Mitsuru Kashiwagi

Parietal dysfunction in developmental coordination disorder: a functional MRI study.

We aimed to detect the mechanisms underlying clumsiness in children with developmental coordination disorder (DCD). A functional magnetic resonance imaging study of a visuomotor task was performed in 12 boys with DCD and 12 healthy boys (controls) (9–12 years old). They tracked a horizontally moving target by manipulating a joystick. With regard to the behavioural performance, DCD children were significantly less accurate than control children. The comparison of the activation maps showed that the brain activity in the left posterior parietal cortex and left postcentral gyrus was lower in the DCD children than in the control children. These results suggest that the dysfunction of these regions may be the neural underpinnings of impaired motor skill in DCD children.

Pelizaeus-Merzbacher disease caused by a duplication-inverted triplication-duplication in chromosomal segments including the PLP1 region.

Pelizaeus-Merzbacher disease (PMD; MIM#312080) is a rare X-linked leukodystrophy presenting with motor developmental delay associated with spasticity and nystagmus. PMD is mainly caused by abnormalities in the proteolipid protein 1 gene (PLP1), most frequently due to duplications of chromosomal segments including PLP1. In this study, a 9-year-old male patient manifesting severe developmental delay and spasticity was analyzed for PLP1 alteration, and triplication of PLP1 was identified. Further examination revealed an underlying genomic organization, duplication-inverted triplication-duplication (DUP-TRP/INV-DUP), in which a triplicated segment was nested between 2 junctions. One of the 2 junctions was caused by inverted homologous regions, and the other was caused by non-homologous end-joining. PMD patients with PLP1 duplications usually show milder-classical forms of the disease compared with patients with PLP1 missense mutations manifesting severe connatal forms. The present patient showed severe phenotypic features that represent an intermediate form of PMD between classical and connatal forms. This is the first report of a patient with PLP1 triplication caused by a DUP-TRP/INV-DUP structure. This study adds additional evidence about the consequences of PLP1 triplication.

Classification of benign infantile afebrile seizures

PURPOSE The aim of this study is to classify infantile cases with benign seizures into known epileptic syndromes, thereby facilitating discussion of clinical factors that could play an important role in diagnosis. SUBJECTS Fifty-seven patients with afebrile seizures fulfilling all of the following criteria were enrolled: (1) normal development prior to the onset, (2) no underlying disorders nor neurological abnormalities, (3) onset before the age of four and (4) normal interictal EEG and neuroimaging findings. RESULTS Thirty-nine cases (Group A) were characterized by an association of mild gastroenteritis. The remaining 18 cases were divided into two groups according to the seizure type. One group had partial seizures (Group B, 13 cases) while the other was suspected to have generalized seizures (Group C, 5 cases). Age at onset was significantly higher for Group A (19.5 +/- 5.5 months) than Groups B (5.3 +/- 1.8 months) (p<0.001) and C (5.8 +/- 3.5 months) (p=0.038). Positive family history of seizure disorder, seizure cluster tendency, and the efficacy of lidocaine against seizure clusters were common in the three groups. CONCLUSIONS Features in Group A were consistent with benign convulsions with mild gastroenteritis (proposed by Morooka) [Morooka, K., 1982. Mild diarrhea and convulsions. Shonika 23, 134-137 (in Japanese)], those of Group B with benign partial epilepsy in infancy [Watanabe, K., Yamamoto, N., Negoro, T., Takaesu, E., Aso, K., Furune, S., Takahashi, I., 1987. Benign complex partial epilepsies in infancy. Pediatr. Neurol. 3, 208-211], and those of Group C with benign infantile convulsions [Fukuyama, Y., 1963. Borderland of epilepsy with special reference to febrile convulsions and so-called infantile convulsions. Seishin Igaku 5, 211-223 (in Japanese)]. The distinction between these syndromes depends upon age at onset, association with gastroenteritis, and ictal symptomatology. In our experience, however, it was not easy to catch seizure type accurately in clinical situations. As far as the results of ictal video-EEG monitoring ever carried out concern, focal initiation of parxysmal discharges was demonstrated in all cases, not only of BPEI but also of apparent generalized seizures examined without exception. These observations led the authors to conclude that the identity of BIC is dubious, most probably it will represent a subtype of BPEI.

