This study assessed the safety and efficacy of buccal midazolam administered by caregivers for status epilepticus within the community setting. Pediatric patients who had previously tolerated and responded to buccally administered midazolam in a phase 3, hospital setting study (SHP615-301) were administered a single buccal midazolam dose by their trained caregiver in a community set-ting, following an episode of status epilepticus and before arriving at the hospital and/or emergency department. Three patients received treatment. All showed cessation of visible seizure activity with-in 5 minutes of treatment and absence of seizures 30 and 60 minutes after treatment. All treatment-emergent adverse events were mild, and no patients experienced respiratory depression. Caregivers reported satisfaction with the treatment experience. Buccally administered midazolam was well tolerated and effective for cessation of status epilepticus, and was safely and conveniently used by caregivers in the community setting in this study. (ClinicalTrials.gov identifier, NCT03336450)

A man in his 60s had undergone clipping for a subarachnoid hemorrhage (SAH) due to a ruptured anterior communicating artery aneurysm in his 40s. He survived cerebral vasospasms following surgery for poor-grade SAH and required anti-seizure medications (ASMs) for post-stroke epilepsy. More than 20 years after the clipping, he developed focal impaired awareness seizure, which decreased his quality of life (QOL). Computed tomography (CT) showed an infarct in the left frontal lobe. ¹²³I-iomazenil single-photon emission CT showed decreased benzodiazepine accumulation in the left frontal and medial temporal lobes. An interictal electroencephalogram showed epileptic discharges in the left temporal region. We diagnosed focal epilepsy and adjusted ASMs based on seizure control. However, the seizures were not controlled, and the adverse effects worsened with dosage increase. The condition was diagnosed as drug-resistant epilepsy, and the patient underwent vagus nerve stimulation. Postoperatively, we confirmed control of seizures and improvement of QOL.

Arterial spin labeling (ASL) imaging with multiple postlabeling delays (PLD) can demonstrate the hemodynamics of peri-ictal hyperperfusion. Labeling methods include pulsed ASL (PASL) and pseudocontinuous ASL (pCASL). Although PASL is more widely used in daily clinical practice, it has several disadvantages because of lower delivery of labeled magnetization. We compared pCASL and PASL images acquired after a 24-h interval, using a 1.5-Tesla machine, in a 62-year-old man with non-convulsive status epilepticus. The pCASL during electrographic status epilepticus clearly demonstrated that ASL signals in the grey matter of the right hemisphere, particularly in the posteromedial part of the right temporal lobe, increased at PLDs of 1.5 s and 1.75 s and were almost washed out at 2.0 s. Although PASL, which was obtained during the ictal-interictal continuum when there were no changes in ictal findings on diffusion-weighted images, showed a similar trend, the increased signals were less pronounced than those of pCASL, with more contamination of arte-rial transit artifact in the subarachnoid space. Although the electroencephalographic findings were not the same when both ASLs were performed, the present study confirms that PASL is somewhat inferior to pCASL in detecting peri-ictal hyperperfusion because of the greater effect of arterial transient artifacts.

The hemodynamics of ictal hyperperfusion in dual pathology was evaluated using arterial spin labeling perfusion images (ASL) with triple postlabeling delays (PLDs). A 62-year-old man with epileptogenic right parietal hematoma cavity and bilateral hippocampal atrophy, particularly on the right, underwent ASL examination during subtle non-convulsive status epilepticus immediately after focal-to-bilateral tonic-clonic seizures. ASL at PLD of 1.5 s showed increased signals in the gray matter of both hemispheres, in addition to the peri-cavitary cortex. At PLD of 1.75 s, these signals were mostly washed out, and there was a marked increase in signals localized to bilateral hippocampal heads. The hippocampal signals were also mostly washed out at PLD of 2.0 s. These findings indicate a close relationship between activities originating from the peri-cavitary cortex and the hippocampus in this case. In terms of the mechanism of hippocampal atrophy, the oxygen supply required for large epileptic activities could not be met.

We describe the courses of treatment for epilepsies in two patients with semilobar type holoprosencephaly (HPE); a 5-year-old girl and a 30-year-old man. Seizure semiology included eye fixation, upward or lateral gaze, horizontal or vertical nystagmus, eyelid flutter, and grinning facial distortion, which frequently evolved to generalized tonic convulsions. In both patients, ictal electroencephalography revealed seizure onset with rhythmic activity in bilateral frontopolar areas. Administration of phenobarbital with subsequent elevation of blood levels to 30–40 μg/ml alleviated the clustered tonic seizures. This allowed dosage reduction of other antiepileptic drugs that had sedative and/or respiratory adverse effects causing significant distress in these patients. Potassium bromide 20–50 mg/kg/day and topiramate 1–3 mg/kg/day were also beneficial in these patients. A combination regimen of these three antiepileptic drugs could be a promising treatment option for intractable epilepsy in HPE.

