How Saccade Intrusions Affect Subsequent Motor and Oculomotor Actions.

In daily activities, there is a close spatial and temporal coupling between eye and hand movements that enables human beings to perform actions smoothly and accurately. If this coupling is disrupted by inadvertent saccade intrusions, subsequent motor actions suffer from delays, and lack of coordination. To examine how saccade intrusions affect subsequent voluntary actions, we used two tasks that require subjects to make motor/oculomotor actions in response to a visual cue.

Saccade abnormalities associated with focal cerebral lesions - How cortical and basal ganglia commands shape saccades in humans.

Objective: To study saccade abnormalities associated with focal cerebral lesions, including the cerebral cortex and basal ganglia (BG).

Methods: We studied the latency and amplitude of reflexive and voluntary saccades in 37 patients with focal lesions of the frontal and parietal cortices and BG (caudate and putamen), and 51 age-matched controls, along with the ability to inhibit unwanted reflexive saccades.

Results: Latencies of reflexive saccades were prolonged in patients with parietal lesions involving the parietal eye field (PEF), whereas their amplitude was decreased with parietal or putaminal lesions.

Pre-movement gating of somatosensory evoked potentials in Segawa disease.

Introduction: Segawa disease (SD), an autosomal dominant dopa-responsive dystonia with marked diurnal fluctuation, can be clinically classified into the postural dystonia type (SD-P) and action dystonia type (SD-A). Compared to SD-A, SD-P has an earlier onset and is characterized by postural dystonia. In SD-A, along with postural dystonia, dystonic movements appear in late childhood.

Top-down but not bottom-up visual scanning is affected in hereditary pure cerebellar ataxia.

The aim of this study was to clarify the nature of visual processing deficits caused by cerebellar disorders. We studied the performance of two types of visual search (top-down visual scanning and bottom-up visual scanning) in 18 patients with pure cerebellar types of spinocerebellar degeneration (SCA6: 11; SCA31: 7). The gaze fixation position was recorded with an eye-tracking device while the subjects performed two visual search tasks in which they looked for a target Landolt figure among distractors.

Congenital myasthenic syndrome in Japan: ethnically unique mutations in muscle nicotinic acetylcholine receptor subunits.

Congenital myasthenic syndromes (CMS) are caused by mutations in genes expressed at the neuromuscular junction. Most CMS patients have been reported in Western and Middle Eastern countries, and only four patients with COLQ mutations have been reported in Japan. We here report six mutations in acetylcholine receptor (AChR) subunit genes in five Japanese patients.

Genetics and pathophysiology of primary dystonia with special emphasis on DYT1 and DYT5.

DYT1 and DYT5 are early-onset dominant inherited dystonias. DYT1 is caused by mutations of the TOR1A gene, located on 9q34, which causes dysfunction of the D1 direct pathway or the indirect pathway. Dysfunction of the former causes postural-type and segmental dystonia; the latter causes action-type dystonia.

Increased number of Hassall's corpuscles in myasthenia gravis patients with thymic hyperplasia.

The thymus is implicated as an organ that contributes to autoimmunity in myasthenia gravis (MG) patients. Hassall's corpuscles (HCs) are assumed to represent the terminally differentiated stage of medullary thymic epithelial cells (mTECs). By using multicolor immunohistofluorescence analysis, we examined HCs in thymuses that were therapeutically excised from MG (+) and MG (-) patients.

Different patterns of cerebellar abnormality and hypomyelination between POLR3A and POLR3B mutations.

Background: Mutations of POLR3A and POLR3B have been reported to cause several allelic hypomyelinating disorders, including hypomyelination with hypogonadotropic hypogonadism and hypodontia (4H syndrome).

Patients And Methods: To clarify the difference in MRI between the two genotypes, we reviewed MRI in three patients with POLR3B mutations, and three with POLR3A mutations.

