Hemispherectomy Outcome Prediction Scale: a validity study.

OBJECTIVE: Hemispherectomy is highly effective for patients with medically refractory epilepsy (MRE) arising from a single hemisphere. Recently, the Hemispherectomy Outcome Prediction Scale (HOPS) was developed as a prediction tool for seizure freedom after hemispherectomy. The authors' goal was to perform a validation study to determine the generalizability of the HOPS score. METHODS: The authors present an observational, retrospective, 20-year, single-institution, two-surgeon experience using the lateral peri-insular hemispherectomy approach to validate the HOPS score. Variables used to derive the HOPS score included seizure onset age, semiology, PET hypometabolism, seizure substrate, and history of prior epilepsy resection. Multivariable logistic regression, multiple imputation, and Bayesian analyses were used to determine validity. RESULTS: The authors' cohort comprised 60 patients; 55% of patients were male and 78% were Caucasian. The median age at first hemispherectomy surgery was 72 months. At 1 year postoperatively, 80% of patients had Engel class I outcomes, analogous to most contemporary series. All patients who experienced seizure recurrence after hemispherectomy did so within the first 2 years postoperatively. Sixteen (27%) and 10 (17%) patients had contralateral MRI findings and hypometabolism on PET, respectively. Both a multivariable logistic regression model using HOPS score variables (model p = 0.2588) and a revised model that included contralateral MRI findings (model p = 0.4715) were not statistically significant in this cohort. Bayesian analysis also did not validate the HOPS score. CONCLUSIONS: While seizure outcome prediction tools may be helpful for counseling patients about postoperative outcomes, rigorous validity and reliability testing are required. Prospective, standardized, and longitudinal evaluation of patients undergoing hemispherectomy are needed.

Longitudinal impact of cannabidiol on EEG measures in subjects with treatment-resistant epilepsy.

OBJECTIVE: To assess the longitudinal impact of highly purified cannabidiol (CBD) on the electroencephalogram (EEG) of children and adults. METHODS: Participants received an EEG prior to starting CBD, after approximately 12 weeks of CBD (FU1) and after approximately one year of CBD therapy (FU2). Longitudinal changes in five EEG measures (background frequency, focal slowing, reactivity, frequency of interictal, and ictal discharges) were examined following CBD exposure. Data were compared between pediatric and adult groups at two follow-up time points and within groups over time. Population-averaged models with generalized estimation equations or linear mixed effects models were used to analyze data where appropriate. Correlation analysis was used to assess any association between changes in seizure frequency and changes in EEG interictal discharge (IED) frequency. An alpha level of 5% was used to assess statistical significance. RESULTS: At FU1, the adult group showed significant decrease in IED/minute (IDR 0.07, 95% CI [0.04, 0.14], P < 0.001); a nonsignificant decrease was observed among children (IDR 0.87, 95% CI [0.47, 0.64], P = 0.67). The difference in changes over time between participant groups was significant after adjusting for last CBD dose (IDR 11.8, 95% CI [4.86, 28.65], P < 0.0001). At FU2 both groups showed significant reduction from baseline after controlling for last CBD dose. This decrease was more pronounced in children (IDR 15.38, 95% CI [4.93, 47.99], P < 0.001). There was no significant correlation between changes in seizure frequency and EEG IED frequency at each timepoint (P = 0.542, 0.917 and 0.989 from baseline to FU1, FU1 to FU2 and baseline to FU2, respectively). SIGNIFICANCE: This longitudinal EEG study shows that highly-purified plant-derived CBD has positive effects on interictal epileptiform discharge frequency but no effects on other EEG measures. The effect of CBD does not appear to be dose or treatment-duration dependent.

Relative contribution of individual versus combined functional imaging studies in predicting seizure freedom in pediatric epilepsy surgery: an area under the curve analysis.

