A 5-year-old boy with super-refractory status epilepticus and RANBP2 variant warranting life-saving hemispherotomy.

Focal cortical dysplasia (FCD) represents the most common cause of drug-resistant epilepsy in adult and pediatric surgical series. However, genetic factors contributing to severe phenotypes of FCD remain unknown. We present a patient with an exceptionally rapid development of drug-resistant epilepsy evolving in super-refractory status epilepticus. We performed multiple clinical (serial EEG, MRI), biochemical (metabolic and immunological screening), genetic (WES from blood- and brain-derived DNA), and histopathological investigations. The patient presented 1 month after an uncomplicated varicella infection. MRI was negative, as well as other biochemical and immunological examinations. Whole-exome sequencing of blood-derived DNA detected a heterozygous paternally inherited variant NM_006267.4(RANBP2):c.5233A>G p.(Ile1745Val) (Chr2[GRCh37]:g.109382228A>G), a gene associated with a susceptibility to infection-induced acute necrotizing encephalopathy. No combination of anti-seizure medication led to a sustained seizure freedom and the patient warranted induction of propofol anesthesia with high-dose intravenous midazolam and continuous respiratory support that however failed to abort seizure activity. Brain biopsy revealed FCD type IIa; this finding led to the indication of an emergency right-sided hemispherotomy that rendered the patient temporarily seizure-free. Postsurgically, he remains on antiseizure medication and experiences rare nondisabling seizures. This report highlights a uniquely severe clinical course of FCD putatively modified by the RANBP2 variant. PLAIN LANGUAGE SUMMARY: We report a case summary of a patient who came to our attention for epilepsy that could not be controlled with medication. His clinical course progressed rapidly to life-threatening status epilepticus with other unusual neurological findings. Therefore, we decided to surgically remove a piece of brain tissue in order to clarify the diagnosis that showed features of a structural brain abnormality associated with severe epilepsy, the focal cortical dysplasia. Later, a genetic variant in a gene associated with another condition, was found, and we hypothesize that this genetic variant could have contributed to this severe clinical course of our patient.

[Status epilepticus after brain tumor surgery]. / Epilepticheskii status posle udaleniya opukholei golovnogo mozga.

BACKGROUND: Status epilepticus (SE) is characterized by continuous course of clinical and/or electrographic epileptic seizures. There are little data on the course and outcomes of SE after resection of brain tumors. OBJECTIVE: To analyze clinical and electrographic manifestations of SE, its course and outcomes in short-term period after resection of brain tumors. MATERIAL AND METHODS: We analyzed medical records of 18 patients over 18 years old between 2012 and 2019. All patients underwent resection of brain tumor and developed SE after surgery. Clinical criteria were repeated epileptic seizures without interictal recovery of consciousness, stereotypical motor phenomena, impaired consciousness with continued epileptic activity according to video-EEG data. We analyzed EEG data, neurological status, CT and laboratory data. RESULTS: Metastases (33%) and meningiomas (16%) prevailed. Supratentorial tumors were observed in 61% of patients. Two patients had preoperative seizures. Non-convulsive SE was diagnosed in 62% of patients. SE was successfully treated in 77% of cases. Mortality rate in patients with SE was 44%. CONCLUSION: Early postoperative SE is rare after brain tumor surgery (about 0.09%). Nevertheless, this complication is associated with high mortality. Non-convulsive SE is common (62%) that should be considered in postoperative management.

Surgical Management in Herpes Simplex Encephalitis: Illustrative Case Report and Systematic Review of the Literature.

