Which children receive vigabatrin? Characteristics of pediatric patients enrolled in the mandatory FDA registry.

Vigabatrin (Sabril®) is an antiepileptic drug (AED) currently indicated in the US as a monotherapy for patients 1month to 2years of age with infantile spasms (IS) and as adjunctive therapy for patients ≥10years of age with refractory complex partial seizures (rCPS) whose seizures have inadequately responded to several alternative treatments and for whom the potential benefits outweigh the risk of vision loss. The approval required an FDA mandated registry. This article describes 5years of demographic and treatment exposure data from US pediatric patients (<17years). Participation is mandatory for all US Sabril® prescribers and patients. A benefit-risk assessment must be documented for patient progression to maintenance therapy. This includes demographic diagnosis and reports of ophthalmologic assessments (where available). Patient data were grouped by age as proxies for indication (IS: <3years, rCPS: ≥3 to <17years). As of August 26, 2014, 5546/6823 enrolled patients were pediatric/total; 4472 (81%) were vigabatrin-naïve. Seventy-one percent of patients were <3years of age; 29% were ≥3 to <17years of age. Etiologies of IS were identified as cryptogenic (21%), symptomatic tuberous sclerosis (17%), and symptomatic other (42%). The majority of patients with IS (56%) attempted no prior treatments; 16% received adrenocorticotropic hormone prior to vigabatrin. A third of patients with IS were receiving 1 concomitant treatment with vigabatrin. For patients with rCPS, 39% attempted 1-3 prior treatments; 27% were receiving 2 concomitant treatments at enrollment. A total of 1852 (41%) patients did not undergo baseline ophthalmological assessment; 25% of patients with IS and 42% of patients with rCPS were exempted for neurologic disabilities. Kaplan-Meier estimates predict that 71% and 65% of vigabatrin-naïve patients with IS and rCPS, respectively, would remain in the registry at 6months. Most pediatric vigabatrin patients have IS as an underlying diagnosis, especially those <3years of age. A proportion of those with rCPS remain on long-term vigabatrin despite the risk of adverse events.

Partial rhombencephalosynapsis and Chiari type II malformation in a child: a true association supported by DTI tractography.

Partial rhombencephalosynapsis (PRECS) has been recently reported in association with Chiari II (CII). However, its existence as a true malformation is challenged due to the anatomical changes potentially induced by CII. The aim of this report was to investigate the contribution of midbrain/hindbrain tractography in this setting. A 13-year-old boy with a known CII malformation and operated myelomeningocele was referred for brain imaging after a first complex partial seizure. In addition to the classical features of CII, MRI showed partially fused cerebellar hemispheres and multiple supratentorial abnormalities. Diffusion tensor imaging (DTI) color map and tractography showed absent transverse fibers on the midsection of the cerebellum, scarce fibers of the middle cerebellar peduncle (MCP), absence of the middle pontine crossing tract, and fibers running vertically in the medial part of the cerebellum. Vertical mediocerebellar fibers are a feature of classical RECS and the paucity or absence of MCP fibers is mainly described in CII. In our patient, DTI and FT therefore demonstrated structural characteristics of both RECS and CII confirming their potential coexistence and suggesting possible shared embryological pathway.

Successful treatment of mesial temporal lobe epilepsy with bilateral hippocampal atrophy and false temporal scalp ictal onset: a case report.

Patients with bilateral hippocampal atrophy (BHA) in a subgroup suffering from mesial temporal lobe epilepsy represent a therapeutic challenge. We achieved successful surgical treatment in a case with BHA and false lateralized ictal onset on video-scalp electroencephalogram (EEG). A 27-year-old male patient with seizures since the age of 15 years showed current seizures consisting of an epigastric aura, a feeling of difficulty in breathing and oroalimentary automatism, which were frequently followed by secondary generalization with right-arm tonic extension. MRI showed BHA with hyperintensity on FLAIR and a slightly smaller volume in the left hippocampus on volumetry. Ictal EEG started from the left anterior temporal and subtemporal regions, spreading to the right anterior to middle temporal region. Interictal EEG was not lateralized, and showed independent spikes in the bilateral anterior temporal and subtemporal regions. The patient underwent chronic intracranial EEG-monitoring, revealing that the seizure onset originated from the right hippocampus with a rapid spread to the hippocampus and lateral temporal cortex on the left side. We performed a right anterior temporal lobectomy with amygdalohippocampectomy. Histological diagnosis was classic hippocampal sclerosis. The patient has since been seizure-free for 4 years. In this case, false lateralization may have been caused by an atypical seizure-propagating route to the contralateral temporal region via the dorsal hippocampal commissure instead of the usual pathway to the ipsilateral temporal neocortex. The technique of bilateral intracranial EEG-monitoring is advantageous to lateralize the actual side, particularly in BHA patients even with clearly and falsely lateralized ictal onset on scalp-EEG.

