We report a 63-year-old woman with sarcoidosis which involved the spinal cord, lower brainstem and extraocular muscules simultaneously. In this patient, uveitis developed in 1991 and the skin lesion ...in 1992. A biopsy of the skin lesion showed changes consistent with sarcoidosis. The ocular and dermal symptoms improved with oral corticosteroid. In October 1997, she noted the left blepharoptosis and numbness of the hands. The MRI showed diffuse swelling of the lower brainstem and the cervical and upper thoracic cord. These lesions showed high intensity signal on T2WI and low intensity signal on T1WI. T1WI with contrast enhancement revealed localized enhancement within the spinal lesion at the C4/5 level. The ocular MRI showed swelling of the left superior rectus muscle and upper levator palpebral muscle. The steroid pulse therapy and subsequent oral administration of prednisolone markedly improved the clinical symptoms. MRI after treatment showed marked improvement of both the spinal cord and ocular muscle lesions. To our knowledge, the simultaneous occurrence of myelopathy and symptomatic extraocular musculopathy in the condition has not been reported previously.
Background: Neuro-Sweet disease is a rare condition of central nervous involvement accompanied by cutaneous Sweet lesions. Neuropathological changes in neuro-Sweet disease are unknown. Objective: To ...describe post-mortem findings of the first case of neuro-Sweet disease. Results: A 44-year-old Japanese man developed recurrent episodes of cerebral and brainstem encephalitis with cutaneous Sweet lesions from the age of 34 years. His HLA typing was B54 and Cw1, and the symptoms and MRI abnormalities markedly subsided following corticosteroid therapy. Histologically, there were multiple lesions of perivascular cuffing of small venules by macrophages without vasculitis in the thalamus, temporal lobe, basal ganglia, pons, leptomeninges or ventricular ependym. Conclusions: The core neuropathological findings were: perivascular cuffing around particularly small veins; absence of granulomatous or necrotic angitis; mainly macrophage infiltration; and the thalamus being most affected. In the present case, the diagnosis of neuro-Sweet disease was made by skin biopsy 5 years after the onset of the central neuron system symptoms. We should pay more attention to skin lesions in steroid responsive recurrent encephalitis in patients who are HLA-B54 or Cw1 positive.
Brains of 41 residents without neurodegenerative diseases in the high-incidence area of ALS/parkinsonism-dementia complex (ALS/PDC) of the Kii Peninsula of Japan were neuropathologically examined. ...Neurofibrillary tangles (NFTs) in the hippocampal area were present in 11 of the 41 cases, but the frequency of NFT-positive cases in each age group was similar to that of the normal Japanese population and far less than that of Guamanians without ALS/PDC.
The growing number of drugs used to treat various diseases and the growing number of invasive procedures used for diagnosis and therapy have generated many iatrogenic diseases. Elderly patients are ...more likely than the young to react adversely to drugs since the physiological functions of the organs, especially of the kidneys, decrease and pharmacokinetic characteristics altered. In addition, multiple disease states are common in the elderly, and multiple drugs are consequently prescribed. In the present study, adverse effects of so-called "cerebroactive drugs" and "cerebral vasodilators" are discussed. More than 30 kinds of these drugs are on the market in Japan and are widely prescribed for "chronic cerebrovascular diseases" and "dementia syndromes" in the elderly. In contrast, they are rarely used in Western Europe and not on the market in the United States. Among them, calcium hopantenate was the first of "cerebral activators" and was the most popular. In 1986, however, the first cases of toxic encephalopathy induced by calcium hopantenate were reported. It resembled Reye syndrome, showing coma, hepatic failure, lactic acidosis and hypoglycemia and was frequently fatal. More than 47 victims including 11 fatal cases have been reported since. Flunarizine, a cerebral vasodilator, produced high rates of parkinsonism and depression. Multicenter studies have revealed that these side effects occurred in 10-30% of the elderly patients who had taken it. These symptoms usually appeared several months after flunarizine was started. Some of the adverse effects of the drugs may be unpredictable and inevitable, but most of them can be prevented or reduced if physicians are more careful with their patients, and drugs and their adverse effects.2
We report the first case of neuropathologically verified parkinsonism‐dementia complex of the Kii peninsula, together with the patient's brother, who had amyotrophic lateral sclerosis. The propositus ...woman developed parkinsonism and dementia at 63 years of age and died at 70 without displaying clinical features of amyotrophic lateral sclerosis. The brain exhibited marked atrophy of the frontal and temporal lobes. Microscopically, there were many neurofibrillary tangles in the central nervous system, most markedly in the mesial temporal lobe and deep nuclei, as well as changes of amyotrophic lateral sclerosis but no senile plaques or Lewy bodies. Neurofibrillary tangles exhibited twisted tubule structures on electon microscopic examination, and an analysis of insoluble tau protein extracted from the fresh brain revealed a 60‐, 64‐, 68‐kD triplet. The tau gene exhibited no mutations. Her brother developed progressive bulbar palsy–type amyotrophic lateral sclerosis at 45 years of age and died at 49 without presenting with dementia or parkinsonism. Neuropathological examination revealed not only pathologic features of amyotrophic lateral sclerosis but also a moderate number of neurofibrillary tangles in the temporal cortex and deep nuclei. The siblings were neuropathologically similar despite their different clinical manifestations. These findings suggest that amyotrophic lateral sclerosis and parkinsonism‐dementia complex of this family may be phenotypic variants of a tauopathy caused by genetic abnormalities. Ann Neurol 2001;49:501–511
