An infantile traumatic brain injury with a bright tree appearance detected before the late seizure.

INDRODUCTION: Infantile traumatic brain injury (TBI) rarely follows a biphasic clinical course and exhibits a bright tree appearance (BTA) on magnetic resonance imaging (MRI). This is termed infantile traumatic brain injury with a biphasic clinical course and late reduced diffusion (TBIRD). TBIRD has clinical features similar to those of acute encephalopathy with biphasic seizures and late reduced diffusion (AESD). It remains to be clarified which patients with infantile TBI will develop TBIRD and the prevention and treatment of TBIRD. CASE AND REVIEW: We report a case of TBIRD that exhibited BTA 1 day before the late seizure and review 12 cases of TBIRD. All patients developed a subdural hematoma (SDH), were younger than 2 years, and presented with a biphasic phase within 3-6 days. The median interval between BTA and TBI was 5 days. Of the 5 cases examined with MRI before the biphasic phase, only our case was detected with BTA 4 days after TBI. CONCLUSION: Predicting the biphasic clinical course may be possible by examining MRI after TBI in patients under 2 years of age who develop SDH with unconsciousness, seizure, or hemiplegia, and these patients should be strictly followed up for 1 week.

Cerebral blood flow abnormalities with central sparing on arterial spin labeling in mild encephalopathy associated with excitotoxicity: a case report.

BACKGROUND: Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) and mild encephalopathy associated with excitotoxicity (MEEX) are the most frequent acute encephalopathies in pediatric patients in Japan. AESD typically presents with biphasic seizures and delayed reduced diffusion in the subcortical area, called bright tree appearance (BTA), on radiological examination. In patients with AESD, arterial spin labeling (ASL) shows decreased cerebral blood flow (CBF) in the hyperacute stage and increased CBF in the acute stage, suggesting the usefulness of ASL for the early diagnosis of AESD. Additionally, proton magnetic resonance spectroscopy (MRS) shows elevated glutamate (Glu) and glutamine (Gln) in AESD. MEEX is a group of mild encephalopathies with transient elevation of Gln on MRS similar to that in AESD; however, MEEX does not include any clinical biphasic course or abnormalities, including BTA on diffusion-weighted imaging. Although the usefulness of ASL for AESD has been reported, there are no reports for patients with MEEX. In this study, we report our experience with a 4-year-old girl diagnosed with MEEX who showed unique findings on ASL. CASE PRESENTATION: The patient was a 4-year-old girl admitted to the emergency room with febrile status epilepticus. Considering the possibility of AESD, vitamin therapy was initiated. ASL-MR imaging (MRI) of the brain performed on the second day showed increased blood flow in the frontal, temporal, and occipital regions with spared central sulcus, which indicated AESD with central sparing. The patient was diagnosed with AESD, and the treatment included pulse steroid therapy and immunoglobulin therapy from day 3. The patient remained mildly unconscious but gradually became conscious by day 7 with no seizures. Brain MRI performed on day 8 did not show any characteristic AESD findings, such as BTA. Furthermore, MRS showed elevated Gln, which, along with the clinical course, led to the diagnosis of MEEX. The patient was discharged on day 16 without obvious sequelae. CONCLUSIONS: ASL may be useful in the early diagnosis of MEEX as well as AESD, facilitating early intervention.

Acute focal bacterial nephritis characterized by acute encephalopathy with biphasic seizures and late reduced diffusion.

Acute focal bacterial nephritis (AFBN) is a localized bacterial infection of the kidney presenting as an inflammatory mass, and some patients show deterioration of clinical condition with neurological symptoms. Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) is a syndrome that is characterized by biphasic seizures and impaired consciousness with reduced diffusion in the subcortical white matter on magnetic resonance imaging, typically observed between days 3 and 9 after clinical onset. Although AFBN sometimes causes neurological symptoms, no cases of AFBN with AESD have been reported, and no studies have presented the cytokine profiles of patients with a severe form of acute encephalopathy with AFBN. We report here a very rare case involving a 6-month-old boy who developed AFBN due to Enterococcus faecalis with both the clinical and radiological features of AESD. In our patient, serum interleukin (IL)-6, IL-10, and interferon (IFN)-γ levels markedly increased on admission, and on day 4, only IL-6 levels significantly increased in the cerebrospinal fluid (CSF). These results suggest that high serum cytokines are produced locally in response to AFBN and elevated IL-6 levels in CSF may have neuroprotective roles.