Results: Though small cerebellar hemispheres and vermis are common MRI findings with both types of mutations, MRI in patients with POLR3B mutations revealed smaller cerebellar structures, especially vermis, than those in POLR3A mutations.

Dopa-responsive dystonia is caused by particular impairment of nigrostriatal dopamine neurons different from those involved in Parkinson disease: evidence observed in studies on Segawa disease.

From the characteristics of its clinical features, Segawa disease is considered to be caused by deficiency of the tyrosine hydroxylase (TH) of the nigrostriatal dopamine neurons, which have high TH activities in the terminal but not in the perikaryon. This hypothesis was confirmed by two autopsied cases. However, these cases were younger than 40 years and left a question as to whether these abnormalities turned to those of Parkinson disease in older ages.

[Neurotransmitter disorders in children--special reference to Segawa disease].

Aminergic neurotransmitter disorders occurring in childhood include metabolic disorders of pteridine and tyrosine hydroxylase (TH). Pteridine metabolic disorders cause a deficiency of serotonin (5-HT) and dopamine (DA) and TH disorder causes a deficiency of noradrenaline (NA) and DA in the terminals of each aminergic neuron. The activities of TH or DA in the terminals are marked in early childhood, and then they show an exponential age-dependent decrement and achieve stationary or minimal levels in the twenties.

Dopa-responsive dystonia.

Clinical characteristics and pahophysiologies of dopa-responsive dystonia are discussed by reviewing autosomal-dominant GTP cyclohydrolase-I deficiency (AD GCHI D), recessive deficiencies of enzymes of pteridine metabolism, and recessive tyrosine hydroxylase (TH). Pteridine and TH metabolism involve TH activities in the terminals of the nigrostriatal dopamine neuron which show high in early childhood and decrease exponentially with age, attaining stational low levels by the early 20s. In these disorders, TH in the terminals follows this course with low levels and develops particular symptoms with functional maturation of the downstream structures of the basal ganglia; postural dystonia through the direct pathway and descending output matured earlier in early childhood and parkinsonism in TH deficiency in teens through the D2 indirect pathway ascending output matured later.

Hereditary progressive dystonia with marked diurnal fluctuation.

Hereditary progressive dystonia with marked diurnal fluctuation (HPD) is a dopa-responsive dystonia, now called autosomal dominant GTP cyclohydrolase 1 deficiency or Segawa disease, caused by mutation of the GCH-1 gene located on 14q22.1 to q22.2.

[Walking abnormalities in children].

Walking is a spontaneous movement termed locomotion that is promoted by activation of antigravity muscles by serotonergic (5HT) neurons. Development of antigravity activity follows 3 developmental epochs of the sleep-wake (S-W) cycle and is modulated by particular 5HT neurons in each epoch. Activation of antigravity activities occurs in the first epoch (around the age of 3 to 4 months) as restriction of atonia in rapid eye movement (REM) stage and development of circadian S-W cycle.

Epilepsy in autism: A pathophysiological consideration.

Eighty cases of idiopathic autism with epilepsy and 97 cases without epilepsy were studied to evaluate the pathophysiology of epilepsy in autism. The initial visit to this clinic ranged 8months-30years 3months of age, and the current ages are 5years 8months-42years 3months, 60% reaching to over 30years of age. The average follow up duration is 22.

[Care continuity for patients with myasthenia gravis during transition from childhood to adulthood].

The onset of myasthenia gravis in Japan shows two peaks, the highest in childhood, which has specific HLA association. The clinical types are ocular, latent general and general types, latent general is most frequently observed. Clinical characteristics and effects of the treatments are associated with the clinical types and ages at onset.

[Carry-over of neurological disorders of infancy and childhood].

Carry-over implies following a patient from the age of childhood to the adulthood. In the developing brain, specific symptoms appear only after development of the neurons of the lesion site and those consisting of the downstream structures. Thus, in the basal ganglia disorders, those involving the striatal direct pathways and the descending output of the basal ganglia develop symptoms in childhood before 10 years old.

