Physician-Reported Perspectives on Myasthenia Gravis in the United States: A Real-World Survey.

INTRODUCTION: Myasthenia gravis (MG) is a rare, debilitating, chronic disorder caused by the production of pathogenic immunoglobulin G autoantibodies against the neuromuscular junction. A lack of real-world studies in rare diseases reflects a relatively limited understanding of the significant unmet needs and burden of disease for patients. We aimed to provide comprehensive real-world insights into the management and burden of MG from treating physicians in the United States (US). METHODS: Data were collected using the Adelphi Real World MG Disease Specific Programme™, a point-in-time survey of physicians and their patients with MG, in the US between March and July 2020. Physician-reported clinical data, including demographics, comorbidities, symptoms, disease history, treatments, and healthcare resource utilization, were collected. RESULTS: In total, 456 patient record forms were completed by 78 physicians based in the US. At time of survey completion, patient mean age was 54.5 years. Mean time from symptom onset to diagnosis was 9.0 months (n = 357). Ocular symptoms were reported in 71.7% of patients. General fatigue affected 47.1% of patients and over half of those reported the severity as moderate or severe (59.5%, n = 128). Acetylcholinesterase inhibitors and/or steroids were the most frequently prescribed first-line treatment type among patients receiving treatment at time of survey completion and with moderate-to-severe symptoms (77.9%, n = 159/204). High-dose steroids (n = 14) and intravenous immunoglobulin (n = 13) were the most prescribed acute treatments among those receiving an acute treatment at time of survey completion (n = 36), with symptom exacerbations or myasthenic crises being the most common reasons for acute treatment. On average, 2.5 healthcare professionals were involved in patient management and 5.0 consultations were made per patient over the last 12 months. CONCLUSIONS: Our findings indicated that, despite treatment, there is a proportion of patients with MG in the US who had a significant need for improved disease management.

Analyses of seizure responses supportive of a novel trial design to assess efficacy of antiepileptic drugs in infants and young children with epilepsy: Post hoc analyses of pediatric levetiracetam and lacosamide trials.

OBJECTIVE: Recently, a novel trial design has been proposed to overcome challenges with traditional placebo-controlled trials of antiepileptic drugs in infants and young children (≥1 month of age) (Auvin S, et al. Epilepsia Open 2019;4:537-43). The proposed time-to-event trial design involves seizure counting by caregivers and allows adjustment of the duration of the baseline period and duration of exposure to placebo or potentially ineffective treatment based on the patient's seizure burden and response. We performed post hoc analyses to mimic this trial design and evaluate its viability. As these analyses required trials with prolonged baseline and treatment periods and diary data, which is not a typical design of trials in infants and young children (1 month to <4 years of age), data from two trials in pediatric patients (4-16 years of age) were used. METHODS: We performed post hoc analyses of two randomized, double-blind, placebo-controlled trials of adjunctive levetiracetam (N159; NCT00615615) and lacosamide (SP0969; NCT01921205) in children and adolescents (4-16 years of age) with focal-onset seizures. In these analyses, patients were followed until they completed the 10-week maintenance period, discontinued during the maintenance period, or reached their "nth" seizure (n = number of seizures patient had during baseline). Efficacy was assessed by determining time to nth seizure. RESULTS: In the analyses of both trials, patients on levetiracetam or lacosamide had a 34% lower risk of reaching their baseline seizure count during their 10-week maintenance period than patients on placebo. The previously published primary results of these trials also demonstrated efficacy of adjunctive levetiracetam and lacosamide. SIGNIFICANCE: Although these were post hoc analyses of trials in older children (4-16 years of age), our results provide supportive evidence for the utility of the novel time-to-event trial design for future trials in infants and young children (1 month to <4 years of age).

Predictors of surgical outcome in medically-resistant temporal lobe epilepsy with bilateral features on pre-operative evaluation.

