No To Hattatsu最新文献

We describe the case of a 15-year-old male with early juvenile type GM2 gangliosidosis. He first manifested with progressive clumsiness in his extremities at the age of 1.5 years, followed by motor regression. Intellectual disability became evident as late as age 6 years. This discrepancy along with rapid motor deterioration after varicella infection, lack of startle response or macrocephaly, and paucity of myoclonus were thought to be characteristic of juvenile GM2 gangliosidosis. In contrast to the cerebellar atrophy as the initial finding in usual juvenile GM2 gangliosidosis, magnetic resonance imaging revealed initially cerebral, and subsequently cerebellar, progressive atrophy. Autistic behavioral problems, including phonophobia, during intellectual regression in this patient was also unusual in juvenile GM2 gangliosidosis. Thus, recognition of these features would prompt proper diagnosis and insights into the pathomechanisms of GM2 gangliosidosis.

A 6-year-old girl experienced nausea and vomiting for 3 weeks and double vision for 1 week prior to her first visit to our hospital. She had bilateral ophthalmoplegia from sixth cranial nerve palsy and papilledema. Her brain MRI showed normal brain parenchyma. The lumbar cerebrospinal fluid (CSF) opening pressure was 1000 mm of water measured with normal CSF contents. From these findings, she was diagnosed with idiopathic intracranial hypertension (IIH). Initial lumbar puncture (LP) immediately improved her symptoms, but acetazolamide, a first line drug for the treatment of IIH, failed to maintain the remission, and three more periodical LP were required to relieve her symptoms every 2 weeks. After the fourth LP, acetazolamide was switched to a second line drug for IIH, topiramate, which was found to be highly effective in controlling IIH in a short time period. The long process of IIH causes vision loss, therefore, its prompt treatment is vital. In cases refractory to medical treatment, surgical treatments such as CSF shunt are considered. Acetazolamide is used in most IIH cases after the initial diagnosis, but in this case, it was ineffective, and topiramate was highly effective. Both acetazolamide and topiramate are inhibitors of carbonic anhydrase isoforms involved in CSF secretion. Inhibition of choroid plexus carbonic anhydrase by these drugs leads to decreased CSF secretion and the consequent control of intracranial pressure. Higher isoform specificity and increased lipophilic nature of topiramate, which are advantageous for passing through the blood brain barrier, may be the reasons for better activity than acetazolamide, at least in the present case. Topiramate might be effective and should be considered for refractory IIH cases before surgical treatments.

We report a 9-year-old girl with Sturge-Weber syndrome (SWS) type III, whose motor function deteriorated after an episode of febrile status epilepticus. The patient had leptomeningeal angiomas in the left temporal, occipital, and parietal lobes. Complex partial seizures, which started at 8 months, were controlled by antiepileptic medications. At 9 years of age, she developed irreversible ischemic lesions in the left temporal and occipital regions after the febrile status epilepticus and her motor function deteriorated. In addition to antiepileptic medications, aspirin therapy was started.SWS type III is a rare disorder characterized by leptomeningeal angiomatosis without facial nevus. In addition to the chronic ischemia in the affected cortex, epileptic seizures result in a phased progression of ischemia in SWS. Although the patient’s complex partial seizures had been well-controlled, a single episode of febrile status epilepticus resulted in permanent brain lesions. The impairment of appropriate hemodynamic response to status epilepticus, together with venous hypertension in the affected side in SWS may have caused the cerebral infarction in our case. Seizure control is crucial to improving the neurological prognosis of SWS.

Objective: The purpose of this study was to test difference between the social skills of adolescents with autism spectrum disorder (ASD) and their typically developing students."

Methods: Participants were 299 junior high school students from public schools. The group included 19 junior high school students with ASD. Participants responded to self-rated questionnaire on social skills, school maladjustment, and stress.

Results: Results showed that adolescent with ASD had mental health difficulties (in stress responses and school maladjustment) and poor social skills as compared to their typically developing peers. A cluster analysis was conducted by dividing the participants into the following four groups based on their z-scores on the social skills scale: “low skill type”, “low skill of continuing relationship type”, “well-balance type”, and “inactive type”. A Chi-square test revealed that a greater portion of the ASD group included students belonging to the “inactive, authoritative and low type” and “inactive type” cluster as compared to the typically developing group.

Conclusions: The Adolescent with ASD have social skills characterized by inactive type that poor entry skills.

