Intractable Status Epilepticus Research Articles

Transsinusal embolization of transverse sigmoid sinus dural arteriovenous fistula in a hybrid operating room: A technical note

BackgroundUsing the transverse sinus as a conduit to treat a transverse sigmoid sinus dural arteriovenous fistula is uncommon. This report describes a minimally invasive direct puncture technique for the transverse sinus to treat a complex dural arteriovenous fistula in a hybrid operating room. CaseThe patient was a 64-year-old man with intractable status epilepticus. Digital subtraction angiography demonstrated a right transverse sigmoid sinus dural arteriovenous fistula (Borden type II, Cognard type IIa+b). We performed a transcranial direct puncture because the femoral vein approach was not feasible due to bilateral thrombosed sinuses. Under general anesthesia and park-bench patient positioning, the transverse sinus was exposed and catheterized, and the affected sinus was embolized using microcoils. The fistula was completely obliterated, resolving the status epilepticus. ConclusionsDirect puncture of the transverse sinus can be effective for treating a transverse sigmoid sinus dural arteriovenous fistula. In a hybrid operating room, combined treatments can be performed comfortably and safely in a single session of general anesthesia. This treatment option is a viable alternative when other methods are unsuccessful.

Probable Sudden Unexpected Death in Dogs With Epilepsy (pSUDED).

Sudden unexpected death in human epileptic patients (SUDEP) is defined as death related to recurrent unprovoked seizures, death occurring unexpectedly, and suddenly in a patient with reasonable state of health, without an obvious medical cause of death, trauma, asphyxia, or intractable status epilepticus, and in post mortem examination no obvious reason for death can be found. “Probable SUDEP” (pSUDEP) is defined as SUDEP not confirmed pathologically. The adapted abbreviation for dogs is used in the following: “pSUDED” (probable sudden unexpected death in dogs with epilepsy). The aim of the present monocentric retrospective study using an online questionnaire was to evaluate the occurrence of pSUDED. Data of canine patients presented with seizures between 01/1998 and 05/2018 were retrospectively analyzed and classified according to their etiology (n = 1,503). Owners were contacted by telephone to participate in answering a validated questionnaire. A total of 509 owners were reached, and 373 owners completed the questionnaire. In addition to signalement (e.g., breed), special attention was paid to the frequency and presentation of seizures and seizures in the context of death. Fifty-one percent (191/373) of the dogs were dead at the endpoint of the study. A large proportion of the dogs was euthanized (149/191) because of seizure severity or health problems unrelated to seizures. Idiopathic epilepsy (IE) was diagnosed in 19/34 dogs which died unexpectedly. Of these seven animals had to be excluded for further investigation of pSUDED because of status epilepticus or aspiration pneumonia as a result of the seizures. In 12 dogs with IE the last seizure event occurred between 6 h and ~3 months before death. pSUDED was suspected in these dogs and an occurrence rate of 4.5–10% was calculated. pSUDED appears in a similar occurrence rate as human SUDEP and should be considered as a possible complication in epileptic dogs. The results of this study suggest that dogs with IE but especially those with brachycephalic syndrome and cluster seizures have an increased risk to die of pSUDED. Owners of dogs with seizures should be educated about the risk of sudden death in dogs with epilepsy.

New-onset Refractory Status Epilepticus Involving the Limbic System, Spinal Cord, and Peripheral Nerves

A healthy 28-year-old woman presented suddenly with intractable status epilepticus: a focal seizure evolved into a generalized seizure preceded by a high fever. Brain magnetic resonance imaging indicated bilateral hyperintensities in the hippocampus on T2-weighted imaging. Electroencephalograms continuously demonstrated diffuse sharp waves and poly-spikes. Comprehensive immunomodulation therapies and anti-epileptic drugs did not lead to any improvements. We therefore diagnosed her with cryptogenic limbic encephalitis and new-onset refractory status epilepticus (NORSE). We detected positive anti-ganglioside antibodies, IgG-GQ1b, GD1a, and GT1b, which were negative at six months after the onset. We emphasize the heterogeneous pathogenesis and intractable conditions of NORSE.

Epilepsy Comorbidity in Children with Cerebral Palsy

Cerebral palsy remains as the most frequent cause of motor delay in the young children. Epilepsy can be found in about one-third of childhood patients with cerebral palsy. All seizure types can be seen. The most common types are partial complex and secondary generalized seizures. Seizures in children associated with cerebral palsy have the tendency of earlier onset, and harder control, correlated with the severity degree of cerebral palsy and the existence of mental impairment. The seizure outcome in patients with cerebral palsy is majorly poor. They usually require long-term medications and polytherapy, with more chance of intractable seizures and/or status epilepticus. The risk of seizure recurrence after stopping anticonvulsants in those with cerebral palsy remains high. Factors related to longer seizure-free period in epileptic children having cerebral palsy are normal intelligence quotient, one seizure type, mono-therapy, and spastic diplegic pattern.