Myelopathy in chronic toluene intoxication is rare. We present obvious lesions of the spinal cord on MRI in a 30-year-old Japanese man with chronic toluene intoxication. He had abused toluene for ...more than 10 years, and developed visual impairment, horizontal nystagmus, pyramidal tract signs, postural tremor, Romberg's sign, and sensory disturbance below the level of Th 2 dermatome. Anti-HTLV-1 antibody titer and vitamin B12 level in the serum were within normal limits. Biochemical analysis showed no increase of very long chain fatty acids. Cerebrospinal fluid showed no abnormal findings. Auditory brainstem response showed delay of I-V interpeak latency. Somatosensory evoked potential with the median nerve stimulation showed delay of N13-N20 central conduction time, which was later followed by absence of N14-N20 components. On MRI in T2 weighted image, marked high intensity was demonstrated in the posterior limbs of the internal capsule, and in the posterior columns and lateral tracts from the cervical through the upper thoracic cord. Cerebral lesions probably reflect demyelination and axonal degeneration produced by chronic toluene abuse. Spinal cord lesions seem to be secondary to nerve fiber changes more proximal to the nerve cell bodies.
An autosomal recessive form of juvenile Parkinsonism (AR-JP) (MIM 600116) is a levodopa-responsive Parkinsonism whose pathological finding is a highly selective degeneration of dopaminergic neurons ...in the zona compacta of the substantia nigra. By linkage analysis of diallelic polymorphism of the Mn-superoxide dismutase gene (SOD2), we found a family with AR-JP showing perfect segregation of the disease with the SOD2 locus. By extending the linkage analysis to 13 families with AR-JP, we discovered strong evidence for the localization of the AR-JP gene at chromosome 6q25.2-27, including the SOD2 locus, with the maximal cumulative pairwise LOD scores of 7.26 and 7.71 at D6S305 (theta = .03) and D6S253 (theta = .02), respectively. Observation of obligate recombination events, as well as multipoint linkage analysis, placed the AR-JP gene in a 17-cM interval between D6S437 and D6S264. Delineation of the AR-JP gene will be an important step toward our understanding of the molecular mechanism underlying selective degeneration of the nigral neurons.
Lewy body-like hyaline inclusion (LI) in the neuronal soma and swollen cord-like processes is a characteristic feature in the anterior horn cells and neurons in thoracic nucleus (Clarke) of familial ...amyotrophic lateral sclerosis (ALS) with posterior column involvement. We have studied the LI in the case of two sisters with this disorders. Microscopically the LI consists of an eosinophilic "core" surrounded by a basophilic "halo". Ultrastructurally the core consists of granule-associated filaments, while the halo consists of normal-looking neurofilament. Immunocytochemistry with anti-ubiquitin antibody shows that these granule-associated filaments in the core are highly ubiquitinated, while the normal-looking neurofilaments in the halo are not recognized by anti-ubiquitin antibody. Our study proves that LI consists of an aggregation of ubiquitinated filaments among a neurofilamentous accumulation, possibly representing a form of neuronal cytoskeletal disorganization in familial ALS.
This chapter reports the clinical and neuropathological findings of eight cases of "diffuse Lewy body disease" verified by autopsy. The age at onset was between 60 and 82 years; the age at death was ...between 75 and 92 years. The initial symptoms were amnesia in three cases, orthostatic dizziness in three, visual hallucination in two, but parkinsonism in none. The cardinal clinical symptoms included dementia in all cases, hallucinatory-delusional state in six, akinesia and rigidity in five, and orthostatic hypotension in five. Antemortem diagnoses were senile dementia in five, and hallucinatory-delusional state, Parkinson's disease and Shy-Drager syndrome in one each. Despite the clinical symptoms differences from each other, neuropathological findings were alike. Abundant Lewy bodies were present in the neurons of the cerebral cortex as well as in the brainstem nuclei and diencephalon. Concomitant senile changes including senile plaques and Alzheimer's neurofibrillary tangles (NFTs) were also present in varying degree. Immunocytochemical study with anti-ubiquitin for Lewy body, anti-tau protein for NFT, and beta-protein of amyloid for senile plaque suggested that dementia of DLBD might have resulted not from a single pathology but from the complex of Lewy bodies, NFTs and senile plaques.
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