Peter Wolf

Juvenile myoclonic epilepsy: A system disorder of the brain

The prevailing understanding of generalized epilepsy is shaped by the traditional definition that the responsible neuronal discharge takes place, if not throughout the entire grey matter, then at least in the greater part of it and simultaneously on both sides. This view is no longer tenable since concurrent findings using multiple methods have accumulated to reveal the role of bilateral networks of distributed and selective cortical and subcortical structures in so-called generalized ictogenesis. Most of this research has been focused on juvenile myoclonic epilepsy (JME), which today is commonly considered the archetypical syndrome of the idiopathic generalized epilepsies. Based upon recent research in the fields of clinical epileptology, neuropsychology and psychiatry, clinical neurophysiology, neuroimaging and epilepsy genetics this article, for the first time, unites these new findings into a comprehensive nosological view. Genetically determined dysfunctions of important cognitive systems like visuomotor coordination and linguistic communication appear now as key mechanisms of seizure generation in JME. This review suggests a new paradigm to consider JME as a system disorder of the brain analogous to other neurological system disorders.

Acute drug administration in epilepsy: a review.

Aims: To review acute administration of drugs in epilepsy for indications other than status epilepticus. Discussion: This review looks into the application of acute drug administration (ADA) against febrile and prolonged nonfebrile seizures in children, seizure clustering (habitual or at drug withdrawal), catamenial epilepsy, response to seizure “warnings”, and prophylaxis of seizures at perceived increased risk (reflex epilepsies, long‐distance travel, lifestyle, and social occasions). The drugs most commonly used for ADA are the benzodiazepines diazepam (oral or rectal), clobazam and buccal or nasal midazolam, and lorazepam. Others include valproic acid, nitrazepam, acetazolamide, chloral hydrate, pyridoxine, and antipyretics. Conclusions: The best evidence for the efficacy of ADA exists in febrile and nonfebrile childhood seizures, whereas the evidence in catamenial epilepsy is weak. Prevention of clusters is a well‐proven principle but its application has been little studied. Prevention of imminent seizures predicted by well‐established triggers, defined risk factors, or premonitory minor seizure activity seems to be at the same time the most intelligent and the least investigated application of ADA and would deserve to be better studied.

Reflex epileptic mechanisms in humans: Lessons about natural ictogenesis

The definition of reflex epileptic seizures is that specific seizure types can be triggered by certain sensory or cognitive stimuli. Simple triggers are sensory (most often visual, more rarely tactile or proprioceptive; simple audiogenic triggers in humans are practically nonexistent) and act within seconds, whereas complex triggers like praxis, reading and talking, and music are mostly cognitive and work within minutes. The constant relation between a qualitatively, often even quantitatively, well-defined stimulus and a specific epileptic response provides unique possibilities to investigate seizure generation in natural human epilepsies. For several reflex epileptic mechanisms (REMs), this has been done. Reflex epileptic mechanisms have been reported less often in focal lesional epilepsies than in idiopathic generalized epilepsies (IGEs) which are primarily genetically determined. The key syndrome of IGE is juvenile myoclonic epilepsy (JME), where more than half of the patients present reflex epileptic traits (photosensitivity, eye closure sensitivity, praxis induction, and language-induced orofacial reflex myocloni). Findings with multimodal investigations of cerebral function concur to indicate that ictogenic mechanisms in IGEs largely (ab)use preexisting functional anatomic networks (CNS subsystems) normally serving highly complex physiological functions (e.g., deliberate complex actions and linguistic communication) which supports the concept of system epilepsy. Whereas REMs in IGEs, thus, are primarily function-related, in focal epilepsies, they are primarily localization-related. This article is part of a Special Issue entitled Genetic and Reflex Epilepsies, Audiogenic Seizures and Strains: From Experimental Models to the Clinic.

Quantitative analysis of surface electromyography: Biomarkers for convulsive seizures.

