Responsive neurostimulation as a therapy for epilepsy following new-onset refractory status epilepticus: Case series and review of the literature.

OBJECTIVE: To report clinical outcomes of patients who presented with new-onset refractory status epilepticus (NORSE), developed drug-resistant epilepsy (DRE), and were treated with responsive neurostimulation (RNS). METHODS: We performed a retrospective review of patients implanted with RNS at our institution and identified three who originally presented with NORSE. Through chart review, we retrieved objective and subjective information related to their presentation, workup, and outcomes including patient-reported seizure frequency. We reviewed electrocorticography (ECoG) data to estimate seizure burden at 3, 6, 12, and 24 months following RNS implantation. We performed a review of literature concerning neurostimulation in NORSE. RESULTS: Use of RNS to treat DRE following NORSE was associated with reduced seizure burden and informed care by differentiating epileptic from non-epileptic events. CONCLUSIONS: Our single-center experience of three cases suggests that RNS is a safe and potentially effective treatment for DRE following NORSE. SIGNIFICANCE: This article reports outcomes of the largest case series of NORSE patients treated with RNS. Since patients with NORSE are at high risk of adverse neuropsychiatric and cognitive sequelae beyond seizures, a unique strength of RNS over other surgical options is the ability to distinguish ictal or peri-ictal from non-epileptic events.

[Long-term follow-up of adult patients with serial and status course of epileptic seizures]. / Dolgosrochnyi katamnez vzroslykh patsientov s epilepsiei s epilepticheskim statusom ili seriinymi pristupami.

OBJECTIVE: To study the follow-up of adult patients with status epilepticus or a history of serial seizures, assessing the likelihood of achieving long-term remission and identifying predictors of treatment effectiveness. MATERIAL AND METHODS: The study included 280 patients divided into 137 patients with epilepsy with a series of seizures or a history of status epilepticus (group 1) and 143 patients, who had not previously received therapy and did not have a series of seizures or a history of status epilepticus (group 2). A clinical and neurological examination, analysis of medical documentation data, electroencephalography, and MRI were performed. RESULTS: After correction of therapy, remission in patients in group 1 was achieved in 21.9%, improvement in 30%, no effect was observed in 48.1%; in group 2 the indicators were 51%, 28.7%, 20.3%, respectively. The onset of epilepsy in childhood, frequent seizures, and regional epileptiform activity were associated with the lack of treatment effect. CONCLUSION: The results confirm the main role of the clinical examination in determining the prognosis of epilepsy in a particular patient. Currently available instrumental techniques have limited predictive value.

Brain connectivity in status epilepticus as a predictor of outcome: A diffusion tensor imaging study.

BACKGROUND AND PURPOSE: We aimed to explore structural connectivity in status epilepticus. METHODS: We enrolled participants who underwent diffusion tensor imaging. We applied graph theory to investigate structural connectivity. We compared the structural connectivity measures between patients and healthy controls and between patients with poor (modified Rankin Scale [mRS] >3) and good (mRS ≤3) admission outcomes. RESULTS: We enrolled 28 patients and 31 healthy controls (age 65.5 vs.62.0 years, p = .438). Of these patients, 16 and 12 showed poor and good admission outcome (age 65.5 vs.62.0 years, p = .438). The assortative coefficient (-0.113 vs. -0.121, p = .021), mean clustering coefficient (0.007 vs.0.006, p = .009), global efficiency (0.023 vs.0.020, p = .009), transitivity (0.007 vs.0.006, p = .009), and small-worldness index (0.006 vs.0.005, p = .021) were higher in patients with status epilepticus than in healthy controls. The assortative coefficient (-0.108 vs. -0.119, p = .042), mean clustering coefficient (0.007 vs.0.006, p = .042), and transitivity (0.008 vs.0.007, p = .042) were higher in patients with poor admission outcome than in those with good admission outcome. MRS score was positively correlated with structural connectivity measures, including the assortative coefficient (r = 0.615, p = .003), mean clustering coefficient (r = 0.544, p = .005), global efficiency (r = 0.515, p = .007), transitivity (r = 0.547, p = .007), and small-worldness index (r = 0.435, p = .024). CONCLUSION: We revealed alterations in structural connectivity, showing increased integration and segregation in status epilepticus, which might be related with neuronal synchronization. This effect was more pronounced in patients with a poor admission outcome, potentially reshaping our understanding for comprehension of status epilepticus mechanisms and the development of more targeted treatments.

