An integrated genetic analysis of epileptogenic brain malformed lesions.

Focal cortical dysplasia is the most common malformation during cortical development, sometimes excised by epilepsy surgery and often caused by somatic variants of the mTOR pathway genes. In this study, we performed a genetic analysis of epileptogenic brain malformed lesions from 64 patients with focal cortical dysplasia, hemimegalencephy, brain tumors, or hippocampal sclerosis. Targeted sequencing, whole-exome sequencing, and single nucleotide polymorphism microarray detected four germline and 35 somatic variants, comprising three copy number variants and 36 single nucleotide variants and indels in 37 patients. One of the somatic variants in focal cortical dysplasia type IIB was an in-frame deletion in MTOR, in which only gain-of-function missense variants have been reported. In focal cortical dysplasia type I, somatic variants of MAP2K1 and PTPN11 involved in the RAS/MAPK pathway were detected. The in-frame deletions of MTOR and MAP2K1 in this study resulted in the activation of the mTOR pathway in transiently transfected cells. In addition, the PTPN11 missense variant tended to elongate activation of the mTOR or RAS/MAPK pathway, depending on culture conditions. We demonstrate that epileptogenic brain malformed lesions except for focal cortical dysplasia type II arose from somatic variants of diverse genes but were eventually linked to the mTOR pathway.

A pediatric case of autoimmune glial fibrillary acidic protein astrocytopathy with unique brain imaging patterns and increased cytokines/chemokines.

BACKGROUND: Autoimmune anti-glial fibrillary acidic protein (GFAP) astrocytopathy represents a new spectrum of autoimmune inflammatory central nervous system disorders. In recent years, there have been an increasing number of reports on pediatric patients with this disease other than those in Japan. CASE REPORT: A 6-year-old previously healthy boy presented with fever persisting for approximately 10 days, consciousness disturbance, anorexia, and hyponatremia (Na, 121 mEq/L). Even after appropriate correction of hyponatremia, consciousness disturbance was prolonged and was accompanied by gait disturbance, visual hallucinations, and autonomic dysfunction (bradycardia and urinary dysfunction). On a plain MRI, T2-weighted and fluid-attenuated inversion recovery images showed abnormal hyperintense lesions in the bilateral basal ganglia, thalamus, and periventricular white matter. The cerebrospinal fluid was positive for anti-GFAP antibody before treatment, and cytokines/chemokines were increased. He received three courses of intravenous methylprednisolone, followed by gradually tapered oral prednisolone for 6 months, without relapse after 1 year of observation. CONCLUSION: In cases of autoimmune encephalitis with prolonged consciousness disturbance, hyponatremia, urinary dysfunction, and MRI findings with hyperintensities in the bilateral basal ganglia, thalamus, and periventricular white matter, anti-glial fibrillary acidic protein antibodies should be examined.

Possible critical region associated with late-onset spasms in 17p13.1-p13.2 microdeletion syndrome: a report of two new cases and review of the literature.

17p13.1-2 microdeletion syndrome is a congenital anomaly syndrome with characteristic facial features and multiple malformations. The prevalence of epilepsy with 17p13.1-2 microdeletion is low, with only one case reported for late-onset spasms. Late-onset spasms is one of the rare epilepsy syndromes and one of the developmental epileptic encephalopathies requiring urgent treatment. We experienced two cases of 17p13.1-2 microdeletion syndrome, one of which presented with epileptic spasms in cluster at 18 months of age. EEG showed symmetrical hypsarrhythmia during interictal periods and a paroxysmal fast wave superimposed on widespread slow waves during seizures, leading to the diagnosis of late-onset spasms. Another case had no epilepsy. Comparing the extent of deletion in the two cases with that of previous reports, the involvement of the USP6 gene was suspected. However, the accumulation of additional case reports is needed to confirm the genetic involvement in late-onset spasms.

Late relapse of anti-N-methyl-d-aspartate receptor encephalitis with amusia and transiently reduced uptake in 123I-iomazenil single-photon emission computed tomography.

