Value of semiology in predicting epileptogenic zone and surgical outcome following frontal lobe epilepsy surgery.

OBJECTIVE: To evaluate the ability of semiology alone in localising the epileptogenic zone (EZ) in people with frontal lobe epilepsy (FLE) who underwent resective surgery. METHODS: We examined data on all individuals who had FLE surgery at our centre between January 01, 2011 and December 31, 2020. Descriptions of ictal semiology were obtained from video-EEG telemetry reports and presurgical multidisciplinary meeting summaries. The putative EZ was represented by the final site of resection. We assessed how well initial and combined set-of-semiologies correlated anatomically with the EZ, using a semiology visualisation tool to generate probabilistic cortical heatmaps of involvement in seizures. RESULTS: Sixty-one individuals had FLE surgery over the study period. Twelve months following surgery, 28/61 (46%) were completely seizure-free, with a further eight experiencing only auras. Comparing the semiology database with the putative EZ, combined set-of-semiology correctly lateralised in 77% (95% CI: 69-85%), localised to the frontal lobe in 57% (95% CI: 48-67%), frontal lobe subregions in 52% (95% CI: 43-62%), and frontal gyri in 25% (95% CI: 16-33%). No difference in degree of correlation was seen comparing those with ongoing seizures 12 months after surgery to those seizure free. SIGNIFICANCE: Semiology alone was able to correctly lateralize the putative EZ in 77%, and localise to a sublobar level in approximately half of individuals who had FLE surgery. Semiology is not adequate alone and must be combined with imaging and EEG data to identify the epileptogenic zone.

Electrophysiologic evaluation of myasthenia gravis and its mimics: real-world experience with single-fiber electromyography.

OBJECTIVES: In centers which routinely perform single fiber electromyography (SFEMG) for suspected myasthenia gravis (MG), the additional benefit of other neurophysiologic investigations and the frequency of myasthenia mimics has not been ascertained. We aimed to illustrate the range of neurological and non-neurological myasthenia mimics referred for evaluation, and contrast features of their electrophysiologic evaluation with confirmed MG. METHODS: We reviewed all SFEMG studies performed at our center between 1 January 2018 and 31 December 2020. Patient demographics, clinical phenotype, antibody status and final diagnosis were recorded. Electrophysiologic findings were correlated with clinical features and sensitivity analyses performed. RESULTS: A total of 528 SFEMG studies were performed, of which 213 (41%) were abnormal. A diagnosis of MG was made in 101 individuals, including 46 with ocular MG and 35 with seronegative disease. Compared to myasthenia mimics with an abnormal SFEMG, individuals with MG had higher median jitter (mean consecutive difference 61 µs vs. 42 µs, p < 0.001) and a greater percentage of abnormal pairs (61% vs. 33%, p < 0.001) on SFEMG. Repetitive nerve stimulation was abnormal in 27.1% of people with MG and was associated with a generalized clinical phenotype (OR 4.17; 95% CI 1.67-10.48). Thirteen (2%) individuals with MG had normal SFEMG, of whom 10 were in clinical remission. Functional neurological disorders, cranial nerve palsies, primary ocular disease and myopathy were frequent myasthenia mimics. CONCLUSION: SFEMG can be abnormal in a number of myasthenia mimics, and routine nerve conduction studies and electromyography should always be undertaken. In centers where SFEMG is performed routinely for the investigation of suspected MG, extensive proximal repetitive nerve stimulation can be foregone without substantially affecting diagnostic evaluation. Normal SFEMG in those with confirmed myasthenia gravis may help indicate clinical remission.

Long-term seizure, psychiatric and socioeconomic outcomes after frontal lobe epilepsy surgery.

