Randomized trial of lacosamide versus fosphenytoin for nonconvulsive seizures.

OBJECTIVE: The optimal treatment of nonconvulsive seizures in critically ill patients is uncertain. We evaluated the comparative effectiveness of the antiseizure drugs lacosamide (LCM) and fosphenytoin (fPHT) in this population. METHODS: The TRENdS (Treatment of Recurrent Electrographic Nonconvulsive Seizures) study was a noninferiority, prospective, multicenter, randomized treatment trial of patients diagnosed with nonconvulsive seizures (NCSs) by continuous electroencephalography (cEEG). Treatment was randomized to intravenous (IV) LCM 400mg or IV fPHT 20mg phenytoin equivalents/kg. The primary endpoint was absence of electrographic seizures for 24 hours as determined by 1 blinded EEG reviewer. The frequency with which NCS control was achieved in each arm was compared, and the 90% confidence interval (CI) was determined. Noninferiority of LCM to fPHT was to be concluded if the lower bound of the CI for relative risk was >0.8. RESULTS: Seventy-four subjects were enrolled (37 LCM, 37 fPHT) between August 21, 2012 and December 20, 2013. The mean age was 63.6 years; 38 were women. Seizures were controlled in 19 of 30 (63.3%) subjects in the LCM arm and 16 of 32 (50%) subjects in the fPHT arm. LCM was noninferior to fPHT (p = 0.02), with a risk ratio of 1.27 (90% CI = 0.88-1.83). Treatment emergent adverse events (TEAEs) were similar in both arms, occurring in 9 of 35 (25.7%) LCM and 9 of 37 (24.3%) fPHT subjects (p = 1.0). INTERPRETATION: LCM was noninferior to fPHT in controlling NCS, and TEAEs were comparable. LCM can be considered an alternative to fPHT in the treatment of NCSs detected on cEEG. Ann Neurol 2018;83:1174-1185.

Direct and indirect costs associated with stereotactic radiosurgery or open surgery for medial temporal lobe epilepsy: Results from the ROSE trial.

OBJECTIVE: To determine whether a less-invasive approach to surgery for medically refractory temporal lobe epilepsy is associated with lower health care costs and costs of lost productivity over time, compared to open surgery. METHODS: We compared direct medical costs and indirect productivity costs associated with treatment with stereotactic radiosurgery (SRS) or anterior temporal lobectomy (ATL) in the ROSE (Radiosurgery or Open Surgery for Epilepsy) trial. Health care use was abstracted from hospital bills, the study database, and diaries in which participants recorded health care use and time lost from work while seeking care. Costs of use were calculated using a Medicare costing approach used in a prior study of the costs of ATL. The power of many analyses was limited by the sample size and data skewing. RESULTS: Combined treatment and follow-up costs (in thousands of US dollars) did not differ between SRS (n = 20, mean = $76.6, 95% confidence interval [CI] = 50.7-115.6) and ATL (n = 18, mean = $79.0, 95% CI = 60.09-103.8). Indirect costs also did not differ. More ATL than SRS participants were free of consciousness-impairing seizures in each year of follow-up (all P < 0.05). Costs declined following ATL (P = 0.005). Costs tended to increase over the first 18 months following SRS (P = 0.17) and declined thereafter (P = 0.06). This mostly reflected hospitalizations for SRS-related adverse events in the second year of follow-up. SIGNIFICANCE: Lower initial costs of SRS for medial temporal lobe epilepsy were largely offset by hospitalization costs related to adverse events later in the course of follow-up. Future studies of less-invasive alternatives to ATL will need to assess adverse events and major costs systematically and prospectively to understand the economic implications of adopting these technologies.

Radiosurgery versus open surgery for mesial temporal lobe epilepsy: The randomized, controlled ROSE trial.