INTRODUCTION: Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis has a high relapse rate at approximately 10-20%. Most relapses occur within 2 years from onset, and 5 years after onset is rare. We report a case of anti-NMDAR encephalitis relapse with amusia 10 years after the initial encephalitis and discuss the usefulness of 123I-iomazenil single-photon emission computerized tomography (IMZ-SPECT) for its diagnosis. CASE: A 13-year-old left-handed girl presented with a depressed level of consciousness and focal to bilateral tonic-clonic seizures. Cerebrospinal fluid (CSF) analysis showed a mildly increased white blood cell count, elevated neopterin levels, and positive oligoclonal bands. Brain MRI was normal. IMZ-SPECT revealed reduced uptake in the right frontoparietal region. She received intravenous pulse methylprednisolone (IVMP) and high-dose intravenous immunoglobulin for autoimmune encephalitis; her symptoms resolved without neurological deficits. At 23 years old, she had mild right-sided numbness, dysarthria, amusia, and tonic-clonic seizures. Although the CSF analysis and brain MRI were normal, IMZ-SPECT revealed reduced uptake, indicating a relapse of encephalitis. IVMP administration resolved the symptoms. After discharge, the initial and relapse CSF analysis revealed anti-NMDAR antibodies. CONCLUSION: An anti-NMDAR encephalitis relapse 10 years after onset has never been reported. IMZ-SPECT may help in the diagnosis of anti-NMDAR encephalitis.

Effect of higher body temperature and acute brain edema on mortality in hemorrhagic shock and encephalopathy syndrome.

OBJECTIVE: Hemorrhagic shock and encephalopathy syndrome (HSES) is a severe subtype of acute encephalopathy with a poor prognosis. The factors associated with acute neurological outcomes in patients with HSES remain unclear. This study aimed to determine the clinical features, laboratory and radiological findings, and treatments that determine the acute outcomes of HSES. METHODS: Forty children with HSES registered in a database of Osaka City General Hospital between 1995 and 2020 were included in this observational study. We retrospectively collected data on clinical features, laboratory and radiological items, and treatments. We divided acute neurological outcomes into two groups: the non-death and death groups in 1 week. Correlations were assessed between these items and acute neurological outcomes. RESULTS: Twenty-seven and 13 patients comprised the non-death and death groups, respectively. Univariate logistic regression analysis showed that higher body temperature, presence of hemorrhagic episode, elevated lactate level, high glucose level in the cerebrospinal fluid, and brain edema at initial computed tomography (CT) were correlated with the death group. Regarding treatments, barbiturate therapy, intravenous immunoglobulin, and intravenous methylprednisolone were significantly initiated in the non-death group. The multivariate logistic regression model showed higher body temperature (odds ratio [OR], 4.210 [1.409-12.584]; p = 0.010) and brain edema on initial head CT (OR, 46.917 [3.995-550.976]; p = 0.002) were independent factors. CONCLUSIONS: Higher body temperature and brain edema at the onset of HSES were associated with acute outcomes. The results of this study may be useful for treatment planning and acute outcomes in patients with HSES.

A case of focal cortical dysplasia type IIa with pathologically suspected bilateral Rasmussen syndrome.

BACKGROUND: Rasmussen syndrome (RS) is a rare neurological disorder characterized by unilateral chronic inflammation, drug-resistant epilepsy, and progressive neurological and cognitive deterioration. There has been no detailed pathological evaluation or finding, including focal cortical dysplasia, for bilateral RS. CASE REPORT: A 13-year-old boy presented with status epilepticus with focal to bilateral tonic clonic seizure starting from the left upper limb. At the age of 15, epilepsia partialis continua of the right face and upper extremities appeared, and MRI showed hemispheric abnormal signal intensities with left frontal lobe predominance. Three months later, MRI showed extensive abnormal signal intensities in the right occipitoparietal and left temporal lobes. Tacrolimus was useful in preventing recurrence. Because the seizures were intractable, a corpus callosotomy was performed at 16 years along with a concurrent brain biopsy from the bilateral lateral frontal cortices. We detected dysmorphic neurons in addition to inflammatory changes suspicious for RS, leading to a diagnosis of focal cortical dysplasia (FCD) type Ⅱa and suspected bilateral RS. Total callosotomy and vagus nerve stimulation were not sufficiently effective. CONCLUSIONS: In bilateral RS, FCD may be present in both cerebral hemispheres. In the current case, an autoimmune response to dysmorphic neurons may have contributed to the pathogenesis of intense inflammation.

