Search

Mothers of children with special healthcare needs often face many extra difficulties, such as being isolated in the community. This study, conducted in the San'in region of Japan between December 2017 and February 2019, aimed to clarify how the mothers established and adapted their connections within their communities through a qualitative descriptive design study. Participants were 12 mothers caring for children with special healthcare needs. Verbatim data on adapting to life after hospital discharge was collected through interviews and analyzed by the modified grounded theory approach. The data generated 14 concepts, which were grouped into four categories, as follows: Difficulties in life that arise from caring for children in social isolation; gaining an objective view of the current situation and future of caring for children with special healthcare needs; collaboration based on the understanding of relationships with others; and feeling fulfilled in life. These describe four phases that the mothers went through which are similar to each stage of the transition theory. Providing support via a collaborative partnership may be effective for mothers experiencing anxiety during the transition stages.

Pitt-Hopkins syndrome is a rare genetic disease, characterised by severe intellectual disability, distinctive dysmorphic features, epilepsy and distinctive breathing abnormalities during wakefulness. Here, we describe the case of a 22-year-old woman with Pitt-Hopkins syndrome who presented with intractable generalised tonic seizures from the age of 11 years, which increased in frequency with age and onset of menstruation despite usage of some anticonvulsant drugs. From the age of 16 years, polysomnography and video-EEG led to the detection of frequent epileptic apnoea during sleep. Although the frequency of generalised tonic seizure clusters was reduced by treatment with phenobarbital and potassium bromide, epileptic apnoea persisted. Furthermore, frequent epileptic apnoea observed in our patient was regarded as a factor for aspiration and deterioration of respiratory function. This study indicates that patients with Pitt-Hopkins syndrome require close monitoring for epileptic apnoea. Moreover, long-term EEG and respiratory monitoring are necessary to distinguish epileptic apnoea from other respiratory disorders in patients with Pitt-Hopkins syndrome.

Objective Gaucher disease (GD) is a lysosomal storage disease characterized by a deficiency of glucocerebrosidase. Although enzyme-replacement and substrate-reduction therapies are available, their efficacies in treating the neurological manifestations of GD are negligible. Pharmacological chaperone therapy is hypothesized to offer a new strategy for treating the neurological manifestations of this disease. Specifically, ambroxol, a commonly used expectorant, has been proposed as a candidate pharmacological chaperone. The purpose of this study was to evaluate the safety, tolerability, and neurological efficacy of ambroxol in patients with neuronopathic GD. Methods This open-label pilot study included five patients who received high-dose oral ambroxol in combination with enzyme replacement therapy. Safety was assessed by adverse event query, physical examination, electrocardiography, laboratory studies, and drug concentration. Biochemical efficacy was assessed through evidence of glucocerebrosidase activity in the lymphocytes and glucosylsphingosine levels in the cerebrospinal fluid. Neurological efficacy was evaluated using the Unified Myoclonus Rating Scale, Gross Motor Function Measure, Functional Independence Measure, seizure frequency, pupillary light reflex, horizontal saccadic latency, and electrophysiologic studies. Results High-dose oral ambroxol had good safety and tolerability, significantly increased lymphocyte glucocerebrosidase activity, permeated the blood–brain barrier, and decreased glucosylsphingosine levels in the cerebrospinal fluid. Myoclonus, seizures, and pupillary light reflex dysfunction markedly improved in all patients. Relief from myoclonus led to impressive recovery of gross motor function in two patients, allowing them to walk again. Interpretation Pharmacological chaperone therapy with high-dose oral ambroxol shows promise in treating neuronopathic GD, necessitating further clinical trials.

A 2-year-old boy had glaucoma, bilateral facial haemangioma and widespread blue nevi on the trunk and extremities since birth. Dilated medullary veins were detected in the left cerebral periventricular white matter on magnetic resonance imaging (MRI). Macrocephaly and delayed psychomotor development were observed during late infancy, and susceptibility-weighted angiography revealed an extensive developmental venous anomaly with multiple caput medusae throughout bilateral hemispheres, accompanied by periventricular hyperintense alterations on MRI and progressive diffuse atrophy of the cerebral mantle with left-sided predominance. Hypoperfusion in the left cerebral and cerebellar hemisphere was also uncovered. No meningeal haemangioma was observed. This patient may represent a novel subgroup of phakomatosis cases that can be regarded as a variant of Sturge-Weber syndrome.