BACKGROUND: Herpes simplex virus (HSV) is a common cause of viral encephalitis and can result in refractory seizures. Although HSV encephalitis (HSVE) is treated primarily with acyclovir, surgery can play a role in medically intractable cases. OBJECTIVE: To systematically review cases describing surgery for the treatment of severe HSVE. We also present an illustrative case of anterior temporal lobectomy (ATL) for refractory status epilepticus in a patient with unilateral HSVE. This case demonstrates one clinical context in which surgery can be a useful adjunct. METHODS: We performed a systematic review using PubMed and Google Scholar, including case reports and series describing surgical interventions for HSVE. Clinical data were extracted from 54 publications that incorporated 67 patient cases. RESULTS: Surgical decompression occurred at a wide range of times after the onset of illness, although most patients were operated on 4 or more days after HSVE symptoms began. Numerous reports indicated that decompressive craniectomy, temporal lobectomy, and hematoma removal could treat intractably elevated intracranial pressure because of HSVE with favorable long-term outcomes. We describe an additional case in which a 52-year-old woman with HSVE developed refractory right temporal lobe seizures. After ATL, the seizures resolved with significant clinical improvement. CONCLUSION: Surgical treatment can be a useful adjunct for treatment of HSVE. There is substantial variability in the timing of surgical decompression in patients with HSVE, which can be necessary up to approximately 3 weeks after illness onset. ATL should be considered for refractory status epilepticus in HSVE with a unilateral seizure focus.

Combined Responsive Neurostimulation and Focal Resection for Super Refractory Status Epilepticus: A Systematic Review and Illustrative Case Report.

OBJECTIVE: Super-refractory status epilepticus (SRSE) is a neurologic emergency with high mortality and morbidity. Although medical algorithms typically are effective, when they do fail, options may be limited, and neurosurgical intervention should be considered. METHODS: We report a case of SRSE treated acutely with responsive neurostimulation (RNS) and focal surgical resection after intracranial monitoring. We also conducted a systematic review of the literature for neurosurgical treatment of SRSE (e.g., neurostimulation). Only published manuscripts were considered. RESULTS: Our patient's seizure semiology consisted of left facial twitching with frequent evolution to bilateral tonic-clonic convulsions. Stereoelectroencephalography and grid monitoring identified multiple seizure foci. The patient underwent right RNS placement with cortical strip leads over the lateral primary motor and premotor cortex as well as simultaneous right superior temporal and frontopolar resection. Status epilepticus resolved 21 days after surgical resection and placement of the RNS. The systematic review revealed 15 case reports describing 17 patients with SRSE who underwent acute neurosurgical intervention. There were 3 patients with SRSE with RNS placement as a single modality, all of whom experienced cessation of SE. Four patients with SRSE received vagus nerve stimulation (3 as a single modality and 1 with combined corpus callosotomy), of whom 1 had SE recurrence at 2weeks. Two patients with SRSE received deep brain stimulation, and the remaining 8 underwent surgical resection; none had recurrence of SE. CONCLUSIONS: RNS System placement with or without resection can be a viable treatment option for select patients with SRSE. Early neurosurgical intervention may improve seizure outcomes and reduce complications.

Surgery for intractable epilepsy after severe encephalopathy with reversible splenial lesion and new onset hippocampal lesion associated with parechovirus.

We describe a case of severe encephalopathy with reversible splenial lesion associated with parechovirus, followed by intractable temporal lobe epilepsy (TLE), which was improved by epilepsy surgery. A 3-year-old girl was admitted because of fever, consciousness disturbance and generalized tonic clonic seizure. Her seizure lasted for four hours. Fluid-attenuated inversion recovery (FLAIR) showed a hyperintensity in the splenium of the corpus callosum. Electroencephalogram (EEG) demonstarated continuous diffuse epileptic activity represented by synchronous and rhythmic high-amplitude spikes and waves, which led to the diagnosis of status epilepticus. Her consciousness was improved with fosphenytoin, midazolam and methylprednisolone pulse after 3 days. Seven days later, FLAIR hyperintensity in the splenium of the corpus callosum was disappeared; however, a hyperintensity in the right hippocampus was detected. Since the stool examination was positive for parechovirus, her final diagnosis was reversible splenial lesion syndrome (RESLES) associated with parechovirus. At age 8, she experienced epigastric sensation and consciousness disturbance once a week. Based on the scalp EEG and radiological findings, she was diagnosed with intractable right TLE. We performed a right selective amygdalohippocampectomy and anterior temporal disconnection at 10 years of age. One year and 3 months after surgery, she was seizure free. To our knowledge, this is the first report of severe febrile epilepticus status. with RESLES associated with parechovirus, followed by intractable TLE, which was resolved by epilepsy surgery.

Management of status epilepticus: a narrative review.

