Dementia in cerebral amyloid angiopathy: a clinicopathological study.

Dementia is in addition to cerebral haemorrhage major symptom of cerebral amyloid angiopathy (CAa). In order to explore the pathological basis for dementia in CAa-related conditions, we made a clinicopathological analysis of CAa, with special attention to dementia. Among 150 patients (mean age 78.6 years) with autopsy-proven intracranial haemorrhage in Tokyo Metropolitan Geriatric Medical Center, CAa with cerebral haemorrhage accounted for 8.0% (12 cases), associated with hypertension and metastatic brain tumour. Among 38 patients with lobar haemorrhage, CAa represented the second most common cause (21.1%) of intracranial haemorrhage after hypertension. A total of 20 patients with CAa (mean age 82.5 years) were studies clinically and pathologically. Hypertension was present in 50%. Thirteen had a history of stroke and others had either ill-defined or no strokes. The average number of strokes 2.9. Fifteen patients (75%) had dementia. Based on the clinicopathological grounds for dementia, CAa-related conditions could be divided into three subtypes: "haemorrhagic", "dementia-haemorrhagic" and "dementia" type. Haemorrhagic type (30%, 6 cases) showed multiple recurrent lobar haemorrhages caused by CAa. Hypertension was present in only 1 patient. The incidence of senile plaques and neurofibrillary tangles was generally correlated with age. Only 1 patient had dementia. The dementia-haemorrhagic type (40%, 8 patients) had recurrent strokes with cerebral haemorrhage after preceding dementia. There were two different neuropathological subsets: CAa with atypical senile dementia of Alzheimer type (SDAT) and CAa with diffuse leucoencephalopathy. Patients with CAa with atypical SDAT had multiple cerebral haemorrhages caused by CAa combined with atypical Alzheimer-type pathology. Patients with CAa with diffuse leucoencephalopathy had cerebral haemorrhages in combination with diffuse white matter damage like Binswanger's subcortical vascular encephalopathy (BSVE). The incidence of senile changes correlated with age. Patients with the dementia type (30%, 6 patients) showed progressive dementia with or without haemorrhage. All had hypertension. They had a combined condition of Alzheimer-type pathology with conspicuous CAa with BSVE. Dementia in CAa-related conditions may be responsible for multiple factors including not Alzheimer-type degeneration, but also diffuse leucoencephalopathy like Binswanger's disease. We also found an asymptomatic type, an ischaemic type, a vasculitis type and an hereditary type in this condition.

Lifetime data analysis of disease and aging by the Weibull probability distribution.

We applied the Weibull distribution to the life-table and age-patterns of diseases in Japan. The life-table follows a composite Weibull distribution composed of initial failure and two stage wear-out failure periods. The extension of lifespan during the past century is manifested as increases in the scale parameters in all three periods and the shape parameters in the wear-out periods with female predominancy. The shape parameters of diseases show time-independent sex-dependent specific values. When consistent changes are observed, such as increases in the shape parameters of tuberculosis and pneumonia, legitimate causes such as prevention and repair at the societal and medical level are present. Cancer and arteriosclerosis share a common range of shape parameters suggesting analogous underlying biological processes. An analysis of the epidemiology of human aging and disease by the Weibull distribution discloses intrinsic properties of man as a biological organization as well as a societal presence.

Does the variability of casual blood pressure contribute to progressive subcortical vascular encephalopathy of Binswanger's type?

Our hypothesis was that progressive subcortical vascular encephalopathy of Binswanger's type (PSVE) in the elderly can be induced by repeated hypotension or greater variability of blood pressure in hypertensives, regardless of antihypertensive therapy. We retrospectively studied PSVE blood pressure, and compared them with those in atherothrombotic cerebral infarction (ACI) or in hypertensive cerebral hemorrhage (HCH). During the last seven years prior to death, neither the annual variability nor the annual mean value of systolic or mean arterial blood pressures in PSVE was different from that in ACI or in HCH. The present study did not support our hypothesis.

[Intradural extramedullary tumor of lower spinal cord in a 89-year-old man with cervical spondylosis and lumbar spondylolisthesis].