OBJECTIVE: The goal of this study was to evaluate the predictive value and relative contribution of noninvasive presurgical functional imaging modalities based on the authors' institutional experience in pursuing seizure-free surgical outcomes in children with medically refractory epilepsy. METHODS: This was a retrospective, single-institution, observational cohort study of pediatric patients who underwent evaluation and surgical treatment for medically refractory partial epilepsy between December 2003 and June 2016. During this interval, 108 children with medically refractory partial epilepsy underwent evaluation for localization and resective epilepsy surgery. Different noninvasive functional imaging modalities, including ictal SPECT, FDG-PET, and magnetoencephalography-magnetic source imaging, were utilized to augment a standardized paradigm (electroencephalography/semiology, MRI, and neuropsychology findings) for localization. Outcomes were evaluated at a minimum of 2 years (mean 7.5 years) utilizing area under the receiver operating characteristic curve analysis. Localizing modalities and other clinical covariates were examined in relation to long-term surgical outcomes. RESULTS: There was variation in the contribution of each test, and no single presurgical workup modality could singularly and reliably predict a seizure-free outcome. However, concordance of presurgical modalities yielded a high predictive value. No difference in long-term outcomes between inconclusive (normal or diffusely abnormal) and abnormal focal MRI results were found. Long-term survival analyses revealed a statistically significant association between seizure freedom and patients with focal ictal EEG, early surgical intervention, and no history of generalized convulsions. CONCLUSIONS: Comprehensive preoperative evaluation utilizing multiple noninvasive functional imaging modalities is not redundant and can improve pediatric epilepsy surgical outcomes.

Surgical treatment of epilepsy in Vietnam: program development and international collaboration.

OBJECTIVE: The purpose of this report was to describe an international collaboration model to facilitate the surgical treatment of children with epilepsy in Vietnam. METHODS: This model uses three complementary methods to achieve a meaningful expansion in epilepsy surgery capacity: US-based providers visiting Hanoi, Vietnam; Vietnamese providers visiting the US; and ongoing telecollaboration, including case review and real-time mentorship using internet-based communication platforms. RESULTS: Introductions took place during a US neurosurgeon's visit to Vietnam in 2014. Given the Vietnamese surgeon's expertise in intraventricular tumor surgery, the focus of the initial visit was corpus callosotomy. After two operations performed jointly, the Vietnamese surgeon went on to perform 10 more callosotomy procedures in the ensuing 6 months with excellent results. The collaborative work grew and matured in 2016-2017, with 40 pediatric epilepsy surgeries performed from 2015 through 2017. Because pediatric epilepsy care requires far more than neurosurgery, teams traveling to Vietnam included a pediatric neurologist and an electroencephalography (EEG) technologist. Also, in 2016-2017, a neurosurgeon, two neurologists, and an EEG nurse from Vietnam completed 2- to 3-month fellowships at Children's of Alabama (COA) in the US. These experiences improved EEG capabilities and facilitated the development of intraoperative electrocorticography (ECoG), making nonlesional epilepsy treatment more feasible. The final component has been ongoing, i.e., regular communication. The Vietnamese team regularly sends case summaries for discussion to the COA epilepsy conference. Three patients in Vietnam have undergone resection guided by ECoG without the US team present, although there was communication via internet-based telecollaboration tools between Vietnamese and US EEG technologists. To date, two of these three patients remain seizure free. The Vietnamese team has presented the results of their epilepsy experience at two international functional and epilepsy surgery scientific meetings. CONCLUSIONS: Ongoing international collaboration has improved the surgical care of epilepsy in Vietnam. Experience suggests that the combination of in-country and US-based training, augmented by long-distance telecollaboration, is an effective paradigm for increasing the capacity for highly subspecialized, multidisciplinary neurosurgical care.

Cannabidiol improves frequency and severity of seizures and reduces adverse events in an open-label add-on prospective study.

The objective of this study was to characterize the changes in adverse events, seizure severity, and frequency in response to a pharmaceutical formulation of highly purified cannabidiol (CBD; Epidiolex®) in a large, prospective, single-center, open-label study. We initiated CBD in 72 children and 60 adults with treatment-resistant epilepsy (TRE) at 5 mg/kg/day and titrated it up to a maximum dosage of 50 mg/kg/day. At each visit, we monitored treatment adverse events with the adverse events profile (AEP), seizure severity using the Chalfont Seizure Severity Scale (CSSS), and seizure frequency (SF) using seizure calendars. We analyzed data for the enrollment and visits at 12, 24, and 48 weeks. We recorded AEP, CSSS, and SF at each follow-up visit for the weeks preceding the visit (seizures were averaged over 2-week periods). Of the 139 study participants in this ongoing study, at the time of analysis, 132 had 12-week, 88 had 24-week, and 61 had 48-week data. Study retention was 77% at one year. There were no significant differences between participants who contributed all 4 data points and those who contributed 2 or 3 data points in baseline demographic and AEP/SF/CSSS measures. For all participants, AEP decreased between CBD initiation and the 12-week visit (40.8 vs. 33.2; p < 0.0001) with stable AEP scores thereafter (all p ≥ 0.14). Chalfont Seizure Severity Scale scores were 80.7 at baseline, decreasing to 39.2 at 12 weeks (p < 0.0001) and stable CSSS thereafter (all p ≥ 0.19). Bi-weekly SF decreased from a mean of 144.4 at entry to 52.2 at 12 weeks (p = 0.01) and remained stable thereafter (all p ≥ 0.65). Analyses of the pediatric and adult subgroups revealed similar patterns. Most patients were treated with dosages of CBD between 20 and 30 mg/kg/day. For the first time, this prospective, open-label safety study of CBD in TRE provides evidence for significant improvements in AEP, CSSS, and SF at 12 weeks that are sustained over the 48-week duration of treatment.