OBJECTIVE: Resective surgery for selected individuals with frontal lobe epilepsy can be effective, although multimodal outcomes are less established than in temporal lobe epilepsy. We describe long-term seizure remission and relapse patterns, psychiatric comorbidity, and socioeconomic outcomes following frontal lobe epilepsy surgery. METHODS: We reviewed individual data on frontal lobe epilepsy procedures at our center between 1990 and 2020. This included the presurgical evaluation, operative details and annual postoperative seizure and psychiatric outcomes, prospectively recorded in an epilepsy surgery database. Outcome predictors were subjected to multivariable analysis, and rates of seizure freedom were analyzed using Kaplan-Meier methods. We used longitudinal assessment of the Index of Multiple Deprivation to assess change in socioeconomic status over time. RESULTS: A total of 122 individuals with a median follow-up of seven years were included. Of these, 33 (27 %) had complete seizure freedom following surgery, with a further 13 (11 %) having only auras. Focal MRI abnormality, histopathology (focal cortical dysplasia, cavernoma or dysembryoplastic neuronal epithelial tumor) and fewer anti-seizure medications at the time of surgery were predictive of a favorable outcome; 67 % of those seizure-free for the first 12 months after surgery never experienced a seizure relapse. Thirty-one of 50 who had preoperative psychiatric pathology noticed improved psychiatric symptomatology by two years postoperatively. New psychiatric comorbidity was diagnosed in 15 (13 %). Persistent motor complications occurred in 5 % and dysphasia in 2 %. No significant change in socioeconomic deciles of deprivation was observed after surgery. SIGNIFICANCE: Favorable long-term seizure, psychiatric and socioeconomic outcomes can be seen following frontal lobe epilepsy surgery. This is a safe and effective treatment that should be offered to suitable individuals early.

Cost of pre-surgical evaluation for epilepsy surgery: A single-center experience.

OBJECTIVE: To estimate the cost and time taken to evaluate adults with drug-resistant focal epilepsy for potentially curative surgery. METHODS: We reviewed data on 100 consecutive individuals at a tertiary referral center evaluated for epilepsy surgery in 2017. The time elapsed between referral and either surgery or a definitive decision not to progress was measured. National Health Service tariffs applicable to our setting were used to estimate the total cost of evaluation for individuals following different routes through the pre-surgical pathway. After surgery, self-reported seizure freedom rates were obtained from each individual to assess the approximate cost of pre-surgical evaluation per additional person seizure-free. RESULTS: Of 100 individuals evaluated, 27 had surgery, 63 had a definitive decision not to have surgery, and ten were awaiting further investigations. The median duration of the pre-surgical evaluation was 29.7 months (IQR 18.6-44.1 months), with a median cost per person of £9138 (IQR £6984-£14,868). Those who proceeded to Stage Two investigations (including fluorodeoxyglucose positron emission tomography, ictal single-photon emission computerized tomography and intracranial electroencephalography) had a higher cost and extended evaluation length. After a median of 3.1 (IQR 2.3-3.7) years, 15/27 people who had surgery were seizure-free. This equated to an approximate cost of £123,500 spent per additional person seizure-free. CONCLUSION: Pre-surgical evaluation is long and costly, particularly for those who require icEEG. For those with drug-resistant focal epilepsy, surgery is, however, associated with a greater chance of seizure freedom. The suitability and risk-benefit ratio of surgery should be considered at each step of the pre-surgical pathway.

Seizure outcomes in people with drug-resistant focal epilepsy evaluated for surgery but do not proceed.

OBJECTIVE: To ascertain seizure outcomes in people with drug-resistant focal epilepsy considered for epilepsy surgery but who did not proceed. METHODS: We identified people discussed at a weekly presurgical epilepsy multi-disciplinary (MDT) meeting from January 2015 to December 2019 and in whom a decision not to proceed to surgery was made. Seizure outcomes were obtained from individuals, primary care physicians and attending neurologists at a minimum of 12 months following the not to proceed decision. RESULTS: We considered 315 people who did not proceed to surgery after evaluation. Nine died, and 25 were lost to follow-up. We included 281 people with a median follow-up of 2.4 (IQR 1.5-4) years. In total, 83 (30%) people reported that seizures had improved or resolved since the MDT meeting. Thirteen (5%) were seizure-free over the last 12 months of follow-up, 70 (25%) had experienced more than 50% reduction in seizure frequency, 180 (64%) had no meaningful change, and 18 (6%) reported a doubling of seizure frequency. Of the 53 (16%) who had vagal nerve stimulation, 19/53 (37%) reported more than 50% reduction in frequency, including one seizure-free. SIGNIFICANCE: The chances of seizure freedom with further medications and neurostimulation are low for people with drug-resistant focal epilepsy who have been evaluated for surgery and do not proceed, but improvement may still occur. Up to a quarter have a > 50% reduction in seizures, and one in twenty become seizure-free eventually. Trying additional anti-seizure medication and neurostimulation is worthwhile in this population.

