Brainstem in Machado-Joseph disease: atrophy or small size?

Machado-Joseph disease (MJD), one of the most common types of hereditary spinocerebellar degeneration caused by abnormal expansion of the CAG repeat in the MJD1 gene, presents atrophy of the infratentorial structures neuropathologically and neuroradiologically. Although a significant positive correlation has been reported between infratentorial atrophy and the number of expanded CAG repeat units, the exact changing course of brainstem size in the individual case remains to be resolved. We investigated seven cases of genetically confirmed MJD longitudinally by magnetic resonance imaging with observation periods of 4.5-10.6 years. Measurement of the midsagittal areas of infratentorial structures disclosed progressive atrophy of the pontine base and cerebellum, which correlated significantly with age, whilst midbrain and pontine tegmentum showed atrophy with no significant progression, suggesting it was better identified as 'small size' and might have mostly been completed before the initial symptoms. Such differences between regions in atrophy progression must be caused by a difference in the neuropathological course.

Ataxic vs painful form of paraneoplastic neuropathy.

OBJECTIVE: To characterize the clinicopathologic features of ataxic and painful forms of paraneoplastic neuropathy. METHODS: Clinical, electrophysiologic, and histopathologic findings were assessed in 17 patients with paraneoplastic neuropathy. RESULTS: Clinical features can be categorized into two groups: one group (13 patients) with predominantly deep sensory disturbance and a second group (4 patients) with predominantly superficial sensory disturbance. The former group showed severe sensory ataxia and predominantly large myelinated fiber loss in the sural nerve. The latter group showed marked pain, in particular, severe mechanical hyperalgesia, and predominantly small myelinated and unmyelinated fiber loss. Nerve conduction assessment indicated an axonal neuropathy pattern in both groups, while sensory action potentials were more markedly diminished in the sensory ataxic form. Anti-Hu antibodies were detected in half of the patients in both groups. Treatment for cancer was effective to improve or stabilize neuropathic symptoms in some cases from both groups. Immunotherapy was effective only for a short time. CONCLUSIONS: Paraneoplastic neuropathy can be characterized into two groups by the presence of sensory ataxia or severe spontaneous pain and severe mechanical hyperalgesia. Preferential small myelinated and unmyelinated fiber loss correlated to the cases of severe pain.

Intramedullary hemorrhage caused by arteriovenous malformation: a case of mixed lateral and medial medullary syndrome.

A 48-year-old man with no known risk factor for cerebrovascular disease, other than cigarette smoking, experienced the sudden onset of a mixed lateral and medial medullary syndrome. Computed tomography scan failed to show any definite abnormality. Magnetic resonance imaging scans revealed hemorrhage restricted to the left dorsolateral medulla. Angiography showed abnormal arteries originating from the left vertebral artery with small niduses located on the surface of the medulla and contralateral cerebellum. Small brain-stem hemorrhages are a contraindication to thrombolytic or anticoagulant therapy, and therefore must be recognized in the acute stage.

Dialysis-related spinal canal stenosis: a clinicopathological study on amyloid deposition and its AGE modification.

Three cases operated for spinal canal stenosis induced by dialysis-related amyloidosis (DRA) were investigated clinicopathologically. Cases were all-male, and had undergone hemodialysis around 20 years. In two cases, cervical plain X-rays showed only minor spondylotic changes. However, magnetic resonance imaging (MRI), myelography, and computed tomography (CT) showed extradural thickness with compression on the cervical spinal cord and cauda equina. In one case cervical X-rays showed typical destructive spondyloarthropathy (DSA), and MRI showed compression myelopathy. Surgical treatment on both cervical and lumbar spine in two cases and on cervical spine only in one case successfully reduced the symptoms. Extradural thickened tissue and ligament flavum obtained during surgery were studied histopathologically and immunostained by using anti-CD68, anti-beta2-microglobulin (beta2m), and anti-advanced glycation end product (AGE) antibody. Congo red stain showed diffuse or nodular amyloid deposition, and immunostaining with anti-beta2m and anti-AGE antibodies also demonstrated the same distribution pattern. Thus, beta2m-positive amyloid tissue in the extradural thickness (extradural amyloid deposition) was immunohistochemically demonstrated to be modified with AGE. Inflammatory reaction with histiocytic and giant cell infiltration was also shown around the amyloid tissues. There were CD68-positive cells, and some cells were positive for AGE and beta2m. These findings suggest that beta2m accumulation and inflammatory reaction finally promote destruction of connective tissues. MRI, CT and/or myelography are necessary for diagnosing spinal canal stenosis accompanied by DRA. In conclusion, we propose a more comprehensive concept of dialysis-related spinal canal stenosis, which includes both DSA and myeloradiculopathy induced by extradural thickness.