AERRPS, DESC, NORSE, FIRES: multi-labeling or distinct epileptic entities?

In this review, we report a case of an adolescent girl presenting with epileptic encephalopathy preceded by febrile illness, demarcate the clinical phenotypic homogeneity among previously reported cases, and hypothesize on potential mechanisms based on current experimental evidence. Our literature review revealed >249 cases that share several main features: febrile illness with no preceding condition, negative laboratory studies including cerebrospinal fluid (CSF) analysis, status epilepticus refractory to conventional pharmacotherapy, and long-term developmental delays. This condition appears to have many names, the most recent of which is "FIRES" (fever-induced refractory epileptic encephalopathy). It seems likely that the described cases are representing the same entity. The possibility of a genetic or acquired channelopathy can be raised in light of negative infectious, autoimmune, microscopic, and gross pathology findings.

Familial mesial temporal lobe epilepsy: a benign epilepsy syndrome showing complex inheritance.

Temporal lobe epilepsy is the commonest partial epilepsy of adulthood. Although generally perceived as an acquired disorder, several forms of familial temporal lobe epilepsy, with mesial or lateral seizure semiology, have been described. Descriptions of familial mesial temporal lobe epilepsy have varied widely from a benign epilepsy syndrome with prominent déjà vu and without antecedent febrile seizures or magnetic resonance imaging abnormalities, to heterogeneous, but generally more refractory epilepsies, often with a history of febrile seizures and with frequent hippocampal atrophy and high T2 signal on magnetic resonance imaging. Compelling evidence of a genetic aetiology (rather than chance aggregation) in familial mesial temporal lobe epilepsy has come from twin studies. Dominant inheritance has been reported in two large families, though the usual mode of inheritance is not known. Here, we describe clinical and neurophysiological features of 20 new mesial temporal lobe epilepsy families including 51 affected individuals. The epilepsies in these families were generally benign, and febrile seizure history was infrequent (9.8%). No evidence of hippocampal sclerosis or dysplasia was present on brain imaging. A single individual underwent anterior temporal lobectomy, with subsequent seizure freedom and histopathological evidence of hippocampal sclerosis was not found. Inheritance patterns in probands' relatives were analysed in these families, together with 19 other temporal lobe epilepsy families previously reported by us. Observed frequencies of epilepsies in relatives were lower than predicted by dominant Mendelian models, while only a minority (8/39) of families could be compatible with recessive inheritance. These findings strongly suggest that complex inheritance, similar to that widely accepted in the idiopathic generalized epilepsies, is the usual mode of inheritance in familial mesial temporal lobe epilepsy. This disorder, which appears to be relatively common, and not typically associated with hippocampal sclerosis, is an appropriate target for contemporary approaches to complex disorders such as genome-wide association studies for common genetic variants or deep sequencing for rare variants.

The ketogenic diet for medically and surgically refractory status epilepticus in the neurocritical care unit.

BACKGROUND: Refractory status epilepticus carries a high risk of morbidity and mortality despite, and at times as a result of, aggressive pharmacologic interventions. Dietary therapies have been used for almost a century in children for controlling medically refractory seizures and status epilepticus and recent studies suggest efficacy and safety in adults as well. METHODS: Case report and literature review. RESULTS: We describe a case of medically and surgically refractory status epilepticus that was controlled after initiation of the ketogenic diet and maintenance with the modified Atkins diet in an adult in the neurocritical care unit. CONCLUSIONS: Dietary therapy should be considered as a treatment option in adult patients with refractory status epilepticus.