A 89-year-old man was admitted because of slowly progressive gait disturbance during these several years. Neurological examination revealed paraparesis with bilateral sensory disturbance in the lower extremities, more severely on the left side. Vibration sense was almost completely disturbed under the level of bilateral crista iliaca. Deep tendon reflexes decreased in the lower extremities. No urinary incontinence was observed. The narrow spinal canal and cervical spondylosis were seen at the C 5-6 level, showing the anterior-posterior distance of 10 mm. Computed tomography of the lumbar spine showed spondylolisthesis between the level 4 and 5. CSF showed high protein concentration (300 mg/dl), whereas normal cell counts. These findings suggested the following two possibilities; cervical myelopathy associated with the disturbance of the cauda equina due to lumbar spondylolisthesis, or the disturbance at the lower thoracic or upper lumbar level of spinal cord. The spinal MRI revealed the irregular mass lesion in the lower spinal cord at the level of spine Th 11-12 on T2 weighted images, with enhancement by Gd-DTPA on T1 weighted images. These MRI findings suggested the intradural extramedullary tumor, such as benign neurinoma or meningioma. No clear cut lesions were found at the cervical spinal cord or at the cauda equina. MRI was useful for the diagnosis of sites and lesions of spinal cord in the present case, whose neurological signs and symptoms could be explained by the coexistent cervical spondylosis and lumbar spondylolisthesis.

Corticofugal projections to the motor nuclei of the brainstem and spinal cord in humans.

We studied corticofugal projections to the motoneurons with Nauta-Gygax's technique in a patient with cerebral infarction of both hemispheres. Motoneurons in the brainstem motor nuclei and spinal anterior horns seem to receive direct cortical projections, except for the oculomotor and abducens nuclei and Onuf's nucleus in the sacral cord.

Nonvalvular atrial fibrillation as a cause of fatal massive cerebral infarction in the elderly.

By studying 3,408 consecutive autopsied elderly patients, we found that two thirds of the 132 massive cerebral infarctions (86) were embolic, of cardiac origin. Embolic infarction associated with nonvalvular atrial fibrillation was seen in 48 cases (36%), half due to the first stroke. Embolic infarction associated with heart disease other than nonvalvular atrial fibrillation was seen in 23 cases (17%), and that from nonbacterial thrombotic endocarditis was seen in 15 cases (11%). Thrombotic infarction or infarction of nonembolic cardiac origin was found in only 39 cases (30%). Of 56 patients with fatal massive cerebral infarction who died less than or equal to 2 weeks after their stroke, 25 (45%) had embolic strokes associated with nonvalvular atrial fibrillation. Our study shows that nonvalvular atrial fibrillation is a very important cause of fatal massive cerebral infarction in the elderly.

Amyotrophic lateral sclerosis: electrophoretic study of amorphous material of skin.

We studied skin from patients with amyotrophic lateral sclerosis (ALS) and controls by electron microscopy, and analyzed it by sodium dodecyl sulfate-poly-acrylamide gel electrophoresis (SDS-PAGE) and two-dimensional gel electrophoresis. On electron microscopy, the most conspicuous finding in ALS was a markedly increased amount of amorphous material in the ground substance, which became more marked in proportion to the duration of ALS. SDS-PAGE analysis showed that in ALS patients the staining intensity of a low-molecular weight band (approx. 12.5 kDa, band "g") became more marked with the duration of ALS. Two-dimensional gel electrophoresis revealed that band "g" consisted of a single component with a basic isoelectric point. It is thought that the substance corresponding to band "g" is a major constituent of the amorphous material.

[Two cases of post-poliomyelitis muscular atrophy].