Status Epilepticus after mechanical thrombectomy: The role of early EEG assessment in Stroke Unit, clinical and radiological prognostication.

BACKGROUND: Convulsive (CSE) and non-convulsive (NCSE) Status Epilepticus are a complication in 0.2-0.3% ischemic strokes. Large stroke and cortical involvement are the main risk factors for developing SE. This study evaluates the prevalence of SE in patients treated with endovascular thrombectomy (EVT) through EEG recording within 72- h from admission. Moreover, we compared clinical, radiological, and outcome measures in SE and no-SE patients. MATERIALS AND METHODS: We collected retrospectively demographical and clinical characteristics of acute ischemic stroke patients who underwent EVT, admitted in the Stroke Unit (SU) of the University Hospital of Trieste between January 2018 and March 2020 who underwent EEG recording within 72- h from the symptoms' onset. RESULTS: Out of 247 EVT patients, 138 met the inclusion criteria, of whom 9 (6.5%) showed SE with median onset time of 1 day (IQR 1-2). No difference was found between the two groups as for age, sex, risk factors, grade of recanalization, etiology of stroke, and closed vessel. The no-SE group presented higher NIHSS improvement rate (p=0.025) compared to the SE group. The sum of the lobes involved in the ischemic lesion was significantly higher in SE group (p=0.048). CONCLUSION: SE after EVT in large strokes is a non-rare complication, with most being NCSE. Performing a rapid EEG assessment in a Stroke Unit setting may allow for a prompt recognition and treatment of SE in the acute/hyper-acute phase. SE may be correlated with worse clinical outcomes in patients with large vessel occlusion.

Phenotype of heterozygous variants of dehydrodolichol diphosphate synthase.

AIM: To further identify and broaden the phenotypic characteristics and genotype spectrum of the dehydrodolichol diphosphate synthase (DHDDS) gene. METHOD: Pathogenic variants of DHDDS were identified by whole-exome sequencing; clinical data of 10 patients (six males, four females; age range 2-14y; mean age 5y 9mo, SD 3y 3mo) were collected and analysed. RESULTS: All patients had seizures, and myoclonic seizures could be seen in eight patients, with myoclonic status epilepticus in three. The interictal electroencephalogram (EEG) in four patients at seizure onset showed generalized slow waves, slow wave mixed spikes, and spike and waves. Tremor, ataxia, and hypertonia was observed in six, five, and three patients respectively. The results of short-latency somatosensory evoked potential in two patients were normal, and the symptom of tremor was captured on EEG without time-locked discharges in one patient, suggesting that the tremor in both patients was a motor impairment rather than myoclonic seizures. Global developmental delay occurred in all patients, among whom nine showed severe intellectual disability and one moderate. Five DHDDS variants were identified, three of which have not been reported previously. INTERPRETATION: Myoclonic seizure is the most common seizure type in heterozygous DHDDS variants, while myoclonic status epilepticus can also occur. The pattern of interictal EEG discharges is characterized by slow waves rather than spike and waves, and generalized discharges was prominent.

Clinical findings, etiological factors, and prognosis markers in status epilepticus: a university hospital experience.