Status epilepticus causes prolonged or repetitive seizures that, if left untreated, can lead to neuronal injury, severe disability, coma and death in paediatric and adult populations. While convulsive status epilepticus can be diagnosed using clinical features alone, non-convulsive status epilepticus requires confirmation by electroencephalogram. Early seizure control remains key in preventing the complications of status epilepticus. This is especially true for convulsive status epilepticus, which has stronger evidence supporting the benefit of treatment on outcomes. When status epilepticus becomes refractory, often due to gamma-aminobutyric acid and N-methyl-D-aspartate receptor modulation, anaesthetic drugs are needed to suppress seizure activity, of which there is limited evidence regarding the selection, dose or duration of their use. Seizure monitoring with electroencephalogram is often needed when patients do not return to baseline or during anaesthetic wean; however, it is resource-intensive, costly, only available in highly specialised centres and has not been shown to improve functional outcomes. Thus, the treatment goals and aggressiveness of therapy remain under debate, especially for non-convulsive status epilepticus, where prolonged therapeutic coma can lead to severe complications. This review presents an evidence-based, clinically-oriented and comprehensive review of status epilepticus and its definitions, aetiologies, treatments, outcomes and prognosis at different stages of the patient's journey.

Role of epilepsy surgery in refractory status epilepticus in children.

INTRODUCTION: Status epilepticus (SE) is one of the most common medical emergencies, requiring urgent treatment; nearly 30 % patients develop refractory SE. The role of epilepsy surgery (ES) for refractory SE however remains unclear with empirical evidence limited to single case reports and small case series. The aim of the present study was to determine the clinical presentation, imaging characteristics and outcome of children with refractory SE who underwent emergency ES for refractory SE. MATERIAL AND METHOD: Patients who had SE, failed to respond to escalating medical treatment of SE with/ without pharmacological suppression therapy, and eventually underwent ES were included. RESULTS: There were ten children, 7 boys and 3 girls (range 6 months to 14 years). The age of onset of epilepsy varied from day 2 of life to 12.8 years. The duration of SE prior to surgery was 2-6 days (mean 3.7 days). Four patients had hemimegalencephaly, 3 had focal cortical dysplasia, 2 had Rasmussen's encephalitis, and one had hemispheric porencephalic cyst. The time interval between onset of seizures and ES ranged from 2 months to 8 years (mean 3.1 year). Seven patients underwent hemispherotomy, resection of dysplasia in two and temporo-parieto-occipital disconnection in one. Nine had Engel I outcome and Engel IIIa in one, at follow up of 12-44 months (mean 31 months). CONCLUSION: Emergency ES is an effective treatment option for termination of refractory SE in children with structural pathology, after failure of medical treatment. Patients with refractory SE with focal or hemispheric structural abnormality on MRI, and concordant semiology with/without concordant EEG can be surgical candidates with or without invasive monitoring.

Surgical management of pediatric patients with encephalopathy due to electrical status epilepticus during sleep (ESES).

ESES is a developmental epileptic disorder directly responsible for progressive encephalopathy and neurocognitive regression. The natural history, indications for surgical intervention, and predictors for favorable seizure and neuropsychological outcome remain unclear. We performed a retrospective review of children who underwent resective or disconnective surgery for ESES between January 2009 and July 2016 at a large tertiary pediatric center. Information on the patients' demographics, seizure semiology, radiographic and electrographic findings, and surgical management was collected. The primary outcome was seizure freedom at last follow-up visit, and secondary outcomes were neuropsychological improvement and electrographic ESES resolution. We identified 11 children who underwent surgery for ESES. The mean ages were 3.2 years for seizure onset, 7.1 years for formal ESES diagnosis, and 9.4 years for surgery. Seizure etiologies included cortical malformations (four patients), encephalomalacia and gliosis from prior hemorrhage or tumor resections (three patients), developmental porencephaly (one patient), and Rasmussen's encephalitis (one patient); the etiology was unknown in two children. Preoperatively, nine children had motor deficits, seven had speech and language delay, and three had visual field defects. All children had seizures and neuropsychological regression prior to surgical consideration. Focal cortical resections were performed in seven children, and hemispherectomies in four. Post-operatively, nine children experienced decreased seizure frequency, eight had neuropsychological improvement, and nine had resolution of electrographic ESES. Patients with poor surgical outcomes had more significant pre-operative comorbidities, in addition to bilateral ESES activity. In this case series, surgery for a carefully selected group of children with ESES is safe and feasible, yielding rates of seizure freedom and neuropsychological improvement that compare favorably with previous reports for antiepileptic drugs, benzodiazepines, and steroids. As we gain greater understanding into the management of ESES, surgery is an increasingly useful tool for patients with mild or moderate neurodevelopmental delay, focal epileptogenic foci, and hemi-ESES electrographic findings.

