Mutations in the NHLRC1 gene are the common cause for Lafora disease in the Japanese population.

Lafora disease (LD) is a rare autosomal recessive genetic disorder characterized by epilepsy, myoclonus, and progressive neurological deterioration. LD is caused by mutations in the EMP2A gene encoding a protein phosphatase. A second gene for LD, termed NHLRC1 and encoding a putative E3 ubiquitin ligase, was recently identified on chromosome 6p22.

[Today and tomorrow in child neurology at a neurological clinic for children--the importance of child neurology as the life-long neurology].

Segawa Neurological Clinic for Children was founded in 1973, and specializes in neurological disorders that start in childhood. In thirty-one years since the foundation, about 16,000 patients visited this clinic. The ages of the first visit to this clinic of the patients are mostly below 15 years.

Rett syndrome.

Purpose Of Review: Nearly 70 reports on Rett syndrome were published in 2004. We have selected 51 articles, including clinical reports, on pathophysiology, genotype-phenotype correlation, and clinical and basic molecular biology studies. These articles explain how mutation of the gene (MECP2) for methyl-CpG-binding protein 2 causes the particular disorders of Rett syndrome, and also induces other neurodevelopmental disorders, clarifying the situation for future studies.

[Inherited dystonia update].

Among idiopathic dystonia, inherited dystonia whose causative gene or linkage has been clarified are named as DYT1 to DYT15. The causative genes of DYT1, 5 and 11 were identified as genes of Torsin A, GTP cyclohydrolase I, and epsilon-sarcoglycan, respectively. All three are inherited dominantly.

Neurophysiology of Tourette's syndrome: pathophysiological considerations.

At present the neurophysiology of Tourette's syndrome (TS) has been investigated largely from two perspectives; one for evaluation of the dysfunction of the cerebral cortex and the other for clarification of the neuronal mechanisms that underlie tics and related symptoms. For the former the following examinations have been conducted: quantitative analyses of scalp electroencephalography (EEG), premovement EEG potentials, contingent negative variation, transcranial magnetic stimulation, and neuroimaging studies, including echo-planar images and positron emission tomography scans. These explorations have revealed the likely involvement of the subcortical and the cortical structures, particularly of the basal ganglia, in the pathophysiology of TS.

Abnormalities of voluntary saccades in Gilles de la Tourette's syndrome: pathophysiological consideration.

Gilles de la Tourette's syndrome (TS) is a neurobehavioral disorder. Although the etiology and the pathophysiology of TS are still unknown, the involvement of the basal ganglia has long been postulated. On the other hand, saccadic eye movement was shown to be a useful measure to assess order and disorder of the function of the basal ganglia.

Neurology of Tourette's syndrome (TS) TS as a developmental dopamine disorder: a hypothesis.

The favorable effect of dopamine (DA) depletors or DA receptor blockers suggested the state of increased transmission of DA system as the pathophysiology of Tourette's syndrome (TS). We have analysed the neurological signs of TS and evaluated the role of levodopa on the symptoms of TS. The data were compared with age-matched patients with Hereditary Progressive Dystonia (HPD) with marked diurnal fluctuation.

Autosomal dominant guanosine triphosphate cyclohydrolase I deficiency (Segawa disease).

Autosomal dominant guanosine triphosphate cyclohydrolase I (GCH-I) deficiency (Segawa disease) is a dopa-responsive dystonia caused by mutation of the GCH-I gene located on 14q22.1-q22.2.

[Pathophysiology of Rett syndrome from the standpoints of clinical characteristics and clinical neurophysiological findings].

The pathophysiology of Rett syndrome (RTT) was discussed by reviewing the characteristic clinical features and neurophysiological studies. The electroencephalography (EEG), sensory evoked potentials (SEP), sleep-wake rhythm (SWR) study and polysomnographical (PSG) study showed age dependent characteristics. The findings in EEG and SEP studies suggested the specific subcortical and cortical involvements taking place during the development.

