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Editorial
Time for a change
Alexis Arzimanoglou, Gilles Cahn
Review article
The evolution of antiepileptic drug development and regulation
Alexis Arzimanoglou, Elinor Ben-Menachem, Joyce Cramer, Tracy Glauser, Rav Seeruthun, Miranda Harrison
was seen as the primary aim of therapy, with much less focus on safety and tolerability. However, experience with thalidomide in the 1960s brought safety to the fore, resulting in an era of much tighter regulatory control that still persists today. A direct consequence of this was an increased emphasis on the importance of evidence from randomised controlled trials. Despite the continuing reliance on randomised controlled trials for regulatory approval and the formulation of evidence-based guidelines, the modern era has seen an increasing acknowledgment of their limitations and the need for complementary sources of ‘real-world’ evidence. Such sources include registries and studies that are designed to provide a much broader assessment of a drug’s overall effectiveness; for example, by incorporating patient-reported outcomes to assess the effects of treatment on quality of life or functional status. Such changes reflect a more patient-centric approach to treatment, since it is now recognised that epilepsy can only be effectively managed if patients’ individual real-life needs are addressed, since a key to successful treatment is long-term compliance. Alongside these changes in approach, the modern era has witnessed important advances in antiepileptic drugs themselves, either through development of novel molecules, or targeted, structural improvements of older agents. [Published with video sequences and a set of slides]
Original article
Seizures in Alzheimer’s disease: a retrospective study of a cohort of outpatients
Silvia Bernardi, Nicola Scaldaferri, Nicola Vanacore, Alessandro Trebbastoni, Ada Francia, Aurelio D’Amico, Massimiliano Prencipe
seizures in patients with Alzheimer’s disease. Methods. In this retrospective study, we analyzed our clinical records to gather information on patients’ demographic, metabolic, cardiovascular and cognitive features. We sought to determine the significance of abnormal neuroimaging findings and the use of potentially epileptogenic drugs on the onset of seizures. From the records of 583 patients referred to the clinic for cognitive disturbances, we identified 145 patients with Alzheimer’s disease. Results. Of these 145 patients, 14 (9.7%) had a history of complex partial or generalised seizures, or both. Of the risk factors identified, onset of seizures was associated with male gender and none of the patients with seizures had diabetes. The risk of seizure onset was higher in Alzheimer’s disease patients with hyperlipaemia and severe dementia. No other risk factors were identified, although hypertensive patients seemed to be protected. Conclusions. Seizures in Alzheimer’s disease are frequent and often under-recognized. In elderly patients, especially those with Alzheimer’s disease, correct diagnosis and treatment are important to prevent disease from worsening and disability from increasing. Patients with dementia should routinely undergo history-taking designed to elicit a history of seizures and define patients at high risk.
Prevalence of epilepsy in northeast Turkey
Sibel K Velioglu, Metin Bakirdemir, Gamze Can, Murat Topbas
in northern Turkey. We surveyed households and identified 34 epileptic patients (prevalence of 6/1,000), 28 of whom had active epilepsy (prevalence of 5/1,000). Only one case of hot water epilepsy was established among the 5,254 participants. Of the various seizure types, the most common were partial seizures (63%), over half of which were secondary generalised seizures. The largest syndromic category was that of localisation-related symptomatic cases (46%). Forty-six percent of cases were of unknown cause, and 16% were resistant to medication. The prevalence rate of active epilepsy in Trabzon is low compared to other parts of Turkey and other developing countries. This may be attributable to several factors, and particularly to variations among socio-economic factors. The population of Trabzon is regarded as relatively stable and homogenous, and socio-demographic and health data for the province of Trabzon are much better than those for the rest of the country.
Selection of ideal candidates for extratemporal resective epilepsy surgery in a country with limited resources
Neera Chaudhry, Ashalatha Radhakrishnan, Mathew Abraham, Chandrasekharan Kesavadas, Venkataraman V Radhakrishnan, P Sankara Sarma, Kurupath Radhakrishnan
facilities. Method. From the prospective database maintained at an epilepsy surgery centre in southern India, we reviewed the attributes of consecutive patients who had completed at least two years of follow-up after resections involving frontal, parietal and occipital lobes for medically refractory focal seizures. Results. Of 386 patients diagnosed with extratemporal refractory epilepsies during the study period, 61 (15.8%) were selected based on the presence of magnetic resonance imaging (MRI)-identified lesions (in all) and concordant scalp recorded electroencephalographic (EEG) data (in nearly two thirds). Seventeen (27.8%) required invasive investigations either to define the ictal onset zone, eloquent area, or both. During a median follow-up period of five years, 63% of our patients were seizure-free, excluding the presence of auras. Permanent disabling neurological sequelae occurred in three (4.9%) patients. According to univariate analysis, pre-operative secondary generalised seizures and interictal epileptiform discharges (IEDs), during a one-year post-operative EEG monitoring period, portended unfavourable seizure outcome. In multivariate analysis, frontal lobe resections and IEDs in post-operative EEGs were independent predictors of unfavourable outcome. Conclusions. Extratemporal resective epilepsy surgery can be undertaken in countries with limited resources with efficacy and safety, comparable to that in developed countries, when patients are selected based on the presence of MRI-identified lesions and scalp EEG concordance. In such patients, invasive EEG examinations, when necessary, can be undertaken by limited coverage of cortical areas at an affordable cost.