Longitudinal electroencephalogram findings predict acute neurological and epilepsy outcomes in patients with hemorrhagic shock and encephalopathy syndrome.

OBJECTIVE: Hemorrhagic shock and encephalopathy syndrome (HSES) is a severe subtype of acute encephalopathy with a poor prognosis. The association between electroencephalogram (EEG) findings and neurological outcomes in patients with HSES, including the onset of epilepsy, remains unclear. METHODS: Thirty-two children with HSES registered in a database of Osaka City General Hospital between 2003 and 2018 were included in this study. The EEG findings which consisted of continuity, reactivity, state change, voltage, rhythmic and periodic patterns, and electrographic or electroclinical seizures, in the onset phase were evaluated for patient outcome. Patients who avoided acute death were investigated for epilepsy by a longitudinal EEG. Seizure types were determined by ictal video recordings. RESULTS: We analyzed EEG findings in the onset phase of 30 patients. Severely to extremely abnormal EEG pattern (deteriorated continuity more than discontinuous pattern, presence of generalized abnormal low voltage slow wave, and presence of generalized rhythmic and periodic patterns) in the onset phase correlated with poor outcome (p = 0.0024). Subsequently, 9/23 patients (39%) developed epilepsy, of which a total of eight had epileptic spasms. A significant correlation between interictal epileptic discharges and the development of epilepsy was observed as early as within three months (p = 0.0003). CONCLUSIONS: EEG pattern in the onset phase may be useful to predict the neurological prognosis in the acute stage. Moreover, this study demonstrated that longitudinal EEG findings after the acute phase of HSES were significantly related to the development of epilepsy. EEG findings are useful for predicting acute prognosis and epilepsy in patients with HSES.

Disconnection surgery to cure or palliate medically intractable epileptic spasms: a retrospective study.

OBJECTIVE: Surgery is a treatment option for medically intractable epileptic spasms (ESs). However, outcomes of ES after surgery are not well understood, especially when surgeries aimed at seizure palliation are included. The purpose of the present study was to 1) investigate the proportion of favorable postoperative ES outcomes, 2) explore the preoperative factors related to favorable postoperative ES outcomes, and 3) examine the timing of ES recurrence after disconnection surgeries, including both curative and palliative indications. METHODS: This retrospective study included patients who underwent disconnection surgery for medically intractable ES at the authors' institution between May 2015 and April 2021. Patients with suggested focal-onset ES based on preoperative evaluations initially underwent lobar disconnection. Patients with suggested generalized or unknown-onset ES underwent corpus callosotomy (CC). If evaluations after initial CC showed focalized or lateralized change, they were considered secondarily revealed focal-onset ES, and lobar disconnection was performed. ES outcomes were evaluated using the International League Against Epilepsy classification. ES outcomes were divided into classes 1-4 as favorable outcomes and classes 5 and 6 as unfavorable outcomes. The relationship between the favorable postoperative ES outcomes and the following preoperative factors was analyzed: sex, age at onset (< or > 1 year), duration between seizure onset and initial surgery (< or > 2 years), type of seizure at onset (ES or others), presence of other types of seizures, substrate, hypsarrhythmia, and MRI abnormalities. The period between the last surgery and ES recurrence was also analyzed. RESULTS: A total of 41 patients were included, of whom 75.6% achieved favorable ES outcomes. A longer seizure duration between seizure onset and initial surgery, presence of hypsarrhythmia, and positive MRI findings led to poorer postoperative ES outcomes (p = 0.0028, p = 0.0041, and p = 0.0241, respectively). A total of 60.9% of patients had ES recurrence during the follow-up period, and their ES recurred within 13 months after the last surgery. CONCLUSIONS: Disconnection surgery is an effective treatment option for medically intractable ES, even when the preoperative evaluation suggests a generalized or unknown onset.

