Yoshio Hashizume

Presence of tetrahydroisoquinoline and 2-methyl-tetrahydroquinoline in Parkinsonian and normal human brains

1,2,3,4-Tetrahydroisoquinoline (TIQ) and 2-methyl-1,2,3,4-tetrahydroquinoline (2-Me-TQ) were identified for the first time by gas chromatography-mass spectrometry in the parkinsonian and normal human brains. TIQ, an analogue of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), was markedly increased in the parkinsonian brain and could be an endogenous neurotoxin to induce Parkinsons disease.

Ubiquitin-positive intraneuronal inclusions in the extramotor cortices of presenile dementia patients with motor neuron disease

SummaryUbiquitin-positive intraneuronal inclusions were found in the extramotor cortices of ten presenile dementia patients with motor neuron disease. There were inclusions in the hippocampal granular cells and in the small neurons of the superficial layers of the temporal and frontal cortices. Bunina bodies were present in the anterior horn cells in all cases. These results suggest that ubiquitin-related cytoskeletal abnormalities are common in cerebral non-motor small neurons in these patients.

Phosphorylated high molecular weight neurofilament protein in lower motor neurons in amyotrophic lateral sclerosis and other neurodegenerative diseases involving ventral horn cells

SummaryLower motor neurons of the spinal cord of patients with amyotrophic lateral sclerosis (ALS), Werdnig-Hoffmanns disease (WH), X-linked recessive bulbospinal neuronopathy (X-BSNP) and multiple system atrophy (MSA), all of which were known to involve the lower motor neurons, were immunohistochemically examined by using a monoclonal antibody (Ta-51) specific to phosphorylated epitopes of high molecular weight subunits of neurofilaments. The incidence of Ta-51-positive neurons was significantly increased in ALS, WH and MSA, but not in X-BSNP. Ta-51-positive neurons showed a wide variety of morphological appearances, including neurons with normal appearance, central chromatolysis, simple atrophy and neurons containing massive neurofilamentous accumulation. In aged-control cases, similar Ta-51-positive neurons were observed, although to a much lesser extent. In ALS, spheroids and globules, which were strongly positive for Ta-51, were also significantly increased. Ta-51-positive motor neurons, spheroids and globules appeared in proportional to the number of remaining large motor neurons in ALS.

Neuronal cell loss of the striatonigral system in multiple system atrophy

We investigated the longitudinal as well as lateral loss of striatal and nigral cells and its distribution in 7 cases of multiple system atrophy. Loss of striatal small cells and nigral pigmented cells was more prominent in the caudal part than in the rostral and mid-parts. Cell loss was especially high in the dorsolateral zone of the caudal putamen and in the lateral zone of the caudal nigra. These findings indicate that MSA predominantly disturbs the striatal and nigral efferent systems, which interlink the caudal and dorsolateral putamen with the caudolateral nigra. In less severe cases, the rostral to mid-parts of the putamen or substantia nigra were almost intact while its caudal portion was clearly affected. The degenerative process of MSA seems to occur initially in the caudal parts of the putamen and substantia nigra, extending later to the rostral parts. Thus striatal small cells and nigral pigmented cells degenerate according to anatomical relationship. In MSA, degeneration of the striatonigral system could well be explained as being transsynaptic.

Disease-specific patterns of neuronal loss in the spinal ventral horn in amyotrophic lateral sclerosis, multiple system atrophy and X-linked recessive bulbospinal neuronopathy, with special reference to the loss of small neurons in the intermediate zone

The ventral horn cells of the fourth lumbar segment were morphometrically analysed in six cases of amyotrophic lateral sclerosis (ALS; three common forms and three pseudopolyneuritic forms), six of multiple system atrophy (MSA) with autonomic failure, four of X-linked recessive bulbospinal neuronopathy (X-BSNP), and seven age-matched autopsy cases of non-neurological disorders. In the common form of ALS, large and medium-sized neurons of the medial and lateral nuclei were markedly lost; small neurons in the intermediate zone were slightly diminished but fairly well preserved. In the pseudopolyneuritic form of ALS, marked loss was present in the large and medium-sized neurons, and in the small neurons located in the intermediate zone as well. In the MSA, in contrast to ALS, there was a marked reduction in small neurons in the intermediate zone, and large and medium-sized neurons of the medial and lateral nuclei tended to be preserved. In X-BSNP, large and medium-sized neurons were almost completely lost and small neurons were also markedly depopulated. These findings indicated that the pattern of neuron loss in the ventral horn is distinct among these diseases depending on size, location and function of the ventral horn cell population. These disease-specific patterns of neuron loss suggest a difference in the process of neuronal degeneration of ventral horn cells among the disease examined.