Spontaneous neonatal subdural haemorrhage: always non-accidental injury?

In any neonate or infant presenting with an acute onset of encephalopathy, and/or retinal haemorrhages with no history of major trauma and imaging showing subdural haemorrhage (SDH), the diagnostic priority is to exclude a non-accidental injury (NAI), given the association of these clinical features with the shaken baby syndrome. However, other causes of SDH may present in a similar manner in neonates and infants, in particular vascular lesions such as aneurysms. A four week old neonate presenting with seizures and retinal haemorrhages, was diagnosed with an acute subdural haemorrhage (ASDH) on imaging with significant midline shift needing surgical evacuation. As there was some blood extending into the left sylvian fissure, further imaging was considered before surgical intervention. This showed a distally located middle cerebral artery aneurysm, which was successfully treated and the neonate made a remarkable recovery. We present a case of a neonate presenting with spontaneous acute subdural haematoma in the absence of classical diffuse subarachnoid haemorrhage, intracerebral haemorrhage or intraventricular haemorrhage, secondary to a ruptured middle cerebral artery aneurysm. The distribution of aneurysms in the neonatal age group is different to adults, with middle cerebral artery aneurysms and more distally located peripheral aneurysms being more common. Vigilance should be borne to exclude the aforementioned as causes for this presentation especially prior to undertaking surgical intervention.

Surgically Treated Status Epilepticus due to Large Cortical Tuber and Long-Term Follow-Up Results.

We present a case of invasive monitoring of a patient while he was being surgically treated in the status state. Our patient was a 27-year-old male who was hospitalized for frequent seizures, which began after a head trauma at the age of 3 years. Video electroencephalography was performed, and 25 clinical seizures were observed in 24 hours. Cranial magnetic resonance imaging (MRI) revealed a right frontal lesion which was hyperintense in T2-weighted and hypointense in T1-weighted images, and a subependymal nodule. For invasive monitoring, subdural electrodes were placed on the cortex surface via a right frontal craniotomy. The patient was re-operated, and the epileptic zone resection was performed. There was no sign of neurological deficit. Histopathological examination revealed cortical tuber, and the patient was scanned for tuberous sclerosis. There was no sign of tuberous sclerosis in other organs. The diagnosis of our patient was tuberous sclerosis, cortical tuber, subependymal nodule, epilepsy, and intermediate mental retardation. Radiological diagnosis should also be considered. Cortical tuber can be confused with focal cortical dysplasia. Finally, staged resection may be performed as a surgical treatment in some cases.

Parasagittal hemispherotomy in hemispheric polymicrogyria with electrical status epilepticus during slow sleep: Indications, results and follow-up.

PURPOSE: Polymicrogyria (PMG), although the most common brain malformation, represents a low percentage among patients operated on for epilepsy. In cases of hemispheric PMG, electrical status epilepticus during slow sleep (ESESS) may occur leading to an aggravation of the neurological condition and a risk of drug resistance. In such cases, surgical treatment can be offered. METHODS: From a population of 230 children who underwent hemispherotomy for epilepsy, we retrospectively reviewed the patients with unilateral PMG and drug-resistant ESESS focusing on clinical charts, electrophysiological data and post-surgical outcome. RESULTS: Eighteen patients were operated on at a mean age of 7.2 years. The average age was 2 years at seizure onset and 4.4 years at diagnosis of ESESS. All the patients preoperatively had some degree of developmental delay associated with a hemiparesis. During ESESS all of them evidenced a cognitive decline and eight experienced a worsening of the hemiparesis; ESESS was resistant to at least three antiepileptic drugs. The outcome of epilepsy, with a mean follow-up of 12.8 years showed that ESESS disappeared in all patients while 16 of 18 became seizure-free. An improvement of behavior and cognitive condition was observed in all. CONCLUSION: Hemispherotomy can be helpful in patients with drug-resistant ESESS and hemispheric PMG while keeping in mind that more often an accurate medical treatment can be sufficient. The main benefit of surgery is to definitively stop the seizures and to withdraw the medical treatment while keeping in mind the risk of motor aggravation.