Brain Mapping of Developmental Coordination Disorder

This chapter discusses the brain mapping of developmental coordination disorder (DCD). DCD is a neurological disorder characterised by impaired motor coordination and impaired performance of daily activities that require motor skills. In the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) [1], DCD is included in the Learning Disorders and the Motor Skills Disorders sections [1]. DCD is one of the most common disorders in childhood, and it affects 5% to 6% of school-age children.

Overlapping MERS and mild AESD caused by HHV-6 infection

We report the case of an overlapping encephalopathy syndrome consisting of clinically mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) and a mild form of acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) caused by human herpesvirus-6. A previously healthy 17-month-old girl was admitted to our hospital as a precaution because of seizures that had developed more than 25 hours (h) after fever. Brain diffusion-weighted images (DWI) showed high signal intensity in the central splenial region on Day 2. She regained consciousness 16 h after the second seizure. On Day 6, she had a secondary cluster of partial seizures. DWI showed resolution of the splenial lesion and revealed reduced diffusion in the fronto-subcortical white matter. She regained consciousness 36 h after the secondary cluster of seizures without any sequelae. A third DWI performed on Day 15 showed that the fronto-subcortical white matter lesions had completely disappeared. Based on the clinicoradiological findings, we diagnosed the patient with overlapping MERS and mild AESD. Our case, together with previous reports, suggests that patients can develop combined encephalopathy syndromes as a phenotype. Many encephalopathy syndromes have been established and classified; however, some may not present as independent syndromes.

Partial seizures during ACTH therapy in a cryptogenic West syndrome patient

BACKGROUND Partial seizures often develop during the clinical course of infantile spasms. Herein, we report a boy with cryptogenic West syndrome, who developed partial seizures that we suspected were induced by the ACTH therapy. SUBJECT The patient developed cryptogenic West syndrome at six months of age and ACTH therapy was started. On the tenth day of treatment, he developed frequent partial seizures, characterized by being motionless during the seizure with eye deviation to the right. The partial seizures stopped after the ACTH was discontinued, although oral carbamazepine was commenced at the same time. Thus, a definitive role for carbamazepine in the treatment of the partial seizures was unclear as the timing of the seizure cessation also corresponded to the discontinuation of the ACTH therapy. We suspected that the partial seizures were induced by the ACTH therapy for the following reasons: (1) seizures appeared only during ACTH therapy, (2) no new epileptic focus was revealed by EEG, MRI, or (99m)TcECD SPECT, and (3) the seizures were different from the epileptic spasms. CONCLUSION Our results suggest that ACTH might induce partial seizures in West syndrome. Further studies are required to confirm this phenomenon.

Outpatient screening of Japanese children with epilepsy for attention-deficit/hyperactivity disorder (AD/HD).

UNLABELLED The significance of the Strengths and Difficulties Questionnaire (SDQ) score for AD/HD (attention-deficit/hyperactivity disorder) screening was assessed in Japanese epileptic children. SUBJECTS AND METHODS Sixty-eight epileptic children were enrolled in this study. Parents were asked to fill out both the SDQ and AD/HD-rating scale (AD/HD-RS) simultaneously. RESULTS The SDQ subscale of hyperactivity showed the highest score. The AD/HD-RS showed higher scores for both inattention and hyperactivity-impulsivity. Twenty-two (32.4%) of these subjects were diagnosed as having AD/HD. The SDQ subscale for hyperactivity showed 86.4% sensitivity and 95% specificity, respectively, for detection of AD/HD. All SDQ subscales correlated significantly with inattention and hyperactivity-impulsivity scores of the AD/HD-RS. CONCLUSIONS The SDQ is a good screening tool which can contribute to the detection of AD/HD, not only of the hyperactive/impulsive but also the inattentive subtype. Furthermore, the SDQ can elucidate more complicated behavioral problems than the core symptoms of AD/HD that are not noticed in the epilepsy clinic.

Targeted temperature management for acute encephalopathy in a Japanese secondary emergency medical care hospital.