Muscle activity during seizures is in electroencephalographical (EEG) praxis often considered an irritating artefact. This article discusses ways by surface electromyography (EMG) to turn it into a valuable tool of epileptology. Muscles are in direct synaptic contact with motor neurons. Therefore, EMG signals provide direct information about the electric activity in the motor cortex. Qualitative analysis of EMG has traditionally been a part of the long-term video-EEG recordings. Recent development in quantitative analysis of EMG signals yielded valuable information on the pathomechanisms of convulsive seizures, demonstrating that it was different from maximal voluntary contraction, and different from convulsive psychogenic non-epileptic seizures. Furthermore, the tonic phase of the generalised tonic-clonic seizures (GTCS) proved to have different quantitative features than tonic seizures. The high temporal resolution of EMG allowed detailed characterisation of temporal dynamics of the GTCS, suggesting that the same inhibitory mechanisms that try to prevent the build-up of the seizure activity, contribute to ending the seizure. These findings have clinical implications: the quantitative EMG features provided the pathophysiologic substrate for developing neurophysiologic biomarkers that accurately identify GTCS. This proved to be efficient both for seizure detection and for objective, automated distinction between convulsive and non-convulsive epileptic seizures.

Validation of diagnostic tests for depressive disorder in drug-resistant mesial temporal lobe epilepsy

PURPOSEnThis study aimed to evaluate the diagnostic accuracy of the Hamilton Rating Scale for Depression (HRSD), the Beck Depression Inventory (BDI), the Hospital Anxiety and Depression Scale (HADS), and the Hospital Anxiety and Depression Scale-Depression subscale (HADS-D) as diagnostic tests for depressive disorder in drug-resistant mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS).nnnMETHODSnOne hundred three patients with drug-resistant MTLE-HS were enrolled. All patients underwent a neurological examination, interictal and ictal video-electroencephalogram (V-EEG) analyses, and magnetic resonance imaging (MRI). Psychiatric interviews were based on DSM-IV-TR criteria and ILAE Commission of Psychobiology classification as a gold standard; HRSD, BDI, HADS, and HADS-D were used as psychometric diagnostic tests, and receiver operating characteristic (ROC) curves were used to determine the optimal threshold scores.nnnRESULTSnFor all the scales, the areas under the curve (AUCs) were approximately 0.8, and they were able to identify depression in this sample. A threshold of ≥9 on the HRSD and a threshold of ≥8 on the HADS-D showed a sensitivity of 70% and specificity of 80%. A threshold of ≥19 on the BDI and HADS-D total showed a sensitivity of 55% and a specificity of approximately 90%. The instruments showed a negative predictive value of approximately 87% and a positive predictive value of approximately 65% for the BDI and HADS total and approximately 60% for the HRSD and HADS-D.nnnCONCLUSIONSnHRSD≥9 and HADS-D≥8 had the best balance between sensitivity (approximately 70%) and specificity (approximately 80%). However, with these thresholds, these diagnostic tests do not appear useful in identifying depressive disorder in this population with epilepsy, and their specificity (approximately 80%) and PPV (approximately 55%) were lower than those of the other scales. We believe that the BDI and HADS total are valid diagnostic tests for depressive disorder in patients with MTLE-HS, as both scales showed acceptable (though not high) specificity and PPV for this type of study.

Acute administration of benzodiazepines as part of treatment strategies for epilepsy.

Ad‐hoc administration of benzodiazepines (BZD) is well established in status epilepticus, but intermittent BZD use in the treatment of chronic epilepsy is little known beyond catamenial epilepsy. We aim to assess the use of acute drug administration (ADA) in the treatment of 24 patients with epilepsy (9 idiopathic generalized, 14 focal symptomatic/cryptogenic, 1 migraine‐epilepsy) receiving ADA for (1) prevention of generalized tonic‐clonic seizures (GTCS) after minor seizures, (2) prevention of seizures at perceived risk, (3) prevention of seizure clusters. Standard ADA was 10 mg oral clobazam (CLB); one patient received 10 mg rectal diazepam. Concomitant antiepileptic drugs (AED) remained unchanged whenever possible. Ten patients used ADA always correctly, 7 mostly, 7 sporadically or not. Outcome considering seizure control was positive in 44% of all patients (59% of those who actually used ADA): 5 patients seizure free, 1 free of disabling seizures, 4 with >50% reduction in seizure frequency. Eleven had minor or no improvement, 3 patients could not be rated. Thirteen (of 19 possible) patients attempted prevention of seizures or clusters, 10 with full or >50% success (52.6 resp. 76.9%). Prevention of clusters sometimes required higher or repetitive CLB dosing. Self rating of patients who did use ADA was positive or very positive in 88.2%. Retention rate was 66.7% of all patients, and 88.2% of those using ADA. The best results were obtained in idiopathic generalized epilepsy (IGE) patients with seizures habitually triggered by typical factors (sleep deprival, alcohol) but also some others were successful. The only adverse effect was gait ataxia in a multiple‐handicapped patient. ADA is an elegant and often successful but underused treatment option for selected patient groups where it can make the difference between becoming seizure free or not. Depending on the individual case it can be applied as monotherapy or in combination with a basis AED. A controlled investigation should follow.