Acute encephalopathy with biphasic seizures and late reduced diffusion in Kawasaki disease.

Herein we describe the case of a 7-month-old girl with Kawasaki disease (KD) in whom status epilepticus with fever developed on day 3 and cluster of seizures on day 6 of illness, followed by severe disturbance of consciousness afterward. Diffusion-weighted magnetic resonance imaging on day 6 of illness showed diffuse high signals in the bilateral subcortical white matter, while electroencephalogram indicated low-voltage slow waves. This indicated acute encephalopathy with biphasic seizures and late reduced diffusion (AESD); severe neurological sequelae remained. This is the first report of AESD as a complication of KD.

Disrupted glutamate-glutamine cycle in acute encephalopathy with biphasic seizures and late reduced diffusion.

INTRODUCTION: Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) is the most common subtype of infectious pediatric encephalopathy in Japan. It is sometimes difficult to make an early diagnosis of AESD; excitotoxicity is postulated to be the pathogenesis based on elevated glutamine (Gln) and glutamate (Glu) complex (Glx = Glu + Gln) observed on MR spectroscopy. It is uncertain whether Gln or Glu contributes to the elevated Glx, or whether MR spectroscopy is useful for an early diagnosis. METHODS: Five Japanese patients with AESD (three boys and two girls, 1 year of age) were enrolled in this study. MR spectroscopy was acquired from the frontal white matter (repetition time (TR) of 5000 ms, echo time (TE) of 30 ms) with a 1.5- or 3.0-T scanner. MR spectroscopy was performed four times for two patients, three times for one patient, and two times for two patients. Quantification of Glu and Gln was performed using LCModel. RESULTS: Glu was elevated in three of four studies on days 1-4 and became normal or low afterward. Gln was normal in three studies on days 1-2, elevated in all seven studies on days 4-12, and became normal or low afterward. CONCLUSION: These findings suggest that MR spectroscopy may be useful for an early diagnosis. Acute Glu elevation changes to subacute Gln elevation, suggesting that a disrupted Glu-Gln cycle may play an important role.

Cytokine and chemokine responses in the blood and cerebrospinal fluid of patients with human herpesvirus 6B-associated acute encephalopathy with biphasic seizures and late reduced diffusion.

Acute encephalopathy with biphasic seizures and late reduced diffusion has become increasingly common among various types of human herpesvirus 6B (HHV-6B) encephalitis at the time of primary viral infection. The aim of the present study is to explore the pathophysiology of HHV-6B-associated acute encephalopathy with biphasic seizures and late reduced diffusion. Five cytokines and five chemokines were measured in serum and cerebrospinal fluid (CSF) obtained from 12 HHV-6B-associated acute encephalopathy with biphasic seizures and late reduced diffusion patients and 19 control exanthem subitum (without complications) patients. Serum interleukin (IL)-10 (P = 0.007) and IL-8 (P = 0.025) were significantly higher in the patients with the disease than controls. Serum IL-1ß (P = 0.034) and monocyte chemoattractant protein (MCP)-1 (P = 0.002) were significantly higher in the controls than patients with the disease. In patients with the disease, IL-10 (P = 0.012), regulated on activation normal T cell expressed and secreted (RANTES; P = 0.001), and monokine induced by interferon γ (MIG; P = 0.001) were significantly higher in serum than CSF, meanwhile IL-6 (P = 0.034), IL-8 (P = 0.034), and MCP-1 (P = 0.001) were significantly higher in CSF than serum. Additionally, serum IL-10 was significantly higher in the disease patients with sequelae than those without sequelae (P = 0.016). Several cytokines and chemokines may be associated with the pathogenesis of acute encephalopathy with biphasic seizures and late reduced diffusion. Moreover, the regulation of cytokine networks appears to be different between peripheral blood (systemic) and central nervous system.

Cyclosporine for acute encephalopathy with biphasic seizures and late reduced diffusion.

