Eculizumab in Adolescent Patients With Refractory Generalized Myasthenia Gravis: A Phase 3, Open-Label, Multicenter Study.

BACKGROUND: This study evaluated the efficacy and safety of eculizumab, a terminal complement C5 inhibitor, in juvenile generalized myasthenia gravis (gMG). METHODS: Adolescents aged 12 to 17 years with refractory anti-acetylcholine receptor (AChR) antibody-positive gMG received eculizumab (weekly induction [one to two doses of 600 mg or four doses of 900 mg] followed by maintenance doses [300 to 1200 mg] every two weeks for up to 26 weeks) in a phase 3, open-label multicenter study (NCT03759366). Change from baseline to week 26 in Quantitative Myasthenia Gravis (QMG) total score (primary end point) and secondary end points including Myasthenia Gravis-Activities of Daily Living (MG-ADL) total score, Myasthenia Gravis Composite score, Myasthenia Gravis Foundation of America postintervention status, EuroQol 5-Dimensions (Youth) and Neurological Quality-of-Life Pediatric Fatigue questionnaire scores, as well as pharmacokinetics, pharmacodynamics, and safety, were recorded. RESULTS: Eleven adolescents (mean ± S.D. age 14.8 ± 1.8 years) were enrolled; 10 completed the primary evaluation period. Least-squares mean changes from baseline at week 26 were -5.8 (standard error [SE] 1.2; P = 0.0004) for QMG total score and -2.3 (SE 0.6; P = 0.0017) for MG-ADL total score. Overall, the primary and all secondary efficacy end point analyses met statistical significance from the first assessment and were sustained throughout. Complete terminal complement inhibition was sustained through 26 weeks in all patients. Treatment-emergent adverse events were all mild/moderate and predominantly unrelated to eculizumab. CONCLUSIONS: Eculizumab was effective in reducing disease burden and was well tolerated in adolescents with refractory AChR antibody-positive gMG.

A Common Marmoset Model of Mother-Infant Intervention for Breastfeeding Disorders in the Presence of Paternal Inhibition and Maternal Neglect.

Parents' psychological stress during the perinatal and neonatal periods continues to increase in an environment of declining birthrates, aging populations, and shrinking family sizes. The increase in child abuse and neglect cases, most likely by inexperienced and insufficiently knowledgeable parents, necessitates education on childcare and intervention techniques in nursing and midwifery training. In particular, attachment formation early in life between mother and infant is crucial. To accurately teach sensitive and comprehensive information on intervention techniques for mother-child attachment formation, realistic videos, and educational materials are necessary. Although pseudoeducational materials are available, they might be limited in explaining complex realism, particularly to support breastfeeding that involves both parents and child and that encourages interaction between the two. In a previous study in a common marmoset (Callithrix jacchus) model, we experimentally controlled infant feeding and nurturing through 24 h of constant sensing and collected 1 month of quantitative data on psychological indices that possibly translated to psychological development. Age-dependent dynamic visualization of these data by multivariate analyses inferred causal relationships between early parental feeding and psychobiological rhythm formation. In the same primate model, we identified a spontaneous case of breastfeeding failure in which the father inhibited his neonatal infant's feeding and the mother appeared to abandon nurturing, leading to clinically significant weight loss in the infant. Thus, we explored intervention techniques to promote mother-infant interaction. The mother was trained to allow the infant to spontaneously explore her breast. Initially, the mother refused to display the feeding pose potentially due to pain associated with breast engorgement. Massage was used to soften the breast and feeding was reintroduced. We hypothesize that activation of instinctive attachment formation mechanisms by encouraging spontaneity in each parent and child is the key to successful feeding intervention.

Efficacy of cEEG and hepatic function to diagnose early acute encephalopathy.