OBJECTIVE: This study identifies potential prognostic factors for favorable anterior mesial temporal lobe (AMTL) resection outcomes in patients with medically refractory temporal lobe epilepsy (TLE) with bilateral features on pre-operative examination. METHODS: Thirty-one patients demonstrated bilateral features defined as: bilateral independent temporal or bitemporal ictal onsets on surface or intracranial EEG, or bitemporal interictal epileptiform abnormalities on surface EEG with bilateral radiographic mesial temporal sclerosis. Surgical outcomes were classified according to reduction in seizure frequency: I (100% reduction), II (≥75% reduction), III (50-74% reduction), IV (<50% reduction). RESULTS: Of 31 patients, 14 (45%) improved to class I and 9 (29%) had a class II outcome at an average of 4 years after surgery. Eight (26%) patients did not exhibit good surgical outcome (class III, class IV). We found that neuropsychological and Wada memory scores were significantly correlated (p<0.05) with surgical outcome, and logistic regression found neuropsychological evaluation significantly predicted better surgical outcome (p<0.05). CONCLUSIONS: When bilateral features are present on pre-operative evaluation, neuropsychological and Wada test results can provide unique data to better identify those patients more likely to achieve substantial seizure reduction.

Sex differences in lateralization of semantic verbal fluency in temporal lobe epilepsy.

When differences exist, women tend to outperform men on measures of verbal fluency, possibly due to greater bilateral language representation. Patients with temporal lobe epilepsy (TLE) have a higher rate of atypical cortical language representation than the general population, making them a population of interest for the study of language. For the current study, 78 TLE patients (51% male, 51% left temporal focus) underwent pre-surgical neuropsychological evaluations. Retrospective data analyses investigated the impact of seizure laterality and sex on letter and semantic verbal fluency. Results indicated an interaction between sex and laterality for semantic, but not letter, verbal fluency. Males with left TLE exhibited significantly worse semantic fluency than males with right TLE, whereas females' semantic fluency did not differ by seizure focus. These data indicate that females with TLE may indeed engage in more bilateral hemispheric processing of semantic verbal fluency, whereas males may be more reliant on left temporal cortical function for this task.

Clinical utility of the Wechsler Memory Scale--Fourth Edition (WMS-IV) in predicting laterality of temporal lobe epilepsy among surgical candidates.

This study evaluated the accuracy of the Wechsler Memory Scale--Fourth Edition (WMS-IV) in identifying functional cognitive deficits associated with seizure laterality in localization-related temporal lobe epilepsy (TLE) relative to a previously established measure, the Rey Auditory Verbal Learning Test (RAVLT). Emerging WMS-IV studies have highlighted psychometric improvements that may enhance its ability to identify lateralized memory deficits. Data from 57 patients with video-EEG-confirmed unilateral TLE who were administered the WMS-IV and RAVLT as part of a comprehensive presurgical neuropsychological evaluation for temporal resection were retrospectively reviewed. We examined the predictive accuracy of the WMS-IV not only in terms of verbal versus visual composite scores but also using individual subtests. A series of hierarchal logistic regression models were developed, including the RAVLT, WMS-IV delayed subtests (Logical Memory, Verbal Paired Associates, Designs, Visual Reproduction), and a WMS-IV verbal-visual memory difference score. Analyses showed that the RAVLT significantly predicted laterality with overall classification rates of 69.6% to 70.2%, whereas neither the individual WMS-IV subtests nor the verbal-visual memory difference score accounted for additional significant variance. Similar to previous versions of the WMS, findings cast doubt as to whether the WMS-IV offers significant incremental validity in discriminating seizure laterality in TLE beyond what can be obtained from the RAVLT.

Sensitivity of Green's Word Memory Test genuine memory impairment profile to temporal pathology: a study in patients with temporal lobe epilepsy.

Performance validity tests (PVTs) such as Green's Word Memory Test (WMT) are designed to have face validity as memory tests while individuals with neurologically based memory deficits can score adequately provided there is sufficient task engagement. Some patients with severe memory loss have performed poorly on the WMT, raising questions about false positive errors. This study compared performances of 43 patients with left, right, or bilateral temporal lobe epilepsy on the WMT to a test known to be sensitive to temporal lobe pathology, the Rey Auditory Verbal Learning Test (RAVLT). The right TLE group outperformed the left on the WMT free recall (FR) scores and RAVLT short-delay and long-delay trials (Trials 6 and 7) (p < .05); no other between-group differences occurred (p ≥ .10). Ten participants (20.4%) performed below the cut-off score on at least one WMT effort subtest, but eight (80%) exhibited the genuine memory impairment profile (GMIP). Logistic regression found no WMT subtest contributed to predicting side of seizure with RAVLT scores in the model. Data suggest WMT primary effort subtests are generally insensitive to known temporal lobe pathology, and using the GMIP is valuable to identify individuals with severe memory loss who score below criterion on WMT primary effort subtests.