[Rett syndrome: correlation of clinical symptoms and the mutations in the gene of methyl CPG binding protein 2 (MeCP2): introductory remarks].

Pathophysiology of Rett syndrome is discussed in relation to the MeCP2 gene. The brainstem aminergic neurons are affected in early infancy, resulting in failure in locomotion, head growth and language. The severity of symptoms is related to the specific loci of a mutation on the methylbinding domain which shows correlation with the degree of heterochronation disturbance.

Development of language in Rett syndrome.

Ninety-nine cases of Rett syndrome (RTT) diagnosed clinically (age range 3 years 6 months to 29 years 9 months) were evaluated for the ability of language. The presence of meaningful words, vocabularies, and ages at the start and disappearance of speech were assessed. Phenotype/genotype correlation was evaluated in 22 cases in whom mutations of the genes of methyl-CpG-binding protein 2 (MECP2) existed.

Discussant--pathophysiologies of Rett syndrome.

Studies on sleep parameters of Rett syndrome revealed hypoactivity of the noradrenaline (NA) and the serotonin (5HT) neuron in early infancy while preserving the function of the dopamine (DA) and the cholinergic neurons of the pons normally. The sleep-wake cycle remains in its development at the level of 4 months of age. Polysomnographies also showed a decrease of the function of the nigrostriatal (NS)-DA neuron in early childhood and suggested the development of receptor supersensitivity in late childhood.

Pathophysiology of Rett syndrome from the stand point of clinical characteristics.

In this report, we reviewed the characteristics of motor development and motor symptoms of Rett Syndrome (RTT) and demarcated the early and pathognomonic motor symptom which correlates to the impairment of the higher cortical function (HCF) assessed by the ability of language. It is suggested that failure of locomotion in late infancy is the primary and pathognomonic symptom. Thus, the impairment of the neurons or neuronal systems involving locomotion is suggested as the primary lesion in the pathophysiology of RTT not only for motor dysfunction but also for the failure in the development of language and cognitive function.

Neurophysiology of Rett syndrome.

Neurophysiological studies on Rett syndrome (RTT) are reviewed, and pathophysiology of RTT is discussed. The electroencephalography (EEG), sensory evoked potentials (SEP), sleep-wake rhythm study and polysomnography (PSG) study showed age-dependent characteristics. PSG revealed the brainstem and midbrain monoaminergic systems are deranged from early developmental stage, that is serotonin and noradrenaline systems seem to be hypoactive and dopaminergic system is also hypoactive associated with receptor supersensitivity.

Two phenotypes and anticipation observed in Japanese cases with early onset torsion dystonia (DYT1) - pathophysiological consideration.

Early onset torsion dystonia (DYT1) is a dominantly inherited dystonia caused by a deletion of three bases, GAG, coding glutamic acid, in chromosome 9q34. The protein coded by this gene was named as torsin A. DYT1 is common among the Ashkenazi Jewish population, but has been thought to be rare among Japanese.

Hereditary progressive dystonia with marked diurnal fluctuation.

Hereditary progressive dystonia with marked diurnal fluctuation or the strictly defined dopa-responsive dystonia (HPD/DRD) is an autosomally dominantly inherited dystonia caused by abnormalities of the gene of the GTP cyclohydrolase I (GCH 1) located on the 14q22. 1-q22.2.

Development of the nigrostriatal dopamine neuron and the pathways in the basal ganglia.

The nigrostriatal (NS) dopamine (DA) neuron and the basal ganglia show marked functional age variation in the first three decades. Neurohistochemical studies revealed marked age variation of activities of tyrosine hydroxylase at the terminal of the NS-DA neuron, which show exponential decremental variation from early childhood and subside in the fourth decade. DA-D2 receptors, examined by PET scan, are in high levels in the third decade which decrease dramatically to the bottom or 'adult' levels in the fourth decade.