BACKGROUND: Early treatment may improve the prognosis of acute encephalopathy (AE). However, methods for early diagnosis have not yet been established. In this paper, we examined methods for the early diagnosis of AE. METHODS: We extracted data on patients with febrile status epilepticus from the electronic medical records in our department between March 2016 and April 2021. Among these, 79 patients who underwent continuous electroencephalography (cEEG) were included in this study. Patients who exhibited psychomotor retardation or abnormal brain magnetic resonance imaging findings were assigned to Group E (n = 20), and the remaining patients were the control group (Group C, n = 59). The following tests were compared retrospectively between these two groups on admission: cEEG, serum hepatic function tests, and blood coagulation tests. RESULTS: The percentage of patients who exhibited high-amplitude slow waves or flat waves on cEEG at the time of admission was statistically significantly higher in Group E than in Group C (p < 0.01). Moreover, the percentage of patients whose high-amplitude slow waves or flat brain waves on admission disappeared within 6 h after an initial episode of convulsion was statistically significantly lower in Group E than in Group C (p < 0.01). Furthermore, all the items in the coagulation and the hepatic function tests were statistically significantly different in Group E from those in Group C (p < 0.05). CONCLUSION: These results showed that cEEG together with hepatic function and coagulation tests may be useful for the differential diagnosis of AE.

Arterial and Venous Thrombosis Complicated in COVID-19: A Retrospective Single Center Analysis in Japan.

Background: Thrombosis is a characteristic complication in coronavirus disease 2019 (COVID-19). Since coagulopathy has been observed over the entire clinical course, thrombosis might be a clue to understanding the specific pathology in COVID-19. Currently, there is limited epidemiological data of COVID-19-associated thrombosis in the Japanese population and none regarding variant strains of SARS-CoV-2. Here, we elucidate the risk factors and the pattern of thrombosis in COVID-19 patients. Methods: The patients consecutively admitted to Tokyo Medical and Dental University Hospital with COVID-19 were retrospectively analyzed. SARS-CoV-2 variants of concern/interest (VOC/VOI) carrying the spike protein mutants E484K, N501Y, or L452R were identified by PCR-based analysis. All thrombotic events were diagnosed by clinical symptoms, ultrasonography, and/or radiological tests. Results: Among the 516 patients, 32 patients experienced 42 thromboembolic events. Advanced age, severe respiratory conditions, and several abnormal laboratory markers were associated with the development of thrombosis. While thrombotic events occurred in 13% of the patients with a severe respiratory condition, those events still occurred in 2.5% of the patients who did not require oxygen therapy. Elevated D-dimer and ferritin levels on admission were independent risk factors of thrombosis (adjusted odds ratio 9.39 and 3.11, 95% confidence interval 2.08-42.3, and 1.06-9.17, respectively). Of the thrombotic events, 22 were venous, whereas 20 were arterial. While patients with thrombosis received anticoagulation and antiinflammatory therapies with a higher proportion, the mortality rate, organ dysfunctions, and bleeding complications in these patients were higher than those without thrombosis. The incidence of thrombosis in COVID-19 became less frequent over time, such as during the replacement of the earlier strains of SARS-CoV-2 by VOC/VOI and during increased use of anticoagulatory therapeutics. Conclusion: This study elucidated that elevated D-dimer and ferritin levels are useful biomarkers of thrombosis in COVID-19 patients. The comparable incidence of arterial thrombosis with venous thrombosis and the development of thrombosis in less severe patients required further considerations for the management of Japanese patients with COVID-19. Further studies would be required to identify high-risk populations and establish appropriate interventions for thrombotic complications in COVID-19.

Development and validation of the Epilepsy Self-Stigma Scale.