[Clinical study of spinal dural arteriovenous fistula-with special reference to neurological symptoms and magnetic resonance imaging].

We have evaluated the backgrounds, neurological symptoms, signs, and magnetic resonance images (MRI) in six cases of spinal dural arteriovenous fistula. The subjects were 2 males and 4 females, and the mean age was 67.2 years old. The cardinal subjective symptoms were progressive motor weakness of lower extremities (2 cases), paroxyomal weakness of lower extremities (3 cases), sensory disturbance of polyneuritic type (2 cases), and intermittent claudication (1 case). Administration of beverages and drugs, which might include vasodilators and taking baths, worsened the symptoms and signs in 3 cases and 2 cases respectively. Concerning to MRI findings, high signal intensities or swellings were observed at mid-thoracic area to upper conus of the spinal cord in all cases. These changes, which would be induced by edema caused by high venous pressure, were especially prominent in the central area of the cords. By these mechanisms, sensory disturbance like polyneuritic type caused by the disturbance in deep areas of posterior columns might more prominent than the disorder of spinothalamic tracts placed in superficial areas of cord in the early stage of the disease. These abnormal intensities of MRI were higher than the level of clinical symptoms and signs. The difference was about 6.5 segments. For this reason, the upper border of the spinal cord lesions could not be identified by the neurological symptoms. Although the clinical features and MRI findings are relatively characteristic, flow void signs by high resonance MRI and abnormal blood vessels by spinal angiography will be necessary to diagnose this disease confidently.

[A case of basilar artery occlusion successfully treated with tissue plasminogen activator].

This case concerns a stroke in the basilar artery territory that was successfully treated with a tissue plasminogen activator (t-PA). A 44-year-old man suddenly lost consciousness. It took fifty minutes to arrive to our hospital after the onset. On admission, his consciousness was in a coma state. A head CT revealed normal findings but a cerebral angiography showed complete occlusion in the basilar artery. We gave 240,000 units t-PA intravenously for 60 minutes. The intravenous t-PA dramatically improved his state of consciousness. After treatment, the brain CT scan showed low-density areas in the left occipital area and right pons. The cerebral angiography showed arterial sclerosis in the basilar artery. There was no parenchymal hemorrhage or hemorrhagic infarction in the patient. The hitherto reports showed the intravenous infusion of t-PA may be particular value in patients with thromboembolic occlusion in the middle cerebral artery. In contrast, our results support its efficacy in strokes in the basilar artery territory.

Reversible limbic encephalitis caused by ovarian teratoma.

A 19-year-old woman developed memory loss followed by psychosis, coma, convulsion, and central hypoventilation requiring mechanical ventilation. MRI of the brain showed minimal changes, and SPECT imaging revealed a small region of increased uptake in the cortex. Intravenous acyclovir and high-dose corticosteroids were administered without any effect. An extensive work-up revealed an elevated serum alpha-fetoprotein (AFP) concentration and the presence of an ovarian tumor. Following resection of the tumor, an immature teratoma by pathology, the patient had significant recovery of her cognitive function with some psychotic sequela. Serum anti-neuronal antibody (anti-Hu) was negative both by immunohistochemistry and by Western blot analysis. A rare combination of paraneoplastic limbic encephalitis and brainstem encephalitis was the suspected diagnosis. Because the tumor contained a neuronal component, we propose an immunologic cross-reaction as the pathomechanism, but the lack of a specific antibody may suggest cell-mediated rather than globulin-mediated immunity.

[Automatic movements of extremities induced in primary massive brain lesion with apneic coma].