BACKGROUND: Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) is the most common syndrome among the acute encephalopathies, and is associated with a high incidence of neurologic sequelae. This study examined the efficacy of cyclosporine (CsA) for the treatment of AESD. METHODS: Fourteen children with AESD were recruited and categorized as group A (not receiving CsA) and group B (receiving CsA). Clinical course, laboratory data, magnetic resonance imaging (MRI), and outcome were analyzed retrospectively. We divided the patients into three types according to the distribution of abnormalities on MRI: frontal lobe predominant type, unilateral cerebral hemisphere type, and diffuse type. We used the Pediatric Cerebral Performance Category scale (PCPC) and the Pediatric Overall Performance Category scale (POPC) as prognostic measures. RESULTS: Of the 14 children, five were boys (age range, 9-32 months). PCPC score was: 1 for seven patients, 2 for three patients, and 3 for four patients. There was no significant difference in PCPC between groups A and B (P = 0.293). POPC score was: 1 for six patients, 2 for five patients, and 3 for three patients. There was a significant difference in POPC between groups A and B when patients with the frontal lobe predominant type were excluded (P = 0.020). CONCLUSIONS: CsA could improve the neurological prognosis of patients with AESD, except for those with frontal lobe predominant type.

Acute encephalopathy with biphasic seizures and late reduced diffusion with concurrent transverse myelitis.

We describe a patient with acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) with unique features, including concurrent transverse myelitis. A 2-year-old previously healthy girl had clinical findings consistent with AESD, occurring in association with influenza A infection. The posterior brain regions were most severely affected, resulting in cortical blindness. She also developed bilateral limb weakness, and spine MRI revealed transverse myelitis in the cervical region. She was treated acutely with intravenous methylprednisolone. Serum anti-myelin oligodendrocyte glycoprotein and anti-aquaporin-4 antibodies were negative, as was an anti-extractable nuclear antigen panel. Although her clinical presentation was severe, she improved dramatically over the following months, and 6 months following initial presentation, her parents felt she had returned to baseline. This is the first report of AESD occurring in combination with transverse myelitis. The co-occurrence of the two conditions is unlikely to be coincidental, suggesting that there may be a shared or overlapping immunological pathway involved. The patient's recovery was impressive, which could partially relate to the acute treatment with corticosteroids.

Risk factors for post-encephalopathic epilepsy in patients with acute encephalopathy with biphasic seizures and late reduced diffusion.

BACKGROUND: Post-encephalopathic epilepsy (PEE) is a serious complication of acute encephalopathy syndromes, and is more frequent in patients with acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) than in children with acute encephalopathy. However, a risk factor analysis using laboratory findings in the acute phase of AESD has not yet been performed. Therefore, the present study examined risk factors of AESD-related PEE using laboratory parameters in the acute phase of AESD. METHODS: We retrospectively screened 27 pediatric patients with AESD for inclusion, and enrolled 20 ("the PEE group", n = 6; "the non-PEE group", n = 14) according to inclusion criteria. RESULTS: The incidence of AESD-related PEE was 30 %, and the median duration from the onset of AESD to the development of PEE was 2.5 months (range, 1-32). The most common types of seizures were focal seizures, epileptic spasms, and startle seizures: 4 out of 6 patients (66.7 %) had intractable epilepsy. The median values of alanine aminotransferase (ALT) in the 1st and 2nd seizure phases of AESD and aspartate aminotransferase (AST) in the 2nd seizure phase were significantly higher in the PEE group than in the non-PEE group (p < 0.01). CONCLUSIONS: This is the first study to report higher serum levels of ALT and AST at the onset of AESD as risk factors for AESD-related PEE. We also provided a detailed description on the clinical characteristics on AESD-related PEE, which are consistent with previous findings.

Factors influencing the development of infantile traumatic brain injury with a biphasic clinical course and late reduced diffusion.