Cognitive and behavioral functioning in Coffin-Siris syndrome and epilepsy: a case presentation.

The authors characterized the cognitive, adaptive, and behavioral sequelae of Coffin-Siris (CS) syndrome and epilepsy in a 7.5-year-old child. Little is known about the early neurobehavioral presentation of CS. Clinical features consistent with this genetic anomaly include underdeveloped tips and nails of the fifth fingers, extended infranasal depression, and craniofacial abnormalities. MRI findings often reveal callosal agenesis. The authors conducted a neuropsychological evaluation and obtained parental ratings of behavioral and adaptive functioning. Attentional abilities were limited. As assessed by the Mullen Scales of Early Learning, receptive language abilities (age equivalent [AE]: 3-3) were relatively stronger than expressive skills (AE: 1-4). Adaptive functioning was low across all domains (Vineland Adaptive Behavior Composite AE: 1-9). On the Behavior Assessment for Children (BASC-2), social skills dysfunction, stereotyped and self-stimulatory behaviors, restricted interests, ritualistic play, and inappropriate object usage were noted. No significant mood disturbances were endorsed. Study findings indicate a diffuse pattern of neurobehavioral deficits in a child with CS and epilepsy. Further clinical assessment and research should include multidimensional assessment techniques, including evaluation of adaptive behavior, in an effort to capture the full range developmental sequelae in children with CS.

Lamotrigine treatment of a patient affected by epilepsy and anxiety disorder.

Epilepsy often occurs in comorbidity with mental diseases and disorders. Early detection and/or treatment of such disorders in patients affected by epilepsy, as well as their socialisation are crucially important since epileptic patients tend to suffer more due to lack of social support than to frequent epileptic seizures. Prevalence of psychiatric disorders is higher in patients with epilepsy than in general population, the most frequent being: anxiety, depression, panic attacks, behavioural disorders as well as psychotic states with paranoid elements. The efficacy of AE treatment of patients affected by epilepsy and mood disorders has also directed clinicians to investigate possible AE benefits in treating other mental disorders such as anxiety states, depression and bipolar disorder. The examined case displays complex partial epilepsy and comorbid mental disorder. The use of lamotrigine, a fourth-generation antiepileptic, which is also a mood stabilizer, has assured a favourable remission of symptoms related to both epilepsy and mood disorders. Side-effects caused by lamotrigine were only temporary and dose reduction was sufficient to eliminate their symptoms.

[Oligoepilepsy: a real entity or the benign form of epileptic disorder?]. / Oligoepilepszia: onálló entitás vagy az epilepsziás készség benignus formája?

BACKGROUND AND PURPOSE: Although oligoepilepsy (OLE) is a used term in many protocols, guidelines and the everyday routine, it is found practically nowhere in the scientific literature. The aim of our study is to investigate and evaluate of the main characteristics of his subcategory of epilepsy. We try to find answer to the basic question of not only theoretical but also great practical importance whether the OLE does really exist, is it an independent entity of epilepsy or only its general benign clinical presentation. METHODS: We considered OLE if the patients had two seizures maximally in the last year of their course. We counted only the two most severe clinical types, the generalized tonic-clonic and the complex partial seizures. We divided the OLE into two subtypes: those patients who had OLE from the beginning of their epilepsy (OLE1) and those in whom the OLE was the result of the treatment (OLE2). We retrospectively analysed the data of 817 "OLE-suspicious" patients taken from our EPIMED database. RESULTS: We found 47 patients met the inclusion criteria (OLE1 = 34, OLE2 = 13). OLE patients did not differ from the general epileptic population according to the age and gender, the type of seizures, the electro-clinical diagnosis and the possible cause of their first seizure. But we found statistically significant differences in two measures. In OLE, far less seizure provoking factors were found in the sporadic seizures. Concerning the social conditions: while the range of employees was equal, the vast majority of OLE patients were able to work at their level of education. CONCLUSION: We found that more than 5% of people with epilepsy can belong to the OLE category. In the majority of OLE patients the seizure frequency is low from the beginning of the disease. The sporadic seizures in OLE are generally not provoked. The chances of OLE patients in the world of job are better for the OLE patients. In our opinion OLE rather seems to be an independent entity among epilepsy. Therefore larger prospective studies are needed to the exact description of OLE and to establish the special standards for the everyday medical practice.