Purpose: We report a case of febrile infection-related epilepsy syndrome (FIRES) with a lesion in the splenium of the corpus callosum, and explore the pathophysiology by conducting a literature review.

Case Report: A 10-year-old Japanese boy developed repetitive seizures after five days of febrile illness. MRI at admission revealed a splenial lesion with reduced diffusivity and low apparent diffusion coefficient. Apneic seizures with ocular gaze, facial twitching, with/without focal or bilateral tonic posturing necessitated high dose phenobarbital therapy under artificial ventilation for seven days. The splenial lesion disappeared on the follow-up MRI on day 3, but bilateral hippocampal lesions emerged on day 10. The seizures were mitigated by potassium bromide. At onset of encephalopathy, the platelet count and C-reactive protein (CRP) level were low.

Methods: Data from 21 individuals with FIRES and 32 individuals with mild encephalopathy/encephalitis with reversible splenial lesion (MERS) were collected from online bibliographic databases. Onset age, prodromal period, blood cell counts, CRP, electrolytes, and liver enzymes were compared between these two groups.

Results: Onset age, prodromal period, and liver enzymes were significantly higher and platelet count and CRP were lower in the FIRES group than in the MERS group.

Discussion: In our case, the initial MRI findings resembled those of MERS, but the subsequent clinical course and seizure semiology, as well as blood test results were consistent with a diagnosis of FIRES. A splenial lesion in FIRES may be associated with the relatively attenuated seizure activity during the acute phase in this and another reported case, which needs further corroborations.

Introduction: Arterial spin labeling (ASL) magnetic resonance (MR) perfusion imaging is useful for diagnosing non-convulsive status epilepticus (NCSE) as it visualizes ictal hyperperfusion in epileptically activated areas.

Case report: A 94-year-old woman presented with inability to communicate. An electroencephalogram revealed generalized periodic discharges with triphasic morphology. However, as her liver and kidney function were normal, it was difficult to distinguish metabolic encephalopathy from NCSE. ASL showed not only diffuse hypoperfusion in the cerebral parenchyma, instead of ictal hyperperfusion, but also marked appearance of arterial transit artifact in the major arteries, probably due to stagnant flow. The patient was therefore diagnosed with hyperammonemic encephalopathy (ammonia level 128 mg/dL) induced by constipation. Along with normalization of the ammonia level, the mental status and ASL findings improved.

Conclusion: In this case, ASL helped visualize the decreased blood flow and velocity secondary to hypometabolism. The addition of ASL to conventional MR images may be useful in differentiating metabolic encephalopathy from NCSE, particularly in neuroemergency situations.

Introduction: Magnetic resonance (MR) perfusion imaging with arterial spin labeling (ASL) can easily detect periictal hyperperfusion accompanying epileptic seizures. Herein, we report two cases in which ASL performed immediately after a seizure was useful for the initial suspicion of temporal lobe epilepsy (TLE).

Case report: Patients 1 and 2 developed focal-to-bilateral tonic-clonic and focal impaired awareness seizures, respectively, and were subsequently transferred to our facility for out-of-hours service. On emergent ASL MR perfusion imaging, a slight increase in signals from the hippocampus and lateral temporal lobe was observed in both patients. However, routine electroencephalography (EEG) performed from 12 h to two days later showed corresponding paroxysmal discharges only in Patient 2.

Conclusion: These cases suggest that MR imaging with ASL perfusion, which can be performed 24 hours a day, is useful for the initial suspicion of TLE, compensating for the limitation of routine EEG. However, to ensure a definitive diagnosis, it is important to evaluate the result together with clinical history, seizure semiology and findings of other modalities centered on EEG.

Introduction: Although drug-resistant epilepsy is a frequent symptom in patients with tuberous sclerosis complex (TSC), there is conflicting evidence regarding whether the epileptogenic zone is present in the tuber itself or in the abnormally developed perituberal cortex.