OBJECTIVE: To determine the factors affecting mortality and disability in status epilepticus (SE) and to evaluate the prediction ability of the Status Epilepticus Severity Score (STESS) for disability and mortality. MATERIALS AND METHOD: The demographic and clinical characteristics, prognosis and prognosis predictors of 72 patients who were diagnosed with SE between 2013 and 2018 were retrospectively evaluated. The STESS was used to predict prognosis, and the modified Rankin scale (mRS) was used to determine the disability at discharge. RESULTS: The study population had a mean age of 45.4 ± 20.7, and it was found that mortality was 22.2% and acute symptomatic etiology played a 54.1% role in etiology. Advanced age, refractory SE or super-refractory SE, acute symptomatic etiology, and a history of epilepsy were related to mortality, symptomatic etiology (acute, progressive, remote), a history of hospitalization and epilepsy in intensive care or in other departments other than the neurology department were associated with disability. The sensitivity of STESS in predicting mortality was 100%, specificity was 69%, accuracy was 76.4%, positive predictive value (PPV) was 48.5%, and the negative predictive value (NPV) was 100%. The sensitivity of STESS in predicting mobilization during discharge was 55.6% with a 63.9% specificity and 59.7% accuracy, PPV was 60.6%, and NPV was 59%. CONCLUSION: It was observed that STESS strongly predicts a good prognosis; however, it was not found to be useful in predicting motor disability during discharge. Thus, new studies should be conducted to predict and evaluate mobility in SE patients at discharge.

Progression of alternating hemiplegia of childhood-related focal epilepsy to electrical status epilepticus in sleep with reversible encephalopathy.

Mutations in the ATP1A3 gene (which encodes the main α subunit in neuronal Na+/K+-ATPases) cause various neurological syndromes including alternating hemiplegia of childhood. This rare disorder is characterized by paroxysmal episodes of hemiplegia, dystonia, oculomotor abnormalities, and occasionally developmental regression. Approximately 50% of alternating hemiplegia of childhood patients also have epilepsy, which is either focal or generalized. Seizures are often drug resistant. We report a 10-year-old girl with the D801N ATP1A3 mutation and alternating hemiplegia of childhood who manifested with drug-resistant focal seizures as an infant and throughout childhood. At the age of about10.5 years, her epilepsy evolved into electrical status epilepticus in sleep with generalized discharges. These changes coincided with developmental regression consistent with epileptic encephalopathy. Additionally, MRI and MR spectroscopy showed new cortical atrophy and markedly depressed N-acetyl aspartate peaks compared to previous normal studies. Electrical status epilepticus in sleep resolved after medication adjustments. She, now, only four months after her diagnosis of electrical status epilepticus in sleep, has regained most of the skills that were lost only a few months earlier. Our observations document that alternating hemiplegia of childhood can result in the above-described unique features; particularly, progression of focal epilepsy to electrical status epilepticus in sleep with generalized features and reversible epileptic encephalopathy.

Acute encephalopathy with biphasic seizures and late reduced diffusion: Predictive EEG findings.

BACKGROUND: Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) is a common type of acute encephalopathy in Japan; the condition is clinically characterized by prolonged seizures as the initial neurological symptom, followed by late seizures 4-6 days later. It is difficult to differentiate AESD from prolonged febrile seizures (PFSs). Here, we explored the use of electroencephalography to differentiate AESD from PFSs. METHODS: We studied the electroencephalograms (EEGs) of children <6 years of age diagnosed with AESD or PFSs; all EEGs were recorded within 48 h of seizure onset (i.e., before the late seizures of AESD). Two pediatric neurologists evaluated all EEGs, focusing on the basic rhythm, slowing during wakefulness/arousal by stimuli, spindles, fast waves, and slowing during sleep. RESULTS: The EEGs of 14 children with AESD and 31 children with PFSs were evaluated. Spindles were more commonly reduced or absent in children with AESD than in those with PFSs (71% vs. 31%, p = 0.021). Fast waves were also more commonly reduced or absent in children with AESD (21% vs. 0%, p = 0.030). The rates of all types of slowing did not differ between children with AESD and those with PFSs, but continuous or frequent slowing during sleep was more common in the former (50% vs. 17%, p = 0.035). CONCLUSIONS: EEG findings may usefully differentiate AESD from PFSs. Reduced or absent spindles/fast waves and continuous or frequent slowing during sleep are suggestive of AESD in children with prolonged seizures associated with fever.

