Objective: Tuberous sclerosis complex (TSC) is a multisystem disorder characterized by the formation of hamartoma in multiple organ systems of the body. However, without a well-established cooperative system involving related departments, some organ lesions might be overlooked until symptoms appear or even until the disorder progresses. Therefore, the purpose of this study is to investigate the current status of follow-ups in the TSC patients in the Department of Child Neurology at Okayama University Medical Hospital. Methods: We performed a retrospective chart review of 38 patients with TSC who visited our hospital at least twice between January 2005 and December 2014. Patients were between 3 years and 48 years of age at their latest visit. We divided the patients into a child group and an adult group, and investigated the patients’ follow-up data while focusing on the various multiorgan systems. Results: The follow-ups were well conducted in the child group in terms of every organ. In the adult group, neuroimaging tests were unsatisfactorily performed. The kidney has not been examined in seven patients more than five years even though these patients all had kidney lesions. The lung was not been examined in 7 out of 14 female patients over 18 years of age who are most at risk for lymphangioleiomyomatosis (LAM). In 12 out of 18 child patients, echocardiograms were performed every few years, while electrocardiograms to assess underlying conduction defects were rarely performed in either age group. Conclusions: In Europe, guidelines for the management of TSC have been well established. However, in our hospital, the multiorgan system follow-up is not satisfactorily performed especially in adult patients. We decided the establishment of a TSC board in our hospital for the management of this multiorgan disorder.

  Objective: The objective of this study was to investigate the trends in the prevalence and characteristics of unilateral spastic cerebral palsy among children born between 1988 and 2007 in Okinawa, Japan. Method: We conducted a surveillance of children with cerebral palsy using the local cerebral palsy registration system. For analysis purposes, the study was divided into two periods: periodⅠ (from 1988 to 1997) and periodⅡ (from 1998 to 2007). We performed a chi-squared test and Poisson regression analysis. Result: We observed a significant trend for an increased prevalence of unilateral spastic cerebral palsy in periodⅡ (p<0.01). The number of children with unilateral spastic cerebral palsy who were born with birth weights of 1500 g or more and/or a gestational age of 32 weeks or more was increased in periodⅡ. In addition, brain magnetic resonance imaging and computed tomography scans showed that porencephaly and periventricular white matter damage were common findings in preterm children of gestational age less than 31 weeks in period II. The most frequently observed neuroimaging feature in children with a gestational age of over 32 weeks was brain infarction. Conclusion: We found a trend for an increased prevalence of unilateral spastic cerebral palsy in periodⅡ. However, the cause of this increase is as yet unknown.

  Objective: We assessed the root mean square (RMS) of angular acceleration and the RMS of an angular jerk as expressions of the transformation of spontaneous movements in early infancy. Methods: During 36-56 weeks post-menstrual age (PMA), 15 premature infants (6 male, 9 female; 36 weeks PMA>) were measured every 4 weeks. A three-dimensional motion analyzer (Fastrak system; Polhemus Inc.) was used to measure spontaneous movements of the upper right limb in the supine infants. Upper limb position data were used to calculate the RMS of angular acceleration and the RMS of angular jerk at the elbow. The calculated data were classified into three terms: 36th and 40th week PMA (termⅠ), the 44th and 48th week PMA (termⅡ), and the 52nd and 56th week PMA (termⅢ). The typical value was the mean value for each term. Results: The RMS of angular acceleration in termⅡ was significantly less than that of termⅠ (p<0.05). The RMS values of angular jerk in termⅡ and termⅢ were significantly less than that of termⅠ (p<0.05). Conclusion: The RMS of angular acceleration and the RMS of the angular jerk are useful for expressing changes in the strength of spontaneous movements of elbow extension-flexion movements.