Effect of EEG electrode number on epileptic source localization in pediatric patients.

OBJECTIVE: To investigate the relationship between EEG source localization and the number of scalp EEG recording channels. METHODS: 128 EEG channel recordings of 5 pediatric patients with medically intractable partial epilepsy were used to perform source localization of interictal spikes. The results were compared with surgical resection and intracranial recordings. Various electrode configurations were tested and a series of computer simulations based on a realistic head boundary element model were also performed in order to further validate the clinical findings. RESULTS: The improvement seen in source localization substantially decreases as the number of electrodes increases. This finding was evaluated using the surgical resection, intracranial recordings and computer simulation. It was also shown in the simulation that increasing the electrode numbers could remedy the localization error of deep sources. A plateauing effect was seen in deep and superficial sources with further increasing the electrode number. CONCLUSION: The source localization is improved when electrode numbers increase, but the absolute improvement in accuracy decreases with increasing electrode number. SIGNIFICANCE: Increasing the electrode number helps decrease localization error and thus can more ably assist the physician to better plan for surgical procedures.

Magnetic source imaging (MSI) in children with neocortical epilepsy: surgical outcome association with 3D post-resection analysis.

OBJECTIVE: To investigate the validity of magnetic source imaging (MSI) to localize seizure-onset zone using 3D analysis of pre-operative MSI source imaging coregistered to post-resection MRI following neocortical epilepsy surgery. METHODS: Twenty-two children who had MSI and epilepsy surgery were studied (median age=11 years, 1 year 2 months-22 years). Only seven (31.8%) had localized lesions on pre-operative conventional brain MRIs. Sixteen (72.7%) underwent intracranial EEG monitoring. Mean post-operative follow-up was 4.7 years (1 year 3 months-8 years 2 months). Fifteen patients (68%) were seizure-free. MEG spike dipole sources were superimposed onto post-operative MRIs. The number and proportion of spike dipoles within resection volume were calculated and compared between seizure free and non-free groups. RESULTS: Both number of dipole clusters and proportion of dipoles in resection volume were not associated with seizure-free outcome (p>0.05). In seven cases with MRI lesions, six of these with a ≥70% dipoles within the resection margin were seizure-free, while one with the proportion <70% was not seizure-free. Further, among the 15 cases with non-localized or normal MRI, five with both the proportion <70% and multiple dipoles clusters were post-operatively seizure free. CONCLUSION: Number and density of clustered spike dipole sources within the surgical resection volume is not associated with postoperative seizure-free outcome. MSI successfully localized the perilesional epileptogenic zone in cases with localized MRI lesions, but not in cases with normal MRI in this study. Even if MEG localizes spikes to a single focal region, confirmation of epilepsy localization with intracranial EEG is still recommended in cases with non-lesional MRI.

Chronic granulomatous herpes encephalitis in a child with clinically intractable epilepsy.

Most patients with herpes simplex virus Type I encephalitis experience an acute, monophasic illness. Chronic encephalitis is much less common, and few late relapses are associated with intractable seizure disorders. A 10-year-old boy was admitted to our institution for intractable epilepsy as part of an evaluation for epilepsy surgery. His history was significant for herpes meningitis at age 4 months. At that time, he presented to an outside hospital with fever for three days, with acyclovir treatment beginning on day 4 of his 40-day hospital course. He later developed infantile spasms and ultimately a mixed seizure disorder. Video electroencephalogram showed a Lennox-Gastaut-type pattern with frequent right frontotemporal spikes. Imaging studies showed an abnormality in the right frontal operculum. Based on these findings, he underwent a right frontal lobectomy. Neuropathology demonstrated chronic granulomatous inflammation with focal necrosis and mineralizations. Scattered lymphocytes, microglial nodules and nonnecrotizing granulomas were present with multinucleated giant cells. Immunohistochemistry for herpes simplex virus showed focal immunoreactivity. After undergoing acyclovir therapy, he returned to baseline with decreased seizure frequency. This rare form of herpes encephalitis has only been reported in children, but the initial presentation of meningitis and the approximate 10-year-time interval in this case are unusual.