A case of bilateral limbic and recurrent unilateral cortical encephalitis with anti-myelin oligodendrocyte glycoprotein antibody positivity.

BACKGROUND: Anti-myelin oligodendrocyte glycoprotein (MOG) antibody can be detected not only in acute disseminated encephalomyelitis or optic neuritis but also in limbic or cortical encephalitis. However, no previous reports have demonstrated a relapsing case of these two types of encephalitis. CASE REPORT: An 11-year-old girl presented with fever, headache, abnormal behavior, focal impaired awareness seizures (FIAS) on the left side, and MRI hyperintensities in the bilateral amygdala, hippocampus, and right posterior temporal cortex. The symptoms were alleviated with two courses of intravenous methylprednisolone (IVMP) and one course of immunoglobulin. At 16 years of age, the patient returned with left-sided headache and MRI hyperintensities in the left temporal, parietal, and insular cortices, which improved after 3 courses of IVMP. Oral prednisolone (PSL) was tapered over 6 months, when FIAS reappeared on the right side of the body. MRI showed recurrence in the same regions as in the second episode. She received 3 courses of IVMP, followed by gradually tapered PSL without relapse for 1.5 year. Anti-MOG antibodies were positive in both serum and the cerebrospinal fluid prior to treatment in all three episodes. CONCLUSION: Our results revealed that anti-MOG antibody-related bilateral limbic and unilateral cortical encephalitis can manifest with a variety of phenotypes over time in the same patient.

MRI findings at neurological onset predict neurological prognosis in hemorrhagic shock and encephalopathy syndrome.

BACKGROUND: Hemorrhagic shock and encephalopathy syndrome (HSES) is a devastating disease and has an uncertain pathogenesis. The aim of this study was to predict neurological outcomes for HSES using magnetic resonance imaging (MRI) findings at neurological onset and elucidate the pathophysiology of HSES in the acute phase from serial MRI changes. MATERIALS AND METHODS: We analyzed the MRI findings of 13 patients who underwent an initial MRI within 24 h of neurological onset. According to neurological prognosis, seven patients were included in the severe group and six in the non-severe group. All patients in the non-severe group had a follow-up MRI. We divided the whole brain into 14 regions and each region was scored according to diffusion-weighted imaging findings. We compared the total scores of each region between the two groups and between onset and follow-up MRI. RESULTS: At neurological onset, symmetrical lesions were found predominantly in the frontal, parietal, and occipital lobes in 12 of 13 patients (92%). In the severe group, the total score for onset MRI was significantly higher than those in the non-severe group (p = 0.003). The total score was significantly higher for follow-up than those of onset MRI (p = 0.036). White matter lesions that showed a bright tree appearance were observed in the follow-up MRIs of all patients. CONCLUSION: Total scores for onset MRIs are useful for predicting neurological prognosis in patients with HSES. In addition to widespread cortical involvement of predominantly watershed areas, white matter lesions may play a role in the progression of brain edema.

Efficacy of long-term adrenocorticotropic hormone therapy for West syndrome: A retrospective multicenter case series.

OBJECTIVES: Long-term adrenocorticotropic therapy (LT-ACTH), which consisted of 2-4 weeks of daily injections of adrenocorticotropic hormone (ACTH) and subsequent months of weekly injections, was tried for relapsed West syndrome (WS) or other intractable epilepsies in small case reports. Our aim was to explore the efficacy of LT-ACTH for preventing WS relapse, as well as the prevalence of its adverse events. METHODS: This is a retrospective, nationwide, multicenter case series of patients with WS who underwent LT-ACTH. Clinical information of the patients and protocol of LT-ACTH were collected from participating institutes in this study. We defined clinical response to ACTH as achievement of hypsarrhythmia and epileptic spasms resolution. Patients who responded to daily ACTH injections were identified and assessed whether they experienced WS relapse during/after the weekly ACTH injection period. The outcome was measured by the nonrelapse rate at 24 months after daily ACTH injections using the Kaplan-Meier method. RESULTS: Clinical information of 16 children with WS was analyzed. The median age at LT-ACTH initiation was 14.5 months (range: 7-68 months). Thirteen (81%) patients had previously undergone conventional ACTH treatment. The LT-ACTH regimens comprised a median of 16 days of daily injections (range: 11-28 days) and 10 months of weekly injections (range: 3-22 months). Seven patients experienced WS relapse during/after subsequent weekly ACTH period, and the nonrelapse rate at 24 months after daily injections was estimated at 60.6% (95% confidence interval: 32.3%-80.0%). Height stagnation, hypertension, and irritability were observed; lethal adverse events were not reported. SIGNIFICANCE: Our study firstly explored the efficacy of LT-ACTH for preventing WS relapse. LT-ACTH might be a treatment option for patients with relapsed or intractable WS; however, we note that our study is limited by its small sample size and the lack of an appropriate control group.