BACKGROUND: Infantile traumatic brain injury (TBI) with a biphasic clinical course and late reduced diffusion (TBIRD) has been reported as a type of TBI. However, it remains uncertain which pediatric patients with TBI develop TBIRD. METHODS: Patients with TBI who were admitted to our hospital and underwent magnetic resonance imaging (MRI) between December 2006 and October 2022 were included in this study. A diagnosis of TBIRD was made in patients with or suspected TBI, with initial symptoms being convulsions or disturbance of consciousness and late-onset subcortical reduced diffusion, the so-called bright tree appearance. Clinical features, neuroimaging (computed tomography (CT) and MRI) findings, laboratory data, and Tada score were retrospectively compared between TBIRD and non-TBIRD patients. Neurological prognosis was assessed using the Pediatric Cerebral Performance Category scale. RESULTS: Of 21 patients who met the inclusion criteria, a diagnosis of TBIRD was made in 7 patients (median age: 8 months). The factors contributing to TBIRD development were seizures lasting over 30 min as the initial symptom (5/7 in TBIRD vs. 0/14 in non-TBIRD), tracheal intubation during initial treatment (5/7 vs. 0/14), and brain parenchymal lesions on CT (3/7 vs. 0/14), suggesting that severe TBI may progress to TBIRD. The Tada score was more positive in patients with TBIRD (6/7) than in those without (0/14). CONCLUSIONS: It is important to monitor infant patients with severe TBI for the development of TBIRD. The Tada score can be a useful tool for TBIRD prediction.

Underlying Disorders in Children With Infection-Related Acute Encephalopathy.

BACKGROUND: Various factors contribute to the development of infection-related acute encephalopathy (AE) in children, such as infectious agents and chronic underlying disorders. We studied underlying disorders in children with AE to identify predisposing factors of AE. METHODS: We investigated underlying disorders or past histories in patients with two types of AE from the database in the Tokai area of Japan between 2009 and 2022: 204 patients with AE with reduced subcortical diffusion (AED) and 137 with clinically mild encephalopathy with a reversible splenial lesion (MERS). We compared them with 89 patients with acute disseminated encephalomyelitis (ADEM) to clarify the specific disorders in the two AE types. RESULTS: The prevalence of underlying disorders in AED (34%, 70 patients) was significantly higher than that in ADEM (12%, 11 patients) (P < 0.01). The prevalence of underlying disorders in MERS was 23% (32 patients). The underlying disorders included seizure disorders, premature birth, genetic/congenital disorders, and endocrine/renal diseases. In patients with seizure disorders in AED, five patients (18%) had Dravet syndrome and four (15%) had West syndrome, whereas none with MERS had these syndromes. Twenty-five (12%) of 204 patients with AED, three (2%) with MERS, and one (1%) with ADEM were preterm or low birth weight. CONCLUSIONS: The high prevalence of seizure disorders suggests that seizure susceptibility is an important predisposing factor in AED. Premature birth also has an impact on the development of AED. Caution is required regarding the development of AE in patients with chronic seizure disorders or premature birth.

Infantile Hypoxic Encephalopathy Mimicking Acute Encephalopathy with Biphasic Seizures and Late Reduced Diffusion (AESD) Identified as an Episode of Brief Resolved Unexplained Event (BRUE).

Acute encephalopathy with biphasic seizures and reduced diffusion (AESD) is characterized by biphasic seizures following febrile viral infections and delayed reduced diffusion of the cerebral white matter on magnetic resonance imaging (MRI) diffusion-weighted imaging (DWI) (bright tree appearance, BTA). However, hypoxic encephalopathy with biphasic seizures and AESD-mimicking imaging findings has not been reported. We report a case of hypoxic encephalopathy due to suffocation with concomitant biphasic seizures and BTA, mimicking AESD. On day 1, a healthy 5-month-old girl was found face down with decreased breathing and a deteriorating consciousness level, suggesting a brief resolved unexplained event (BRUE). Electroencephalography (EEG) revealed periodic epileptic discharges, suggesting possible nonconvulsive status epilepticus. Despite improvements in consciousness level and EEG abnormalities on day 2, her consciousness level deteriorated again with generalized tonic-clonic seizures on day 3, and a head MRI-DWI revealed restricted diffusion predominantly in the subcortical areas, suggesting BTA. Treatment for acute encephalopathy resolved the clinical seizures and EEG abnormalities. Persistence of abnormal EEG, reflecting abnormal excitation and accumulation of neurotoxic substances caused by hypoxia, may have contributed to the development of AESD-like findings. As hypoxic encephalopathy causes AESD-like biphasic seizures, monitoring consciousness level, seizure occurrence, and EEG abnormalities even after acute symptoms have temporarily improved following hypoxia is essential.