Automated real-time detection of tonic-clonic seizures using a wearable EMG device

Objective To determine the accuracy of automated detection of generalized tonic-clonic seizures (GTCS) using a wearable surface EMG device. Methods We prospectively tested the technical performance and diagnostic accuracy of real-time seizure detection using a wearable surface EMG device. The seizure detection algorithm and the cutoff values were prespecified. A total of 71 patients, referred to long-term video-EEG monitoring, on suspicion of GTCS, were recruited in 3 centers. Seizure detection was real-time and fully automated. The reference standard was the evaluation of video-EEG recordings by trained experts, who were blinded to data from the device. Reading the seizure logs from the device was done blinded to all other data. Results The mean recording time per patient was 53.18 hours. Total recording time was 3735.5 hours, and device deficiency time was 193 hours (4.9% of the total time the device was turned on). No adverse events occurred. The sensitivity of the wearable device was 93.8% (30 out of 32 GTCS were detected). Median seizure detection latency was 9 seconds (range −4 to 48 seconds). False alarm rate was 0.67/d. Conclusions The performance of the wearable EMG device fulfilled the requirements of patients: it detected GTCS with a sensitivity exceeding 90% and detection latency within 30 seconds. Classification of evidence This study provides Class II evidence that for people with a history of GTCS, a wearable EMG device accurately detects GTCS (sensitivity 93.8%, false alarm rate 0.67/d).

Epilepsia partialis continua: A review

Epilepsia partialis contina (EPC) in a narrow definition is a variant of simple focal motor status epilepticus in which frequent repetitive muscle jerks, usually arrhythmic, continue over prolonged periods of time. In a broader definition (used in this review) it also includes non-motor manifestations otherwise known as aura continua. EPC may occur as a single episode, repetitive episodes, it may be chronic progressive or non-progressive. It appears as an unusual manifestation of epilepsy in which more typical paroxysmal events are partly or entirely replaced by the sustained repetition of seizure fragments in rapid succession. The minimum duration is defined as one hour but EPC may continue for up to many years. There are multiple possible etiologies which can be local or systemic, including two disease entities, Rasmussen encephalitis and Russian tick-borne spring-summer encephalitis. Among systemic brain disorders, mitochondrial diseases and non-ketotic hyperglycemia are particularly likely to cause EPC whereas stroke is a frequent cause of acute EPC. The symptoms of motor EPC have been interpreted as cortical reflex myocloni but the pathophysiology is probably not uniform for all cases. In pathophysiological terms, EPC seems to represent an oscillation of excitation and inhibition in a feedback loop whose mechanisms are still poorly understood. However, EPC only seems to occur rarely in an otherwise healthy brain. Treatment has to take account of the etiology but, in general, EPC tends to be drug-resistant. Epilepsy surgery is often indicated in Rasmussen encephalitis.

Predictors of meaningful improvement in quality of life after temporal lobe epilepsy surgery: A prospective study

To investigate prospectively the independent predictors of a minimum clinically important change (MCIC) in quality of life (QOL) after anterior temporal lobectomy (ATL) for drug‐resistant mesial temporal lobe epilepsy related to hippocampal sclerosis (MTLE‐HS) in Brazilian patients.

Orofacial reflex myocloni. Definition, relation to epilepsy syndromes, nosological and prognosis significance. A focused review

PURPOSEnThere is increasing awareness that reflex epileptic mechanisms provide unique insight into ictogenesis in human epilepsies. Among the complex triggers of seizures, this review considers orofacial reflex myocloni (ORM) from the aspects of history and delineation, clinical and electroencephalographic presentation, syndromatic relations, prevalence, mechanisms of ictogenesis and nosological implications, treatment and prognosis.nnnMETHODSnWe reviewed all published articles and case reports on ORM in order to clarify clinical and electroencephalographic findings, treatment and outcome.nnnRESULTSnORM, besides Reading Epilepsy (RE), is closely related to idiopathic generalized epilepsies especially Juvenile Myoclonic Epilepsy (JME) where hyperexcitability of the network supporting linguistic communication seems to provide the precondition for eliciting reflex myocloni in the perioral muscles active in the precipitating task.nnnCONCLUSIONnThe conclusions on ictogenesis derived from ORM support the concept of both, RE and JME, as system disorders of the brain.