Total Corpus Callosotomy for Medically Refractory Status Epilepticus Due to Progressive Myoclonic Epilepsy: A Clinically Challenging Case.

BACKGROUND: Progressive myoclonic epilepsy (PME) is a syndrome characterized by development of progressive myoclonus, cognitive impairment, and other neurologic deficits. Despite major advances in medical treatment of epilepsy, some PME patients remain refractory to antiepileptic drugs. This may further accentuate cognitive impairment and deteriorate functional capacity. Corpus callosotomy (CC) is used in patients with drug-resistant epilepsy who are not candidates for either excisional epilepsy surgery or neurostimulation. We report the application of the standard complete callosotomy to control medically refractory status epilepticus in a patient with PME. CASE DESCRIPTION: A 16-year-old boy was referred to the emergency department with generalized tonic-clonic seizures. He was known to have PME since 5 years earlier, with frequent generalized seizures requiring hospitalization and reloading of the drugs. The patient was discussed by the epilepsy surgery working group, and corpus callosotomy was considered as a last resort to control the refractory status epilepticus. The patient experienced no generalized seizures during the 3-month postoperative period (Engel class IIIB). CONCLUSIONS: Inasmuch as surgery was the last resort to control severe disabling status epilepticus, because most of the epileptogenic discharges were originating from the parieto-occipital regions and profound cognitive impairment was present, we decided to perform a complete rather than just an anterior callosotomy. CC may be considered to prevent secondary generalized seizures as the most disabling attacks in patients with certain epilepsy syndromes. Nevertheless, the impact of palliative surgical intervention on the overall disease course of patients with an underlying diffuse pathologic state remains to be determined.

Human induced pluripotent stem cell-derived MGE cell grafting after status epilepticus attenuates chronic epilepsy and comorbidities via synaptic integration.

Medial ganglionic eminence (MGE)-like interneuron precursors derived from human induced pluripotent stem cells (hiPSCs) are ideal for developing patient-specific cell therapy in temporal lobe epilepsy (TLE). However, their efficacy for alleviating spontaneous recurrent seizures (SRS) or cognitive, memory, and mood impairments has never been tested in models of TLE. Through comprehensive video- electroencephalographic recordings and a battery of behavioral tests in a rat model, we demonstrate that grafting of hiPSC-derived MGE-like interneuron precursors into the hippocampus after status epilepticus (SE) greatly restrained SRS and alleviated cognitive, memory, and mood dysfunction in the chronic phase of TLE. Graft-derived cells survived well, extensively migrated into different subfields of the hippocampus, and differentiated into distinct subclasses of inhibitory interneurons expressing various calcium-binding proteins and neuropeptides. Moreover, grafting of hiPSC-MGE cells after SE mediated several neuroprotective and antiepileptogenic effects in the host hippocampus, as evidenced by reductions in host interneuron loss, abnormal neurogenesis, and aberrant mossy fiber sprouting in the dentate gyrus (DG). Furthermore, axons from graft-derived interneurons made synapses on the dendrites of host excitatory neurons in the DG and the CA1 subfield of the hippocampus, implying an excellent graft-host synaptic integration. Remarkably, seizure-suppressing effects of grafts were significantly reduced when the activity of graft-derived interneurons was silenced by a designer drug while using donor hiPSC-MGE cells expressing designer receptors exclusively activated by designer drugs (DREADDs). These results implied the direct involvement of graft-derived interneurons in seizure control likely through enhanced inhibitory synaptic transmission. Collectively, the results support a patient-specific MGE cell grafting approach for treating TLE.

Dietary, immunological, surgical, and other emerging treatments for pediatric refractory status epilepticus.