Epidural and foramen-ovale electrodes in the diagnostic evaluation of patients considered for epilepsy surgery
Pedro Beleza, Jan Rémi, Berend Feddersen, Aurelia Peraud, Soheyl Noachtar
59 epilepsy patients, who underwent recordings with epidural (n = 59) and foramen-ovale electrodes (n = 46) as part of their pre-surgical evaluation between 1990-1999. The epidural and foramen-ovale evaluation was based on the results of the non-invasive EEG-video recordings in patients, in whom non-invasive evaluation failed to localise seizure onset (75%, 44 patients) or where EEG, and imaging studies were discrepant (25%, 15 patients) but allowed a testable hypothesis on the seizure onset zone. Results. Most patients (n = 57) were evaluated between 1990-1994. Only two patients were evaluated later. The results of the epidural (n = 559) and foramen-ovale (n = 83) electrode recordings allowed us to proceed to resective epilepsy surgery in 31% (n = 18) and to exclude further invasive evaluation in 15% (n = 9) of the patients. In 49% (n = 29) of the patients the results guided further invasive recordings using subdural and/or depth electrodes. For only three patients no additional information was gained by the electrode recordings. Temporary morbidity included local infection (epidural; n = 1) and facial pain (foramen ovale; n = 1) but no permanent complication occurred. Discussion. Epidural and foramen-ovale electrodes have almost been abandoned in recent years, most likely because of the improvement of neuroimaging techniques such as MRI, PET and ictal SPECT. However, in selected patients, epidural electrodes and foramen-ovale electrodes are either useful as a measure to avoid invasive evaluation or serve to guide invasive evaluation.
Long-term and late seizure outcome after surgery for temporal lobe epilepsy
José Pimentel, Carla Bentes, Alexandre Campos, A Gonçalves Ferreira, the Epilepsy Surgery Group
to properly define outcome. Methods. Longitudinal, long-term, post-operative seizure follow-up in TLE patients with outcome analysed using Engel’s classification. Three groups were considered according to the type of resection: isolated amygdalohippocampectomy (IAH), further divided into anterior and complete, AH plus focal neocortical resections (AH + FR) and focal neocortical resections (FR). Results. Eighty-nine patients were enrolled (61 in the IAH group, 24 in the AH + FR group, and four in the FR group), with a mean follow-up time of 46.7 months. For the three groups together, 90.9% and 86.7% of the patients were in Engel class I for six months and five years, respectively. Kaplan-Meir analysis of the IAH and AH + FR groups showed that, while 82.2% of patients of the IAH group tended to remain in class I within 84 months after surgery, 86.7% of the AH + FR group tended to remain in class I within 12 months. Kaplan-Meier analysis of the IAH sub-groups showed that more patients (91.0%) with anterior resection tended to remain in class I, although for a longer period of time (36 months), compared to those with complete resection (84.0% of patients and 12 months, respectively). For the IFR group, only three patients were in Engel class I for long-term follow-up. Conclusions. High rates of seizure freedom were obtained and stably maintained for years. The reasons for better long-term prognosis of the anterior IAH group are so far unclear, the IFR group was too small to draw any conclusive data.
Significance of interictal occipital epileptiform discharges in children
Chunyang Wang, Divya S Khurana, Sanjeev V Kothare, Agustin Legido, Geoffrey Harrison, Karen S Carvalho, Ignacio Valencia
A search was performed on the EEG database for the keywords “occipital”, “spike”, “sharp wave” and “epileptiform”. Patients were divided into two groups based on the absence of all (group 1) or presence of any (group 2) of the following criteria: mental retardation, cerebral palsy, neurological deficits, abnormal MRI and/or intractable epilepsy. Special attention was given to the spike/sharp wave amplitude/duration and background slowing. Results. A total of 44 children (eight months to 15 years) were studied. Groups 1 and 2 were each composed of 22 children. Background slowing was more frequent in group 2 (10/22, 45%) compared to group 1 (1/22, 4.5%; p = 0.002). In group 2, 8/22 (36%) had spikes or sharp waves with amplitudes below 50 μV or above 150 μV with a positive predictive value of 89%, and a negative predictive value of 39%. Only 1/22 (4.5%) in group 1 had epileptiform activity outside of the 50-150 μV range. Conclusions. The presence of very high or low-amplitude occipital epileptiform abnormalities or background slowing may be indicative of encephalopathy.
