensive transverse myelitis and left eye optic neuritis; aquaporin-4 antibodies were elevated. Biopsy of mediastinal adenopathy was positive for SCLC. Malignancy should be considered in any patient with an atypical presentation of NMOSD, or who does not respond to traditional therapies.

Barriers to the use of intravenous tissue plasminogen activator for in-hospital strokes.

BACKGROUND: Patients who have ischemic strokes (ISs) while hospitalized for other conditions may be less likely to receive intravenous tissue plasminogen activator (IV tPA) when compared to patients who have strokes in the community. This study explored possible barriers to IV tPA use in these patients. METHODS: Stroke diagnosis was confirmed by chart review for all adult patients admitted to Bellevue Hospital between January 1, 2004 and December 31, 2008 who were discharged with a primary or secondary International Classification of Diseases, 9th edition code for transient ischemic attack, intracerebral hemorrhage, or IS. Circumstances at stroke onset were recorded for all patients who had strokes while hospitalized for another reason. RESULTS: Seventy-nine in-hospital IS cases were identified; 18 (23%) occurred <2 weeks after major surgery, and another 14 (18%) had a delayed diagnosis because signs were not readily detectable on clinical examination. Twenty-four patients (30%) were eligible for IV tPA, of whom 13 were identified within 3 hours of onset and 10 (13%) were treated with IV tPA. The median National Institutes of Health Stroke Scale score was higher in hospitalized patients (13) than in patients admitted through the emergency department (5; P < .001 using the Wilcoxon rank sum test). CONCLUSIONS: Seventy percent of in-hospital IS cases in our single hospital retrospective study were postoperative, clinically subtle, or had contraindications to IV tPA, preventing its use. Of the remaining untreated patients, the biggest barrier to IV tPA administration was delay in stroke discovery, which was largely dependent on observation by hospital staff or family rather than patient report.