BACKGROUND The goals of this study, conducted in our secondary emergency care hospital, were to assess the effectiveness of targeted temperature management (TTM) for acute encephalopathy secondary to status epilepticus and to consider appropriate adaptations for use of TTM in this setting. METHODS Medical records of patients admitted with acute encephalopathy to Hirakata City Hospital between January 2010 and December 2014 were retrospectively reviewed. Cases treated with TTM (36 °C) and methylprednisolone pulse (MP) therapy (TTM/MP) were compared with those treated with conventional MP regarding clinical courses and outcomes. RESULTS In total, 20 children were retrospectively enrolled. In the TTM/MP group (10 cases) all survived intact. In the MP group (10 cases), 4 cases were left with neurological sequelae. Furthermore, in the TTM/MP group, the body temperature dropped more quickly. For pediatricians in this secondary emergency hospital, implementing the body temperature management system was not difficult. There were no complications caused by hypothermia. DISCUSSION Use of TTM as the initial treatment for acute encephalopathy in the early-onset stage is possible in a secondary emergency care hospital. However, some acute encephalopathy cases are the so-called fulminant type; DIC or shock develops soon after onset and so it is sometimes difficult to introduce TTM. Fulminant-type patients should be transported to tertiary emergency care hospitals. Secondary emergency care hospitals must carefully select cases for TTM, keeping the possibility of transport to a tertiary emergency hospital in mind at all times.

Differential diagnosis of delirious behavior in children with influenza

Delirious behavior (DB) in children infected with influenza virus is an important symptom associated with encephalopathy. As children with influenza-associated DB with encephalopathy may require therapy whereas children with influenza-associated DB without encephalopathy do not, distinguishing between these conditions is essential. To clarify these differences and identify the most common features of acute encephalopathy, we retrospectively reviewed the clinical course, laboratory data, magnetic resonance imaging (MRI) and electroencephalography (EEG) findings, therapy, and prognosis of 48 children with influenza exhibiting DB. Of the 48 children, 37 and 11 were diagnosed with influenza A and B, respectively. Moreover, 40 were diagnosed with DB without encephalopathy (DBNE group) and 8, with DB with encephalopathy (DBE group). Reversible splenial lesion (RESLE) was detected in 7 patients in the DBNE group, mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) in 2 patients, and a mild form of acute encephalopathy with biphasic seizures and late reduced diffusion in 1 patient in the DBE group. Serum sodium levels <136mEq/L were observed in 28 cases. Disturbance of consciousness was observed in 25 cases, seizure in 20, and slow waves on EEG in 22. Methylprednisolone pulse therapy was administered in 8 cases. No cases of neurological sequelae were observed. Although most of the clinico-radiological features of the DBNE and DBE groups did not differ substantially, marked differences were observed in the age at onset, initial neurological symptoms, duration of DB, rate of seizure, and slowing of background activity on EEG. These differences should be considered when distinguishing between DBNE and DBE in children.

Post-vaccination MDEM associated with MOG antibody in a subclinical Chlamydia infected boy.

The mechanism of post-vaccination acute disseminated encephalomyelitis (ADEM) has been hypothesized as resulting from vaccination-injected antigens cross-reacting with myelin components, however, a precise etiology has been uncertain. In this report, we describe the case of a 6-year-old Japanese boy who had multiphasic disseminated encephalomyelitis (MDEM), and was positive for both anti-myelin oligodendrocyte glycoprotein (MOG) antibodies and Chlamydophila pneumoniae antibodies. After vaccinations that were the second one for measles and rubella, and the booster immunization for Japanese encephalitis, the patient presented with fever, headache, vomiting, and a change in personality. He was treated with a high-dose of intravenous methylprednisolone in the diagnosis of ADEM. However, these symptoms recurred with different magnetic resonance imaging lesion, and he was diagnosed as MDEM. Retrospective testing for pathogens revealed C. pneumoniae IgM and IgG antibodies, and it was considered that he was infected with C. pneumoniae subclinically. The patients serum indicated a positive response for the anti-MOG antibody from the onset of the ADEM diagnosis and in all recurrent episodes. Chlamydia species infection has been known to play a role in demyelinating diseases. It is also known that the anti-MOG antibody may be present but not exhibit its pathogenesis in the absence of a cell-mediated inflammatory response; however, the precise mechanism of action of the anti-MOG antibodies is not yet determined. We propose the possibility that post-vaccination demyelinating disease may result from the synergistic effects of a preceding anti-MOG antibody, possibly produced in response to a subclinical Chlamydia species infection.