Anticonvulsive Effects of Chondroitin Sulfate on Pilocarpine and Pentylenetetrazole Induced Epileptogenesis in Mice.

Chondroitin sulfate is a proteoglycan component of the extracellular matrix (ECM) that supports neuronal and non-neuronal cell activity, provides a negative domain to the extracellular matrix, regulates the intracellular positive ion concentration, and maintains the hypersynchronous epileptiform activity. Therefore, the present study hypothesized an antiepileptic potential of chondroitin sulfate (CS) in pentylenetetrazole-induced kindled epilepsy and pilocarpine-induced status epilepticus in mice. Levels of various oxidative stress markers and inflammatory mediators were estimated in the brain tissue homogenate of mice, and histopathological changes were evaluated. Treatment with valproate (110 mg/kg; i.p.) as a standard drug and chondroitin sulfate (100 & 200 mg/kg, p.o.) significantly (p < 0.01) and dose-dependently prevented the severity of kindled and spontaneous recurrent seizures in mice. Additionally, chondroitin sulfate showed its antioxidant potential by restoring the various biochemical levels and anti-inflammatory properties by reducing NF-kB levels and pro-inflammatory mediators like TNF-alpha, IL-1ß, and IL-6, indicating the neuroprotective effect as well as the suppressed levels of caspase-3, which indicated a neuroprotective treatment strategy in epilepsy. The proteoglycan chondroitin sulfate restores the normal physiology and configuration of the neuronal tissue. Further, the molecular docking of chondroitin sulfate at the active pockets of TNF-alpha, IL-1ß, and IL-6 showed excellent interactions with critical amino acid residues. In conclusion, the present work provides preclinical evidence of chondroitin sulfate as a new therapeutic approach in attenuating and preventing seizures with a better understanding of the mechanism of alteration in ECM changes influencing abnormal neuronal activities.

Altered cardiac structure and function is related to seizure frequency in a rat model of chronic acquired temporal lobe epilepsy.

OBJECTIVE: This study aimed to prospectively examine cardiac structure and function in the kainic acid-induced post-status epilepticus (post-KA SE) model of chronic acquired temporal lobe epilepsy (TLE), specifically to examine for changes between the pre-epileptic, early epileptogenesis and the chronic epilepsy stages. We also aimed to examine whether any changes related to the seizure frequency in individual animals. METHODS: Four hours of SE was induced in 9 male Wistar rats at 10 weeks of age, with 8 saline treated matched control rats. Echocardiography was performed prior to the induction of SE, two- and 10-weeks post-SE. Two weeks of continuous video-EEG and simultaneous ECG recordings were acquired for two weeks from 11 weeks post-KA SE. The video-EEG recordings were analyzed blindly to quantify the number and severity of spontaneous seizures, and the ECG recordings analyzed for measures of heart rate variability (HRV). PicroSirius red histology was performed to assess cardiac fibrosis, and intracellular Ca2+ levels and cell contractility were measured by microfluorimetry. RESULTS: All 9 post-KA SE rats were demonstrated to have spontaneous recurrent seizures on the two-week video-EEG recording acquired from 11 weeks SE (seizure frequency ranging from 0.3 to 10.6 seizures/day with the seizure durations from 11 to 62 s), and none of the 8 control rats. Left ventricular wall thickness was thinner, left ventricular internal dimension was shorter, and ejection fraction was significantly decreased in chronically epileptic rats, and was negatively correlated to seizure frequency in individual rats. Diastolic dysfunction was evident in chronically epileptic rats by a decrease in mitral valve deceleration time and an increase in E/E` ratio. Measures of HRV were reduced in the chronically epileptic rats, indicating abnormalities of cardiac autonomic function. Cardiac fibrosis was significantly increased in epileptic rats, positively correlated to seizure frequency, and negatively correlated to ejection fraction. The cardiac fibrosis was not a consequence of direct effect of KA toxicity, as it was not seen in the 6/10 rats from separate cohort that received similar doses of KA but did not go into SE. Cardiomyocyte length, width, volume, and rate of cell lengthening and shortening were significantly reduced in epileptic rats. SIGNIFICANCE: The results from this study demonstrate that chronic epilepsy in the post-KA SE rat model of TLE is associated with a progressive deterioration in cardiac structure and function, with a restrictive cardiomyopathy associated with myocardial fibrosis. Positive correlations between seizure frequency and the severity of the cardiac changes were identified. These results provide new insights into the pathophysiology of cardiac disease in chronic epilepsy, and may have relevance for the heterogeneous mechanisms that place these people at risk of sudden unexplained death.