Reasons for not having epilepsy surgery.

OBJECTIVE: This study was undertaken to determine reasons for adults with drug-resistant focal epilepsy who undergo presurgical evaluation not proceeding with surgery, and to identify predictors of this course. METHODS: We retrospectively analyzed data on 617 consecutive individuals evaluated for epilepsy surgery at a tertiary referral center between January 2015 and December 2019. We compared the characteristics of those in whom a decision not to proceed with surgical treatment was made with those who underwent definitive surgery in the same period. Multivariate logistic regression was performed to identify predictors of not proceeding with surgery. RESULTS: A decision not to proceed with surgery was reached in 315 (51%) of 617 individuals evaluated. Common reasons for this were an inability to localize the epileptogenic zone (n = 104) and the presence of multifocal epilepsy (n = 74). An individual choice not to proceed with intracranial electroencephalography (icEEG; n = 50) or surgery (n = 39), risk of significant deficit (n = 33), declining noninvasive investigation (n = 12), and coexisting neurological comorbidity (n = 3) accounted for the remainder. Compared to 166 surgically treated patients, those who did not proceed to surgery were more likely to have a learning disability (odds ratio [OR] = 2.35, 95% confidence interval [CI] = 1.07-5.16), normal magnetic resonance imaging (OR = 4.48, 95% CI = 1.68-11.94), extratemporal epilepsy (OR = 2.93, 95% CI = 1.82-4.71), bilateral seizure onset zones (OR = 3.05, 95% CI = 1.41-6.61) and to live in more deprived socioeconomic areas (median deprivation decile = 40%-50% vs. 50%-60%, p < .05). SIGNIFICANCE: Approximately half of those evaluated for surgical treatment of drug-resistant focal epilepsy do not proceed to surgery. Early consideration and discussion of the likelihood of surgical suitability or need for icEEG may help direct referral for presurgical evaluation.

Progressive cranial neuropathy and uterine involvement in myeloid sarcoma.

A rare extramedullary manifestation of haematological malignancy, myeloid sarcoma is most commonly seen in patients with acute myeloid leukaemia. We report on an adult patient who presented with an atypical phenotype of progressive cranial neuropathy without blood or bone marrow involvement, and in whom obtaining material for pathological diagnosis was made challenging by unusual findings of absent fluorodeoxyglucose-positron emission tomography avidity and involvement of sites not readily accessible to biopsy (orbital apex and cauda equina). The eventual diagnosis was obtained through biopsy of the uterine cervix before being verified on repeat lymph node and cerebrospinal fluid sampling prior to initiation of chemotherapy.

Acute cholestatic hepatitis induced by Epstein-Barr virus infection in an adult: a case report.

BACKGROUND: Acute cholestatic hepatitis without features of infectious mononucleosis is a rare presentation of primary Epstein-Barr infection, with only several cases previously reported in the medical literature. Early investigation for Epstein-Barr virus in febrile patients with deranged liver function tests and no demonstrable biliary obstruction on imaging can expedite both diagnosis and treatment, thereby avoiding costly or invasive procedures such as liver biopsy. CASE PRESENTATION: A 59-year-old white woman of Anglo-Saxon descent presenting with a febrile illness was noted to have a cholestatic picture of deranged liver function tests. Over the following week a progressive obstructive jaundice developed, with no evidence of choledocholithiasis on ultrasound or magnetic resonance cholangiopancreatography. Specific immunoglobulin M antibodies against Epstein-Barr virus were detected in her serum and the diagnosis of Epstein-Barr hepatitis was confirmed by polymerase chain reaction testing. Supportive treatment was implemented and her liver function had normalized 3 months after presentation. CONCLUSIONS: Epstein-Barr virus is associated with a wide variety of clinical manifestations and can present as cholestatic hepatitis with or without features of infectious mononucleosis. While the diagnosis is often suggested by serological testing, Epstein-Barr virus polymerase chain reaction is a new non-invasive laboratory study that can help identify infection in cases where the clinical presentation is atypical.