Potential efficacy of zonisamide in refractory juvenile myoclonic epilepsy: retrospective evidence from an Irish compassionate-use case series.

To retrospectively evaluate the efficacy of zonisamide as adjunctive therapy in the treatment of refractory juvenile myoclonic epilepsy. We retrospectively reviewed the records of seven patients with refractory juvenile myoclonic epilepsy, commenced on a compassionate-use basis on zonisamide as adjunctive treatment between October 2001 and September 2004. We found significant response rates (>50% reduction in seizure frequency) of 83.3%, 100% and 100% for generalised convulsions, myoclonus, and absence seizures respectively. These results were sustained over more prolonged follow-up in five of seven patients, with one patient improving further over time. Two patients became seizure free with the introduction of zonisamide. Two patients were able to reduce the number of anti-epileptic medications and maintain >75% and 100% reduction in seizure frequency respectively. Four patients initially had minor side-effects that resolved during the maintenance period. In this retrospective study, zonisamide was effective and well-tolerated as adjunctive therapy in patients with refractory juvenile myoclonic epilepsy

Germline mosaicism in a family with MBD5 haploinsufficiency

Haploinsufficiency of the methyl-CpG-binding domain protein 5 (MBD5) gene causes a neurodevelopmental disorder that includes intellectual disability, developmental delay, speech impairment, seizures, sleep disturbances, and behavioral difficulties. Microdeletion of 2q23.1 is the most common cause of haploinsufficiency, although MBD5 haploinsufficiency may also cause this genetic disorder. We report a family harboring a heterozygous loss-of-function variant in MBD5 (NM_018328.5:c.728delC; p.Pro243Hisfs*26), which includes three affected siblings with varying phenotypic features. Both parents were phenotypically normal but deep coverage sequencing of the parents showed germline mosaicism in the mother. </p

LoVE in a time of CoVID: Clinician and patient experience using telemedicine for chronic epilepsy management.

As part of our ongoing interest in patient- and family-centered care in epilepsy, we began, before the onset of the CoVID-19 pandemic, to evaluate the concerns and preferences of those delivering and receiving care via telemedicine. CoVID-19 arrived and acted as an unexpected experiment in nature, catalyzing telemedicine's widespread implementation across many disciplines of medicine. The arrival of CoVID-19 in Ireland gave us the opportunity to record these perceptions pre- and post-CoVID. Data were extracted from the National Epilepsy Electronic Patient Record (EEPR). Power BI Analytics collated data from two epilepsy centers in Dublin. Analysis of data on reasons for using the telephone support line was conducted. A subset of patients and clinicians who attended virtual encounters over both periods were asked for their perception of telemedicine care through a mixed methods survey. Between 23rd December 2019 and 23rd March 2020 (pre-CoVID era), a total of 1180 patients were seen in 1653 clinical encounters. As part of a telemedicine pilot study, 50 of these encounters were scheduled virtual telephone appointments. Twenty eight surveys were completed by clinicians and 18 by patients during that period. From 24th March 2020 to 24th June 2020, 1164 patients were seen in 1693 encounters of which 729 (63%) patients were seen in 748 scheduled virtual encounters. 118 clinician impressions were captured through an online survey and 75 patients or carers completed a telephone survey during the post-CoVID era. There was no backlog of appointments or loss of care continuity forced by the pandemic. Clinicians expressed strong levels of satisfaction, but some doubted the suitability of new patients to the service or candidates for surgery receiving care via telemedicine. Patients reported positive experiences surrounding telephone appointments comparing them favorably to face-to-face encounters. The availability of a shared EEPR demonstrated no loss of care contact for patients with epilepsy. The survey showed that telemedicine is seen as an effective and satisfactory method of delivering chronic outpatient care

Development of a genomics module within an epilepsy-specific electronic health record: Toward genomic medicine in epilepsy care

Objectives: Both clinical genomics and e-Health technology are changing the way medicine is being practiced. Although the basic clinical methodology of good medical care will remain unchanged, the combined power of genomics and electronic health records has the capability of enhancing, and in some cases transforming, the practice of medicine. This is particularly true in the care of patients with complex long-term medical conditions such as chronic refractory epilepsy, especially in those with related complex comorbidities including intellectual disability and psychiatric disease.Methods: Herein we outline the development and integration of an epilepsy genomics module into a preexisting epilepsy electronic patient record (EPR) system.Results: We describe how this EPR infrastructure is used to facilitate discussion at multidisciplinary clinical meetings around molecular diagnosis and resulting changes in management.Significance: This work illustrates the role of eHealth technology in embedding genomics into the clinical pathway.</div

A comparison of genomic diagnostics in adults and children with epilepsy and comorbid intellectual disability

Next generation sequencing provides an important opportunity for improved diagnosis in epilepsy. To date, the majority of diagnostic genetic testing is conducted in the paediatric arena, while the utility of such testing is less well understood in adults with epilepsy. We conducted whole exome sequencing (WES) and copy number variant analyses in an Irish cohort of 101 people with epilepsy and co-morbid intellectual disability to compare the diagnostic yield of genomic testing between adult and paediatric patients. Variant interpretation American College of Medical Genetics and Genomics (ACMG) guidelines. We demonstrate that WES, in combination with array-comparative genomic hybridisation, provides a diagnostic rate of 27% in unrelated adult epilepsy patients and 42% in unrelated paediatric patients. We observe a 2.7% rate of ACMG-defined incidental findings. Our findings indicate that WES has similar utility in both adult and paediatric cohorts and is appropriate for diagnostic testing in both epilepsy patient groups