OBJECTIVE: To compare stereotactic radiosurgery (SRS) versus anterior temporal lobectomy (ATL) for patients with pharmacoresistant unilateral mesial temporal lobe epilepsy (MTLE). METHODS: This randomized, single-blinded, controlled trial recruited adults eligible for open surgery among 14 centers in the USA, UK, and India. Treatment was either SRS at 24 Gy to the 50% isodose targeting mesial structures, or standardized ATL. Outcomes were seizure remission (absence of disabling seizures between 25 and 36 months), verbal memory (VM), and quality of life (QOL) at 36-month follow-up. RESULTS: A total of 58 patients (31 in SRS, 27 in ATL) were treated. Sixteen (52%) SRS and 21 (78%) ATL patients achieved seizure remission (difference between ATL and SRS = 26%, upper 1-sided 95% confidence interval = 46%, P value at the 15% noninferiority margin = .82). Mean VM changes from baseline for 21 English-speaking, dominant-hemisphere patients did not differ between groups; consistent worsening occurred in 36% of SRS and 57% of ATL patients. QOL improved with seizure remission. Adverse events were anticipated cerebral edema and related symptoms for some SRS patients, and cerebritis, subdural hematoma, and others for ATL patients. SIGNIFICANCE: These data suggest that ATL has an advantage over SRS in terms of proportion of seizure remission, and both SRS and ATL appear to have effectiveness and reasonable safety as treatments for MTLE. SRS is an alternative to ATL for patients with contraindications for or with reluctance to undergo open surgery.

Combined Responsive Neurostimulation and Focal Resection for Super Refractory Status Epilepticus: A Systematic Review and Illustrative Case Report.

OBJECTIVE: Super-refractory status epilepticus (SRSE) is a neurologic emergency with high mortality and morbidity. Although medical algorithms typically are effective, when they do fail, options may be limited, and neurosurgical intervention should be considered. METHODS: We report a case of SRSE treated acutely with responsive neurostimulation (RNS) and focal surgical resection after intracranial monitoring. We also conducted a systematic review of the literature for neurosurgical treatment of SRSE (e.g., neurostimulation). Only published manuscripts were considered. RESULTS: Our patient's seizure semiology consisted of left facial twitching with frequent evolution to bilateral tonic-clonic convulsions. Stereoelectroencephalography and grid monitoring identified multiple seizure foci. The patient underwent right RNS placement with cortical strip leads over the lateral primary motor and premotor cortex as well as simultaneous right superior temporal and frontopolar resection. Status epilepticus resolved 21 days after surgical resection and placement of the RNS. The systematic review revealed 15 case reports describing 17 patients with SRSE who underwent acute neurosurgical intervention. There were 3 patients with SRSE with RNS placement as a single modality, all of whom experienced cessation of SE. Four patients with SRSE received vagus nerve stimulation (3 as a single modality and 1 with combined corpus callosotomy), of whom 1 had SE recurrence at 2weeks. Two patients with SRSE received deep brain stimulation, and the remaining 8 underwent surgical resection; none had recurrence of SE. CONCLUSIONS: RNS System placement with or without resection can be a viable treatment option for select patients with SRSE. Early neurosurgical intervention may improve seizure outcomes and reduce complications.

New-Onset Seizure With Possible Limbic Encephalitis in a Patient With COVID-19 Infection: A Case Report and Review.

With the outbreak of COVID-19 (coronavirus disease 2019) as a global pandemic, various of its neurological manifestations have been reported. We report a case of a 54-year-old male with new-onset seizure who tested positive for severe acute respiratory syndrome coronavirus 2 from a nasopharyngeal swab sample. Investigative findings, which included contrast-enhancing right posterior temporal lobe T2-hyperintensity on brain magnetic resonance imaging, right-sided lateralized periodic discharges on the electroencephalogram, and elevated protein level on cerebrospinal fluid analysis, supported the diagnosis of possible encephalitis from COVID-19 infection. The findings in this case are placed in the context of the existing literature.

Myasthenia Gravis Masquerading as an Idiopathic Unilateral Facial Paralysis (Bell's Palsy)-A Very Rare and Unique Clinical Find.

Myasthenia gravis (MG) is an uncommon autoimmune neuromuscular junction disorder manifesting as fluctuating weakness of skeletal muscles. To add to its repertoire of mimicking a wide range of neurological disorders, the present case report is, to the best of our knowledge, the very first to describe MG masquerading as an idiopathic unilateral facial paralysis (Bell's palsy, BP). Our case report is distinct, highlights a novel clinical occurrence, offers new insights of how different neurological disorders may overlap with each other, and reminds neurologists to have a very broad and thorough comprehension for effective diagnoses and treatment plans. Several other conditions that produce facial nerve palsy identical to BP have also been discussed.