Lateralized Periodic Discharges: Which patterns are interictal, ictal, or peri-ictal?

There is an ongoing debate if Lateralized Periodic Discharges (LPDs) represent an interictal pattern reflecting non-specific but irritative brain injury, or conversely, is an ictal pattern. The challenge is: how to correctly manage these patients? Between this apparent dichotomous distinction, there is a pattern lying along the interictal-ictal continuum (IIC) that we may call "peri-ictal". Peri-ictal means that LPDs are temporally associated with epileptic seizures (although not necessarily in the same recording). Their recognition should lead to careful EEG monitoring and longer periods of video-EEG to detect seizure activity (clinical and/or subclinical seizures). In order to distinguish which kind of LPDs should be considered as representing interictal/irritative brain injury versus ictal/peri-ictal LPDs, a set of criteria, with both clinical/neuroimaging and EEG, is proposed. Among them, the dichotomy LPDs-proper versus LPDs-plus should be retained. Spiky or sharp LPDs followed by associated slow after-waves or periods of flattening giving rise to a triphasic morphology should be included in the definition of LPDs-plus. We propose defining a particular subtype of LPDs-plus that we call "LPDs-max". The LPDs-max pattern corresponds to an ictal pattern, and therefore, a focal non-convulsive status epilepticus, sometimes associated with subtle motor signs and epileptic seizures. LPDs-max include periodic polyspike-wave activity and/or focal burst-suppression-like patterns. LPDs-max have a posterior predominance over the temporo-parieto-occipital regions and are refractory to antiseizure drugs. Interpretations of EEGs in critically ill patients require a global clinical approach, not limited to the EEG patterns. The clinical context and results of neuroimaging play key roles.

Epidemiology and outcome of status epilepticus in children: a Scottish population cohort study.

AIM: To describe the epidemiology and outcomes of convulsive status epilepticus (CSE) since the introduction of buccal midazolam and the change in International League Against Epilepsy definition of CSE to include seizures of at least 5 minutes. METHOD: All children presenting to paediatric emergency departments with CSE (2011-2017) in Lothian, Scotland, were identified. Data, collated from electronic health records, included patient demographics, clinical characteristics, acute seizure management, and adverse outcomes (for example admission to intensive care). RESULTS: Six hundred and sixty-five children were admitted with CSE who had 1228 seizure episodes (381 males, 284 females; median age 3y 8mo; age range 0-20y 11mo). CSE accounted for 0.38% (95% confidence interval 0.34-0.42) of annual attendances at emergency departments. Annual prevalence was 0.8 per 1000 children aged 0 to 14 years. Thirty-four per cent of children had recurrent CSE. Sixty-nine per cent of seizures lasted 5 to 29 minutes (median duration 10min). Buccal midazolam was given to 30% of children with CSE and had no effect on need for ventilatory support. Seventy per cent of children with CSE required hospital admission. Four per cent resulted in adverse outcome and there were only two deaths. Recurrent seizures, longer duration, and unprovoked seizures increased the odds of adverse outcome. INTERPRETATION: Adverse outcomes have decreased and the use of buccal midazolam is promising. Identifying high-risk groups provides an opportunity for early intervention. These data form the basis for an extensive evaluation of acute seizure management and monitoring long-term outcomes. What this paper adds The annual prevalence of convulsive status epilepticus in Lothian, Scotland, was 0.8 per 1000 children. There was a decrease in case-fatality proportion from 3-9% to 0.2%. Use of buccal midazolam has increased, with no increase in adverse outcomes.