OBJECTIVE: Self-stigma is the internalization of negative public attitudes and is often experienced by patients with epilepsy (PWE). Greater self-stigma is associated with lower self-esteem and hinders therapeutic behavior. The study aims were to develop the Epilepsy Self-Stigma Scale (ESSS) to assess self-stigma in PWE and to examine the scale's reliability and validity. METHODS: We created a test scale based on items from an existing stigma scale and the results of a previous qualitative analysis we conducted. We recruited 200 outpatients from departments specializing in epilepsy (psychiatry, neurology, and pediatric neurology) at four facilities in Tokyo and Saitama prefecture, Japan, between September and December 2020. Participants also completed the Rosenberg Self-Esteem Scale (RSES) and Beck Depression Inventory (BDI-II). RESULTS: Questionnaires were returned from 102 participants (response rate: 51%). After excluding two participants with incomplete questionnaires, data for 100 participants were analyzed (53 women, 47 men; mean age [standard deviation]: 39.86 [17.45] years). Exploratory factor analysis extracted eight items loading on three factors: internalization of stigma, societal incomprehension, and confidentiality. Cronbach's α for all items and each factor demonstrated acceptable internal consistency (α = 0.76-0.87). Test-retest reliability was confirmed using data from 21 participants who completed the scale twice (r = 0.72 to 0.90). ESSS total scores and subscale scores correlated with RSES and BDI-II scores (r = -0.30 to 0.55). The ESSS demonstrated substantial constructive validity. However, total scores did not significantly correlate with objective physician assessment of self-stigma. SIGNIFICANCE: The results showed that the eight-item ESSS has high reliability and validity. This scale could facilitate the examination of factors associated with self-stigma in PWE, which could inform the development of effective interventions for reducing stigma.

HPeV3-associated acute encephalitis/encephalopathy among Japanese infants.

OBJECTIVE: The current study aimed to identify and compare the clinical characteristics of human parechovirus type 3 (HPeV3)-associated acute encephalitis/encephalopathy (HPeV3E/E) between infants with abnormal brain magnetic resonance imaging (MRI) findings (typical, or MRI-positive HPeV3E/E) and those with MRI-negative findings (MRI-negative HPeV3E/E). METHODS: This is a retrospective study on patients with HPeV3 infection, and a two-step questionnaire survey performed on 837 hospitals in Japan between 2014 and 2016. RESULTS: We identified 240 infants with HPeV3 infection, of which 34 had been clinically-diagnosed HPeV3E/E (cHPeV3E/E). However, detailed clinical data were provided by 32 of the 34 patients. Among these 32, 23 had undergone MRI and were categorized into two groups, MRI-positive (n = 17) and -negative (n = 6). There were no significant intergroup differences in clinical lab results or symptoms, except for gastrointestinal symptoms that were only present in the MRI-negative patients. The MRI-positive group showed white matter involvement on brain MRI during the acute phase, and 8 patients presented with lesions on follow-up MRI. Furthermore, 4 (50%) of the 8 patients had neurological sequelae. CONCLUSION: Clinical characteristics of cHPeV3E/E patients with and without lesions on brain MRI showed no significant differences. Therefore, considering the difficulty in distinguishing febrile infants with cHPeV3E/E from those with a sepsis-like illness, during an HPeV3 infection epidemic, it is imperative to frequently perform brain MRI in febrile infants presenting with severe disease for the early diagnosis of HPeV3E/E presenting with brain lesions.

Guidelines for the diagnosis and treatment of acute encephalopathy in childhood.

The cardinal symptom of acute encephalopathy is impairment of consciousness of acute onset during the course of an infectious disease, with duration and severity meeting defined criteria. Acute encephalopathy consists of multiple syndromes such as acute necrotizing encephalopathy, acute encephalopathy with biphasic seizures and late reduced diffusion and clinically mild encephalitis/encephalopathy with reversible splenial lesion. Among these syndromes, there are both similarities and differences. In 2016, the Japanese Society of Child Neurology published 'Guidelines for the Diagnosis and Treatment of Acute Encephalopathy in Childhood', which made recommendations and comments on the general aspects of acute encephalopathy in the first half, and on individual syndromes in the latter half. Since the guidelines were written in Japanese, this review article describes extracts from the recommendations and comments in English, in order to introduce the essence of the guidelines to international clinicians and researchers.