The combination of EEG source imaging and EEG-correlated functional MRI to map epileptic networks.

Functional electrophysiologic techniques such as electroencephalography (EEG) and magnetoencephalography (MEG) give insights into the dynamics of the networks involved in the generation of interictal and ictal epileptic activity and their interaction with physiologic brain activity. With recent advances in methodology and clinical validation, EEG source imaging (ESI) may now be used to map epileptic activity as well as evoked responses to external stimuli. By its ability to show hemodynamic changes time locked to epileptic activity in the whole brain, EEG-correlated functional magnetic resonance imaging (fMRI) (EEG-fMRI) is the natural counterpart of ESI, circumventing some of its limitations, the former adding data from the depths of the brain, and the latter temporal resolution. To better understand the potential and limitations of both techniques, this review starts with a description of the neurophysiologic mechanisms that give rise to the measured signals, followed by validation studies based on comparison with intracranial EEG and surgical outcome. We then discuss analysis strategies to combine both techniques by reviewing studies in epilepsy, current methodologic development, and future directions of this fast-developing field.

Vagus nerve stimulation might have a unique effect in reflex eating seizures.

We studied the effects of vagus nerve stimulation (VNS) on eating seizures, which theoretically would be triggered by neural activity and signaling from organs innervated by the vagus nerve. Three adult patients with daily nonreflex and reflex eating seizures were studied; one patient also had hot-water seizures. One patient had bilateral polymicrogyria and two had normal magnetic resonance imaging (MRI) findings. All patients were submitted to VNS implantation and had at least 2 years of postimplantation follow-up. Final stimulation parameters were 2.0-2.5 mA, 500 micros, and 30 Hz. Eating seizures decreased 70-95% and nonreflex seizures decreased 0-40% after VNS. There was no improvement in hot-water seizures. VNS seems to be an especially useful treatment modality in patients with reflex eating seizures not amenable to resective surgery.

Etomidate accurately localizes the epileptic area in patients with temporal lobe epilepsy.

PURPOSE: A variety of drugs have been used to activate and identify the epileptogenic area in patients during presurgical evaluation. We have evaluated the safety and usefulness of etomidate in identifying the epileptic zone by measuring bioelectrical brain activity and cerebral blood flow (CBF). METHODS: We studied 13 men and 9 women under presurgical evaluation for temporal lobe epilepsy. We applied etomidate (0.1 mg/kg) while patients were monitored by video-electroencephalography (VEEG) with foramen ovale electrodes. In a subset of 15 patients, we also measured CBF with single photon emission computed tomography (SPECT). RESULTS: (1) Etomidate induced seizures in 2 of 22 patients. (2) The main side-effects observed were myoclonus (14 of 20) and moderate pain (3 of 20). (3) No changes in capillary oxygen saturation, respiration, or heart rate were observed. (4) Irritative activity specifically increased in the temporal mesial and lateral areas. No spikes were observed in other areas, aside from those observed under baseline conditions. (5) Irritative activity induced by etomidate correctly lateralized the ictal onset zone in 19 of 20 patients. In addition, the two etomidate-induced seizures appeared in the same regions as spontaneous ones. (6) The kinetics of pharmacologically induced activity was higher in the region of the ictal-onset zone. (7) Etomidate increased the CBF in the basal ganglia and especially in the posterior hippocampus of the temporal mesial region contralateral to the ictal-onset zone. DISCUSSION: Etomidate activation is a safe, specific, and quick test that can be used to identify the epileptic region in patients evaluated as candidates for temporal lobe epilepsy surgery.

A seizure response dog: video recording of reacting behaviour during repetitive prolonged seizures.