We report two males with progressive post-poliomyelitis muscular atrophy (PPMA) who developed slowly progressive weakness and atrophy in the previously unaffected muscles 50 years after acute poliomyelitis. Case 1 is a 61-year-old male who had suffered from poliomyelitis at the age of 3 years. After recovery from acute symptoms, paralysis remained in the right face, left upper extremity and right lower extremity. Paralysis had remained unchanged until the age of 55 years, when he felt increased fatigue and progressive muscle weakness of all extremities. Neurological examination revealed muscle atrophy of the left upper and right lower extremities, and muscle hypertrophy of the left lower extremity. Deep tendon reflexes were decreased or absent. Babinski sign was negative. Reduction of his physical level and administration of anticholinesterase agents improved his feeling of fatigue. Case 2 is a 66-year-old male who suffered from poliomyelitis in his infancy, and paralysis remained in the left hand and right lower extremity. At the age of 50 years, he felt fatigue, muscle weakness of the previously unaffected legs and joint pain. Neurological examination revealed proximal muscle atrophy and weakness of lower extremities. Deep tendon reflexes were decreased and Babinski sign was negative. Needle electromyography of both cases showed typical neurogenic pattern or high amplitude and polyphasic long duration MMUs. Muscle biopsy of them from quadriceps femoris showed variability in fiber size, moderate increase of internal nuclei, fiber splitting, type grouping, grouped atrophy and scattered small angulated fibers, indicating chronic denervation and reinnervation. The clinical features and laboratory findings of the present two cases are consistent with those of PPMA.(ABSTRACT TRUNCATED AT 250 WORDS)

Differential diagnosis between amyotrophic lateral sclerosis and spinal muscular atrophy by skin involvement.

Amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA) might be clinical variants caused by the same etiology, or different diseases altogether. We studied the skin in 12 patients with ALS and 7 patients with SMA. The "delayed return phenomenon" (DRP) was observed only in ALS patients. On light microscopy, collagen bundles in ALS dermis were seen to be less numerous, thinner and more loosely woven than in SMA. Electron microscopy revealed that in ALS (1) collagen fibers became thinner as the disease lasted longer, and (2) collagen bundles were separated by much more amorphous material. These findings were not observed in SMA. Our observations show that ALS may be distinguished from SMA by the presence of abnormal dermal collagen. Therefore, we suggest that comparable clinical and pathological skin analysis is the most important diagnostic tool in differentiating between ALS and SMA.

[A semiquantitative study on Alzheimer neurofibrillary tangles demonstrated immunohistochemically with anti-tau antibodies, in the brains of non-demented and demented old people].

Submitted for the study were 116 autopsy brains, from 65 non-demented people, 24 patients with dementia of Alzheimer type (DAT) and 27 patients with vascular dementia, aged between 50 s and 100 s. Formalin-fixed, paraffin-embedded coronal sections of the brains at the level of the lateral geniculate body were immunohistochemically stained with the avidin-biotin-peroxidase complex procedure, using the anti-bodies to tau protein purified from human brains (anti-tau) as the primary antibodies. Alzheimer neurofibrillary tangles (NFTs) which were specifically and selectively stained by anti-tau were semiquantitatively counted in the areas of the hippocampus, parahippocampal gyrus and lateral occipitotemporal gyrus. The results were as follows: 1) In non-demented subjects, NFTs in the hippocampus and parahippocampal gyrus were scanty in the 50 s: they increased markedly after 60 years until 90 as the patients' age increased; they tended to decrease over 90 years. In contrast, NFTs in the lateral occipitotemporal gyrus remained none or scanty, always less than 10/mm2 field, throughout the ages between 50 s and 100 s. 2) In DAT cases, NFTs in the hippocampus and parahippocampal gyrus were numerous in all cases at any ages. NFTs in the lateral occipitotemporal gyrus were also many, and always more than 10/mm2 in all cases except a few ones over 80 years of age. The numbers of NFTs of the three areas were significantly higher in DAT cases than in non-demented subjects. 3) In most cases of vascular dementia, the density and distribution pattern of NFTs were essentially similar to those of non-demented subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

[Progressive supranuclear palsy accompanied with progressive subcortical vascular encephalopathy of Binswanger type--a case report].