In three cases of primary massive brain lesion with apneic coma, various automatic movements of the extremities were elicited by physical or sensory stimulation. In each case, these movements appeared after a period of cessation of spontaneous respiration followed by flaccid tetraplegia. Brainstem reflexes were absent throughout in all cases. The movements were induced mainly by ventroflexion of the neck, and each case showed movements as described below: in the first case, the patient flexed her elbows and raised both arms slowly, a typical Lazarus sign; in the second case, the patient raised both arms and showed myoclonic movements; and the third case showed abduction of both legs and extension in the upper extremities. Pathology in the first case showed ischemic changes in the entire brain and brainstem. Although ischemic change was also found in the anterior horn cells and white matter of the spinal cord of C1-C4 and of T4 and below, the spinal cord of C5-T3 was relatively well-preserved. These movements appear to have essentially originated in spinal neurons; however, it is assumed that they must have recovered from spinal shock which occurred due to upper level transection. These movements were induced by ventroflexion of the neck, so mechanical extension of the spinal roots, mechanical compression of the spinal cord, and various modalities of the sensation afferent might have some relation to these movements. As tonic neck reflex might also be a cause of these, movements, association with the lower medulla could not be ruled out completely. These movements appeared nearing or after brain death. Although in each case of brain death the spinal cord may have been affected by specific conditions, such as impaired circulation of whole central nervous sysytem, it might have been transversed at upper level, which then causes spinal automatism. These movements might appear even in the state of brainstem death. In each case, the distribution and severity of hypoxic changes in the spinal cord may have resulted in variations in the type and characteristics of these movements.

Amyloid beta 2-microglobulin is modified with imidazolone, a novel advanced glycation end product, in dialysis-related amyloidosis.

We have recently demonstrated by immunohistochemistry that amyloid beta 2-microglobulin (beta 2m) is modified with advanced glycation end products (AGEs) in dialysis-related amyloidosis (DRA). To further investigate the role of the Maillard reaction in the pathogenesis of DRA, we produced a monoclonal antibody to imidazolone, a novel AGE, and a reaction product of arginine and 3-deoxyglucosone (3-DG) which was accumulated in uremic serum. Then we determined the localization of imidazolone in the amyloid tissues by immunohistochemistry using the antibody. The connective tissues in carpal tunnel and ligamentum flavum were obtained from six patients with carpal tunnel syndrome and two patients with destructive spondyloarthropathy. Imidazolone was localized to all the beta 2m-positive amyloid deposits in these patients. Western blotting using the antibody demonstrated that beta 2m extracted from the synovium amyloid of hemodialysis patients was modified with imidazolone. Further, beta 2m isolated from the blood ultrafiltrate of hemodialyzed patients was also modified with imidazolone. In vitro incubation of beta 2m with 3-DG produced imidazolone-modified beta 2m. In conclusion, amyloid tissue beta2m is modified with imidazolone in patients with DRA. 3-DG accumulating in uremic serum may be involved in the modification of beta 2m with imidazolone.

[Expiration-like movement and spino-bulbo-spinal reflex in a patient with apneic coma caused by anoxic encephalopathy].

A 72-year-old female patient, hospitalized for parkinsonism, suffered cardiopulmonary arrest without any certain causes. The patient was successfully resuscitated and her life was sustained by artificial ventilator for 100 days. All brainstem reflexes were absent, and flat electroencephalogram and no response of brainstem auditory evoked potentials were confirmed twice with an interval of over 6 hours. Flexion of the arm induced reflex rectus abdominis muscle contraction, resembling expiratory movement. Muscle stretch reflexes on rectus abdominis were hyperactive. The expiration-like movement appeared in an apnea test seven minutes after a cessation of artificial ventilation. Electrical stimuli on femoral nerve induced complex action potentials with a 70.2 +/- 6.9 msec latency and 300 msec duration in rectus abdominis muscle, which were similar to the spino-bulbo-spinal reflex. Single photon emission tomography showed only slight cerebral cortical blood flow. The expiration-like movements observed in this case suggest a relationship not only with the spinal cord reflex but also with polysynaptic reflexes to reticular formation in the medulla oblongata.

[Clinical and pathological study of myelopathy accompanied with cervical spinal canal stenosis--with special reference to complication of mental retardation or cerebral palsy].