A serial analysis of serum aspartate aminotransferase levels in patients with acute encephalopathy with biphasic seizures and late reduced diffusion and prolonged febrile seizure.

BACKGROUND: There are no established biomarkers for diagnosing acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) in the early acute phase, called "the 1st seizure phase". Based on our clinical experience, we hypothesized that serial examinations of blood levels of aspartate aminotransferase (AST) in children with febrile convulsive status epilepticus (FCSE) revealed higher levels in patients with AESD in the 1st seizure phase than in those with prolonged febrile seizures (PFs). METHODS: To test our presented hypothesis, we retrospectively investigated changes in serum AST in patients with FCSE due to AESD (n = 11) or PFs (n = 27) who were serially examined within 48 h of the onset of convulsions. RESULTS: The rate of increase in AST was significantly higher in patients with AESD than in those with PFs. The rate of increase in AST correlated with previously reported scoring systems, i.e., Yokochi and Tottori scores, for the prediction of AESD. A positive correlation between the rate of increase in AST and creatinine levels in the first examination were observed; however, creatinine levels did not significantly differ between the AESD and PFs groups in the first or second examination. Blood levels of pH, ammonia, and sugar in the first examination and C-reactive protein in the second examination were significantly higher in the AESD group than in the PFs group. CONCLUSIONS: The present study revealed that the rate of increase in AST was significantly higher in patients with AESD than in those with PFs. A novel predictive scoring system needs to be established in combination with the rate of increase in AST and reported clinical parameters, which will improve the prognosis of patients with FCSE.

Restricted Diffusion in the Bilateral Subcortical Motor Areas Associated with Status Epilepticus in an Infant with Kawasaki Disease.

Status epilepticus (SE) often causes neuronal death in the cerebrum and consequent long-term sequelae. Acute encephalopathy with biphasic seizures and late reduced diffusion is clinically characterized by SE associated with fever and seizure clusters that occur 3-9 days after symptom onset. MRI reveals reduced diffusion in the frontal or frontoparietal subcortical white matter, with sparing of the perirolandic region following seizure clusters. Kawasaki disease (KD) is an acute self-limited vasculitis secondary to activation of the immune system; KD is rarely complicated by acute encephalopathy. We report the case of a male infant who developed SE associated with KD and showed late reduced diffusion in the subcortical white matter beneath the bilateral motor cortices (primary motor, premotor and supplementary motor areas) and the right frontal cortex. The patient had characteristic neurological sequelae in the chronic phase, including clumsiness of fingers and forearms, impaired discrimination of tactile sensation and position sense on digits in his hands and feet, corresponding to the lesions with reduced diffusion at the acute phase.

Neuroimaging in acute infection-triggered encephalopathy syndromes.

Acute encephalopathy associated with infectious diseases occurs frequently in Japanese children (400-700 children/year) and is the most common in infants aged 0-3 years. Acute encephalopathy is classified into several clinicoradiological syndromes; acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) is the most common subtype, followed by clinically mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) and acute necrotizing encephalopathy (ANE). Neuroimaging, especially magnetic resonance imaging (MRI), is useful for the diagnosis, assessment of treatment efficacy, and evaluation of the pathophysiology of encephalopathy syndromes. MRI findings essential for diagnosis include delayed subcortical reduced diffusion (bright tree appearance) for AESD, reversible splenial lesions with homogeneously reduced diffusion for MERS, and symmetric hemorrhagic thalamic lesions for ANE. We reviewed several MRI techniques that have been applied in recent years, including diffusion-weighted imaging for the characterization of cerebral edema, arterial spin labeling for evaluating cerebral perfusion, and magnetic resonance spectroscopy for evaluating metabolic abnormality.

Severe pediatric acute encephalopathy syndromes related to SARS-CoV-2.