Preliminary report for Epilepsia Open A case of West syndrome with severe global developmental delay and confirmed KIF5A gene variant.

Objective: Kinesin family member 5A (KIF5A) is a molecular motor protein responsible for intracellular transport, specifically in neurons. While abnormalities in the KIF5A gene have been reported in the onset of various neurological diseases, there are no studies demonstrating an association between this gene and West syndrome. Methods: In the case presented here, epileptic spasms appeared at 7 months; electroencephalogram (EEG) investigation confirmed hypsarrhythmia, resulting in a diagnosis of West syndrome. The patient exhibited peculiar facies, hypotonia, failure to thrive, and severe global developmental delay. Results: Cranial magnetic resonance imaging (MRI) revealed severe delayed myelination. 123I-iomazenil SPECT image at 7 months demonstrated decreased accumulation in bilateral areas, including the primary somatosensory and motor cortices, and the primary and association visual areas compared to an age-matched control. Whole exome sequencing analysis demonstrated a novel de novo heterozygous missense variant in KIF5A, (NM_004984.4:c.710A>T: p. Glu237Val). Significance: It was concluded that the KIF5A variant impaired the transport of GABAA receptors to the cell membrane surface, thus leading to an imbalance of these receptors between regions of the cerebrum and resulting in the onset of epilepsy.

Distinct dual cortico-cortical networks successfully identified between supplemental and primary motor areas during intracranial EEG for drug-resistant frontal lobe epilepsy.

We present a case of drug-resistant focal motor seizures in which separate cortico-cortical epileptic networks within the supplementary motor area (SMA) proper and primary motor area (PMA) were proven by ictal high-frequency oscillation (HFO) and cortico-cortical evoked potential (CCEP). A 12-year-old girl presented with two types seizures: type A, tonic extension and subsequent clonic movements of the right arm; and type B, tonic and clonic movements of the right leg. MRI was normal and karyotype genetic analysis revealed 46,X,t(X;14)(q13;p12). She underwent placement of chronic subdural electrodes over the left hemisphere. We recorded a total of nine seizures during 10 days of epilepsy monitoring. Type A seizures started from the lower part of the left SMA proper and early spread to the hand motor area of the PMA. Type B seizures started from the upper part of the SMA proper and early spread to the leg motor area of the PMA. CCEPs of both SMA proper and PMA activated two identical routes for evoked potentials correlating with separate pathways. Corticectomy of the left SMA proper and PMA achieved seizure-free without hemiparesis. Within a small homunculus of the SMA proper, separate epileptic networks were proven and validated by seizure semiology, ictal HFO, and CCEP.

Intrathecal dexamethasone therapy for febrile infection-related epilepsy syndrome.