Long-term radiosurgery effects in the treatment of temporal lobe epilepsy.

Epilepsy surgery is an effective treatment for medically resistant temporal lobe epilepsy (TLE). To minimize complication rates and potentially improve neuropsychology outcomes, stereotactic radiosurgery (SRS) has been explored as an alternative. Two pilot trials have demonstrated the effectiveness of SRS for the treatment of medically resistant TLE, with seizure-free outcomes for approximately 65% of patients at last follow-up. Despite encouraging results, no conclusive long-term outcomes are available for SRS. This article discusses a single patient who presented with recurrent seizures, worsening headaches, and persistent abnormal MRI findings 7 years and 8 months after SRS. This 29-year-old woman with a history of medically refractory complex partial seizures since childhood was referred for evaluation. Medical management had failed in this patient. The workup was compatible with left mesial temporal lobe onset, with MRI findings suggestive of mesial temporal sclerosis. In 2003, at the age of 23 years, she underwent Gamma Knife surgery (GKS) targeting the left temporal mesial area with a dose of 24 Gy at the 50% marginal isodose line. After GKS, the patient's seizures decreased in frequency over several months, but auras were persistent. Nine months after treatment, she developed worsening headaches. A follow-up MRI study demonstrated a thick, irregular, enhancing lesion in the medial part of the temporal lobe. She was placed on corticosteroids, with resolution of her headaches. Her seizures and headaches recurred in March 2010. An MRI study showed a 2.2-cm, ill-defined, enhancing cystic lesion in the left mesial temporal lobe with T2 and FLAIR hyperintensity, which was presumably radiation induced. At that time, the patient opted for left temporal lobe resection to control her seizures. Histological examination showed moderately severe, remote, longstanding sclerosis at the level of the hippocampus. A vascular lesion was identified, and it was most consistent with radiation-induced capillary hemangioma. The entorhinal region was severely damaged, with hemorrhage, necrosis, neuronal loss, astrogliosis, and hemosiderin deposition. There was evidence of radiation vasculopathy. Radiation-induced lesions after SRS for the treatment of epilepsy are not well documented. Although GKS is a promising technique for the treatment of medically resistant TLE, the ideal candidate is not yet well defined. The selection of the appropriate technical parameters to obtain a desirable functional effect without histological damage to the surrounding neural tissue remains a challenge. This case illustrates the need for long-term follow-up when radiosurgery is used for epilepsy.

The yield of routine outpatient electroencephalograms in the veteran population.

The objective of this study is to determine the yield of routine outpatient electroencephalogram (EEG) in the diagnosis of epilepsy in the veteran population. All consecutive outpatient EEGs at the James A. Haley Veterans Affairs Hospital in Tampa, FL from October 31, 2005, to October 30, 2007, were retrospectively reviewed. During the 2 years of the study, 636 routine outpatient EEGs were performed at James A. Haley Veterans Affairs Hospital. The age range for the patients was 21 to 97 years with a mean age of 55 years. Eighty-five EEGs (13.4%) were classified as abnormal. Nineteen EEGs (3%) in the past 2 years contained epileptiform abnormalities. Sixty-eight EEGs (10.7%) had other abnormalities such as slowing, asymmetry, excessive beta activity, or a combination of abnormalities. Thirty-six EEGs (5.7%) clearly demonstrated psychogenic nonepileptic attacks as documented by normal EEG and video recording of the patient's habitual event. Single routine outpatient EEG has been reported to have a sensitivity of 29% to 55% in detecting interictal epileptiform discharges in patients with a suspected diagnosis of epilepsy. In our study, only about 3% of the patients had clear abnormalities suggestive of epilepsy. Interestingly, by using routine EEGs, we were able to definitively diagnose more patients with psychogenic nonepileptic attacks than epileptic seizures.

Essential oils as a cause of breakthrough seizure after temporal lobectomy.

Breakthrough seizures are often encountered in patients with well-controlled epilepsy for no obvious reason. We report a case of a breakthrough seizure after temporal lobectomy secondary to topical administration of essential oils. We recommend inquiring about the use of essential oils in patients with well-controlled epilepsy who experience breakthrough seizures.