  Objective: Anti-epileptic drugs, such as carbamazepine (CBZ) or phenytoin, may induce hypothyroidism in epilepsy patients. We assessed thyroid function of chronic patients with severe motor and intellectual disabilities (SMID) in our hospital. Methods: We examined thyroid-stimulating hormone (TSH), free thyroxine (fT4), and free thyronine (fT3) in 73 patients with SMID (47 men and 26 women, average age 48.4 years, range 30-68 years) without thyroid hormone supplement therapy. We determined the relationship between the thyroid function of patients taking the anti-epileptic drugs CBZ, valproate (VPA), and phenobarbital, other medications including anti-psychotic drugs, and treatments without anti-epileptic or anti-psychotic drugs. Results: TSH levels were not significantly different between the groups taking CBZ (CBZ+med), other anti-epileptic drugs or anti-psychotic drugs (CBZ-med), and only medications without anti-epileptic or anti-psychotic drugs (Non-med). The CBZ+med group had significantly lower fT4 levels than the CBZ-med or Non-med groups. There was a negative correlation between thyroid function level and the phenobarbital groups. TSH levels of the VPA+med group were significantly higher than VPA-med and Non-med group; fT3 and fT4 levels were not significantly different. Conclusions: Our results indicate that hypothyroidism may be present in patients with SMID taking anti-epileptic drugs. This suggests it is important to regularly measure thyroid function in patients with SMID taking anti-epileptic drugs, especially CBZ.

  An 11-year-old boy with Lesch-Nyhan syndrome (LNS) had persistently injured himself by biting his lips and buccal mucosa since infancy. Risperidone was only partially effective in suppressing this behavior. Oral administration of S-adenosylmethionine (SAMe), involving increasing the dose from 400 mg to 1 g, resulted in the amelioration of self-injurious behavior and anxiety as well as marked improvement in his self-esteem, performance at school, and friendships. No adverse effects were noted. SAMe may have a favorable effect on symptoms of LNS by activating monoaminergic pathways and/or increasing the adenosine pool in the salvage pathway of guanosine monophosphate synthesis. Defects in these pathways have been essentially implicated in the neurological pathophysiology of LNS.

  CDKL5 gene mutations are the cause of symptomatic infantile epilepsy in some patients. Such patients present with partial seizures and characteristic hand movements that are often observed in patients with Rett syndrome. This clinical entity has recently been recognized as CDKL5 disorder. In a girl with CDKL5 disorder, who had been treated with combinatory therapy using many anti-epileptic drugs, we were able to control the seizures with valproate monotherapy. As a result of the monotherapy, the patient’s seizures ameliorated temporarily and her quality of life improved. Some patients show improvement in seizures during the natural course of CDKL5 disorder. Therefore, there is a possibility that this was also the case in our patient. However, the patient and her family were satisfied with the improvement in quality of life after the withdrawal of the multi-drug combinatory therapy. Thus, it is important to select the best therapy for patients with intractable epilepsy through long term follow-up.

  We report the case of a 14-month-old girl with Dravet syndrome carrying a splice-site mutation of c. 1170+1G>A on neuronal sodium channel alpha 1 subunit (SCN1A). She had a history of recurrent febrile or afebrile seizures since 4 months of age and developed acute encephalopathy due to infection with human herpesvirus-6, which presented with high grade fever, severe consciousness disturbances, and prolonged and clustered seizures. Electroencephalography showed a generalized slow activity. Intensive treatments, including mechanical ventilation, continuous thiopental infusion, and high-dose steroid therapy were initiated, and she gradually recovered. During the recovery phase, choreoathetosis-like involuntary movements appeared on the face and limbs, which were treated successfully with haloperidol. MRI findings during the acute phase were normal; however, diffuse cerebral atrophy became evident during the recovery phase. Single photon emission computed tomography (SPECT) of the brain revealed decreased cerebral perfusion over bilateral frontal and temporal lobes; however, perfusion of the occipital lobes, basal ganglia, and cerebellum remained normal. The patient showed serious developmental regression at discharge, with the loss of head control and meaningful words. Patient’s clinical course and the findings of SPECT resembled those of acute encephalopathy with biphasic seizures and late reduced diffusion (AESD), with the exception of lack of reduced diffusion of the subcortical white matter on the acute phase MRI and the prolonged and severe clinical symptoms. It has been reported that patients with Dravet syndrome are prone to complications, including various types of acute encephalopathies. Therefore, clinicians should carefully manage prolonged febrile seizures in patients with Dravet syndrome.

