Junichiro Kawamura

Clinical similarities of hereditary progressive/dopa responsive dystonia caused by different types of mutations in the GTP cyclohydrolase I gene.

OBJECTIVE Hereditary progressive dystonia with pronounced diurnal fluctuation ((HPD)/dopa responsive dystonia (DRD)) is a childhood onset dystonia which responds to levodopa. Various clinical signs and symptoms of HPD/DRD have been recognised to date. Mutations in the GTP cyclohydrolase I (GTP-CH-I) gene were recently identified as the cause of HPD/DRD. In the present study, the GTP-CH-I gene and the clinical features of eight HPD/DRD patients from six families were analysed to determine the correlations between clinical expression and the mutations in the GTP-CH-I gene. METHODS The exons, exon-intron junctions, and an indispensable part of the 5’ flanking region of the GTP-CH-I gene were sequenced in the eight clinically diagnosed patients with HPD/DRD and their asymptomatic parents. RESULTS Three independent mutations in the GTP-CH-I gene were found in three patients. One of the patients and her asymptomatic mother were heterozygous for a novel mutation at the initiation codon. The three patients with dissimilar GTP-CH-I mutations exhibited similar clinical features. The other five patients with normal sequences presented several features not manifested by the three patients with the mutations. No mutation was found in the 5′ flanking region of any patients or their parents. CONCLUSIONS A novel initiation codon mutation was found in a Japanese patient with HPD/DRD. The clinical manifestations common to the patients with HPD/DRD with a mutated GTP-CH-I gene were also identified. Although focal manifestations of HPD/DRD associated with the mutations of this gene will be broadened, it is inferred that these clinical features are fundamental to HPD/DRD caused by mutations in this gene.

Waveform changes of compound muscle action potential (CMAP) with muscle length

Changes in finger positions influence the waveform of CMAP recorded from the muscle that moves that finger. The present study suggested that the muscle length, dependent on the finger position, was a main factor affecting the waveform. On shortening the muscle length, the amplitude of CMAP increased with concomitant reduction in the duration, and on lengthening, the amplitude decreased with concomitant increase in the duration. These changes are considered due to changes in propagation velocities of muscle fibers dependent on the muscle length. In nerve conduction studies, it is important to carefully monitor the finger position to distinguish the waveform changes with muscle length from those due to nerve lesions.

Monoamine oxidase-containing nerve fibers in the major cerebral arteries of rats

The localization of monoamine oxidase (MAO) in nerve fibers associated with the major cerebral arteries in rats was studied using a new coupled peroxidation method modified by adding nickel ammonium sulfate at the electron microscopic level. MAO was, localized in some unmyelinated axons, both in the adventitia and in the periadventitial nerve bundles. Schwann cell cytoplasm encircling myelinated axons in the periadventitial nerve bundles also contained a MAO-reactive substance. The incidences of MAO-containing axons in the adventitial layer of the anterior cerebral, middle cerebral, internal carotid and basilar arteries were 32.3%, 29.5%, 29.6% and 21.1%, respectively. In the periadventitial nerve bundles, MAO activity was also demonstrated in 10.8% among unmyelinated axons. Preincubation with clorgyline, a specific inhibitor of MAOA, suppressed staining in the axons, both in adventitia and in periadventitial nerve bundles, but not in the Schwann cell cytoplasm. Conversely, preincubation with deprenyl, a specific inhibitor of MAOB, suppressed staining in the Schwann cell cytoplasm, but not in the axons. Therefore, MAO in the axons is regarded as MAOA and MAO in the Schwann cell cytoplasm as MAOB. In immunosympathectomized rats (anti-NGF-treated rats), MAO reactivity was suppressed in axons associated with cerebral arteries, but was retained in some Schwann cell cytoplasm. The results indicate that the MAO-containing unmyelinated axons coincide with the postganglionic noradrenergic ones. Thus, histochemical MAO staining may be utilized to study postganglionic sympathetic nerve fibers presumably innervating the major cerebral arteries at the electron microscopic level.

Subacute dementia with necrotising encephalitis selectively involving the fornix and splenium: Retrograde development of Alzheimer's neurofibrillar tangles in the subiculum

An elderly woman developed subacute progressive dementia with predominant impairment in recent memory and CT findings indicating an enhancing lesion near the splenium of the corpus callosum. Autopsy four months after the onset of the symptoms revealed necrotising encephalitis selectively involving the bilateral fornices and the adjacent splenium. Degeneration was marked in the contiguous right fimbria hippocampi. Particularly numerous Alzheimers neurofibrillar tangles (NFTs) were present in the right subiculum, while they were scattered in Sommers sectors and parahippocampal gyri and were practically nonexistent elsewhere. Senile plaques were rare. Electron microscopy disclosed that the right subicular tangles were composed mostly of 15-nm straight tubules which were also frequently observed in the myelinated axons. Since the major projection fibers to the fornix originate in the subiculum, the distinctive pattern of NFT distribution might be derived from the retrograde neuronal changes secondary to the fornix-fimbria lesion. This case represents a rare form of amnesia-dementia confirmed anatomically to have been caused by fornix lesions.

Bromocriptine Therapy in Early-Stage Parkinson’s Disease

We evaluated bromocriptine monotherapy during the early stage of Parkinsons disease (Hoehn and Yahr stage I or II). Of the 120 patients registered as participants in this trial, 96 were studied. The follow-up period was 48 weeks. For the first 24 weeks they were all placed on bromocriptine with or without anticholinergic drugs; for the second 24 weeks, 75 of them were still kept on the same medication, with 21 requiring additional levodopa. Clinically, the former group showed a good response to the bromocriptine monotherapy, while the latter responded poorly to it (requiring in addition levodopa). We think that Parkinsons disease encompasses a heterogeneous group of patients of whom about 75% are well treated by bromocriptine alone at the early stages of the illness.

Bifurcation of P9 far-field potentials induced by changes in the shoulder position.

Somatosensory evoked potentials to stimulation of the left median nerve were recorded from normal adults with reference to the right knee in the usual shoulder position and in an elevated shoulder position. A single peak of the P9 potentials in the former position bifurcated into two peaks in the latter position without changing the onset latency. This waveform change can be accounted for by changes in the resistance of the volume conductor around the nerve trunk.