Seizure response and alerting behaviour may spontaneously develop in dogs living with children or adults with epilepsy. Some dogs can also be reliably trained to respond and anticipate seizures. We describe the case of a dog, not previously trained for assistance work, showing complex seizure response behaviour. This is the first release of a home video recording of a dog reacting to its owner's seizure.

Periictal diffusion abnormalities of the thalamus in partial status epilepticus.

PURPOSE: To identify and describe thalamic dysfunction in patients with temporal as well as extratemporal status epilepticus (SE) and to also analyze the specific clinical, radiological, and electroencephalography (EEG) characteristics of patients with acute thalamic involvement. METHODS: We retrospectively identified patients who presented with clinical and electrographic evidence of partial SE and had thalamic abnormalities on diffusion-weighted imaging (DWI) within 5 days of documentation of lateralized epileptiform discharges (group 1). The spatial and temporal characteristics of the periodic lateralized epileptiform discharges (PLEDs) and the recorded electrographic seizures were analyzed and correlated with magnetic resonance imaging (MRI)-DWI hyperintense lesions. The findings of group 1 patients were compared with those of patients with partial SE without thalamic abnormalities on DWI (group 2). RESULTS: The two groups were similar with regard to clinical presentation and morphology of epileptiform discharges. Group 1 patients had thalamic hyperintense lesions on DWI that appeared in the region of the pulvinar nucleus, ipsilateral to the epileptiform activity. Statistically significant relationship was noted between the presence of thalamic lesions and ipsilateral cortical laminar involvement (p = 0.039) as well as seizure origin in the posterior quadrants (p = 0.038). A trend towards PLEDs originating in the posterior quadrants was also noted (p = 0.077). DISCUSSION: Thalamic DWI hyperintense lesions may be observed after prolonged partial SE and are likely the result of excessive activity in thalamic nuclei having reciprocal connections with the involved cortex. The thalamus likely participates in the evolution and propagation of partial seizures in SE.

Spectrum of epilepsy and electroencephalogram patterns in Wolf-Hirschhorn syndrome: experience with 87 patients.

To define the spectrum of epilepsy in Wolf-Hirschhorn syndrome (WHS) better, we studied 87 patients (54 females, 33 males; median age 5.6 years; age range 1-25.6 years) with confirmed 4p16.3 deletion. On the basis of clinical charts, we retrospectively analyzed the evolution of the electroencephalogram (EEG) findings and seizures. Epilepsy occurred in 81 patients (93%) within the first 3 years of life. Sixty out of 81 (74%) had generalized tonic-clonic seizures, which was the only seizure pattern in 32. Tonic spasms occurred in 15 out of 81 (18%), complex partial seizures in 10 out of 81 (12%), and clonic seizures in 6 out of 81 (7%). Seizures were frequently triggered by fever (59 out of 81; 73%), and occurred in clusters in 36 out of 72 (50%). In the same 36 (50%), unilateral or generalized clonic or tonic-clonic status epilepticus occurred during the first 3 years of life. Twenty-seven out of 81 patients (33%) developed atypical absences between 1 and 6 years, accompanied by a myoclonic component involving the eyelids and the hands. Distinctive EEG abnormalities were observed in 73 out of 81 (90%). Epilepsy was well controlled in 65 out of 81 (81%), mainly with valproate and phenobarbital, and improved with age in all. Thirty-two out of 58 (55%) are currently seizure-free. Seizures stopped at a median age of 4 years 6 months. Epilepsy represents a major clinical challenge in WHS; however, it has a good prognosis. Early diagnosis and treatment of atypical absences, subtle and often misdiagnosed, is mandatory.

Is postoperative CT scanning predictive of subdural electrode placement complications in pediatric epileptic patients?