Effect of epilepsy magnetic source imaging on intracranial electrode placement.

OBJECTIVE: Intracranial electroencephalography (ICEEG) with chronically implanted electrodes is a costly invasive diagnostic procedure that remains necessary for a large proportion of patients who undergo evaluation for epilepsy surgery. This study was designed to evaluate whether magnetic source imaging (MSI), a noninvasive test based on magnetoencephalography source localization, can supplement ICEEG by affecting electrode placement to improve sampling of the seizure onset zone(s). METHODS: Of 298 consecutive epilepsy surgery candidates (between 2001 and 2006), 160 patients were prospectively enrolled by insufficient localization from seizure monitoring and magnetic resonance imaging results. Before presenting MSI results, decisions were made whether to proceed with ICEEG, and if so, where to place electrodes such that the hypothetical seizure-onset zone would be sampled. MSI results were then provided with allowance of changes to the original plan. RESULTS: MSI indicated additional electrode coverage in 18 of 77 (23%) ICEEG cases. In 39% (95% confidence interval, 16.4-61.4), seizure-onset ICEEG patterns involved the additional electrodes indicated by MSI. Sixty-two patients underwent surgical resection based on ICEEG recording of seizures. Highly localized MSI was significantly associated with seizure-free outcome (mean, 3.4 years; minimum, >1 year) for the entire surgical population (n = 62). INTERPRETATION: MSI spike localization increases the chance that the seizure-onset zone is sampled when patients undergo ICEEG for presurgical epilepsy evaluations. The clinical impact of this effect, improving diagnostic yield of ICEEG, should be considered in surgery candidates who do not have satisfactory indication of epilepsy localization from seizure semiology, electroencephalogram, and magnetic resonance imaging.

Advances in intracranial monitoring.

Intracranial monitoring using electroencephalography (IC-EEG) continues to play a critical role in the assessment of patients with medically intractable localization-related epilepsy. There has been minimal change in grid or electrode design in the last 15-20 years, and the surgical approaches for implantation are unchanged. Intracranial monitoring using EEG allows detailed definition of the region of ictal onset and defines the epileptogenic zone, particularly with regard to adjacent potentially eloquent tissue. Recent developments of IC-EEG include the coregistration of functional imaging data such as magnetoencephalography to the frameless navigation systems. Despite significant inherent limitations that are often overlooked, IC-EEG remains the gold standard for localization of the epileptogenic cortex. Intracranial electrodes take a variety of different forms and may be placed either in the subdural (subdural strips and grids, depth electrodes) or extradural spaces (sphenoidal, peg, and epidural electrodes). Each form has its own advantages and shortcomings but extensive subdural implantation of electrodes is most common and is most comprehensively discussed. The indications for intracranial electrodes are reviewed.

Functional imaging: II. Prediction of epilepsy surgery outcome.

OBJECTIVE: To gain information on the value of magnetic source imaging (MSI), 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET), and ictal single photon emission computed tomography (SPECT) to predict seizure-free outcome following epilepsy surgery in patients who require intracranial electroencephalography (ICEEG). METHODS: This work was part of a prospective observation study of epilepsy surgery candidates not sufficiently localized with scalp EEG and MRI. Of 160 patients enrolled 62 completed ICEEG and subsequent surgical resection. Sixty-one percent resulted in an Engel I seizure-free outcome at a minimum of one-year follow-up (mean = 3.4 years). Sensitivity, specificity, and predictive values were computed for each modality. Multivariate logistical regression was used to identify prediction of surgical outcome by imaging test. RESULTS: MSI sensitivity for a conclusively localized study was 55% with a positive predictive value of 78%. Eliminating non-diagnostic MSI cases (no spikes captured during recording) yielded a corrected negative predictive value of 64%. With available comparison subgroups FDG-PET and ictal SPECT values were similar to MSI. The OR (adjusted for epilepsy and MRI classification) for MSI prediction of seizure-free outcome was 4.4 (p =0.01). In cases with both PET and MSI, the adjusted OR for PET was 7.1 (p <0.01) and for MSI was 6.4 (p = 0.01). In the cases with all three tests (n = 27), ictal SPECT had the highest OR of 9.1 (p = 0.05). INTERPRETATION: MSI, FDG-PET, and ictal SPECT each have clinical value in predicting seizure-free surgical outcome in epilepsy surgery candidates who typically require ICEEG.