Comparative profile of refractory status epilepticus models following exposure of cholinergic agents pilocarpine, DFP, and soman.

Status epilepticus (SE) is a medical emergency with continuous seizure activity that causes profound neuronal damage, morbidity, or death. SE incidents can arise spontaneously but mostly are elicited by seizurogenic triggers. Chemoconvulsants such as the muscarinic agonist pilocarpine and, organophosphates (OP) such as the pesticide diisopropylfluorophosphate (DFP) and, the nerve agent soman, can induce SE. Pilocarpine, DFP, and soman share a common feature of cholinergic crisis that transitions into a state of refractory SE, but their comparative profiles remain unclear. Here, we evaluated the comparative convulsant profile of pilocarpine, DFP, and soman to produce refractory SE and brain damage in rats. Behavioral and electrographic seizures were monitored for 24 h after exposure, and the extent of brain injury was determined by histological markers of neuronal injury and degeneration. Seizures were elicited rather slowly after pilocarpine as compared to DFP or soman, which caused rapid onset of spiking that swiftly developed into persistent SE. Time-course of SE activity after DFP was comparable to that after soman, a potent nerve agent. Diazepam controlled pilocarpine-induced SE, but it was ineffective in reducing OP-induced SE. All three agents produced modestly different degrees of neuronal injury and neurodegeneration in the brain. These results reveal distinct convulsant and neuronal injury patterns following exposure to cholinergic agonists, OP pesticides, and nerve agents. A battery of SE models, especially SE induced by cholinergic agents and other etiologies including epilepsy and brain tumors, is essential to identify novel anticonvulsant therapies for the management of refractory SE.

Reactive astrocyte-driven epileptogenesis is induced by microglia initially activated following status epilepticus.

Extensive activation of glial cells during a latent period has been well documented in various animal models of epilepsy. However, it remains unclear whether activated glial cells contribute to epileptogenesis, i.e., the chronically persistent process leading to epilepsy. Particularly, it is not clear whether interglial communication between different types of glial cells contributes to epileptogenesis, because past literature has mainly focused on one type of glial cell. Here, we show that temporally distinct activation profiles of microglia and astrocytes collaboratively contributed to epileptogenesis in a drug-induced status epilepticus model. We found that reactive microglia appeared first, followed by reactive astrocytes and increased susceptibility to seizures. Reactive astrocytes exhibited larger Ca2+ signals mediated by IP3R2, whereas deletion of this type of Ca2+ signaling reduced seizure susceptibility after status epilepticus. Immediate, but not late, pharmacological inhibition of microglial activation prevented subsequent reactive astrocytes, aberrant astrocyte Ca2+ signaling, and the enhanced seizure susceptibility. These findings indicate that the sequential activation of glial cells constituted a cause of epileptogenesis after status epilepticus. Thus, our findings suggest that the therapeutic target to prevent epilepsy after status epilepticus should be shifted from microglia (early phase) to astrocytes (late phase).

Neuroprotection by delayed triple therapy following sarin nerve agent insult in the rat.