Isolated oculomotor nerve palsy as a manifestation of diffuse large B cell lymphoma: A case report.

An isolated third nerve palsy presenting as the primary manifestation of a lymphoma is rare, with only few cases having been described. The present study reports an unusual case of a healthy 67-year old male diagnosed with isolated right oculomotor nerve palsy (ONP), who was found to have an underlying B cell lymphoma. The patient's medical records were accessed upon consent. A thorough physical examination, including stroke and infections work-ups were performed. A chest computerized tomography (CT), brain magnetic resonance imaging and positron emission tomography (PET) scans and a mediastinal tissue biopsy, were performed as part of systematic diagnostic evaluations. The current report suggests that a PET fluorodeoxyglucose study or a CT scan of the chest, abdomen and pelvis (with contrast) may help in the early diagnosis of a cancer responsible for ONP, particularly if brain vessel imaging does not show a posterior cerebral artery aneurysm as a cause for the defect.

Generalized tonic-clonic seizures with post-ictal atrial fibrillation.

Convulsive seizures are known to cause severe cardiopulmonary changes and increased autonomic activity. Limited reports describe peri-ictal cardiac arrhythmias such as atrial fibrillation (AF) with generalized tonic-clonic seizures (GTCS). We present a unique case of a healthy 23-year-old male patient with new onset prolonged AF in the setting of new onset seizures, occurring on three independent occasions. Over two years, our patient had multiple hospitalizations for seizures with an electrocardiogram (ECG) diagnosis of AF made on three different occasions, occurring during his post-ictal state (all within 30 min of seizure onset). These seizures were never captured by electroencephalography (EEG) or witnessed by the medical staff, but were reported by family and/or reviewed on video provided by them. After his first GTCS, his AF persisted and was medically cardioverted. Two additional instances of AF after witnessed GTCS have been captured. After his second unprovoked seizure, an anti-seizure drug (ASD) was prescribed. A multi-disciplinary approach may be adopted to address comorbidities associated with seizures. Aggressive evaluation and treatment should be employed for newly diagnosed and refractory seizure patients associated with arrhythmias, in our case AF. Peri-ictal arrhythmias may be considered a potential marker for increased sudden unexpected death in epilepsy (SUDEP) risk.

Surgery for pharmacoresistant epilepsy in the developing world: A pilot study.

Epilepsy prevalence in the developing world is many fold that found in developed countries. For individuals whose conditions failed to respond to pharmacotherapy, surgery is the only opportunity for cure. In Uganda, we developed a center for treatment of intractable temporal lobe epilepsy (iTLE) that functions within the technologic and expertise constraints of a severely low resource area. Our model relies on partnership with epilepsy professionals and training of local staff. Patients were prescreened at regional clinics for iTLE. Individuals meeting inclusion criteria were referred to the treating Ugandan hospital (CURE Children's' Hospital of Uganda, CCHU) for video-EEG (electroencephalography), computed tomography (CT) imaging, and neuropsychological evaluation. Data were transferred to epilepsy experts for analysis and treatment recommendations. Ten patients were diagnosed with iTLE and surgically treated at CCHU. Six (60%) were seizure free, and there was no neurologic morbidity or mortality. Our model for surgical treatment of pharmacoresistant TLE has functioned successfully in a true developing world low resource setting.

Temporal lobectomy for refractory status epilepticus in a case of limbic encephalitis.

The authors report a case of status epilepticus secondary to limbic encephalitis that was successfully treated with temporal lobectomy. A 45-year-old woman presented in status epilepticus refractory to high-dose suppressive medical therapy. Magnetic resonance imaging of the brain showed T2- and FLAIR-weighted hyperintensities in the right temporal lobe, left and right frontal lobes, and pons. A lumbar puncture revealed normal findings. Continuous electroencephalography monitoring showed continued right temporal seizure activity. A paraneoplastic panel was positive for N-type voltage-gated calcium channels. Subsequent bronchial biopsy revealed small cell carcinoma of the lung. A right temporal lobectomy was performed due to refractory status, resulting in resolution of seizure activity and recovery of good neurological function. The authors describe their case and review the literature on surgical therapy for refractory status epilepticus and limbic encephalitis.