Spinal and cranial motor nerve roots in amyotrophic lateral sclerosis and X-linked recessive bulbospinal muscular atrophy: Morphometric and teased-fiber study

SummaryAmyotrophic lateral sclerosis (ALS) and adult onset X-linked recessive bulbospinal muscular atrophy (SPMA), constituting the category of adult onset form of motor neuron disease, were analyzed on motor nerve roots. The results of morphometric analysis on ventral spinal roots (VSR) of all spinal segments from ALS and SPMA revealed the following three findings: (1) the large-myelinated α-motoneuron fibers were markedly decreased in number throughout all segments; (2) thin-myelinated autonomic preganglionic fibers were almost completely preserved; (3) small-intermediate-myelinated fibers which are considered to correspond to γ-motoneuron fibers were generally well preserved in ALS, but decreased by one-half to one-third in SPMA. However, all the components of the nerve roots of the oculomotor, trochlear, and abducent nerves were completely preserved in both ALS and SPMA. Moreover, the teasedfiber study showed that the regenerating-sprouting process rarely occurred in the VSR of ALS and SPMA. The present study suggested that the site of the primary lesion seems to be in the α-motoneuron fibers in motor neuron diseases, such as ALS or SPMA. However, the marked discrepancy in the pathologic change in the α-motoneuron fibers in the VSR and the nerve roots innervating the external ocular muscles was noteworthy.

Ubiquitin-positive inclusion in anterior horn cells in subgroups of motor neuron diseases: A comparative study of adult-onset amyotrophic lateral sclerosis, juvenile amyotrophic lateral sclerosis and werdnig-hoffmann disease

This report concerns the expression of ubiquitin in anterior horn cells of various subgroups of adult and infantile motor neuron disease (MNDs); immunohistochemical techniques were employed. Ubiquitin-positive skein-like inclusions (SLIs) were found in all cases of adult-onset amyotrophic lateral sclerosis (ALS), including 16 cases with sporadic ALS, two cases of familial ALS with posterior column degeneration and Lewy body-like hyaline inclusions (LBHIs), two sporadic ALS cases with LBHIs, and three cases of sporadic ALS with dementia. SLIs were not found in anterior horn cells of 5 cases with Werdnig-Hoffmann disease (WHD). However, granular ubiquitin-positive deposits were seen in ballooned neurons of WHD patients. No ubiquitinated materials were found in the perikarya of two sporadic juvenile ALS patients with basophilic inclusions (BIs), but granular ubiquitin-immunoreactive deposits were occasionally observed in the BIs. These results suggest that ubiquitin-positive SLIs are characteristic features of various forms of adult-onset ALS and that aggregated ubiquitinated granules are characteristic of ballooned neurons of WHD. Ubiquitinated structures and their distribution patterns may reflect degenerative processes of anterior horn cells, and may be useful for classifying subgroups of motor neuron diseases.

A histometrical and comparative study on Purkinje cell loss and olivary nucleus cell loss in multiple system atrophy.

We examined pathologically 21 cases of multiple system atrophy (MSA). Density of Purkinje cell in 16 cases and of olivary nucleus cell in 20 cases was quantitatively measured, and their distribution as well as degree were studied. Contrary to the findings of previous reports, Purkinje cell loss was more pronounced in the vermis than in the hemispheres. Olivary nucleus cell loss was more outstanding in the accessory nucleus than in the inferior nucleus. A topographical characteristic of cell degeneration exists between the Purkinje layer and the olivary nucleus. Significant sparing of the nodulus apparently related to that of the vestibular system was found. While the common distribution of cell loss was seen, its degree varied considerably case by case. The degree was related to both duration of illness and, to some extent, clinical subtypes of MSA.

Intramedullary spinal cord metastasis - Pathologic findings in five autopsy cases

SummaryThis report describes the pathologic findings in five autopsy cases with intramedullary spinal cord metastasis. In an autopsy series over a 30-year period, the incidence of intramedullary metastasis among the metastatic tumors to the spine was 3.5%, and the incidence among the central nervous system (CNS) metastasis was 4.2%. Primary site of tumor was the lung in four cases, and cancer of the thyroid was suspected in one case.On transverse section, the tumor was located mainly in the ventral part of the posterior horn and the medial part of the lateral column. Involvement was focal extending over one to six segments.In two cases, secondary hemorrhage occurred in the posterior horn or the posterior column. In three cases, central ischemic infarction was noted cephalad and caudad to the tumor metastasis. The mode of tumor spread to the spinal cord is not clear, but the autopsy findings in our series suggest that intramedullary tumor may result from hematogenous spread via the arterial circulation.

OCCLUSION OF THE BASILAR ARTERY

The present report dealt with thirteen autopsied cases of basilar artery occlusion. The age of the patients ranged from fifty one to seventy six years with a mean age of fifty six years, and there were eleven males and two females. Basilar artery occlusion was found in one in every 160 autopsies. The average length of the clinical course of the disease was five months. Many patients had a history of hypertension, diabetes mellitus, and cerebrovascular attacks. The neurological signs and symptoms of basilar artery occlusion extremely varied and were complicated. In our series, occular bobbing, palatal myoclonus, Foville syndrome, and Millard‐Gubler syndrome are significant. Arteriosclerotic thrombosis is the most important etiologic factor. The site of occlusion was most frequently encountered in the lower third of the basilar artery. Areas of softening were prominent in the midbrain and the pons. In the cerebellum, softenings were present particularly in the areas supplied by the superior cerebellar artery. Infarcts in the thalamus and the temporo‐occipital lobes supplied by the posterior cerebral artery were observed very frequently. The distribution of softening was related to the site of occlusion of the basilar artery and the collateral circulation through the Willis ring.