Seizure freedom without seizure medication following stereoelectroencephalography implantation: a case report of drug-resistant post-traumatic epilepsy.

Achieving seizure freedom following failure of several antiseizure medications (ASMs) is rare, with the likelihood of achieving further control decreasing with each successive ASM trial. When cases of drug-resistant epilepsy arise, a diagnostic procedure known as stereoelectroencephalography (sEEG) can be used to identify epileptogenic zones (EZ) within the brain. After localization of these zones, they can be targeted for future surgical intervention. Here, we describe a case of complete seizure freedom off medication after sEEG without resection or other therapeutic intervention. In 2017, a 36-year-old right-handed male presented with drug-resistant epilepsy stemming from prior traumatic brain injury. Due to ongoing seizures, in 2020 a robotic-assisted sEEG electrode placement procedure was employed to localize the seizure onset zone. During sEEG monitoring, a single event was captured where the patient had dysarthric speech, left arm dystonic flexion, and difficulty responding to questioning. Notably, this event had no sEEG correlate, suggesting seizure occurrence in a region not monitored by implanted electrodes, which prompted the placement of scalp electrodes following this event. However, no further clinical events consistent with seizure were provoked through the remainder of recording. Following the 13-day admission, the patient chose to self-discontinue all seizure medications and has remained seizure free as of October 2023, more than 3.5 years later. While sEEG is considered a relatively safe procedure for seizure localization in drug resistant epilepsy, the possibility of microlesions created by sEEG depth electrodes remains largely unexplored. Further evaluation should be performed into potential tissue injury produced by depth electrode insertion.

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.

Derivation and initial validation of a surgical grading scale for the preliminary evaluation of adult patients with drug-resistant focal epilepsy.

OBJECTIVE: Presently, there is no simple method at initial presentation for identifying a patient's likelihood of progressing to surgery and a favorable outcome. The Epilepsy Surgery Grading Scale (ESGS) is a three-tier empirically derived mathematical scale with five categories: magnetic resonance imaging (MRI), electroencephalography (EEG), concordance (between MRI and EEG), semiology, and IQ designed to stratify patients with drug-resistant focal epilepsy based on their likelihood of proceeding to resective epilepsy surgery and achieving seizure freedom. METHODS: In this cross-sectional study, we abstracted data from the charts of all patients admitted to the New York University Langone Medical Center (NYULMC) for presurgical evaluation or presented in surgical multidisciplinary conference (MDC) at the NYU Comprehensive Epilepsy Center (CEC) from 1/1/2007 to 7/31/2008 with focal epilepsy, who met minimal criteria for treatment resistance. We classified patients into ESGS Grade 1 (most favorable), Grade 2 (intermediate), and Grade 3 (least favorable candidates). Three cohorts were evaluated: all patients, patients presented in MDC, and patients who had resective surgery. The primary outcome measure was proceeding to surgery and seizure freedom. RESULTS: Four hundred seven patients met eligibility criteria; 200 (49.1%) were presented in MDC and 113 (27.8%) underwent surgery. A significant difference was observed between Grades 1 and 3, Grades 1 and 2, and Grades 2 and 3 for all presurgical patients, and those presented in MDC, with Grade 1 patients having the highest likelihood of both having surgery and becoming seizure-free. There was no difference between Grades 1 and 2 among patients who had resective surgery. SIGNIFICANCE: These results demonstrate that by systematically using basic information available during initial assessment, patients with drug-resistant epilepsy may be successfully stratified into clinically meaningful groups with varied prognosis. The ESGS may improve communication, facilitate decision making and early referral to a CEC, and allow patients and physicians to better manage expectations.

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.

Peculiar neuroimaging and electrophysiological findings in a patient with biotinidase deficiency.

We report a patient with biotinidase deficiency with peculiar findings on her MRI brain. Subcortical cysts combined with Dandy Walker cyst on the brain MRI have never been reported. There are many documented case reports of biotinidase deficiency and several of them have included findings on neuroimaging. Subcortical cysts have been documented in one patient with biotinidase deficiency previously and on autopsy in one other patient. Video EEG on the same patient showed evidence of symptomatic generalized epilepsy.

Efficacy of levetiracetam at 12 months in children classified by seizure type, cognitive status, and previous anticonvulsant drug use.

In a retrospective study of 59 children (ages 9 months to 23 years; mean age 11 years) with intractable epilepsy, seizure frequency was determined before and after 12 months of levetiracetam therapy. Charts were reviewed for seizure type (focal, generalized, or mixed), cognitive function (no special education versus special education), concomitant anticonvulsant medications (range 0-5), and the number of previous anticonvulsant drugs (range 1-12). Good to excellent seizure control (50-100% reduction) was attained in 6 (40%) patients with focal seizures, 16 (55%) patients with generalized seizures, and 8 (61%) patients with mixed seizures; these efficacy rates were not significantly different. The efficacy of levetiracetam was independent of cognitive status. Adverse effects were not associated with higher mean doses. This could be attributable to different rates of metabolism or represent idiosyncratic responses to the medication. Our finding that those children taking the combination of levetiracetam and zonisamide had a significantly worse outcome than those on levetiracetam and a different drug warrants further study, both clinically and from the standpoint of the mechanisms of action of levetiracetam and zonisamide and/or their pharmacodynamic interactions.

Broad-spectrum efficacy of zonisamide at 12 months in children with intractable epilepsy.

In a retrospective study of 35 children (ages 8 months to 22 years; mean age 9 years) with intractable epilepsy, seizure frequency was determined before and after 12 months of zonisamide therapy. Charts were reviewed for seizure type (focal, generalized, or mixed), cognitive function (no special education versus special education), concomitant anticonvulsant medications, and the number of previous anticonvulsant drugs. Good to excellent seizure control (50-100% reduction) was attained in seven (54%) patients with generalized seizures, two (40%) patients with focal seizures, five (35%) patients with mixed seizures, and one (33%) patient with infantile spasms. In this group of children, the efficacy of zonisamide was comparable for focal, generalized, and mixed seizures. The efficacy of zonisamide was independent of cognitive status. Adverse effects were not associated with a higher mean dose. This could be attributable to different rates of metabolism or represent idiosyncratic responses to the medication. Our finding that those children taking the combination of zonisamide and levetiracetam had a significantly worse outcome than those on levetiracetam and a different drug warrants further study, both clinically and from the standpoint of mechanisms of action of zonisamide and levetiracetam and/or their pharmacodynamic interactions.