Inexpensive Home Infrared Living/Environment Sensor with Regional Thermal Information for Infant Physical and Psychological Development.

The use of home-based image sensors for biological and environmental monitoring provides novel insight into health and development but it is difficult to evaluate people during their normal activities in their home. Therefore, we developed a low-cost infrared (IR) technology-based motion, location, temperature and thermal environment detection system that can be used non-invasively for long-term studies in the home environment. We tested this technology along with the associated analysis algorithm to visualize the effects of parental care and thermal environment on developmental state change in a non-human primate model, the common marmoset (Callithrix jacchus). To validate this system, we first compared it to a manual analysis technique and we then assessed the development of circadian rhythms in common marmosets from postnatal day 15-45. The semi-automatically tracked biological indices of locomotion velocity (BV) and body surface temperature (BT) and the potential psychological index of place preference toward the door (BD), showed age-dependent shifts in circadian phase patterns. Although environmental variables appeared to affect circadian rhythm development, principal component analysis and signal superimposing imaging methods revealed a novel phasic pattern of BD-BT correlation day/night switching in animals older than postnatal day 38 (approximately equivalent to one year of age in humans). The origin of this switch was related to earlier development of body temperature (BT) rhythms and alteration of psychological behavior rhythms (BD) around earlier feeding times. We propose that this cost-effective, inclusive sensing and analytic technique has value for understanding developmental care conditions for which continual home non-invasive monitoring would be beneficial and further suggest the potential to adapt this technique for use in humans.

Epidemiological changes of acute encephalopathy in Japan based on national surveillance for 2014-2017.

BACKGROUND: We previously reported the nationwide, epidemiological data of acute encephalopathy in Japan during 2007-2010. Here we conducted the second national survey of acute encephalopathy during 2014-2017, and compared the results between the two studies to elucidate the trends in the seven years' interval as well as the influence of changes in pediatric viral infections and guidelines for acute encephalopathy in Japan. METHODS: The Research Committee on Acute Encephalopathy supported by the Japanese Government sent a questionnaire to 507 hospitals throughout Japan, and collected the responses by mail. RESULTS: A total of 1115 cases from 267 hospitals reportedly had acute encephalopathy during April 2014-June 2017. In this study, the age at onset was younger, the ratios of recently established syndromes, such as acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) and clinically mild encephalitis/encephalopathy with a reversible splenial lesion (MERS), were higher, and the ratio of influenza-associated encephalopathy was lower, than in the previous study. The age at onset of influenza-associated encephalopathy was lower, and that of HHV-6/7-associated encephalopathy higher, compared to the first survey. The outcomes of entire acute encephalopathy remained unchanged. CONCLUSION: Some of these changes reflected the recent trends of viral infectious diseases including 2009 influenza pandemic, and others the standardization of the diagnosis of acute encephalopathy in Japan.

Nationwide epidemiological survey of holoprosencephaly in Japan.

BACKGROUND: Holoprosencephaly (HPE) is a congenital malformation with an estimated prevalence of 0.10-6.06 per 10 000 births but with no nationwide data specific to Japan. METHODS: This nationwide retrospective questionnaire survey was conducted from 2011 to 2013. All 467 training hospitals for perinatal and neonatal care certified by the Japan Society of Perinatal and Neonatal Medicine were contacted. The birth prevalence rate (BPR) was assessed from the primary survey and clinical characteristics from the secondary survey. RESULTS: We received valid responses from 253 hospitals in the primary survey (54.6%). Of 390 342 live births, 60 were diagnosed with HPE (23 males and 37 females), resulting in an actual BPR of 1.54 per 10 000 live births. The point estimate for HPE cases was 100 (95% confidence interval [CI]: 80.7-120), and the estimated BPR of HPE was calculated to be 0.32 per 10 000 live births (95% CI: 0.26-0.38) based on 3 117 853 live births according to Japanese national statistics during the study period. In the secondary survey, we obtained data for 49 cases (19 males and 30 females). Of these, 20 were alobar (40.8%), 20 were semilobar (40.8%), five were lobar (10.4%), and four were of unknown type. Genetic examination was performed in 37 of the 49 HPE patients and revealed that chromosomes 13, 18, and 7 were affected in eight, six, and four patients, respectively. CONCLUSIONS: This is the most extensive survey on holoprosencephaly to date in Japan. The estimated BPR was consistent with that reported in previous research.