OBJECTIVE: Increasing reports suggest a role for immunological mechanisms in febrile infection-related epilepsy syndrome (FIRES). The objective of this study was to elucidate the efficacy and safety of intrathecal dexamethasone therapy (IT-DEX). METHODS: We assessed six pediatric patients with FIRES who were administered add-on IT-DEX in the acute (n = 5) and chronic (n = 1) phases. We evaluated clinical courses and prognosis. We measured cytokines/chemokines in cerebrospinal fluid (CSF) from FIRES patients at several points, including pre- and post-IT-DEX, and compared them with control patients with chronic epilepsy (n = 12, for cytokines/chemokines) or with noninflammatory neurological disease (NIND, n = 13, for neopterin). RESULTS: Anesthesia was weaned after a median of 5.5 days from IT-DEX initiation (n = 6). There was a positive correlation between the duration from the disease onset to the introduction of IT-DEX and the length of ICU stay and the duration of mechanical ventilation. No patient experienced severe adverse events. Seizure spreading and background activities on electroencephalography were improved after IT-DEX in all patients. The levels of CXCL10, CXCL9, IFN-γ, and neopterin at pre-IT-DEX were significantly elevated compared to levels in epilepsy controls, and CXCL10 and neopterin were significantly decreased post-IT-DEX, but were still higher compared to patients with chronic epilepsy. IL-6, IL-8, and IL-1ß were significantly elevated before IT-DEX compared to epilepsy controls, though there was no significant decrease post-treatment. INTERPRETATION: IT-DEX represents a therapeutic option for patients with FIRES that could shorten the duration of the critical stage of the disease. The effect of IT-DEX on FIRES might include cytokine-independent mechanisms.

Phase-amplitude coupling of interictal fast activities modulated by slow waves on scalp EEG and its correlation with seizure outcomes of disconnection surgery in children with intractable nonlesional epileptic spasms.

OBJECTIVE: Epileptic spasms (ESs) are classified as focal, generalized, or unknown onset ESs. The classification of ESs and surgery in patients without lesions apparent on MRI is challenging. Total corpus callosotomy (TCC) is a surgical option for diagnosis of the lateralization and possible treatment for ESs. This study investigated phase-amplitude coupling (PAC) of fast activity modulated by slow waves on scalp electroencephalography (EEG) to evaluate the strength of the modulation index (MI) before and after disconnection surgery in children with intractable nonlesional ESs. The authors hypothesize that a decreased MI due to surgery correlates with good seizure outcomes. METHODS: The authors studied 10 children with ESs without lesions on MRI who underwent disconnection surgeries. Scalp EEG was obtained before and after surgery. The authors collected 20 epochs of 3 minutes each during non-rapid eye movement sleep. The MI of the gamma (30-70 Hz) amplitude and delta (0.5-4 Hz) phase was obtained in each electrode. MIs for each electrode were averaged in 4 brain areas (left/right, anterior/posterior quadrants) and evaluated to determine the correlation with seizure outcomes. RESULTS: The median age at first surgery was 2.3 years (range 10 months-9.1 years). Two patients with focal onset ESs underwent anterior quadrant disconnection (AQD). TCC alone was performed in 5 patients with generalized or unknown onset ESs. Two patients achieved seizure freedom. Three patients had residual generalized onset ESs. Disconnection surgeries in addition to TCC consisted of TCC + posterior quadrant disconnection (PQD) (1 patient); TCC + AQD + PQD (1 patient); and TCC + AQD + hemispherotomy (1 patient). Seven patients became seizure free with a mean follow-up period of 28 months (range 5-54 months). After TCC, MIs in 4 quadrants were significantly lower in the 2 seizure-free patients than in the 6 patients with residual ESs (p < 0.001). After all 15 disconnection surgeries in 10 patients, MIs in the 13 target quadrants for each disconnection surgery that resulted in freedom from seizures were significantly lower than in the 26 target quadrants in patients with residual ESs (p < 0.001). CONCLUSIONS: In children with nonlesional ESs, PAC for scalp EEG before and after disconnection surgery may be a surrogate marker for control of ESs. The MI may indicate epileptogenic neuronal modulation of the interhemispheric corpus callosum and intrahemispheric subcortical network for ESs. TCC may be a therapeutic option to disconnect the interhemispheric modulation of epileptic networks.

A case of infantile Tay-Sachs disease with late onset spasms.

