Risks and management of antiepileptic drug induced skin reactions in the adult out-patient setting.

Adverse cutaneous reactions caused by mostly aromatic antiepileptic drugs (AED) affect 50.000 people a year in the United Kingdom (UK; incidence 75.7/100.000). Optimal management of these cases is often difficult, as the patient may report symptoms to a general practitioner, attend Accident & Emergency or inform a specialist over the telephone or via email. When clinical assessment is limited it is thought safest to withdraw offending medication and inform the patient of a new drug allergy. This may unjustifiably restrict future treatment choices, and increase cost. Most frequent offenders are aromatic AEDs: carbamazepine, oxcarbazepine, eslicarbazepine, phenytoin, lamotrigine, phenobarbitone, primidone (recently licensed lacosamide associated with lower risk) and the sulpha-derivative zonisamide. Our study provides a summary of severe delayed allergic reactions and offers a pragmatic management pathway for patients suffering a suspected drug-induced rash. We include UK pretreatment screening guidelines, step by step clinical assessment of rash and associated symptoms aiding early identification of patients at risk of developing severe allergic reactions. At the same time our manuscript reviews published data informing best choice and titration of alternative medication when allergy confirmed. Finally we summarize current knowledge on genetic predisposition and other personalized risks of AED allergies identifying gaps in our current understanding.

Brivaracetam in adults with drug-resistant epilepsy and psychiatric comorbidities.

This is a case series of 25 patients with drug-resistant epilepsy and psychiatric comorbidities who started on brivaracetam (BRV) at St George's University Hospitals and Frimley Health in London. Median BRV dose was 150 mg for a median follow-up period of 8 months. Twenty had focal epilepsy, four had generalized epilepsies, and one had unclassified epilepsy; 76% had mood disorders (either depression or bipolar disorder), 12% intellectual disabilities with autism spectrum disorder and challenging behavior, and 12% psychoses. Forty percent of patients presented at least 50% seizure reduction, but none of them became seizure-free. A total of 44% of patients discontinued BRV, 20% because of adverse events, 20% because of inefficacy, and 4% because of both. Depression was reported by 8%, aggressive behavior by 8%, while 4% reported both. A total of 91.6% had received levetiracetam (LEV) before, in whom LEV was discontinued because of psychiatric adverse events (PAEs) in half. Seventy-seven percent of patients who developed PAEs with LEV did not do so on BRV suggesting that BRV is better tolerated than LEV in complex patients with psychiatric comorbidities and that the synaptic vesicle glycoprotein 2A (SV2A) protein modulation is unlikely to be implicated in LEV-related PAEs.

Cognitive improvement following repair of a basal encephalocele.

We report the case of a 55-year-old woman presenting with progressive memory impairment secondary to a transsphenoidal encephalocele involving her dominant medial temporal lobe. Her clinical deterioration was accompanied by radiological progression in the encephalocele's size and associated encephalomalacia. Through a temporal craniotomy, her encephalocele was resected and the defect closed. Baseline neuropsychological assessment indicated global cognitive impairment, but post-operatively, she reported improved memory and concentration. Standardized assessment reflected an improvement in perceptual skills and an associated improved recall of a complex figure. This is the first case report to date of a patient's memory improving following treatment of a basal encephalocele.

Fatigue during treatment with antiepileptic drugs: A levetiracetam-specific adverse event?

PURPOSE: To examine the prevalence and clinical correlates of fatigue as an adverse event (AE) of antiepileptic drug (AED) treatment in patients with epilepsy. METHODS: Data from 443 adult outpatients with epilepsy assessed with the Adverse Event Profile (AEP) and the Neurological Disorder Depression Inventory for Epilepsy (NDDIE) were analysed. RESULTS: Fatigue is reported by 36.6% of patients as always a problem during AED treatment. Fatigue is more likely to be reported by females (64.8% vs. 35.2%; Chi-Square=16.762; df=3; p=0.001) and during treatment with levetiracetam (42.3% vs. 33.2%; Chi-Square=11.462; df=3; p=0.009). The associations with the female gender and levetiracetam treatment were not mediated by depression, as identified with the NDDIE, and could not be simply explained by the large number of subjects on levetiracetam treatment, as analogous figures resulted from the analysis of a monotherapy subsample (41.7% vs. 30.3%; Chi-Square=11.547; df=3; p=0.009). CONCLUSIONS: One third of patients with epilepsy reports fatigue as a significant problem during AED treatment. Fatigue is more likely to be reported by females and seems to be specifically associated with LEV treatment. However, fatigue is not mediated by a negative effect of LEV on mood.

Different attachment styles correlate with mood disorders in adults with epilepsy or migraine.