Comparison of the ventilation characteristics in two adult oscillators: a lung model study.

BACKGROUND: Two recent large randomized controlled trials did not show the superiority of high-frequency oscillatory ventilation (HFOV) in adults with ARDS. These two trials had differing results, and possible causes could be the different oscillators used and their different settings, including inspiratory time % (IT%). The aims of this study were to obtain basic data about the ventilation characteristics in two adult oscillators and to elucidate the effect of the oscillator and IT% on ventilation efficiency. METHODS: The Metran R100 or SensorMedics 3100B was connected to an original lung model internally equipped with a simulated bronchial tree. The actual stroke volume (aSV) was measured with a flow sensor placed at the Y-piece. Carbon dioxide (CO2) was continuously insufflated into the lung model ([Formula: see text]CO2), and the partial pressure of CO2 (PCO2) in the lung model was monitored. Alveolar ventilation ([Formula: see text]A; L/min) was estimated as [Formula: see text]CO2 divided by the stabilized value of PCO2. [Formula: see text]A was evaluated with several stroke volume settings in the R100 (IT = 50%) or several airway pressure amplitude settings in the 3100B (IT = 33%, 50%) at a frequency of 6 and 8 Hz, a mean airway pressure of 25 cmH2O, and a bias flow of 30 L/min. Assuming that [Formula: see text]A = frequencya × aSVb, values of a and b were determined. Ventilation efficiency was calculated as [Formula: see text]A divided by actual minute ventilation. RESULTS: The relationship between aSV and [Formula: see text]A or ventilation efficiency were different depending on the oscillator and IT%. The values of a and b were 0 < a < 1 and 1 < b < 2 and were different for three conditions at both frequencies. [Formula: see text]A and ventilation efficiency were highest with R100 (IT = 50%) and lowest with 3100B (IT = 33%) for high aSV ranges at both frequencies. CONCLUSIONS: In this lung model study, ventilation characteristics were different depending on the oscillator and IT%. Ventilation efficiency was highest with R100 (IT = 50%) and lowest with 3100B (IT = 33%) for high aSV ranges.

Pattern Visually Evoked Potentials in Japanese Girl With Optic Neuritis and Seropositive to Anti-myelin Oligodendrocyte Glycoprotein (MOG) Antibody.

Purpose: To describe a Japanese girl with unilateral optic neuritis who was seropositive for the anti-myelin-oligodendrocyte glycoprotein (MOG). Serial recordings of the pattern visual evoked potentials (pVEPs) were made to follow the dynamic changes of the disease activity. Observations: A 5-year-old girl developed a sudden reduction of vision and deep ocular pain in her right eye. On examination at our university hospital, the best-corrected visual acuity (BCVA) was light perception, and a swelling of the optic disc and tortuous vessels at the posterior pole of the right eye were observed. MRI demonstrated that her right optic nerve was hyperintense on short TI inversion recovery (STIR) sequence. A diagnosis of right papillitis was made, and she was treated with steroid pulse therapy followed by a gradual tapering of oral prednisolone. The visual acuity decreased to no light perception and plasmapheresis combined with high-dose intravenous immunoglobulin therapy was performed. The decimal visual acuity rapidly improved and recovered to 1.2, and no recurrence was observed for at least 1 year. On day 19, she was found to be anti-MOG antibody positive and anti-Aquaporin 4 antibody negative. pVEPs were recorded during the course of the disease process which showed the dynamic changes of the physiology of the visual pathways. The implicit times of the N75 and P100 components were prolonged in the right eye in the acute phase. The right visual acuity remained at 1.2 for at least 1 year, but the implicit times of the N75 and P100 components of the pVEPs of the right eye were still prolonged compared to left eye. Conclusion: Our findings indicate a positive relationship between the anti-MOG antibodies-positivity and the prolonged pVEPs. Further analyses of the pVEPs and other clinical findings of the optic neuritis are needed to establish the clinical significance of the anti-MOG antibodies positivity and optic neuritis for the diagnosis, treatment, and prognosis for this disease.