Autosomal dominant GTP cyclohydrolase I (AD GCH 1) deficiency (Segawa disease, dystonia 5; DYT 5).

Autosomal dominant GTP cyclohydrolase I (AD GCH 1) deficiency (Segawa disease) is an autosomal dominant dopa responsive dystonia caused by heterozygous mutation of the GCH 1 gene located on 14q22.1-q22.2.

[Case of DYT1 dystonia (early-onset torsion dystonia) showing long-term focal dystonia in the arm].

DYTI dystonia (DYT1-D, early-onset torsion dystonia) is caused by a GAG deletion in the DYTI gene. Here we report a girl with child-onset familial DYT1-D showing localized arm involvement. The patient developed postural and action dystonia in the right and left arms at 7 and 9 years, respectively.

[Development of intellect, emotion, and intentions, and their neuronal systems].

Intellect, emotion and intentions, the major components of the human mentality, are neurologically correlated to memory and sensorimotor integration, the neuronal system consisting of the amygdale and hypothalamus, and motivation and learning, respectively. Development of these neuronal processes was evaluated by correlating the pathophysiologies of idiopathic developmental neuropsychiatric disorders and developmental courses of sleep parameters, sleep-wake rhythm (SWR), and locomotion. The memory system and sensory pathways develop by the 9th gestational months.

[Segawa disease].

The first report of Segawa disease was a report of two girls, cousin each other, with dystonic posture, under the title of "Hereditary progressive basal ganglia disorder" in 1971. After accumulation of cases with an adult case, I confirmed this disease does not transform to Parkinson's disease in adulthood and published with a nomenclature of "Hereditary progressive dystonia with marked diurnal fluctuation" in 1976. Polysomnographical examination for evaluating the sleep effects and correlation of the natural course to the age variation of the tyrosine hydroxylase activities in the striatum, these speculated this is a particular disorder caused by non-progressive decrement of the tyrosine hydroxylase at the terminal of the nigrostriatal dopamine neuron.

[Japanese originality, clinical symptoms to the causative gene 1 Segawa disease].

Segawa disease was first reported in 1971 as 'Hereditary progressive basal ganglia disease with marked diurnal fluctuation'. In 1976, after experience of a 51 year old patient with 43 years non-treatment periods, I confirmed this disease as dystonia. Polysomnographies revealed selective involvement of the dopamine (DA) neuron without involvement of the D2 receptors.

Early behavior characteristics and sleep disturbance in Rett syndrome.

This paper reviews the early features of Rett syndrome (RTT). The behavioral characteristics of RTT were analyzed retrospectively by taking history and asking about early infancy behaviors. The earliest behavioral characteristics are thought to be autistic features and hypotonia of trunkal muscles.

Early motor disturbances in Rett syndrome and its pathophysiological importance.

Assessment of the development of motor function of Rett syndrome (RTT) revealed hypotonia with failure of crawling and disturbance in skillful hand manipulation are shown as early motor signs. Clinical evaluation has revealed the former as postural hypotonia with failure in locomotion and neurophysiological examinations have showed this to be due to hypofunction of the aminergic neurons of the brainstem. The latter signs are considered to indicate dysfunction of the corticospinal tract at higher levels.

A missense mutation in SCN1A in brothers with severe myoclonic epilepsy in infancy (SMEI) inherited from a father with febrile seizures.

Severe myoclonic epilepsy in infancy (SMEI) is an age-dependent epileptic encephalopathy occurring in the first year of life and is one of the intractable epilepsies. Heterozygous mutations in the voltage-gated sodium channel alpha subunit type1 gene (SCN1A) are frequently identified in patients with SMEI; two-thirds of these mutations are truncation mutations (non-sense and frameshift), and one-third are missense mutations. Although most reported SMEI cases arise as sporadic mutations, close relatives of SMEI patients have also been shown to manifest other types of epilepsies at a higher rate than that in the general population.