PURPOSE: To summarize the evidence regarding dietary, immunological, surgical, and other emerging treatments for refractory status epilepticus (RSE)/super-RSE (SRSE). METHODS: Narrative literature review including relevant human studies. RESULTS: Hypothermia and brenaxolone were tested in randomized controlled trials for RSE/SRSE management, while other interventions have only limited evidence for their efficacy and safety. Clinical trials including the HYBERNATUS study found the efficacy of therapeutic hypothermia to be no better than placebo for RSE/SRSE, and raised concerns about its safety. Ketogenic diet has shown possible efficacy in RSE/SRSE in several case series, with electrographic seizure resolution within 7 days in 20%-90% patients in larger (n = 8-17) reports. A review of 37 pediatric patients reported seizure control with immunotherapy in only 7 patients. A phase 3 double-blind trial showed that brexanolone was no better than placebo for successful wean of 3rd line anesthetic agent(s) and freedom from RSE for ≥24 hours. Epilepsy surgery has been reported to successfully control seizures in small series; however, pre-surgical evaluation is confounded by ongoing ictal activity and anesthetic infusions. Vagus nerve stimulation was reported to be associated with cessation of RSE/SRSE in 21/28 patients in a review of anecdotal reports. There is no evidence for use of pyridoxine and magnesium outside of specific indications. CONCLUSIONS: There is only anecdotal evidence for dietary, immunological, surgical, and other treatments for RSE/SRSE, often confounded by multiple concurrent treatments, and heterogeneity in their use and assessment of outcomes. Clinical trials for therapeutic hypothermia and brexanolone have not shown a significant advantage over comparators.

The phenotype of bilateral hippocampal sclerosis and its management in "real life" clinical settings.

OBJECTIVE: There is little detailed phenotypic characterization of bilateral hippocampal sclerosis (HS). We therefore conducted a multicenter review of people with pharmacoresistant epilepsy and bilateral HS to better determine their clinical characteristics. METHODS: Databases from 11 EPIGEN centers were searched. For identified cases, clinicians reviewed the medical notes, imaging, and electroencephalographic (EEG), video-EEG, and neuropsychometric data. Data were irretrievably anonymized, and a single database was populated to capture all phenotypic information. These data were compared with phenotyped cases of unilateral HS from the same centers. RESULTS: In total, 96 patients with pharmacoresistant epilepsy and bilateral HS were identified (43 female, 53 male; age range = 8-80 years). Twenty-five percent had experienced febrile convulsions, and 27% of patients had experienced status epilepticus. The mean number of previously tried antiepileptic drugs was 5.32, and the average number of currently prescribed medications was 2.99; 44.8% of patients had cognitive difficulties, and 47.9% had psychiatric comorbidity; 35.4% (34/96) of patients continued with long-term medical therapy alone, another 4 being seizure-free on medication. Sixteen patients proceeded to, or were awaiting, neurostimulation, and 11 underwent surgical resection. One patient was rendered seizure-free postresection, with an improvement in seizures for 3 other cases. By comparison, of 201 patients with unilateral HS, a significantly higher number (44.3%) had febrile convulsions and only 11.4% had experienced status epilepticus. Importantly, 41.8% (84/201) of patients with unilateral HS had focal aware seizures, whereas such seizures were less frequently observed in people with bilateral HS, and were never observed exclusively (P = .002; Fisher's exact test). SIGNIFICANCE: The current work describes the phenotypic spectrum of people with pharmacoresistant epilepsy and bilateral HS, highlights salient clinical differences from patients with unilateral HS, and provides a large platform from which to develop further studies, both epidemiological and genomic, to better understand etiopathogenesis and optimal treatment regimes in this condition.

Transient Focal Magnetic Resonance Imaging Abnormalities After Status Epilepticus Showed 11C-Methionine Uptake with Positron Emission Tomography in a Patient with Cerebral Cavernous Malformation.