  We report the case of a patient born with extreme muscle hypotonia, respiratory failure, and slightly elevated serum levels of lactic acid. Histochemical examination and mitochondrial respiratory chain enzyme activities of a muscle biopsy specimen revealed reduced activities of complexes Ⅰ, Ⅲ, and Ⅳ, diagnostic of mitochondrial respiratory chain disorder. Hypertrophic cardiomyopathy developed as a complication and additional therapy was administered at 3 months after birth. He was able to be discharged to home on applied home mechanical ventilation with tracheotomy at 1 year old. The patient survived until 4 years and 10 months of age, upon which he died of bronchitis. Early-onset mitochondrial respiratory chain disorder shows very poor prognosis and long-term survival has not been reported. Prompt assessment of mitochondrial respiratory chain enzyme activities is necessary for the diagnosis of congenital nonspecific multiple-organ failure, and early intervention may achieve better prognosis for mitochondrial respiratory chain disorder.

  A 3-month-old male was brought to our hospital due to fever, poor sucking, and a bulging anterior fontanel. His general condition was poor. Analysis of the cerebrospinal fluid (CSF) showed increases in the cell count (8/μl) and the polymorphonuclear leukocyte count (2/μl) but normal sugar (66 mg/dl) and protein (28 mg/dl) levels. A CSF smear showed no bacterial cells. The administration of antibacterial drugs was initiated, and head MRI was performed on the next day. Plain images revealed no abnormalities. However, contrast-enhanced fluid-attenuated inversion recovery (FLAIR) MRI showed clear contrast enhancement along the brain surface in the meninges of the left and right frontal and left parietal lobes and fluid retention accompanied by contrast enhancement in a part of the adjacent subdural space. These findings could be confirmed only by contrast-enhanced FLAIR MRI. A diagnosis of bacterial meningitis with an unknown cause was made, and the administration of 2 antibacterial drugs was continued. MRI on day 8 of the illness showed the disappearance of contrast enhancement, and plain FLAIR also facilitated a diagnosis of a subdural hygroma. The treatment was effective. At present, the patient is 1 year and 6 months old without sequelae. The diagnosis of bacterial meningitis in infants is difficult based on only symptoms. In its early stage with few abnormal findings in the CSF, diagnosis is sometimes difficult. Antibacterial drug administration should be immediately initiated. However, definite findings are necessary for the continuation of large amounts of antibacterial drugs. Contrast-enhanced FLAIR allows the sensitive visualization of meningeal inflammation and is useful as a complementary diagnostic method for meningitis. In addition, this technique can reveal marked inflammatory lesions such as a subdural hygroma in the early stage, providing information useful for making a diagnosis of bacterial meningitis.

  To evaluate the diagnostic value of SPECT (single photon emission computed tomography) brain blood flow imaging for patients with non-herpetic acute limbic encephalitis (NHALE). A retrospective review of three patients who had clinical symptoms compatible to NHALE and were positive for anti-N-methyl-d-aspartate-type glutamate receptor (GluRε2) antibody. The patients consisted of a 6-year-old female, a 10-year-old female and a 13-year-old male, all of whom had limbic symptoms and were anti-GluRε2 antibody-positive. In all cases, brain MRI failed to detect any abnormality, but SPECT brain blood flow imaging was able to detect blood flow changes. All three cases showed some abnormality in their brain waves, and one of them also developed epilepsy. SPECT brain blood flow imaging may therefore be helpful for diagnosing NHALE which can lead to the development of either epilepsy or cognitive impairment.