E. Ohama

Parkinson's disease: the presence of Lewy bodies in Auerbach's and Meissner's plexuses

SummaryWe systematically studied the enteric nervous system of the alimentary tract in seven patients with Parkinsons disease. In all patients, characteristic inclusions histologically and ultrastructurally identical to Lewy bodies were found in Auerbachs and Meissners plexuses. They were most frequent in the Auerbachs plexus of the lower esophagus. Lewy bodies were found in 8 out of 24 age-matched nonparkinsonian patients. However, they were obviously small in number. These findings clearly indicate that the plexuses are also involved in Parkinsons disease.

Familial juvenile parkinsonism : clinical and pathologic study in a family

We describe a family with juvenile-onset parkinsonism, which improved following sleep. Four of the five siblings in this family developed a similar onset of parkinsonism at an early age, and the parents were first cousins. In one of the siblings, a 67-year-old woman, pathologic changes at autopsy were confined to the substantia nigra pars compacta (SNPC) and locus ceruleus. The SNPC revealed obvious neuronal loss and gliosis in the medial and ventrolateral regions. In the remainder of the SNPC and the locus ceruleus, the population of neurons was reduced and there was low melanin content in most of the neurons but no detectable gliosis or extraneuronal free melanin pigment suggestive of a neurodegenerative process. There were no Lewy bodies. The entire pathologic picture was different from that of Lewy body Parkinsons disease.

Mitochondrial angiopathy in cerebral blood vessels of mitochondrial encephalomyopathy

SummaryWe studied cerebral blood vessels of two autopsied patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS). All the main cerebral arteries in the proximal portion at the brain base and more distal portion at the cortical surface, as well as within the brain parenchyma were examined by electron microscopy. There was a striking increase in number of mitochondria in the smooth muscle and endothelial cells, which were most prominent in the pial arterioles and small arteries up to 250 μm in diameter and less frequent and severe in the larger pial arteries and intracerebral arterioles and small arteries. These vascular changes have not hitherto been described in MELAS, or in other disorders affecting blood vessels of the brain and other organs. It is suggested that the vascular changes are caused by primary mitochondrial dysfunction in the vascular smooth muscle and endothelial cells of the brain and that they constitute the pathogenic base of the brain lesions and their unusual distribution pattern in MELAS.

Parkinson's disease : an immunohistochemical study of Lewy body-containing neurons in the enteric nervous system

SummaryWe performed immunohistochemical analysis of specimens from three autopsied patients with Parkinsons disease, using antibodies to tyrosine hydroxylase (TH), vasoactive intestinal polypeptide (VIP), somatostatin, met-enkephalin, leu-enkephalin and substance P in an attempt to reveal the types of neurons that contain Lewy bodies (LBs) in the paravertebral and celiac sympathetic ganglia and in the enteric nervous system of the alimentary tract. In the sympathetic ganglia, almost all LB-containing neuronal cell bodies and processes were immunoreactive for TH. In the alimentary tract, however, most LBs were found in the VIP-immunoreactive (VIP-IR) neuronal cell bodies and processes. In spite of the significant presence of TH-IR neuronal cell bodies and processes in the alimentary tract, LB-containing TH-IR neuronal elements were rarely encountered. These findings indicate that in the alimentary tract, the VIP neuron system is mainly involved in the disease process of Parkinsons disease.

Parkinson's disease: Distribution of Lewy bodies and monoamine neuron system

SummaryA systematic study of the central and peripheral nervous systems in 3 cases of Parkinsons disease has demonstrated that Lewy bodies are present in 27 nuclei. Of these 20 nuclei (12 pigmented and 8 unpigmented) are involved in 2 or all 3 cases.It is noticed that the distribution of Lewy bodies in Parkinsons disease described here corresponds surprisingly well to that of monoamine (dopamine, noradrenaline and serotonin) cell bodies demonstrated in rats by the histochemical fluorescence method. This correlation is similar to that of Alzheimers neurofibrillary changes in postencephalitic Parkinsonism as described by Ishii. Inasmuch as these viewpoints are also in agreement with previously reported biochemical data on Parkinsonism, it is suggested that Parkinsonism (idiopathic and postencephalitic) should represent a system degeneration of monoamine neuron systems.