AIMS: To understand the reliability of postoperative CT scans to predict the development of intracranial hemorrhagic complications associated with subdural electrode implants for monitoring intractable seizure, we reviewed the data of a consecutive series of children treated at our institution. METHODS: Forty children (mean age: 11.4 years) with subdural electrode implants were reviewed. The immediate postoperative CT scans were evaluated for the presence of hemorrhagic complications and/or brain swelling resulting in a midline shift. RESULTS: Twenty-six patients (65%) presented a postoperative midline shift (range = 2-10 mm; mean shift = 4.0 mm). Two children had a midline shift of >5 mm. Two patients with a shift of <5 mm at the first CT scan required a repeat craniotomy. These patients experienced worsening neurologic symptoms in a delayed fashion on postoperative days 1 and 4, respectively. This was correlated to an increase in midline shift of >5 mm. CONCLUSIONS: Subdural electrode implants in children are safe. The presence of a midline shift of <5 mm is common postoperatively. The presence and extension of the midline shift at the first CT scan does not seem to be predictive of the development of symptomatic complications with a mass effect. Complications happened in a delayed fashion.

Accidental fall due to abnormal behavior after experiencing a Streptococcus pyogenes infection: febrile delirium or pediatric autoimmune neuropsychiatric disorder associated with streptococcal infection?

An 11-year-old boy with a high fever (39.4 degrees C) presented at a local medical institution. His condition was diagnosed as hemolytic streptococcal infection, and he was prescribed an antibiotic. After returning home, he took a dose of his medication and rested; however, he suddenly began to run around while yelling incomprehensible words. He ran up to his room on the second floor and fell from the second floor window down to the ground. He lost consciousness and was transferred to our department. His history included being born as a twin with a low birth weight and pneumonia at 1 year of age. He regained consciousness on the seventh hospital day and was discharged without any neurological abnormality on the 14th day. His abnormal behavior might have resulted from febrile delirium or an unusual expression of pediatric autoimmune neuropsychiatric disorder associated with a streptococcal infection.

[Non convulsive status epilepticus]. / Etats de mal épileptiques non convulsifs.

Non convulsive confusional status epilepticus is classically divided on the basis of the ictal EEG into absence status (AS) and complex partial status epilepticus (CPSE). The clinical presentation is often insufficient to establish diagnosis and emergency EEG is required. AS is a polymorphic condition that can complicate many epileptic syndromes. In half of cases, confusion of varying intensity is associated with bilateral periocular myoclonias. Clinical and EEG normalization is obtained after intravenous benzodiazepine injection. From a nosographic point of view, four types of AS may be recognized. Typical AS occurs as part of an idiopathic generalized epilepsy. Atypical AS occurs in patients with symptomatic or cryptogenic generalized epilepsies. "De novo" AS of late onset is characterized by toxic or metabolic precipitating factors in middle-aged subjects with no previous history of epilepsy. AS with focal characteristics occurs in subjects with a preexisting or newly developing partial epilepsy, most often of extratemporal origin. Most cases are transitional forms between these four entities. CPSE is characterized by continuous or rapidly recurring complex partial seizures which may involve temporal and/or extratemporal regions. Cyclic disturbance of consciousness is characteristic of CPSE of temporal lobe origin, which requires vigorous treatment to prevent recurrence or cognitive sequelae. CPSE of frontal lobe origin is a diagnostic challenge: it is rare, the symptoms are unusual, and extensive documentation is required. A focal, frontal lesion is discovered in one third of cases.

[Convulsions following dialysis sessions]. / Convulsions dans le décours de séances de dialyse.

A bipolar patient with renal angiosclerosis due to lithium intoxication showed convulsive crises for about four months after each haemodialysis session. Aetiological work up was not able to isolate a unique cause, but modifications in treatment relieved the symptoms.

Intravenous levetiracetam in the treatment of benzodiazepine refractory status epilepticus.

In 2006, levetiracetam was approved as the first of the newer anticonvulsive drugs as an intravenous formulation (ivLEV) for patients with epileptic seizures who are unable to take oral medication. We report our experience with the use of ivLEV for the treatment of 18 episodes of benzodiazepine refractory focal status epilepticus (SE) in 16 patients, including four patients with secondary generalised SE. SE was controlled in all patients by the given combination of drugs; application of further antiepileptic medications after ivLEV was necessary in two episodes. No severe side effects occurred. Our data suggest that ivLEV may be an alternative for the treatment of SE in the future, even in patients that did not respond to benzodiazepines. A large prospective, randomised, controlled study is warranted to investigate the efficacy and safety of ivLEV for the treatment of SE.