Visual field defects after radiosurgery versus temporal lobectomy for mesial temporal lobe epilepsy: Findings of the ROSE trial.

PURPOSE: Stereotactic radiosurgery (SRS) may be an alternative to anterior temporal lobectomy (ATL) for mesial temporal lobe epilepsy (MTLE). Visual field defects (VFD) occur in 9-100% of patients following open surgery for MTLE. Postoperative VFD after minimally invasive versus open surgery may differ. METHODS: This prospective trial randomized patients with unilateral hippocampal sclerosis and concordant video-EEG findings to SRS versus ATL. Humphries perimetry was obtained at 24 m after surgery. VFD ratios (VFDR = proportion of missing homonymous hemifield with 0 = no VFD, 0.5 = complete superior quadrantanopsia) quantified VFD. Regressions of VFDR were evaluated against treatment arm and covariates. MRI evaluated effects of volume changes on VFDR. The relationships of VFDR with seizure remission and driving status 3 years after surgery were evaluated. RESULTS: No patients reported visual changes or had abnormal bedside examinations, but 49 of 54 (91%) of patients experienced VFD on formal perimetry. Neither incidence nor severity of VFDR differed significantly by treatment arm. VFDR severity was not associated with seizure remission or driving status. CONCLUSION: The nature of VFD was consistent with lesions of the optic radiations. Effective surgery (defined by seizure remission) of the mesial temporal lobe results in about a 90% incidence of typical VFD regardless of method.

Surgery for temporal lobe epilepsy.

Intractable epilepsy is a debilitating disease with significant associated morbidity and mortality. Uncontrolled epilepsy is socially disabling causing stigma, social exclusion, and often preventing employment. After an individual has tried and failed three or four of the standard anticonvulsants, it is very unlikely any further medications or combinations of medications will control the epilepsy. The major Neurology, Neurosurgery, and Epilepsy medical societies recommend all individuals with medically intractable epilepsy be evaluated in a comprehensive epilepsy program. In selected individuals, surgery for epilepsy has tremendous potential to cure or control intractable epilepsy. At West Virginia University Health Sciences Center, 48 individuals underwent surgery for intractable temporal lobe epilepsy over a 2.5 year period. Thirty-five (73%) of individuals were seizure free after surgery, and 96% were seizure free or significantly improved. Surgery for epilepsy has a high likelihood for success in medically intractable temporal lobe epilepsy, and is superior to medical treatment alone.

Fluorodeoxyglucose-positron emission tomographic imaging for the diagnosis of mesial temporal lobe epilepsy.

OBJECTIVE: Fluorodeoxyglucose (FDG)-positron emission tomographic (PET) imaging plays an important role in the evaluation of intractable epilepsy. The metabolic defect has proven utility in the lateralization of temporal lobe epilepsy. However, the role of FDG-PET imaging in the localization of a seizure focus within the temporal lobe is uncertain. We evaluated FDG-PET imaging for the capability to localize a temporal seizure focus within the mesial structures. METHODS: Twenty-eight patients who underwent selective amygdalohippocampectomy for intractable temporal lobe epilepsy were studied. Patients were divided into 2 groups: those who were free of seizures (FS) and those with persisting seizures postoperatively. FS patients were defined by having mesial temporal lobe epilepsy (MTLE). Preoperative FDG-PET activity was evaluated in temporal lobe structures and contrasted with magnetic resonance imaging (MRI) for usefulness in identifying MTLE in an individual. RESULTS: Pathology of the hippocampus revealed mesial temporal sclerosis in all but 1 patient. Qualitative visual inspection of the MRI scan was not reliable in the identification of MTLE (P = 0.15). MRI volumetry found smaller mesial temporal structures (P = 0.04) in FS patients. Mesial temporal metabolic activity was reduced in the FS group (hippocampus, P = 0.001). However, a combination of imaging modalities was found to be the best predictor of MTLE. PET imaging plus MRI qualitative inspection identified all patients with and without MTLE correctly and was superior to MRI alone (P = 0.01 and P = 0.02, respectively). CONCLUSION: MRI volumetry and PET imaging were comparable (P = 0.73) and able to identify MTLE in most patients, but a combination of PET imaging and MRI visual inspection was superior in the recognition of MTLE.