We studied 3 cases with myelopathy caused by cervical spinal canal stenosis (developmental), who had been suffering from walking difficulty followed by tetraplegia, clinically and pathologically. In all 3 cases, mental retardation and/or cerebral palsy was diagnosed. We hypothesized that the brain damage in the developmental stage might also cause developmental disturbance in the cervical spine. In all cases, pathological investigation showed decreased antero-posterior diameter and degeneration in the gray matter and in the lateral and posterior column in the involved cervical spinal cord. The findings, such as relative preservation of the anterior column and cyst formation in the gray matter, were thought to be in common with cervical spondylotic myelopathy or ossification of the occipital longitudinal ligament (OPLL) which had been reported before. In one case we found aberrant peripheral nerve bundles and peripheral type remyelination in the transverse spinal cord lesion. Compared to the pathological change in the OPLL, our cases showed more severe degenerative change in the spinal segments with a relatively preserved antero-posterior diameter of the spinal cord, which supports the theory that the dynamic factor plays a more important role than the static compression factor. We concluded that the aging process and/or dystonic neck movement added spondylotic change to the narrow canal, and excess movement of the neck and/or falls caused dynamic injury to the spinal cord and secondary circulatory disturbance further worsened spinal lesions. When elderly patients with cerebral palsy develop motor symptoms, we should consider cervical spinal stenosis as a possible cause.

[A case of an aged patient suspected of craniopharyngioma with a chief symptom of eunuchoidism accompanied with panhypopituitarism].

A 78-year-old man with developmental disturbance of the genital organs and eunuchoidism was reported. He also had a high pitched voice, thickness of the lower lip and kyphosis of the thorax. He seemed to be fretful, but his intelligence was normal. Neurological tests revealed bilateral hemianopsia and decreased tendon reflexes. A plain skull radiograph clearly showed an egg shaped calcified mass extending upward from the sella turcica which resembled a ballooning shape. Brain CTs showed a high density round mass which expanded the sella turcica and raised the floor of the third ventricle. The inner part of the tumor showed irregular high density. T1-weighted MR imaging revealed an iso signal intensity, and T2 showed low signal intensity in the mass. These findings strongly supported the diagnosis of calcificated craniopharyngioma. Endocrinological study showed panhypopituitarism caused by the tumor compressing the pituitary gland and the hypothalamus. The main reasons why there were no apparent symptoms of hypopituitarism were because the receptors were up-regulated and secondarily because the thyroid and the adrenal cortical functions decreased while struggling to maintain balance with each other. There was also a possibility that these symptoms might have been masked by normal aging. Benign monoclonal hypergammopathy was also indicated, although we could not find a clear correlation between this finding and others.

[Intellectual ability and activity of daily living of centenarians in institutions for the elderly].

The purpose of this study was to assess the intellectual ability and activity of daily living (ADL) of 12 centenarians in institutions for the elderly and to compare them with individuals in the 62-99 age group. At the time of our study, 66.7% of the centenarians were severely demented, three quarters of them suffering from Alzheimer's type dementia and the other one quarter the mixed type. There were qualitative differences between non-demented centenarians and the demented elderly in general, particularly in regard to understanding of surrounding objects and the presence or absence of mental symptoms indicating intellectual deterioration. A total of 50% of the centenarians were bedridden, but 41.7% of them could eat without assistance. Intellectual ability and ADL directly decreased with aging. We think centenarians do not present a special case and our clinical observations suggest a continuous process of aging. Five of the centenarians recently died and were autopsied. The agreement rate between clinical diagnoses and pathological findings with respect to dementia was 80%.

[Five year follow-up study on dementia in institutions for the elderly].

The purpose of this study was to clarify the prognosis of senile dementia based on a 5-year follow-up study in institutions for the elderly. The subjects consisted of 747 cases over 60 years of age. Of these 316 cases showed clinical dementia but 431 cases had no intellectual disturbance in July, 1987. The mortality rate (56.3%) of the demented group was significantly higher than that (31.8%) of the non-demented group. The mortality rate of patients increased with aging. However, the mortality rate of the demented group did not correlate with the severity of dementia. An autopsy study revealed that the direct causes of death in 51.1% of demented patients were pneumonia and cardiovascular diseases. Among the demented patients followed up for 5 years, 22.5% showed severe worsening of dementia, 25.8% showed slight or moderate degree of worsening and 51.7% showed no change. Factors causing exacerbation of dementia included cerebrovascular disease and bone fracture.