Patients with spinal muscular atrophy type Ⅰ (SMA Ⅰ) with the onset before the age of 3 months are considered as severe form of SMA Ⅰ (severe SMA Ⅰ) and have poor prognosis. Here, we report the efficacy of non-invasive positive pressure ventilation (NPPV) in a patient with severe SMA Ⅰ. She was born with generalized hypotonia and feeding difficulties, and had SMN1 gene mutations (the deletion of exons 7 and 8). At 1 month of age, she was intubated because of respiratory failure due to a respiratory tract infection, and extubation proved difficult. Her parents decided that NPPV and a mechanical in-exsufflator (MI-E) should be used for respiratory management rather than a tracheotomy. The NPPV improved her peripheral coldness, cold sweats, chest wall movement, and heart rate and enabled her to sleep well. At 1 year and 2 months, chest computed tomography revealed mild pneumonia and did not show any atelectasis. The NPPV facilitated discharge, and the patient had a good quality of life (QOL) from the point of view of voice production, the ability to move easily, the simplicity of bathing, and the low level of discomfort she experienced. However, she suffered repeated episodes of aspiration pneumonia and airway obstruction (by sputum) after 11 months of age. Thereafter, she required continuous NPPV and high-span inspiratory positive airway pressure (21 cmH2O). At 1 year and 4 months, she died of respiratory failure at home. As her bulbar weakness worsened, respiratory management with NPPV became difficult. However, the long-term use of NPPV together with high-span positive inspiratory pressure plus positive end-expiratory pressure, and a high-pressure MI-E at an early age might improve respiratory management outcomes and patient prognosis. In our case, NPPV was effective at improving ventilation and preventing atelectasis and helped to provide the patient with a good QOL.

Objective: Bone fractures in patients with severe motor and intellectual disabilities (SMIDs) have become an important problem to be solved. These fractures may result from disuse osteoporosis. Bisphosphonate administration is generally the most established treatment for patients with osteoporosis. However, traditional oral bisphosphonate use is associated with esophagitis as a side effect and may increase the risk of reflux esophagitis for bedridden patients. Intravenous alendronate, one of the bisphosphonates, was released in 2012 in Japan. Though it is appropriate for patients with SMIDs, there are no reports about the effects of intravenous alendronate on osteoporosis in SMID patients. Therefore, the efficacy of intravenous alendronate for osteoporosis was investigated in SMID patients.

Methods: The subjects were 62 SMID patients with osteoporosis (20 to 60 years old) in our hospital. They were divided two groups, bisphosphonate treatment group (32 patients) and age-matched controls (30 patients). Patients in bisphosphonate treatment groups were given 900μg intravenous alendronate once a month. All patients were also administered oral vitamin D3. Serial bone density, bone metabolism markers, and existence of fractures were compared in both groups before and after treatment (6 months, 1 years, and 2 years).

Results: In bisphosphonate treatment group, the change rate of bone density was significantly increased and bone metabolism markers were improved at 6 months and 1 year after starting treatment. After a year, 16 patients in treatment group changed into other treatments, and 12 controls started bisphosphonate treatment. In remaining treatment group (16 patients), the change rate of bone density and bone metabolism markers were improved significantly at 2 years after starting treatment. A patient in control group had a bone fracture, but no patients in bisphosphonate treatment groups had fractures or severe adverse effects.

Conclusion: Intravenous alendronate is an effective treatment for osteoporosis in SMID patients.

A male infant suffered from partial seizures at four months of age, and developed West syndrome at eight months of age. ACTH therapy was effective for the West syndrome. However, partial seizures recurred at 14 months of age, which could not be sufficiently controlled with an anti-epileptic drug. A characteristic facial appearance, great toe abnormalities, and developmental retardation were noted. An interstitial deletion of 2q was detected by chromosomal G-banding and array comparative genomic hybridization (CGH) confirmed the deletion as arr 2q24.3q31.3 (166,303,447-180,982.972) ×1 (build19). He presented with clinical findings similar to those of the recently defined 2q31.1 deletion syndrome. The deletion extended to the SCN1A gene, a gene responsible for Dravet syndrome, mapped to the 2q24.3 region. No deletion was noted in the adjacent SCN2A gene. Thus, for interstitial deletions, detailed breakpoints should be identified by array CGH. The frequency of epilepsy varies with deletion ranges in the 2q24-q31 region, suggesting that deletions in the SCN1A gene deletion, as well as in the 2q31.1 region, are involved in the development of West syndrome.

Even though evidence-based clinical guidelines are useful for the management of common diseases, there are several problems in applying such guidelines to patients with rare diseases. First, there are few references providing high-level evidence pertaining to such diseases, and randomized control as well as large cohort studies are lacking. Most grades of recommendation are “suggest” rather than “recommend” or, often, are based on “expert opinion”. Juvenile myasthenia gravis (MG) is a rare disease and has mainly been reported in East Asia. In 2014, evidence-based clinical guidelines for MG diagnosis and treatment were published in Japan. Since references were scarce, these guidelines were also based on expert opinions such as those of a few institutes or specialists who had gathered most of the patients in Japan. The guidelines might be of limited usefulness for general pediatricians or pediatric neurologists with no MG experience, and we should be aware of strengths and pitfalls when applying such guidelines. For example, while knowing when to start steroid administration or the appropriate steroid dose is feasible, the optimal timing of switching from an anti-cholinesterase drug to a steroid or adding an anti-inflammatory drug and how to decrease or stop steroid administration cannot be ascertained from the guidelines. The lack of references with high-level evidence makes the guidelines difficult to apply, since this would be the information most desired by clinicians. Another problem is that a recommendation may easily be reversed if opposing results are obtained in a single study of a rare disease. Thymectomy was recognized as not being beneficial for MG without thymoma but one recent study reversed this recommendation in the guidelines. Herein, we discuss pitfalls in applying diagnostic and treatment guidelines in patients with juvenile MG.