Cortical neurons and networks are dormant but fully responsive during isoelectric brain state.

A continuous isoelectric electroencephalogram reflects an interruption of endogenously-generated activity in cortical networks and systematically results in a complete dissolution of conscious processes. This electro-cerebral inactivity occurs during various brain disorders, including hypothermia, drug intoxication, long-lasting anoxia and brain trauma. It can also be induced in a therapeutic context, following the administration of high doses of barbiturate-derived compounds, to interrupt a hyper-refractory status epilepticus. Although altered sensory responses can be occasionally observed on an isoelectric electroencephalogram, the electrical membrane properties and synaptic responses of individual neurons during this cerebral state remain largely unknown. The aim of the present study was to characterize the intracellular correlates of a barbiturate-induced isoelectric electroencephalogram and to analyse the sensory-evoked synaptic responses that can emerge from a brain deprived of spontaneous electrical activity. We first examined the sensory responsiveness from patients suffering from intractable status epilepticus and treated by administration of thiopental. Multimodal sensory responses could be evoked on the flat electroencephalogram, including visually-evoked potentials that were significantly amplified and delayed, with a high trial-to-trial reproducibility compared to awake healthy subjects. Using an analogous pharmacological procedure to induce prolonged electro-cerebral inactivity in the rat, we could describe its cortical and subcortical intracellular counterparts. Neocortical, hippocampal and thalamo-cortical neurons were all silent during the isoelectric state and displayed a flat membrane potential significantly hyperpolarized compared with spontaneously active control states. Nonetheless, all recorded neurons could fire action potentials in response to intracellularly injected depolarizing current pulses and their specific intrinsic electrophysiological features were preserved. Manipulations of the membrane potential and intracellular injection of chloride in neocortical neurons failed to reveal an augmented synaptic inhibition during the isoelectric condition. Consistent with the sensory responses recorded from comatose patients, large and highly reproducible somatosensory-evoked potentials could be generated on the inactive electrocorticogram in rats. Intracellular recordings revealed that the underlying neocortical pyramidal cells responded to sensory stimuli by complex synaptic potentials able to trigger action potentials. As in patients, sensory responses in the isoelectric state were delayed compared to control responses and exhibited an elevated reliability during repeated stimuli. Our findings demonstrate that during prolonged isoelectric brain state neurons and synaptic networks are dormant rather than excessively inhibited, conserving their intrinsic properties and their ability to integrate and propagate environmental stimuli.

ATAXIA AND EPILEPSY DUE TO A RARE AUTOSOMAL MITOCHONDRIAL DISEASE

We report a case of a twenty three year old female presenting with status epilepticus due to a rare mutation in a nuclear gene causing mitochondrial dysfunction. She had previously...

ONYX versus n-BCA for embolization of cranial dural arteriovenous fistulas

PurposeTo evaluate the efficacy of n-butyl-2-cyanoacrylate (Trufill n-BCA) versus ethylene vinyl alcohol copolymer (ONYX) for the embolization of cranial dural arteriovenous fistulas (DAVF).MethodsFifty-three consecutive patients with cranial dural AVF were...

Delineating Cortical Networks Underlying Epileptic Encephalopathy and Cognitive Impairment with PET: A Perspective

Sometimes childhood epilepsy may present with an acute onset of catastrophic seizures, rapidly progressing to intractable status epilepticus with poor outcome. One such example is postencephalitic epilepsy ([1][1]), which is a rare epileptic condition and is characterized by different names, such as

Efficacy of ketogenic diet in severe refractory status epilepticus initiating fever induced refractory epileptic encephalopathy in school age children (FIRES)

Fever induced refractory epileptic encephalopathy in school age children (FIRES) is a devastating condition initiated by prolonged perisylvian refractory status epilepticus (SE) triggered by fever of unknown cause. SE may last more than 1 month, and this condition may evolve into pharmacoresistant epilepsy associated with severe cognitive impairment. We aimed to report the effect of ketogenic diet (KD) in this condition. Over the last 12 years we collected data of nine patients with FIRES who received a 4:1 ratio of fat to combined protein and carbohydrate KD. They presented with SE refractory to conventional antiepileptic treatment. In seven patients, KD was efficacious within 2-4 days (mean 2 days) following the onset of ketonuria and 4-6 days (mean 4.8 days) following the onset of the diet. In one responder, early disruption of the diet was followed by relapse of intractable SE, and the patient died. Epilepsy affected the other six responders within a few months. KD may be an alternative therapy for refractory SE in FIRES and might be proposed in other types of refractory SE in childhood.