The development of refractory status epilepticus (SE) induced by sarin intoxication presents a therapeutic challenge. In our current research we evaluate the efficacy of a delayed combined triple treatment in ending the abnormal epileptiform seizure activity (ESA) and the ensuing of long-term neuronal insult. SE was induced in male Sprague-Dawley rats by exposure to 1.2LD50 sarin insufficiently treated by atropine and TMB4 (TA) 1 min later. Triple treatment of ketamine, midazolam and valproic acid was administered 30 min or 1 h post exposure and was compared to a delayed single treatment with midazolam alone. Toxicity and electrocorticogram activity were monitored during the first week and behavioral evaluation performed 3 weeks post exposure followed by brain biochemical and immunohistopathological analyses. The addition of both single and triple treatments reduced mortality and enhanced weight recovery compared to the TA-only treated group. The triple treatment also significantly minimized the duration of the ESA, reduced the sarin-induced increase in the neuroinflammatory marker PGE2, the brain damage marker TSPO, decreased the gliosis, astrocytosis and neuronal damage compared to the TA+ midazolam or only TA treated groups. Finally, the triple treatment eliminated the sarin exposed increased open field activity, as well as impairing recognition memory as seen in the other experimental groups. The delayed triple treatment may serve as an efficient therapy, which prevents brain insult propagation following sarin-induced refractory SE, even if treatment is postponed for up to 1 h.

Excitatory synaptic transmission in hippocampal area CA1 is enhanced then reduced as chronic epilepsy progresses.

This study examines changes in synaptic transmission with progression of the chronic epileptic state. Male Sprague-Dawley rats (P40-45) were injected with either saline or pilocarpine. In rats injected with pilocarpine, status epilepticus ensued. Hippocampal slices were cut 20-60 days or 80-110 days post-treatment. Evoked and miniature EPSCs (mEPSCs) were recorded from CA1 pyramidal neurons using whole-cell voltage-clamp. Fiber volleys were also recorded from stratum radiatum. Evoked EPSCs from the pilocarpine-treated cohort showed enhanced amplitudes 20-60 days post-treatment compared to the saline-treated cohort, whereas mEPSCs recorded from the same age group showed no change in event frequency and a slight but significant decrease in mEPSC amplitude distribution. In contrast, comparing evoked EPSCs and mEPSCs recorded 80-110 days after treatment indicated reduced amplitudes from pilocarpine-treated animals compared to controls. mEPSC inter-event interval decreased. This could be explained by a partial depletion of the ready releasable pool of neurotransmitter vesicles in Schaffer collateral presynaptic terminals of the pilocarpine-treated rats. In both saline- and pilocarpine-treated cohorts, concomitant decreases in mEPSC amplitudes as time after treatment progressed suggest that age-related changes in CA1 circuitry may be partially responsible for changes in synaptic transmission that may influence the chronic epileptic state.

Acute encephalopathy with biphasic seizures and late reduced diffusion; posterior frontal hyperperfusion before late seizures revealed by arterial spin labeling: A case report.

BACKGROUND: Arterial spin labeling, a magnetic resonance imaging modality that can evaluate cerebral perfusion without using a contrast material or ionizing radiation, is becoming increasingly accessible. However, only a few reports have used this method to assess the perfusion abnormalities observed in acute encephalopathy with biphasic seizures and late reduced diffusion. PATIENT DESCRIPTION: A 10-month-old Japanese girl presented with febrile status epilepticus (early seizures). Her convulsions ceased after the administration of intravenous phenobarbital, although her impaired consciousness was protracted. Five days later, diffusion-weighted imaging revealed slightly high signal intensity lesions in the bilateral posterior frontal areas. Arterial spin labeling revealed bilateral frontal-dominant hypoperfusion and posterior frontal hyperperfusion. On day 6, she had three convulsions (late seizures) and was diagnosed with acute encephalopathy with biphasic seizures and late reduced diffusion. She received treatment accordingly and recovered eventually. DISCUSSION: Based on previous reports, hypoperfusion within 1-2 days of early seizures and hyperperfusion accompanied by bright tree appearance on diffusion-weighted imaging within 1-2 days of late seizures are typical in acute encephalopathy with biphasic seizures and late reduced diffusion. In our patient, the first magnetic resonance imaging scan was performed one day prior to the onset of late seizures. We observed posterior frontal hyperperfusion accompanied by high signals on diffusion-weighted imaging, which leads us to speculate that this could be a predictive marker of late seizures.