Functional imaging: I. Relative predictive value of intracranial electroencephalography.

OBJECTIVE: To gain information on the predictive and prognostic value of magnetic source imaging (MSI), 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography ((18)FDG-PET), and ictal single-photon emission computed tomography (SPECT) as compared with intracranial electroencephalography (ICEEG) localization in epilepsy surgery. METHODS: This work was part of a cohort study of epilepsy surgery candidates not sufficiently localized with noninvasive studies. Of 160 patients enrolled over 4 years, 77 completed ICEEG seizure monitoring. Sensitivity, specificity, and predictive values relative to ICEEG were computed for each modality. RESULTS: Seizures were not captured in five patients. Of the 72 diagnostic ICEEG studies, seizure localization results were 74% localized, 10% multifocal, and 17% nonlocalized. Sixty-one percent were localized to neocortical regions. Depending on patient subgroup pairs, sensitivity ranged from 58 to 64% (MSI), 22 to 40% (PET), and 39 to 48% (SPECT); specificity ranges were 79 to 88% (MSI), 53 to 63% (PET), and 44 to 50% (SPECT). Gains in diagnostic yield were seen only with the combination of MSI and PET or MSI and ictal SPECT. Localization concordance with ICEEG was greatest with MSI, but a significant difference was demonstrated only between MSI and PET. Moderate redundancy was seen between PET and ictal SPECT (kappa = 0.452; p = 0.011). INTERPRETATION: Conclusively positive MSI has a high predictive value for seizures localized with ICEEG. Diagnostic gain may be achieved with addition of either PET or ictal SPECT to MSI. Diagnostic values for imaging tests are lower than "true values" because of the limitations of ICEEG as a gold standard.

Vagus nerve stimulation in children less than 5 years old.

INTRODUCTION: Vagus nerve stimulation (VNS) has been used in both adults and older children with varying success. MATERIALS AND METHODS: We retrospectively reviewed our experience with VNS in very young children (below 5 years old). The mean age at stimulator implantation was 20.5 months. Two patients were below 2 years old at implantation and two patients were below 1 year old at their initial surgery. The average follow up time for this group was 22 months. RESULTS: Of the six patients (three males and three females) with long-term follow up, 83% had a significant decrease in the frequency of their seizure. Of these, two are seizure-free (33%), three are improved (50%), and one (17%) has had no change in seizure status at their most recent clinical examination. Age at implantation of the vagus nerve stimulator did not seem to correlate with patient success. In this group, atonic seizures were found to best respond to VNS with cessation of this type of seizure in two patients. No patients were made worse by the procedure and no morbidity was observed related to VNS. CONCLUSIONS: Based on our small patient cohort, it appears that VNS in very young children with life-threatening epilepsy can be efficacious. Larger groups and other institutional experiences are now needed to verify our findings.

Magnetic source imaging versus intracranial electroencephalogram in epilepsy surgery: a prospective study.

OBJECTIVE: Noninvasive brain imaging tests can potentially supplement or even replace the use of intracranial electroencephalogram (ICEEG), an invasive, costly procedure used in presurgical epilepsy evaluation. This study prospectively examined the agreement between magnetic source imaging (MSI) and ICEEG localization in epilepsy surgery candidates. METHODS: Patients completing video monitoring with scalp EEG who had intractable partial epilepsy based on ictal electro-clinico-anatomical features were screened. Forty-nine enrolled patients (mean age, 27 years; range, 1-61 years) completed MSI and ICEEG studies. Decisions about ICEEG and surgery were made at a consensus conference where MSI could only influence ICEEG coverage by indicating supplemental coverage to that already planned by an original hypothesis. RESULTS: The positive predictive value of MSI for seizure localization was 82 to 90%, depending on whether computed against ICEEG alone or in combination with surgical outcome. The kappa score of agreement for MSI with ICEEG was 0.2744 (p < 0.01) INTERPRETATION: MSI yields localizing information with a high positive predictive value in epilepsy surgery candidates who typically require ICEEG. This finding suggests that enough clinical validity exists for MSI to potentially replace ICEEG for seizure localization.