Extensive apoptosis in a case of intractable infantile status epilepticus

A previously healthy 8 1/2-month-old girl underwent epilepsy surgery for intractable focal seizures with secondary generalization that progressed to status epilepticus. The major neuropathologic finding was extensive apoptosis. Investigations did not reveal any etiology for the apoptosis or the seizures. This is the first report of apoptosis, without necrosis, in association with intractable status epilepticus in the developing human brain. The findings suggest that new treatment strategies targeted to prevent apoptosis may be useful in children with prolonged status epilepticus.

Delayed diagnosis of SLE in a patient presenting with intractable status epilepticus

Delayed diagnosis of SLE in a patient presenting with intractable status epilepticus

Two-methyl-6-phenylethynyl-pyridine (MPEP), a metabotropic glutamate receptor 5 antagonist, with low doses of MK801 and diazepam: A novel approach for controlling status epilepticus

By intravenous administration of group I metabotropic glutamate receptor antagonists at 1 or 2 h during pilocarpine induced status epilepticus (PISE), we showed that mGluR1 antagonists AIDA or LY367385 (at dosages ranging from 25 to 200 mg/kg), mGluR5 antagonists SIB1757 (at dosages ranging from 25 to 200 mg/kg), SIB1893 (from 25 to 100 mg/kg), MPEP (from 25 to 100 mg/kg) injected at 1 or 2 h during PISE were ineffective in controlling status epilepticus (SE). However, when administered at 1 h during PISE, MPEP at 200 mg/kg, combination of MPEP (200 mg/kg) with MK801 (0.1 mg/kg) or with MK801 (0.1 mg/kg) and diazepam (0.5 mg/kg), combination of SIB1893 (200 mg/kg) with MK801 (0.1 mg/kg) could effectively control behavioral SE, and were neuroprotective. In particular, the combination of MPEP with MK801 and diazepam could stop both behavioral SE and electrical SE (under EEG monitoring) within a few minutes after the administration. HPLC study showed that a high level of MPEP was maintained in the blood and its metabolism rate was slow in experimental mice with PISE. We therefore concluded that the combination of MPEP (200 mg/kg) with MK801 (0.1 mg/kg) and diazepam (0.5 mg/kg) could effectively stop SE and its subsequent neuronal loss in the hippocampus when administered 1 h during PISE. It may provide a new approach to effectively control intractable SE.

Devastating epileptic encephalopathy in school-aged children (DESC): A pseudo encephalitis

Purpose To describe the characteristics of a previously overlooked devastating epileptic encephalopathy that presents as intractable bilateral perisylvian epilepsy starting with prolonged status epilepticus (SE) in normally developing school-aged children. Methods Retrospective study over 7 years of all normally developing children admitted in our institution for a prolonged SE following non-specific febrile illness with at least one seizure recorded on EEG. Results Fourteen children were included at a median age of 7.5 years (4–11) (median follow-up of 4 years (1–7)). Intractable SE lasted 4–60 days (median 30). CSF cell count was normal in five cases and moderately increased in the others. During SE, seizures were recorded in 11 patients and involved temporal lobes in 7; the other 4 patients exhibited perisylvian clinical features with secondary generalization. Intractable epilepsy followed SE in all cases without any latent period. Persisting seizures were recorded in 10 patients and involved temporo-perisylvian regions in 8, frontal regions in 2; 3 others had perisylvian ictal semiology. Spiking was bilateral in 10 cases. MRI showed bilateral hippocampal hypersignal and/or atrophy in 10 cases (extended to the neocortex in 3). All children had major cognitive sequelae. When feasible (six patients), detailed neuropsychology suggested fronto-temporal impairment. Conclusions Among so called grey matter encephalitis patients, we identified a recognizable pattern we propose to call Devastating Epileptic encephalopathy in School-age Children (DESC) that begins with prolonged SE triggered by fever of unknown cause, and persists as intractable perisylvian epilepsy with severe cognitive deterioration.