BACKGROUND: Epilepsy is known to be associated with Tay-Sachs disease (TSD); however, no detailed reports are available. This case report aimed to present the clinical features of late onset spasms (LOS) in a patient with infantile TSD, and to elucidate the pathophysiology leading to LOS, using proton magnetic resonance spectroscopy (MRS). CASE PRESENTATION: At 11 months old, our patient had an afebrile seizure. At 14 months, he showed developmental stagnation and an increase in the frequency of epileptic seizures. Magnetic resonance imaging (T2-weighted images) showed high signal intensities in the thalamus bilaterally, and in the head of the caudate nucleus. Serum ß-hexosaminidase enzyme activity was reduced, and he was diagnosed with TSD with a homozygous pathogenic variant of the HEXA gene (c. 571-1 G > T [IVS5, -1 G > T]), confirmed using direct sequence analysis. At 20 months, epileptic spasms in series around times of drowsiness and waking were observed on long-term video-electroencephalogram monitoring, in which ictal findings were different from those of startle seizures and non-epileptic myoclonus. Therefore, the epilepsy was classified as LOS. Epileptic spasms stopped following adrenocorticotropic hormone therapy, after which his vitality and consciousness improved. Serial MRS results showed a progressive decline in N-acetyl aspartate, and an increase in myoinositol in the grey matter over time. DISCUSSION AND CONCLUSION: Our patient's MRS results suggested that cortical and subcortical axonal and neuronal degeneration with widespread gliosis in the cerebrum might lead to the development of LOS, and that LOS might be underestimated in patients with TSD.

Thyroid crisis mimicking clinically mild encephalitis/encephalopathy with a reversible splenial lesion: A pediatric case report.

BACKGROUND: Reversible lesions in the splenium of the corpus callosum (SCC) with viral infections are associated mainly with clinically mild encephalitis/encephalopathy with a reversible splenial lesion (MERS). We report a pediatric patient in thyroid crisis with reversible SCC lesions. CASE DESCRIPTION: We diagnosed a 9-year-old girl with thyroid crisis. She had presented with fever, tachycardia, and impaired consciousness. Magnetic resonance imaging revealed hyperintense signals in the splenium and genu of the corpus callosum and a white matter lesion of the left hemisphere in diffusion-weighted imaging. The initial, tentative diagnosis was clinically mild encephalitis/encephalopathy with a reversible splenial lesion (MERS). We initiated intravenous methylprednisolone pulse therapy; thereafter, her level of consciousness rapidly improved. On admission, thyroid function studies revealed elevation of free thyroxine and a low level of thyroid stimulating hormone with thyroid-related autoantibodies. She was begun on thiamazole and was discharged without neurological sequelae. CONCLUSION: Thyroid crisis is similar to acute encephalitis or encephalopathy associated with viral infection, especially with MERS, because the clinical and radiological features resemble those of thyroid crisis; therefore, thyroid diseases should be considered as a possible cause of reversible lesions in the splenium of the corpus callosum.

Engagement of cortico-cortical and cortico-subcortical networks in a patient with epileptic spasms: An integrated neurophysiological study.

OBJECTIVE: We aimed to delineate the engagement of cortico-cortical and cortico-subcortical networks in the generation of epileptic spasms (ES) using integrated neurophysiological techniques. METHODS: Seventeen-year-old male patient with intractable ES underwent chronic subdural electrode implantation for presurgical evaluation. Networks were evaluated in ictal periods using high-frequency oscillation (HFO) analysis and in interictal periods using magnetoencephalography (MEG) and simultaneous electroencephalography, and functional magnetic resonance imaging (EEG-fMRI). Cortico-cortical evoked potentials (CCEPs) were recorded to trace connections among the networks. RESULTS: Ictal HFO revealed a network comprising multilobar cortical regions (frontal, parietal, and temporal), but sparing the positive motor area. Interictally, MEG and EEG-fMRI revealed spike-and-wave-related activation in these cortical regions. Analysis of CCEPs provided evidence of connectivity within the cortico-cortical network. Additionally, EEG-fMRI results indicate the involvement of subcortical structures, such as bilateral thalamus (predominantly right) and midbrain. CONCLUSIONS: In this case study, integrated neurophysiological techniques provided converging evidence for the involvement of a cortico-cortical network (sparing the positive motor area) and a cortico-subcortical network in the generation of ES in the patient. SIGNIFICANCE: Cortico-cortical and cortico-subcortical pathways, with the exception of the direct descending corticospinal pathway from the positive motor area, may play important roles in the generation of ES.