Bias flow rate and ventilation efficiency during adult high-frequency oscillatory ventilation: a lung model study.

BACKGROUND: Bias flow (BF) is essential to maintain mean airway pressure (MAP) and to washout carbon dioxide (CO2) from the oscillator circuit during high-frequency oscillatory ventilation (HFOV). If the BF rate is inadequate, substantial CO2 rebreathing could occur and ventilation efficiency could worsen. With lower ventilation efficiency, the required stroke volume (SV) would increase in order to obtain the same alveolar ventilation with constant frequency. The aim of this study was to assess the effect of BF rate on ventilation efficiency during adult HFOV. METHODS: The R100 oscillator (Metran, Japan) was connected to an original lung model internally equipped with a simulated bronchial tree. The actual SV was measured with a flow sensor placed at the Y-piece. Carbon dioxide (CO2) was continuously insufflated into the lung model ([Formula: see text]CO2), and the partial pressure of CO2 (PCO2) in the lung model was monitored. Alveolar ventilation ([Formula: see text]A) was estimated as [Formula: see text]CO2 divided by the stabilized value of PCO2. [Formula: see text]A was evaluated by setting SV from 80 to 180 mL (10 mL increments, n = 5) at a frequency of 8 Hz, a MAP of 25 cmH2O, and a BF of 10, 20, 30, and 40 L/min (study 1). Ventilation efficiency was calculated as [Formula: see text]A divided by the actual minute volume. The experiment was also performed with an actual SV of 80, 100, and 120 mL and a BF from 10 to 60 L/min (10 L/min increments: study 2). RESULTS: Study 1: With the same setting SV, the [Formula: see text]A with a BF of 20 L/min or more was significantly higher than that with a BF of 10 L/min. Study 2: With the same actual SV, the [Formula: see text]A and the ventilation efficiency with a BF of 30 L/min or more were significantly higher than those with a BF of 10 or 20 L/min. CONCLUSIONS: Increasing BF up to 30 L/min or more improved ventilation efficiency in the R100 oscillator.

Psycho-Cognitive Intervention for ASD from Cross-Species Behavioral Analyses of Infants, Chicks and Common Marmosets.

Educational treatment to support social development of children with autism spectrum disorder (ASD) is an important topic in developmental psychiatry. However, it remains difficult to objectively quantify the socio-emotional development of ASD children. To address this problem, we developed a novel analytical method that assesses subjects' complex behaviors using multivariate analysis, 'Behavior Output analysis for Quantitative Emotional State Translation' (BOUQUET). Here, we examine the potential for psycho-cognitive ASD therapy based on comparative evaluations of clinical (human) and experimental (animal) models. Our observations of ASD children (vs. their normally developing siblings) and the domestic chick in socio-sensory deprivation models show the importance of unimodal sensory stimulation, particularly important for tactile- and auditory-biased socialization. Identifying psycho-cognitive elements in early neural development, human newborn infants in neonatal intensive care unit as well as a New World monkey, the common marmoset, also prompted us to focus on the development of voluntary movement against gravity. In summary, striking behavioral similarities between children with ASD and domestic chicks' socio-sensory deprivation models support the role of multimodal sensory-motor integration as a prerequisite step for normal development of socio-emotional and psycho-cognitive functions. Data obtained in the common marmoset model also suggest that switching from primitive anti-gravity reflexes to complex voluntary movement may be a critical milestone for psycho-cognitive development. Combining clinical findings with these animal models, and using multivariate integrative analyses may facilitate the development of effective interventions to improve social functions in infants and in children with neurodevelopmental disorders.