Hereditary dentatorubral‐pallidoluysian atrophy Clinical and pathologic variants in a family

We describe a family showing dentatorubral-pallidoluysian atrophy. Three patients appeared through three successive generations and displayed a wide variety of clinical pictures. The male proband with onset in childhood showed progressive myoclonus epilepsy syndrome. The father experienced cerebellar ataxia, myoclonus, and mild dementia starting in middle age; the paternal grandmother had progressive symptoms of cerebellar ataxia, choreiform movements, and dementia, but neither myoclonus nor epilepsy in senescence. Neuropathologic examination of two patients, the proband and the paternal grandmother, revealed combined degeneration of the dentatorubral and pallidoluysian systems and obvious degeneration involving the striatum in the proband and the cerebellar cortex in the grandmother. The present study indicates that this disease can include many clinical and pathologic variants even in the same family.

A mitochondrial encephalomyopathy with cardiomyopathy ☆: A case revealing a defect of complex I in the respiratory chain

We describe a 16-year-old Japanese girl with a mitochondrial encephalomyopathy who presented with progressive dementia, limb weakness and atrophy, episodic vomiting, generalized convulsions, myoclonic seizures, and hypertrophic cardiomyopathy. CT scan revealed transient focal low density areas in her occipital and parietal lobes, and cerebellar atrophy. The clinical features were consistent with mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes (MELAS). Microscopically, most of muscle fibers in the skeletal muscles and heart were occupied by markedly increased mitochondria. Polarographic studies on mitochondria isolated from postmortem heart muscle showed severe impairment of oxidation of NADH-linked substrates in contrast to normal succinate oxidation. The rotenone-sensitive NADH-coenzyme Q reductase activity was markedly decreased in heart, skeletal muscle and liver mitochondria. The biochemical investigations have led to the identification of a defect of complex I in the respiratory chain. Reported cases of a defect of complex I have revealed pure myopathy, encephalopathy or encephalomyopathy. The reason for a varied clinical expression of a single defect remains to be clarified.

Distribution of serotonin-containing cell bodies in the brainstem of the human fetus determined with immunohistochemistry using antiserotonin serum

The distribution of serotonin (5HT) neurons was investigated in the brainstem of 8 human fetuses ranging in age from 15 to 27 weeks of gestation. We conducted the peroxidase-antiperoxidase (PAP) immunohistochemical technique using antiserotonin serum to detect the cell bodies of 5HT-containing neurons. Positively stained 5HT neurons were clearly demonstrated in the brainstem of all fetuses examined. They varied in shape, showing round to oval cell bodies with unipolar, bipolar, or multipolar processes. A large number of 5HT neurons were located in the midline raphe nuclei. In addition, numerous 5HT neurons were observed widely in the other tegmental areas. The nuclei containing 5HT neurons were listed according to the terminology by Olszewski and Baxter for human brainstem, and an atlas was given. The distribution of 5HT neurons in the raphe nuclei of human fetuses was essentially similar to those of many mammals already reported. However, the lateral extension of 5HT neurons to the other tegmental areas beyond the midline raphe nuclei was much greater in human fetuses compared to other mammals.

Lewy bodies in the lower sacral parasympathetic neurons of a patient with Parkinson's disease

SummaryLewy bodies were observed incidentally in the neurons of the dorsal group of nucleus intermediolateralis of the 3rd sacral segment of the spinal cord in a 74-year-old male with Parkinsons disease. The findings indicate the degeneration of the preganglionic parasympathetic neurons innervating the internal anal sphincter. The correlation between the findings and the mechanism of constipation in this disease are discussed.

Pleiotropic molecular defects in energy-transducing complexes in mitochondrial encephalomyopathy (MELAS)

The extent of molecular defects in the mitochondrial energy-transducing system was examined in autopsied tissues of a 14-year-old male with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) in order to elucidate the underlying molecular and genetic abnormalities. The patient also had other multiorganic disorders: hypertrophic cardiomyopathy, nephrotic syndrome, and pseudohypoparathyroidism. Enzymic activities of complex I and IV were severely decreased, and those of complex III and V were mildly decreased in the mitochondria isolated from various tissues, but the severity of the deficiencies varied from tissue to tissue. In contrast, complex II and citrate synthase activities were normal or were decreased to a lesser extent than the enzymic activities of other complexes in all the tissues examined. These results suggest that the energy-transducing complexes, namely complexes, I, III, IV, and V, that contain mitochondrially synthesized subunits, were selectively affected. Immunoblot analysis demonstrated that the decreased enzymic activities were based on decreased contents of subunits in these complexes. The multiorganic manifestation of the disorder may result from wide and uneven distribution of abnormal mitochondria that have pleiotropic molecular defects in the energy-transducing complexes among the organs of the patient.