Clinical commentary
Partial seizures with affective semiology versus pavor nocturnus
Cesare Maria Cornaggia, Massimiliano Beghi, Simona Giovannini, Antonella Boni, Giuseppe Gobbi
seizures, particularly in children. We describe the case of a normally developed boy who, at the age of two years, experienced nocturnal paroxysmal events that occurred about one hour after falling asleep and lasted up to 15 minutes. The clinical picture was characterized by sudden arousal, fear, inconsolable crying and an apparently voluntary search for his mother. The state of consciousness was basically maintained, and the inter-ictal EEG pattern showed independent bilateral centro-temporal spikes and spike-and-wave complexes. The child had a family history of benign partial epilepsy of childhood with rolandic spikes, and the paroxysmal events remitted after valproic acid treatment. This case report highlights the difficulties in the differential diagnosis of panic attacks, nightmares, pavor nocturnus and focal nocturnal epileptic seizures, especially those arising from the temporal and frontal lobes. [Published with video sequences]
Stimulus-sensitive post-anoxic focal motor seizures evolving into generalised myoclonic status epilepticus: a video-EEG study
José L Fernández-Torre, Carlos Santos-Sánchez, Francisco Casariego-Pola, Jesús Calleja
into a generalised myoclonic status epilepticus. Both the severely decremented background activity on the EEG, and the absence of median and trigeminal somatosensory evoked potentials were in keeping with a devastating post-hypoxic encephalopathy and the patient died. Our clinical and electrophysiology data suggest that generalised myoclonic status epilepticus may occur in patients in whom the existence of severe cerebral damage prevents a complete development of all phases of classic generalised tonic-clonic seizures. [Published with video sequences]
Reversible sleep-related stridor during vagus nerve stimulation
Erik K St. Louis, Kevin Faber
sleep-related stridor during the course of parameter titration. Reduction of VNS current during polysomnography completely eliminated stridor. We conclude that VNS may cause sleep-related stridor in rare cases, expanding the spectrum of known sleep-disordered breathing disorders associated with VNS therapy. Parameter adjustment during polysomnography may resolve nocturnal stridor caused by VNS. [Published with video sequences]
Unexpected gamma glutamyltransferase rise increase during levetiracetam monotherapy
Marcella Broli, Federica Provini, Ilaria Naldi, Francesca Bisulli, Claudia Sama, Agostino Baruzzi, Paolo Tinuper, Roberto Riva
increase in gamma glutamyltransferase (γGT) while on levetiracetam monotherapy.
Focal epileptic seizure induced by transient hypoglycaemia in insulin-treated diabetes
Leonardo Lapenta, Carlo Di Bonaventura, Jinane Fattouch, Francesca Bonini, Simona Petrucci, Silvia Gagliardi, Sara Casciato, Mario Manfredi, Massimiliano Prencipe, Anna Teresa Giallonardo
tonic-clonic type, with focal events only exceptionally being reported and documented. Hypoglycaemia can modify cortical excitability by determining an imbalance between excitation and inhibition; some brain structures, such as the temporal lobe and hippocampus, appear to be particularly susceptible to this insult. We describe a case of a 61-year-old diabetic patient in whom insulin-induced transient hypoglycaemia triggered a focal seizure of temporal origin that was well documented by EEG during 24-hour ambulatory monitoring. This is, to our knowledge, one of the few, well-documented cases of this type of seizure.
Bathing epilepsy: report of two Caucasian cases
Emilio Franzoni, Valentina Gentile, Salvatore Grosso, Daniela Brunetto, Duccio Maria Cordelli, Paolo Balestri
This condition has been confused with true hot water epilepsy, even though bathing in water at normal temperature is the trigger. Focal seizures predominate with a staring gaze, pallor and generalised features followed by prolonged postictal somnolence. A variable percentage of patients may also show unprovoked seizures. The prognosis is usually favourable, and modifying bathing habits may prevent further seizures. We report two Caucasian patients with bathing epilepsy. In one, seizures were provoked by water immersion. In the other, we noted an unusual triggering factor; pouring of lukewarm water over the genitalia.
Letter to the Editor
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