[A case of brain dead patient with a spinal pathology of preserved marginal white matter and pencil-shaped softening--a theory for pathogenesis of pencil-shaped softening].

We reported a case of brain death which had been caused by massive cerebral hemorrhage. The spinal pathology showed preserved marginal parts of spinal white matter in the segments of C7 to T5 and S1 to S3, and the other parts showed necrosis. We found pencil-shaped softening (PS)-like lesion in the segment C8 to T2, but the lesion was more preserved than the surrounding tissue. The intraspinal structure of C5 was distorted by the necrotic cerebellar tissue in the subarachnoid space of the segment and the posterior column area was decreased. The posterior column in C5 and PS showed the same severe pathology. Because the pia mater of the spinal cord is not so easily torn, and has some elasticity, swollen spinal necrotic tissue has no place to move but in a longitudinal direction; that circumstance may cause the PS. In this case the subarachnoid cerebellar tissue restricted the expansion of the spinal cord in C5, which might have helped cause PS. So we suggest that the subarachnoidal cerebellar tissue and changes of antero-posterior diameter in the spinal column, when the spine is flexed or extended, may contribute to the pathogenesis of PS. In this case the pathology of the PS was reversed as compared to the usual PS, because the PS was relatively preserved while the surrounding tissue was necrotic. There have been only a few reports which show preserved marginal white matter of the spinal cord.(ABSTRACT TRUNCATED AT 250 WORDS)

[Bedridden elderly and dementia].

The purpose of this study is to clarify possible correlations between dementia and long term bedridden elderly patients in our special nursing home and geriatric hospital. At the time of our study, 42.6% of all our patients were bedridden, and the ratio increased in those groups of advanced age. The percentage of bedridden female patients was higher than that of males. Most bedridden patients, suffered disorders of the nervous system particularly disorders caused by cerebrovascular disease. Among the bedridden patients, the incidence of dementia was 82.8%. In most these cases, the degree of dementia was severe. The types and respective percentages of dementia were as follows: Vascular type 45.1%, Alzheimer's type 23.2%, mixed type 19.5% and others 12.2%. We think that Alzheimer's type dementia may cause a patient to become bedridden. On the other hand, vascular type dementia may be promoted by a patient's being bedridden for a long time. Tube-fed patients comprised 20% of all bedridden patients and all of these patients showed dementia. We believe that a patient's getting out of bed and receiving rehabilitation as soon as possible is vital to the prevention of becoming permanently bedridden. In respect to the present study of bedridden dementia patients, we would like to further study tube feeding and terminal care.

Granulovacuolar degeneration in the hippocampal cortex of aging and demented patients--a quantitative study.

The occurrence and topographic analysis of granulovacuolar degeneration (GVD) in the hippocampal cortex of mentally normal controls (75 cases) and patients with Alzheimer's dementia (AD; 17 cases which included Alzheimer's disease and senile dementia of Alzheimer type), multi-infarct dementia (MID; 16 cases), Pick's disease (PD; 5 cases) and atypical dementia [5 cases; non-Alzheimer, non-Pick dementia with Fahr's syndrome (NANPDF)] were investigated. GVD was rarely found in control cases below the age of 60 years. In elderly normal brains, the statistically most representative ranking order of predilection for GVD (in decreasing severity) was: in the 60 s, CA1 > prosubiculum > CA2 (no GVD was found in the CA3 and CA4); in the 70 s, CA1 > prosubiculum > CA2 > CA3 > CA4; in the 80 s, CA1 > prosubiculum > CA2 > CA3 > CA4; in the 90 s, CA1 > prosubiculum > CA2 > CA3 > CA4. In the brains of demented patients, the rank order for GVD was: for AD, CA1 > CA2 > CA3 > prosubiculum > CA4; for MID, CA1 > prosubiculum > CA2 > CA3 > CA4; for PD, CA1 > CA2 > CA3 > prosubiculum > CA4; and for atypical dementia (NANPDF), CA1 > CA2 > prosubiculum > CA3 > CA4. The similarity of the predilection to ranking order was noted both in normal aged subjects and in MID as well as both in AD and in PD.(ABSTRACT TRUNCATED AT 250 WORDS)