Background and objectives: To clarify whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection cause acute encephalopathy in children and which are the most common syndromes that cause them and what are the outcomes. Methods: A nationwide web-based survey among all members of the Japanese Society of Child Neurology to identify pediatric patients aged < 18 years who developed acute encephalopathy in Japan between 1 January 2020 and 31 May 2022 associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection confirmed by polymerase chain reaction or antigen tests using pharyngeal swabs. Acute encephalopathy was defined as acute onset of impaired consciousness lasting > 24 h or an altered mental state; neurological symptoms arising within 2 weeks of onset of COVID-19 or multisystem inflammatory syndrome in children (MIS-C)/pediatric inflammatory multisystem syndrome (PIMS); evidence of SARS-CoV-2 infection; and reasonable exclusion of other diseases. Patients were divided into the known clinico-radiological acute encephalopathy syndrome group and unexplained or unclassifiable acute encephalopathy group. Outcomes were assessed by pediatric cerebral performance category (PCPC) score at hospital discharge. Results: Of the 3,802 society members, 217 representing institutions responded, and 39 patients with suspected acute encephalopathy were reported, of which 31 met inclusion criteria. Of these patients, 14 were diagnosed with known clinico-radiological acute encephalopathy syndromes, with acute encephalopathy with biphasic seizures and late reduced diffusion (five patients) being the most common. Five developed acute encephalopathy associated with MIS-C/PIMS. Among 31 patients, 9 (29.0%) had severe sequelae or died (PCPC ≥ 4). Two of three patients with encephalopathy with acute fulminant cerebral edema and two with hemorrhagic shock and encephalopathy syndrome died. The PCPC scores were higher in the known clinico-radiological acute encephalopathy syndrome group than in the unexplained or unclassifiable acute encephalopathy group (P < 0.01). Discussion: Acute encephalopathy related to SARS-CoV-2 infection was demonstrated to be more severe than that caused by other viruses in Japan. Acute encephalopathy syndromes characterized by specific neuroradiological findings was associated with poor clinical outcomes.

Arterial spin labeling image findings in the acute phase in paediatric patients with acute encephalopathy with biphasic seizures and late reduced diffusion.

Introduction: Diagnosing acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) after the first seizure (early seizure/seizures, ES/ESs) is challenging because a reduced apparent diffusion coefficient (ADC) in the cortical or subcortical white matter, often described as having a "bright-tree appearance (BTA)," is usually not observed until secondary seizures (late seizures, LSs) occur. Previous studies have reported hypoperfusion on arterial spin labeling (ASL) within 24 h after ES/ESs in patients with AESD and hyperperfusion within 24 h after LS onset. This study aimed to investigate cerebral blood flow in the hyperacute phase (between ES/ESs and LSs) using ASL in patients with AESD. Methods: Eight ASL images were acquired in six patients with AESD admitted to our hospital from October 2021 to October 2022. ASL findings in the hyperacute phase were investigated and video-electroencephalogram findings obtained around ASL image acquisition in the hyperacute phase were evaluated. Results: Four ASL images were obtained for three patients before LS onset, with three images showing hyperperfusion areas and one image showing hypoperfusion areas. These hyperperfuion regions coincided with BTA on subsequent images of these patients.In one patient, the first ASL image was obtained in the late hyperacute phase and revealed hyperperfusion areas with a slightly abnormal change on diffusion-weighted image (DWI), which were not accompanied by ADC abnormalities. The second ASL image obtained 51 h after the first ASL, and before LS onset revealed more prominent hyperperfusion areas than the first ASL image, which were accompanied by BTA. In another patient, the ASL image obtained 82 h after ES revealed hyperperfusion areas without abnormal change on DWI or ADC. Conclusion: This study revealed that two patients exhibited hyperperfusion regions and another patient exhibited hypoperfusion regions among three patients who underwent ASL imaging during the period from 24 h after ES/ESs to LSs in patients with LSs or cooling initiation in patients without LSs due to early anaesthesia induction (late hyperacute phase). Further prospective studies on cerebral blood flow are required to explore the relationship among the timing of image acquisition, the presence of electrographic seizures, and ASL findings in patients with AESD.

Involuntary movements as a prognostic factor for acute encephalopathy with biphasic seizures and late reduced diffusion.