BACKGROUND: Transient focal magnetic resonance imaging (MRI) abnormalities after status epilepticus (SE) are rarely seen in patients with benign brain tumors, and the underlying mechanism is still unknown. We report a rare case of cerebral cavernous malformation with transient focal MRI abnormalities around the tumor and accumulation of 11C-methionine on positron emission tomography (PET) after SE. These findings mimicked those of a glioma because the MRI and methionine PET findings were similar. We also speculate about the cause of this phenomenon in relation to pathologic findings of this case. CASE DESCRIPTION: A 51-year-old man suffered from SE. MRI demonstrated a focal T2/fluid-attenuated inversion recovery hyperintense area. 11C-methionine PET showed high accumulation of methionine in the same lesion. The initial diagnosis was low-grade glioma. However, these MRI abnormalities were transient and completely resolved. The patient underwent surgical removal of the tumor, and the histologic diagnosis was typical cavernous malformation. Pathologic findings of the gyrus around the tumor revealed mild gliosis with proliferating astrocytes but no evidence of glioma. CONCLUSIONS: This case suggests that transient focal MRI abnormalities after SE may indicate reversible cortical brain edema. Accumulation of 11C-methionine on PET could occur in the corresponding lesion even if no malignant tumor is present. Because distinguishing transient MRI abnormalities after SE from a glioma is difficult, repeated imaging studies should be performed in patients with brain tumor-related seizures.

Outcomes in Children Treated with Pentobarbital Infusion for Refractory and Super-Refractory Status Epilepticus.

BACKGROUND: Functional neurologic outcome for children with refractory and super-refractory status epilepticus has not been well defined. METHODS: Retrospective chart review including children age 0-17 years who received pentobarbital infusion from 2003 to 2016 for status epilepticus. Outcomes were defined in terms of mortality, need for new medical technology assistance at hospital discharge and functional neurologic outcome determined by pediatric cerebral performance category score (PCPC). Potential patient characteristics associated with functional neurologic outcome including age, sex, ethnicity, etiology of the status epilepticus, and duration of pentobarbital infusion were evaluated. RESULTS: Forty children met inclusion criteria. In-hospital mortality was 30% (12/40). Of survivors, 21% (6/28) returned to baseline PCPC while half (14/28) declined in function ≥ 2 PCPC categories at hospital discharge. 25% (7/28) of survivors required tracheostomy and 27% (7/26) required new gastrostomy. Seizures persisted at discharge for most patients with new onset status epilepticus while the majority of patients with known epilepsy returned to baseline seizure frequency. Etiology (p = 0.015), PCPC at admission (p = 0.0006), new tracheostomy (p = 0.012), and new gastrostomy tube (p = 0.012) were associated with increase in PCPC score ≥ 2 categories in univariable analysis. Duration of pentobarbital infusion (p = 0.005) and length of hospital stay (p = 0.056) were longer in patients who demonstrated significant decline in neurologic function. None of these variables maintained statistical significance when multiple logistic regression model adjusting for PCPC score at admission was applied. At long-term follow-up, 36% (8/22) of children demonstrated improvement in PCPC compared to discharge and 23% (5/22) showed deterioration including three additional deaths. CONCLUSIONS: Mortality in this population was high. The majority of children experienced some degree of disability at discharge. Despite prolonged pentobarbital infusion, there were cases of survival with good neurologic outcome.

Intravenous infusion of mesenchymal stem cells reduces epileptogenesis in a rat model of status epilepticus.

OBJECTIVE: Status epilepticus (SE) causes neuronal cell death, aberrant mossy fiber sprouting (MFS), and cognitive deteriorations. The present study tested the hypothesis that systemically infused mesenchymal stem cells (MSCs) reduce epileptogenesis by inhibiting neuronal cell death and suppressing aberrant MFS, leading to cognitive function preservation in a rat model of epilepsy. METHODS: SE was induced using the lithium-pilocarpine injection model. The seizure frequency was scored using a video-monitoring system and the Morris water maze test was carried out to evaluate cognitive function. Comparisons were made between MSCs- and vehicle-infused rats. Immunohistochemical staining was performed to detect Green fluorescent protein (GFP)+ MSCs and to quantify the number of GAD67+ and NeuN+ neurons in the hippocampus. Manganese-enhanced magnetic resonance imaging (MEMRI) and Timm staining were also performed to assess the MFS. RESULTS: MSC infusion inhibited epileptogenesis and preserved cognitive function after SE. The infused GFP+ MSCs were accumulated in the hippocampus and were associated with the preservation of GAD67+ and NeuN+ hippocampal neurons. Furthermore, the MSC infusion suppressed the aberrant MFS in the hippocampus as evidenced by MEMRI and Timm staining. CONCLUSIONS: This study demonstrated that the intravenous infusion of MSCs mitigated epileptogenesis, thus advancing MSCs as an effective approach for epilepsy in clinical practice.