Case report: A 45-year-old man with TSC developed clustering of generalized tonic-clonic seizures (GTCSs) that lasted for approximately 1 day. Magnetic resonance imaging, including arterial spin labeling (ASL) perfusion images, was performed approximately 4 hours after the last apparent seizure. The fusion image of the ASL and fluid-attenuated inversion recovery sequence clearly demonstrated that the ASL hyperperfusion site was located in the perituberal cortex of the left frontal lobe, where the tubers were most prominent.

Conclusion: The present study suggests epileptogenicity of the perituberal cortex for GTCSs in this patient. In the future, the epileptogenicity of TSC may be further clarified by conducting ictal or periictal ASL in a large number of TSC patients.

Purpose: To determine the utility of stereoelectroencephalography (SEEG) in detecting the spatiotemporal dynamics of auditory naming-related high-gamma modulation.

Methods: This cross-sectional study investigated eight patients with drug-resistant focal epilepsy who performed an auditory naming task with vocal responses during SEEG recording. We generated time-frequency plots and animation videos delineating the dynamics of auditory naming-related high-gamma activity at 60-140 Hz.

Results: Auditory naming elicited high-gamma augmentation in the bilateral superior temporal gyri, insula, left triangular part of the inferior frontal gyrus, precentral gyrus, and right lateral occipital complex between 160 and 210 ms after stimulus onset, followed by the right cuneus after 1080 ms. Augmentation in the bilateral superior temporal gyri continued during stimulus presentation. Around the stimulus offset, the left precentral gyrus showed reaugmentation, followed by the right lingual gyrus and bilateral superior temporal gyri. Frontotemporal activation was consistent with the results of previous electrocorticography (ECoG) studies. These studies did not detect any activity in the insula associated with auditory naming.

Conclusion: This study demonstrated the utility of SEEG for analyzing high-gamma modulations by replicating the spatiotemporal dynamics determined in previous ECoG studies. Compared to ECoG, SEEG may be beneficial for detecting high-gamma modulations in deep brain structures such as the insula.

Crossed cerebellar diaschisis (CCD) was originally defined as depression of metabolism and blood flow in the cerebellar hemisphere contralateral to a supratentorial lesion in hemispheric stroke. Arterial spin labeling (ASL) magnetic resonance (MR) perfusion imaging with multiple postlabeling delays (PLDs) is useful for non-invasive detection of the hemodynamics of (peri)ictal hyperperfusion. Previous reports using ASL with a 3-Tesla (T) MR machine showed crossed cerebellar hyperperfusion (CCH) associated with supratentorial hyperperfusion, probably through the same mechanism as CCD, in patients with epilepsy during the ictal period. However, there are no reports on 1.5-T ASL, which is widely used in neuroemergencies. Here we evaluated the hemodynamics of (peri) ictal hyperperfusion and CCH using 1.5-T ASL in an 84-year-old man with right lesional temporal lobe epilepsy who experienced three episodes of convulsive status epilepticus (CSE). The ASL obtained was evaluated on fusion images with conventional MR images and subtracting ictal-interictal 1.5-Tesla ASL images co-registered to conventional MR images. Repeated ASL examinations performed 1 day after the first CSE, immediately after the second CSE, and during the third CSE demonstrated CCH in addition to right hemispheric hyperperfusion. The CCH became progressively stronger with increase in visualization of right hemispheric hyperperfusion. Furthermore, both showed the same hemodynamics; the ASL signals increased at PLD of 1.5 s and gradually decreased at PLDs of 1.75 s and 2.0 s. Increase in signal intensity was noted on the right side of the midbrain and pons as well as somwehat in the contralateral cerebellar peduncle. In this case, 1.5-T ASL demonstrated that the cortico-pontine-cerebellar pathway was strongly involved in the development of CCH in epilepsy similar to CCD in stroke.

The prevalence of elderly-onset epilepsy is expected to increase as the world's population ages. The etiology of elderly-onset epilepsy is multifaceted, involving cerebrovascular diseases, neurodegenerative conditions such as Alzheimer's disease, and unknown causes that account for approximately one-quarter of all cases. The diagnosis and management of elderly-onset epilepsy pose challenges due to the atypical clinical presentations and coexisting health conditions commonly observed in this population. The diagnostic process is further complicated by a broad range of differential diagnoses. Medical treatment must be modified to accommodate physiological changes commonly observed in this population, such as decreased drug metabolism. Despite these challenges, appropriate management can substantially improve the quality of life of affected individuals. In this article, we review key factors of elderly-onset epilepsy management.