BACKGROUND: Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) is characterized by biphasic seizures and white matter lesions with reduced diffusion, which are often accompanied by involuntary movements. The neurological outcomes of AESD vary from normal to mild or severe sequelae, including intellectual disability, paralysis, and epilepsy. The present study aimed to clarify the prognostic factors of AESD, including involuntary movements. METHODS: We enrolled 29 patients with AESD admitted to Tottori University Hospital from 1991 to 2020 and retrospectively analyzed their clinical data. Neurological outcomes were assessed by the Pediatric Cerebral Performance Category score and cerebral paralysis as neurological sequelae. RESULTS: Of the 29 patients, 12 had favorable outcomes and 17 had unfavorable outcomes. Univariate analysis revealed that the presence of underlying diseases, a decline in Glasgow Coma Scale (GCS) score 12-24 h after early seizures, and involuntary movements were associated with unfavorable outcomes. In multivariate analysis, a decline in GCS score and involuntary movements were associated with unfavorable outcomes. The sensitivities and specificities of underlying diseases, a decline of ≥ 3 points in GCS score 12-24 h after early seizures, and involuntary movements for unfavorable outcomes were 53% and 92%, 92% and 65%, and 59% and 92%, respectively. CONCLUSIONS: The appearance of involuntary movements may be associated with unfavorable outcomes of AESD. The prognostic factors identified herein are comparable with previously known prognostic factors of consciousness disturbances after early seizures.

Refractory status epilepticus with fever due to mumps vaccine-induced encephalitis caused secondary encephalopathy mimicking acute encephalopathy with biphasic seizures and late reduced diffusion.

BACKGROUND: Encephalitis due to vaccination for mumps is a rare complication that occurs in 0.00004% of recipients, and there has been no report of serious neurological sequelae. Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) has been reported as the most frequent type among acute encephalopathy syndromes in the pediatric population in Japan. There has been no report of AESD caused by vaccinations. Case presentation We present the clinical course of a 1-year and 10-month-old boy who had no preexisting condition, and developed mumps vaccine-induced severe primary encephalitis. Refractory status epilepticus due to encephalitis persisted for 16 h and resulted in secondary encephalopathy as a form of AESD mimic. He had serious neurological sequelae, such as West syndrome, transient spastic tetraplegia, and intellectual disability, despite intensive treatments. DISCUSSION: The presented boy is the first patient to develop mumps vaccine-induced primary encephalitis with severe central nervous system (CNS) damage. Screening of the immunological background in the presented patient revealed no abnormalities; therefore, it is unclear why he developed such severe adverse events. In patients with acute encephalitis caused by the herpes simplex virus 1, inborn immune errors in CNS based on mutations in single genes are involved in its pathophysiology. Consequently, some immunogenetic alterations could be found by further analysis in the presented patient.

Association of IL-1B rs16944 Polymorphism With Acute Encephalopathy With Biphasic Seizures and Late Reduced Diffusion Is Opposite to That of Febrile Seizures.

Objective: Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) is a severe neurologic complication of febrile infectious diseases in children. At the onset, AESD is clinically manifested as febrile status epilepticus. Subsequent damage to the cerebral cortex is ascribed to neurotoxicity. The incidence of AESD is remarkably high in Japan, suggesting the involvement of genetic factors. The expression of interleukin 1 beta (IL-1ß), a member of the cytokine family involved in the inflammatory response, is reportedly associated with rs16944, a polymorphism in the upstream region of the IL-1B gene, being higher in TT genotype. Previous association studies of rs16944 with febrile seizures (FS) have demonstrated a significant excess in the TT vs. CC + CT genotype in the Asian population. Here, we conducted a case-control association study of rs16944 in AESD. Methods: We genotyped rs16944 by Sanger sequencing on 283 patients with AESD. As controls, we used genotyping data of 104 Japanese individuals obtained from the 1,000 Genomes Project. Then, we performed a case-control association study using the chi-square test. Results: The ratio of individuals with TT vs. those with CC+CT genotype was significantly lower in AESD than in the controls [p-value 0.021, Odds Ratio (OR) 0.52]. This finding was opposite to that of a previously reported FS. Conclusion: The AESD has a genetic background distinct from FS and is not a severe type of FS.