Background: Early predictors of status epilepticus (SE)-associated mortality and morbidity have not been systematically studied in children, considerably impeding the identification of patients at risk. Objectives: To determine reliable early predictors of SE-associated mortality and morbidity and identify the etiology of SE-associated sequelae in Japanese children. Methods: We conducted a prospective multicenter study of clinical findings and initial laboratory data acquired at SE onset, and assessed outcomes at the last follow-up examination. In-hospital death during the acute period and neurological sequelae were classified as poor outcomes. Results: Of the 201 children who experienced their first SE episode, 16 exhibited poor outcome that was most commonly associated with acute encephalopathy. Univariate analysis revealed that the following were associated with poor outcomes: young age (⩽24months); seizure duration >90min; seizure intractability (failure of the second anticonvulsive drug); biphasic seizures; abnormal blood glucose levels ( 250mg/dL); serum aspartate aminotransferase (AST) ⩾56U/L; and C-reactive protein (CRP) levels >2.00mg/dL. Multivariate analysis revealed that young age, seizure intractability, abnormal blood glucose levels, and elevated AST and CRP levels were statistically significant. Conclusions: Young age and seizure intractability were highly predictive of poor outcomes in pediatric SE. Moreover, abnormal blood glucose levels and elevated AST and CRP levels were predictors that might be closely associated with the etiology, especially acute encephalopathy and severe bacterial infection (sepsis and meningitis) in Japanese children.

Patients with microdeletions in the 19p13.2 chromosomal region show developmental delays, overgrowth, and distinctive features with big head appearances. These manifestations are now recognized as Sotos syndrome-like features (Sotos syndrome 2) or Malan syndrome. We identified three female patients with 19p13.2 deletions involving NFIX, a gene responsible for Malan syndrome. We compared the genotypic and phenotypic data of these patients with those of the patients previously reported. The most of the clinical features were found to overlap; however, Chiari malformation type I was observed in two of the three patients evaluated in this study. Because Chiari malformation type I has never been reported in the patients with NSD1-related Sotos syndrome, this finding indicates the possible role of 19p13.2 deletion in patients with mimicking features of Sotos syndrome but have negative NSD1 testing results. © 2015 Wiley Periodicals, Inc.

Aim To report on sleep hypercapnia in Becker muscular dystrophy (BMD) at earlier stages than ever recognized. Subjects and methods This retrospective study examined nocturnal hypercapnia in six young Becker muscular dystrophy (BMD) patients with deletions of one or more exons of DMD gene. Clinical information, consecutive data on forced vital capacity (FVC%), forced expiratory volume in one second (FEV1%), peak expiratory flow (PEF%), peak cough flow (PCF), average PCO2 in all-night monitoring, and left ventricular ejection fraction (LVEF) were reviewed. Results In five BMD patients, including three who were still ambulant, nocturnal average PCO2 was elevated to >45 mmHg at 12–31 years of age. Noninvasive positive pressure ventilation was initiated in four patients. Gradual declines in FVC% and PEF% were evident in one BMD patient with exon 3–7 deletion, whereas these functions did not change in the remaining BMD patients. PCF, FEV1%, and LVEF were less informative for the assessment of respiratory function in this patient series. Conclusion Sleep hypercapnia was present in certain BMD patients, which was unexpected from the routine pulmonary function tests. Individualized assessment of nocturnal PCO2, partly based on the deletion types, should be further explored in the clinical practice of BMD patients.

The hallmark of neuronopathic Gaucher disease (GD) is oculomotor abnormalities, but ophthalmological assessment is difficult in uncooperative patients. Chromatic pupillometry is a quantitative method to assess the pupillary light reflex (PLR) with minimal patient cooperation. Thus, we investigated whether chromatic pupillometry could be useful for neurological evaluations in GD. In our neuronopathic GD patients, red light-induced PLR was markedly impaired, whereas blue light-induced PLR was relatively spared. In addition, patients with non-neuronopathic GD showed no abnormalities. These novel findings show that chromatic pupillometry is a convenient method to detect neurological signs and monitor the course of disease in neuronopathic GD.