Life‐saving epilepsy surgery for status epilepticus caused by cortical dysplasia

ABSTRACT A uniquely successful neurosurgical intervention in a four‐ month‐old child suffering from status epilepticus (SE) caused by focal cortical dysplasia is reported. Seizures appeared at postnatal day 10 and culminated as medically intractable focal motor SE three months later. The first MRI scan at postnatal week 2 was inconclusive; electroclinical features typical of malformations of cortical development led to the repetition of MRI at the age of 3 months that confirmed the correct diagnosis. Since all medical trials including thiopental anaesthesia have been unsuccessful in treatment of SE, urgent resection of the right frontal and parietal lobes was performed at 4 months of age. One month later, the child had become seizure‐free and her psychomotor development is proceeding well. Histopathological analysis of the resected brain tissue revealed abnormalities typical of the Taylor's type of focal cortical dysplasia. The aim of the report is to encourage considering surgery in selected patients suffering from medically intractable SE early in life.

Long-term observations of two siblings with Lafora disease treated with zonisamide

We have reported long-term clinical follow-up for two siblings with Lafora disease, a brother and sister, one of whom autopsied. Both siblings had repeated attacks of severe myoclonus, tonic and tonic–clonic convulsions, and intractable status epilepticus. The addition of orally administered zonisamide brought about striking effective seizure control for about 12–14 years in both patients, relieving not only myoclonus and generalized tonic–clonic seizures but also intractable status epilepticus.

Neurosurgical treatment of medically intractable status epilepticus

Medically intractable status epilepticus can be defined as status epilepticus (SE) that persists or recurs despite medical treatment with intravenous agents that suppress cortical activity. We describe the successful neurosurgical treatment of three patients with medically intractable status epilepticus who responded either to focal resection, multiple subpial transection, or callosal section. The duration of medically intractable status epilepticus before surgery ranged between 23 and 42 days, and multiple medical complications occurred during the failed medical therapy. We suggest that patients with medically intractable status epilepticus who fail to respond to three courses of cerebral suppressant therapy for ∼2 weeks be considered for surgical treatment in the absence of any known remitting etiology. Focal resection and/or subpial transection is preferred for intractable partial SE with focal electrographic changes or a focal lesion demonstrated by structural or functional neuroimaging. Corpus callosotomy may be used for patients with generalized or non-localizable intractable status epilepticus.

Fatal hyperammonemia following orthotopic lung transplantation

There have been anecdotes of unexplained coma and death in patients after otherwise successful orthotopic lung transplantation. A patient with primary pulmonary hypertension who underwent a technically uncomplicated single orthotopic lung transplantation is described. The patient developed intractable status epilepticus 4 days after surgery in association with the presence of a markedly elevated plasma ammonium level. Despite multiple therapeutic interventions, the hyperammonemia ultimately resulted in the patient's death. Both metabolic and enzymatic studies showed that the unique physiological disturbance in this disorder results at least in part from defective in vivo conversion of waste nitrogen to urea and increased production of waste nitrogen. Although the rate of hepatic ureagenesis was therefore insufficient to prevent accumulation of ammonium, the cause was not severe liver disease. Liver histology showed widespread, microvesicular steatosis on light-microscopic examination, but only electron- microscopic examination showed severe microvesicular steatosis with severe mitochondrial injury. As in Reye's syndrome, it was unclear whether the hepatic mitochondrial injury played a role in development or if it was the result of hyperammonemia. We recommended that any patient with an unexplained alteration of mental status after solid organ transplantation be evaluated for hyperammonemia. (Gastroenterology 1997 Jan;112(1):236-40)

Valproate in status epilepticus.

In patients with intractable status epilepticus who have not responded to therapy with benzodiazepines, phenytoin, and barbiturates, valproate may be a reasonable option. Extemporaneously prepared valproate rectal suppositories or retention enemas have been given in dosages of 200-1200 mg q6h in addition to phenytoin, phenobarbital, or both in adults. The pediatric dose used was 15-20 mg/kg, in addition to phenytoin and/or phenobarbital.

Intractable status epilepticus

Optimal treatment strategies and mortality for prolonged generalized convulsive status epilepticus (SE) remain uncertain. This is especially so in cases in which SE recurs after initial treatment with pentobarbital (“intractable SE”). Two patients exhibited intractable SE for 26 and 56 days. When pentobarbital produced systemic hypotension, a continuous infusion of lorazepam was substituted without hypotension. Both patients survived and recovered adequately to be discharged home. EEG was monitored continuously in both patients. An orderly sequence of electrographic SE stages was seen as SE was terminated or recurred. These findings indicate survival after intractable SE is possible and also suggest lorazepam may be an effective alternative to pentobarbital for treatment of such severe cases.

Chlormethiazole in treatment of status epilepticus.

Chlormethiazole (Heminevrin) was successful in controlling fits in seven out of nine episodes of intractable status epilepticus. It was administered as a constant intravenous injection at rates of up to 0.7g/h. No serious side effects were encountered, and the drug deserves wider recognition as a useful therapeutic agent in the management of status epilepticus.