Diagnostic Yield of Routine EEG in Adults with Active Epilepsy

Routine electroencephalogram (rEEG) is an important investigation in suspected seizures but can be normal in people with epilepsy. The diagnostic yield of rEEG varies considerably according to the patient group studied. We aimed to estimate the diagnostic yield of rEEG in a real-world cohort of adults with active epilepsy­a population not previously reported. This single centre study evaluated neurophysiology findings for adults with prolonged inpatient video EEG (vEEG)-confirmed active epilepsy, who had at least one prior rEEG. Sixty-eight patients had a total of 171 rEEGs, of which 93 (54.4%) were normal, 42 (24.6%) found non-specific abnormalities and 36 (21.1%) captured interictal epileptiform abnormalities (IIEAs). Serial rEEGs revealed a 22.1% yield of IIEAs on the first test, with the cumulative yield peaking at 33.8% on the fourth rEEG. This study adds to existing evidence regarding the limited diagnostic usefulness of serial rEEG in patients with active epilepsy.

Investment in epilepsy monitoring units improves epilepsy care-experience in a regional neuroscience centre.

An evaluation of the clinical yield of inpatient long-term video-EEG (vEEG) in a new epilepsy monitoring unit (EMU) was undertaken, with findings compared to the centre's prior method of bedside vEEG recording in a standard neurology ward, as reported in 2004. A retrospective analysis of neurophysiology reports for all adults who underwent elective vEEG monitoring in the EMU at Cork University Hospital between January 2015 and July 2016 was conducted. Of 115 vEEG studies in the EMU, 100 (87.0%) were deemed diagnostically conclusive, 14 (12.2%) failed to catch any clinical events and showed normal EEG throughout, and one (0.9%) captured spells of unclear clinical significance - the corresponding figures reported in 2004 for bedside vEEGs were 21.3%, 77% and 1.6%, respectively. The EMU offers a more effective method of recording inpatient vEEG, which aids decision-making and improves clinical outcomes. Some evidence-based measures which could further enhance diagnostic yield are discussed.

No major role of common SV2A variation for predisposition or levetiracetam response in epilepsy.

Levetiracetam (LEV), a newer antiepileptic drug (AED) useful for several epilepsy syndromes, binds to SV2A. Identifying genetic variants that influence response to LEV may allow more tailored use of LEV. Obvious candidate genes are SV2A, SV2B and SV2C, which encode the only known binding site, synaptic vesicle protein 2 (SV2), with LEV binding to the SV2A isoform. SV2A is an essential protein as homozygous SV2A knockout mice appear normal at birth but fail to grow, experience severe seizures and die by 3 weeks. We addressed characterising AED response issues in pharmacogenetics and whether variation in these genes associates with response to LEV in two independent cohorts with epilepsy. We also investigated whether variation in these three genes associated with epilepsy predisposition in two larger cohorts of patients with various epilepsy phenotypes. Common genetic variation in SV2A, encoding the actual binding site of LEV, was fully represented in this study whereas SV2B and SV2C were not fully covered. None of the polymorphisms tested in SV2A, SV2B or SV2C influence LEV response or predisposition to epilepsy. We found no association between genetic variation in SV2A, SV2B or SV2C and response to LEV or epilepsy predisposition. We suggest this study design may be used in future pharmacogenetic work examining AED or LEV efficacy. However, different study designs would be needed to examine common variation with minor effect sizes, or rare variation, influencing AED or LEV response or epilepsy predisposition.

Predicting drug-resistant patients who respond to add-on therapy with levetiracetam.

INTRODUCTION: Levetiracetam (LEV) is approved for use as add-on therapy in adult patients with partial epilepsy. It is apparent from clinical trials that up to 8% of previously drug-resistant patients may be rendered seizure-free by adding-on levetiracetam. As yet there is no way of predicting these unexpectedly responsive patients. We set out to identify our previously refractory patients who had demonstrated unexpected responsiveness to add-on therapy with levetiracetam, and compared these to patients who had not responded to the drug. We then attempted to characterise any clinical features that differentiated these groups of patients. METHODS: We included all patients with a history of present or previous exposure to levetiracetam who had been unresponsive to at least two other prior anti-epileptic drugs (AEDs) and recorded their demographic and clinical data. We divided response into (a) 'seizure-free' (seizure-free for a minimum of 6 months after commencing LEV); (b) 'partial > 50%' (greater than 50% reduction in seizures for a minimum of 6 months after commencing LEV); (c) 'honeymoon' (seizure-free for less than 6 months after commencing LEV and then returned towards baseline frequency); and (d) 'no-response'. For the purpose of analysis we considered the 'seizure-free' and 'partial > 50%' groups as 'responders', and the 'no response' group as 'non responders'. RESULTS: 344 patients were included in the analysis. Fifty-six patients (16.3%) were rendered seizure-free on levetiracetam. Idiopathic generalised epilepsy and post-traumatic partial epilepsy were more common in the responder than the non-responder group (p = 0.005 and 0.05 respectively). Lamotrigine was used significantly more often in combination with levetiracetam in responders than non-responders (p = 0.003). The mean daily dose of levetiracetam was lower in responders than non-responders. DISCUSSION: A higher than expected number of previously drug resistant patients was rendered seizure-free by add-on therapy with levetiracetam. Those who respond best appear to do so at relatively low doses and our data suggest the possibility of a beneficial pharmacodynamic interaction between levetiracetam and lamotrigine. We were unable to identify any clinical factors that clearly predicted which patients would become seizure-free and we hypothesise that response may be determined by genetic or molecular factors. All drug-resistant patients, including those being assessed for surgery, should be considered for a trial of levetiracetam, regardless of their epilepsy classification.

Lymphocytic meningitis: incidence, causes and outcomes over five years.

Over a five-year period 114 cases of lymphocytic meningitis were admitted to a general hospital. Case notes were reviewed to determine incidence, causes and outcomes and to identify what clinical features, cerebrospinal fluid (CSF) parameters or other tests were useful in elucidating a cause. Of 114 patients with lymphocytic meningitis 44 had viral meningitis, six viral encephalitis, and seven had other infective meningo-encephalitis. Seven patients had carcinomatous meningitis, nine had an autoimmune/inflammatory process, thirteen had a demyelinating central nervous system (CNS) disorder, and two had an inflammatory neuropathy. In 26 patients no diagnosis was reached. Six of these showed clear steroid responsiveness. Overall lymphocytic meningitis had a good prognosis. Clinical and CSF characteristics were important in diagnosis and prognosis. Recommendations on management of these cases are presented.