Understanding autism and other neurodevelopmental disorders through experimental translational neurobehavioral models.

Neurodevelopmental disorders (NDDs) are highly prevalent and severely debilitating brain illnesses caused by aberrant brain growth and development. Resulting in cognitive, social, motor, language and affective disabilities, common NDDs include autism spectrum disorder (ASD), intellectual disability, communication/speech disorders, motor/tic disorders and attention deficit hyperactivity disorder. Affecting neurogenesis, glia/neuronal proliferation and migration, synapse formation and myelination, aberrant neural development occurs over a substantial period of time. Genetic, epigenetic, and environmental factors play a key role in NDD pathogenesis. Animal models are an indispensable tool to study NDDs. Paralleling clinical findings, we comprehensively evaluate various preclinical tests and models which target key (social, cognitive, motor) neurobehavioral domains of ASD and other common NDDs. Covering both traditional (rodent) and alternative NDD models, we outline the emerging areas of research and emphasize how preclinical models play a key role in gaining translational and mechanistic insights into NDDs and their therapy.

[Successful treatment with chloramphenicol in four pediatric cases of intractable bacterial meningitis].

Chloramphenicol (CP) is recently one of the rarely-used antibiotics. In this study, we present four patients with intractable bacterial meningitis, who were successfully treated with CP and discuss the therapeutic indications of CP in these pediatric cases. The patients were diagnosed as bacterial meningitis at the ages ranging from 2 months to 1 year and 4 months. The causative organisms found in three of the patients were H. influenzae and in the fourth patient, S. pneumoniae. According to the microbial sensitivity tests, these organisms were highly sensitive to antibiotics including ceftriaxone, meropenem and/or panipenem/betamipron. Treatment with these antibiotics was initially effective; however, recurrences of meningitis appeared in all patients. Administration of CP (100 mg/kg/day) started between the 11th and the 58th days, and was continued for 9 days up to 19 days. Their fever had disappeared within four days after the administration of CP, and it was confirmed that all patients completely recovered from meningitis. Two of the patients developed a mild degree of anemia, but soon recovered after the discontinuation of CP. None of them had neurological sequela. We recommend CP as one of the choices for the treatment of intractable bacterial meningitis.

Manifestations and characteristics of congenital adrenal hyperplasia-associated encephalopathy.

BACKGROUND: This study aimed to clarify the characteristics of acute encephalopathic episodes in patients with congenital adrenal hyperplasia (CAH), which we termed "CAH-associated encephalopathy (CAHE)." METHODS: This retrospective study was conducted using a questionnaire as a nationwide survey of patients with CAH with acute encephalopathy and related episodes. RESULTS: Fifteen patients were recruited on the bases of clinical data that supported a diagnosis of CAHE. Fourteen patients displayed seizures at onset, and 12 patients exhibited refractory seizures. Deep coma lasting >24h was noted in 12 patients. Neuroimaging studies revealed some heterogeneous features. Diffuse or focal edematous lesions in the cerebrum, which produce high signal intensity on diffusion-weighted magnetic resonance imaging or low density on computer tomography, were found in the acute period in all 15 patients. In the chronic period, 14 patients survived, 11 of whom had some degree of neurological sequelae. Moreover, various degrees of cerebral shrinkage were observed in 11 of 14 surviving patients. Surprisingly, there were no abnormal neuroimaging findings in the basal ganglia, brainstem, and cerebellum in any patient. CONCLUSION: Our results indicated that patients with CAH have a risk of developing CAHE, and thus, they should be followed closely because not only status epilepticus or deep coma but also minor symptoms, such as fever and nausea, may lead to CAHE. Because CAHE may feature some heterogeneous encephalopathic episodes, further validation is needed to clarify its etiology.