Chorea as manifestation of epilepsia partialis continua in a child.

The authors present a case of a child with epilepsy who developed choreoathetotic movements coinciding with the development of epilepsia partialis continua. His abnormal movements and seizures resolved after successful management of his epilepsia partialis continua with intravenous immunoglobulin and steroid therapy. The authors propose that the chorea was an unusual manifestation of epilepsia partialis continua.

High plasma branched-chain amino acids:aromatic amino acids ratio in children on the ketogenic diet: a mechanism in controlling epilepsy.

BACKGROUND: The authors proposed that ketogenic diets will produce an increase in the ratio of branched chain amino acids (BCAAs) and aromatic amino acids (BCAAs) in plasma of children who are on the diets. SUBJECTS AND METHOD: A sample of plasma amino acids sample before initiation of fasting and on day 10 of the dietary treatment was obtained in patients with refractory epilepsy who were newly admitted for initiation of ketogenic diet. Plasma amino acids were determined by high performance liquid chromatography equipment. RESULTS: There are 20 patients with refractory epilepsy participating in this study. Outcomes of ketogenic diet therapy were satisfactory. Nineteen cases out of 20 cases had a significantly higher ratio of plasma BCAAs:ARAAs during ketogenic diets than before the diet (P < 0.001). CONCLUSION: The ketogenic diets produced an increased ratio of plasma BCAAs:ARAAs. Whether the increased ratio of plasma BCAAs:ARAAs plays an important role in controlling epilepsy is yet to be elucidated.

Vigabatrin therapy in infantile spasms.

RATIONALE: To determine the clinical outcome and side effects of vigabatrin (VGB) in the treatment of infantile spasms (IS) and its long-term outcome. METHOD: All children with IS treated with vigabatrin were studied. Clinical data regarding age of onset, duration of IS before therapy started, recurrence of IS, types of seizures that relapse, clinical outcome and side effects were monitored. RESULTS: 36 children (17 girls, 19 boys) with IS participated in the study. The mean age of onset of IS was 115.55 +/- 67.3 days old (range, 15 to 300 days). Six were cryptogenic IS and 30 were symptomatic IS. The etiologies of symptomatic IS in this study were tuberous sclerosis, hypoxic ischemic encephalopathy (HIE)/periventricular leukomalacia, porencephaly, partial agenesis of corpus callosum, hemimegalencephaly, cortical dysplasia, and microcephaly. 66.67 per cent (24 of 36) of patients responded to VGB within a mean 2.95 +/- 2.25 days (range, 1 to 7 days). In those who responded to VGB, 3 patients developed recurrent IS within 69.3 +/- 46.7 days (range, 30 to 121 days). Five patients developed epilepsy with different types of seizure during long-term follow-up. The mean duration of subsequent epilepsy after cessation of IS was 16.4 months (range, 5 months to 3 years 10 months). The mean duration of follow-up was 2.74 years (range, 1.09 years to 5.76 years). 10 patients were successfully weaned off VGB after a mean IS free period of 22.5 +/- 5.5 months (range, 12 to 27 months). Transient drowsiness was seen in 4 patients. Three patients had transient abnormal sleep patterns and irritability. Visual field abnormalities were not found but difficult to assess fully in this study. CONCLUSION: VGB therapy has a high response rate for the control of IS and is well tolerated in most children. All patients who responded to VGB and were spasm free for more than one year were successfully weaned off VGB therapy. Because serious side effects such as visual field abnormalities are difficult to monitor, the authors propose that VGB could be withdrawn or switched to another AED after a spasm-free period of more than one year.

Childhood onset myasthenia gravis.

The authors share experiences in taking care of 27 cases of childhood onset myasthenia gravis (MGS). In all cases, the diagnosis was confirmed by a combination of clinical examination and Neostigmine test. The majority (92%) had localized ocular myasthenia with median onset of symptoms at 33 months of age. About 24 per cent of them progressed to generalized MGS. A few (8%) presented with respiratory failure that required ventilatory support with onset of symptoms at about 22 months. Thymectomy was performed in 10 cases. Complete and partial remissions were achieved in about 70 per cent and 26 per cent of cases respectively with the combination of an immunosuppressant (azathioprine) and a Cholinesterase inhibitor (pyridostigmine). None experienced a myasthenic crisis with proper management and good follow-up using the above combinations.