We report the clinical and neuropathological findings in an autopsy case of progressive dementia, Parkinsonism, pseudobulbar palsy and supranuclear ophthalmoplegia. Since 70 years old, this hypertensive patient developed forgetfulness, unsteady gait and festination. These symptoms rapidly worsened and he was admitted in October 1983, at age 71. He had severe dementia and showed stiff face. Voluntary vertical movement of the eyes was severely disturbed, but reflex vertical movement by the doll's head eye maneuver was not affected. Muscle tone in the limbs increased slightly, and deep tendon reflexes were hyperactive in jaw and the upper extremities. Babinski sign was negative bilaterally. Sensation and coordination remained normal. Although he was not paretic or ataxic, his movements were very slow. He could not stand by himself and easily fell backward. These clinical features resembled those of progressive supranuclear palsy except for severe dementia and rapid progression. Brain CT scan revealed marked dilatation of the lateral ventricles, prominent periventicular lucency and atrophy of brainstem and cerebral cortex. Treatment with levodopa slightly improved his movement, but difficulty in swallowing worsened increasingly. He died of hypoglycemic coma and aspiration pneumonia in September 1984, about two years after the initial symptoms. General autopsy showed severe pneumonia and atrophy of the liver. The brain weighed 1,210g. Atherosclerotic change in the cerebral arteries were mild. Coronal sections of the cerebral hemispheres revealed diffuse ischemic change and multiple small infarctions in the bilateral cerebral white matter. Cortical atrophy was observed in the cerebral hemispheres. The basal ganglia, thalamus, and pons showed status lacunaris. Atrophy of midbrain and depigmentation of the substantia nigra were observed macroscopically.

[Multi-infarct dementia clinically simulating dementia of Alzheimer type. A comparison with angular gyrus syndrome].

A 74-year-old right-handed man with multiple cerebral infarction who presented with dementia simulating dementia of Alzheimer type (DAT) is reported. He had been well until April 20, 1987 when he developed transient right hand palsy lasting overnight. Eleven days later, he became confused, disorientated, and amnestic. He was admitted to this hospital on June 8. Physical examination revealed hypertension (170/90mmHg). On neurological examination, his consciousness was clear but he was demented. He showed disorientation, amnesia, and urinary incontinence. His most prominent symptom was disturbance of speech, including fluent aphasia and alexia with agraphia. Additionally, he showed ideomotor apraxia, construction apraxia, right-left agnosia, finger agnosia, and acalculia. On July 9, he had a transient attack of right hemiplegia with confusion. The brain CT scan performed on admission was unremarkable except for cavum septi pellucidum and a small low density area in the right basal ganglia. However, single photon emission computed tomography (SPECT) by 123I-labeled N-isopropyl-p-iodoamphetamine disclosed hypoperfusion of the cerebral blood flow in the border zones of the temporoparietal and frontal lobes on the left. A follow-up brain CT scan taken one month later demonstrated low density in the new areas corresponding to hypoperfusion shown by SPECT. Although the clinical features of the present case resembled those of DAT, dementia in this case was regarded as the result of multiple cerebral infarction since it occurred acutely with mild motor deficits, and brain CT scans and SPECT showed lesions indicating focal cerebral ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Anticoagulant therapy in recurrent cerebral embolism: a retrospective study in non-valvular atrial fibrillation.

For the prevention of recurrent embolic stroke, 23 elderly patients with non-valvular atrial fibrillation (NVAF) were treated with oral anticoagulants (warfarin) during a mean period of 3.8 years. Only one patient suffered recurrent embolism, and another had acute myocardial infarction. There was no cerebral haemorrhage during the treatment. In an untreated control group (from an autopsy series), recurrent embolic strokes occurred in 18 of 70 NVAF patients (26%) during a mean period of 1.3 years. Long-term anticoagulant therapy appears to be effective in the prevention of recurrent embolic stroke in elderly patients with NVAF.

"Delayed return phenomenon" in amyotrophic lateral sclerosis.

When the skin of patients with amyotrophic lateral sclerosis (ALS) is stretched, it returns only sluggishly to its original position. We term this property of skin the "delayed return phenomenon" (DRP). The reticular dermis was examined in patients with ALS and controls with or without DRP, respectively. On light microscopy, ALS patients with DRP showed collagen bundles which were reduced in amount, more loosely woven, and separated by wide space, while controls with DRP revealed decrease of dermal thickness, without abnormalities of collagen bundles. Electron microscopy disclosed a markedly large amount of amorphous material positive for ruthenium red, separating collagen fibrils and bundles in ALS patients with DRP. These observations suggest that DRP in ALS is a specific feature not previously reported in cases of ALS.

The Marfan syndrome with an XYY chromosome pattern.

A 36-year-old man who was diagnosed to have the Marfan syndrome with an XYY chromosome pattern is reported. He was tall with long limbs and arachnodactylia, and had severe aortic regurgitation (AR). The chromosome pattern studied in specimens of blood and bone marrow revealed an XYY chromosome pattern. The relationship between the Marfan syndrome and an XYY chromosome pattern is discussed.