Background Acute pancreatitis in patients with severe motor and intellectual disability (SMID) is a rare but life-threatening condition. Possible causes of acute pancreatitis in these patients including valproic acid therapy, hypothermia and nasoduodenal tube feeding, have not yet been investigated in detail. The aim of this study was therefore to investigate the risk factors for acute pancreatitis in patients with SMID. Methods Five SMID patients with acute pancreatitis and 15 SMID patients without acute pancreatitis were reviewed. Age; serum total cholesterol, triglyceride, total protein, and albumin; height; bodyweight; body surface area; body mass index; daily calorie intake; daily calorie intake per unit of body mass surface area; daily calorie intake per kilogram bodyweight; and valproic acid usage were examined. Results A statistically significant difference was observed in serum albumin level between the two groups (P = 0.026). Conclusion The mechanism of acute pancreatitis in these patients was considered as pancreatic morphological change, acinar damage, and elevated serum trypsinogen level caused by malnutrition. It is likely that acute pancreatitis in patients with SMID occurs due to the same mechanism as in anorexia nervosa and malnourished patients. To prevent acute pancreatitis in these patients, it is important to maintain adequate nutritional status.

Patients with microdeletions in the 19p13.2 chromosomal region show developmental delays, overgrowth, and distinctive features with big head appearances. These manifestations are now recognized as Sotos syndrome-like features (Sotos syndrome 2) or Malan syndrome. We identified three female patients with 19p13.2 deletions involving NFIX, a gene responsible for Malan syndrome. We compared the genotypic and phenotypic data of these patients with those of the patients previously reported. The most of the clinical features were found to overlap; however, Chiari malformation type I was observed in two of the three patients evaluated in this study. Because Chiari malformation type I has never been reported in the patients with NSD1-related Sotos syndrome, this finding indicates the possible role of 19p13.2 deletion in patients with mimicking features of Sotos syndrome but have negative NSD1 testing results.

Acute pancreatitis in patients with severe motor and intellectual disability (SMID) is a rare but life-threatening condition. Possible causes of acute pancreatitis in these patients including valproic acid therapy, hypothermia and nasoduodenal tube feeding, have not yet been investigated in detail. The aim of this study was therefore to investigate the risk factors for acute pancreatitis in patients with SMID.Five SMID patients with acute pancreatitis and 15 SMID patients without acute pancreatitis were reviewed. Age; serum total cholesterol, triglyceride, total protein, and albumin; height; bodyweight; body surface area; body mass index; daily calorie intake; daily calorie intake per unit of body mass surface area; daily calorie intake per kilogram bodyweight; and valproic acid usage were examined.A statistically significant difference was observed in serum albumin level between the two groups (P = 0.026).The mechanism of acute pancreatitis in these patients was considered as pancreatic morphological change, acinar damage, and elevated serum trypsinogen level caused by malnutrition. It is likely that acute pancreatitis in patients with SMID occurs due to the same mechanism as in anorexia nervosa and malnourished patients. To prevent acute pancreatitis in these patients, it is important to maintain adequate nutritional status.

Objective Congenital white matter disorders are a heterogeneous group of hypomyelination disorders affecting the white matter of the brain. Recently, mutations in the genes encoding the subunits of RNA polymerase III (Pol III), POLR3A and POLR3B , have been identified as new genetic causes for hypomyelinating disorders. Method Whole-exome sequencing was applied to identify responsible gene mutations in a 29-year-old female patient showing hypomyelination of unknown cause. To investigate the pathological mechanism underlying the hypomyelination in this patient, the expression level of 7SL RNA, a transcriptional target of Pol III, was analyzed in cultured skin fibroblasts derived from the patient with POLR3A mutations. Results Novel compound heterozygous mutations of POLR3A were identified in the patient, who started to show cerebellar signs at 3 years, lost ambulation at 7 years, and became bedridden at 18 years. Brain magnetic resonance imaging showed severe volume loss in the brainstem, the cerebellum, and the white matter associated with hypomyelination. In addition to hypodontia and hypogonadism, she showed many pituitary hormone-related deficiencies. The expression level of 7SL RNA in cultured skin fibroblasts derived from this patient showed no significant abnormality. Conclusion The many pituitary hormone-related deficiencies identified in this patient may be an essential finding for the Pol III-related leukodystrophies spectrum. Further investigation is needed for a better understanding of the disease mechanism.