PURPOSE: Interpersonal relationships are viewed as important contexts within which psychopathology emerges and persists or desists. Attachment theory describes the dynamics of long-term relationships between humans especially in families and lifelong friendships. The present study was aimed at investigating attachment styles in adult patients with epilepsy as compared to subjects with migraine and their potential correlates with a history of mood disorders. METHODS: A consecutive sample of 219 adult outpatients with epilepsy (117) or migraine (102) was assessed with the Attachment Style Questionnaire (ASQ). RESULTS: Patients with epilepsy and a lifetime history of mood disorders presented elevated scores for Need for approval (p<0.001) and Preoccupation with relationships (p<0.001). Age correlated with the Relationships as secondary (r=0.322; p<0.001) and Need for approval (r=0.217; p=0.019) subscales while age at onset correlated only with Relationships as secondary (r=0.225; p=0.015). Seizure-free patients presented lower scores for Need for approval (p=0.003). Patients with migraine and a lifetime history of mood disorders presented lower scores in Confidence (p=0.002) and higher scores in Discomfort with closeness (p=0.026). CONCLUSIONS: An anxious-preoccupied attachment correlated with mood disorders in epilepsy while it was an avoidant pattern in migraine. Our results bring further data on the role of psychological variables in mood disorders in epilepsy. Further studies will allow early identification of patients at risk and the development of preventive strategies.

Self-reported aggressiveness during treatment with levetiracetam correlates with depression.

PURPOSE: The purpose of this study was to identify clinical correlates of self-reported aggressiveness (SRA) in patients with epilepsy treated with levetiracetam (LEV) with special reference to the role of depression. METHODS: A consecutive sample of adult outpatients with epilepsy was assessed with the Neurological Disorder Depression Inventory for Epilepsy, the Adverse Event Profile (AEP), and the Emotional Thermometer. RESULTS: From a total sample of 163 consecutive patients treated with LEV, SRA at any level (from rarely a problem to always) was associated with a 7-fold increased risk of being depressed (95% CI: 3.0-17.5; p<0.001). Self-reported aggressiveness was reported as "always" a problem by 9.8% of the patients. In these patients, apart from depression, SRA was associated with high AEP total scores (55.1 vs. 39.3; p<0.001) and polytherapy (43.8% vs. 19.8%; p=0.034). Anxiety scores were not elevated (4.9 vs. 3.6; p=0.183). CONCLUSIONS: Self-reported aggressiveness during treatment with LEV is not an isolated symptom but is associated with depressed mood. Anxiety-mediated mechanisms do not seem to be involved.

Myoclonus: a pragmatic approach.

Myoclonus is a brief (less than half a second)contraction involving agonist and antagonist muscles, leading to a sudden jerk. It may be a normal phenomenon,as in the so-called 'sleep starts'. When pathological, myoclonus is a symptom of a broad range of neurological and systemic diseases. Alternatively, it may signal non-organic illness (8% of myoclonus is psychogenic). This review provides pragmatic and systematic guidance to the assessment and differential diagnosis of adult patients presenting with myoclonus.

Retrospective audit of postictal generalized EEG suppression in telemetry.

Sudden unexpected death in epilepsy (SUDEP) has on rare occasions occurred during electroencephalography (EEG) telemetry, and in such cases postictal EEG suppression (PI EEG-SUP) was frequently observed. More recently a retrospective case-control study reported this pattern as a risk factor for SUDEP. We retrospectively audited frequency and electroclinical features of this pattern as well as immediate management following tonic-clonic seizures during telemetry. Forty-eight patients with tonic-clonic seizures were identified from 470 consecutive EEG-videotelemetry reports. Thirteen patients (27%) with PI EEG-SUP (mean duration 38.1 s, range 6-69 s, median 38 s) were compared to 12 randomly selected controls. One seizure was analyzed per individual. Those with PI EEG-SUP were significantly more likely to be motionless after the seizure and have simple nursing interventions performed (suction, oxygen administration, placed in recovery position, vital signs checked). This pattern is relatively common and requires further study as a potential marker for increased mortality in epilepsy.

Epilepsy: recent advances.

This short review summarizes epilepsy papers published in the Journal of Neurology in 2009, covering pathophysiology (inflammation; propagation pathways), new treatments (oxcarbazepine in paediatrics; levetiracetam in status epilepticus), and non-seizure outcomes (violence; foetal/pregnancy).

Cannabis-induced propriospinal myoclonus.

We report on a case of a 25-year-old woman with clusters of myoclonus induced by a single exposure to inhaled cannabis. Investigations excluded a structural abnormality of the spine. Multi-channel surface EMG with parallel frontal EEG recording confirmed the diagnosis of propriospinal myoclonus.