An autopsy case of dentatorubropallidoluysian atrophy showing marked atrophy of the brain stem

An autopsy case of a 66 year-old woman is reported. She developed personality change and psychotic symptoms at the age of 58. She began to show gait disturbance and forgetfullness at the age of 60. She was admitted to Okayama University Hospital at the age of 61, when she showed personality change, dementia, cerebellar sings and chorea like involuntary movement. The illness progressed slowly and she died of septicemia at the age of 66. At autopsy brain weighed 990 g. Macroscopically, the atrophy of the brain stem was severe, and the cerebellum was slightly atrophic. Microscopically, the globus pallidus was almost intact, but the degeneration involved dentate nuclei, their projections, red nucleus and the subthalamic nuclei, so this case was considered to be a case of pseudo-Huntington form of dentatorubropallidoluysian atrophy, proposed by Hirayama. The most striking feature of this case was marked atrophy of the brain stem and her intense familial history. Investigation of her familial history revealed that there were 18 affected cases in 5 successive generations. Their onset of the disease varied from the age of 10 to 60 years old. Cases of juvenile onset showed myoclonus and convulsion as the initial symptoms, and convulsion as the initial symptoms, and those of presenile onset showed dementia, cerebellar ataxia and chorea like involuntary movement. And in some of these cases it was proved by NMR-CT that their brain stem were small. We discussed the meaning of the atrophy of the brain stem in these cases and the difference of the symptoms between the cases of juvenile onset and the cases of presenile onset.     

An autopsy case of dentatorubropallidoluysian atrophy (DRPLA) clinically diagnosed as Huntington's chorea

An autopsy case of a 65-year-old female with dentatorubropallidoluysian atrophy (DRPLA) is reported. Her mother had gait disturbance and died at the age of 63. Her mother's brother developed psychotic symptoms. A daughter of her older sister was observed to have involuntary movement when she admitted to a mental hospital due to post-delivery psychotic state. Her younger brother has developed gait disturbance from about 56-year-old. Her older son has suffered from schizophrenia for long years. Since 58-year-old, she developed cerebellar ataxic gait and three years later, choreic involuntary movement developed in her extremities and face and progressively became prominent. Since 63-year-old, abnormal behavior brought about by the visual hallucination was occasionally observed. At the age of 63, she admitted to a mental hospital because of persistent persecutive delusion for her husband and was clinically diagnosed as Huntington's chorea for her remarkable choreic movement and psychotic state with dementia. Hypertension was also noticed. At the age of 65, she died of acute pneumonia. The duration of her illness was about 6 years. Histopathological findings of the CNS: the brain weighed 1,014 g. Brainstem and spinal cord were noticed to be relatively small in size. The cerebral cortex was well preserved. The cerebral white matter was diffusely demyelinated in the central semiovale where arteriosclerotic change of the small vessels was remarkable. Significant pathological changes consisted of marked symmetrical atrophy of the following two systems, i. e., dentatofugal pallidoluysian systems.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hereditary dentatorubropallidoluysian atrophy--clinical variants in a family and degeneration of cerebral white matter in a proband]

We describe a family with hereditary dentatorubropallidoluysian atrophy (DRPLA). 4 patients through 3 successive generations showed a wide clinical variety. The female proband with onset in the elderly developed choreiform involuntary movement, dementia, hyperreflexia and, at the progressive stage, mild ataxia. However she had never displayed epilepsy and myoclonus. The 2 sons showed dementia, choreoathetoid movement and ataxia. The grandson developed typical signs and symptoms of progressive myoclonus epilepsy. The brain CT in the proband showed severe cerebellar and brain stem atrophy, moderate cerebral cortical atrophy and diffuse low density lesions in the deep cerebral white matter. Her neuropathological examination revealed the atrophy and gliosis of cerebral and cerebellar white matter concomitant with both dentatorubral and pallidoluysian system degeneration. The present study indicates that hereditary DRPLA can include multiple clinical variants even in the same family and the degeneration of cerebral and cerebellar white matter besides dentatorubral and pallidoluysian system.     

Disproportionate atrophy of cerebral white matter in chronic alcoholics

Morphometric analysis of postmortem brains from chronic ethyl alcohol abusers and controls was performed to determine the regional distribution and extent of atrophy in the cerebral hemispheres of alcoholics. This study was performed by digitizing photographs of coronal slices of the brains to compute the cross-sectional area of the cerebrum, cerebral cortex, subcortical nuclei, cerebral white matter, and the ventricular system at five standardized levels. Although the alcoholics and controls had similar demographic features and mean brain weights, brains from the alcoholic group showed mild but consistent atrophy of the cerebral cortex (2.5% to 4.2% reductions in cross-sectional area at all five levels), moderate atrophy of cerebral white matter (6.1% to 17.5% reductions), and enlargement of the ventricular system (31.8% to 71.9% increases). There were no differences in the sizes of subcortical nuclei. The absolute increase in the size of the ventricles in the alcoholic group was roughly equal to the amount of tissue lost in cerebral white matter, thereby representing hydrocephalus ex vacuo. The disproportionate loss of cerebral white matter relative to cerebral cortex suggests that a major neurotoxic effect of chronic alcohol intoxication in the central nervous system is axonal degeneration.     

MELAS with diffuse degeneration of the cerebral white matter: Report of an autopsy case

Up to now diffuse white matter demyelination of the cerebrum has been reported in only a few cases of mitochondrial encephalopathy with lactic acidosis and stroke‐like episodes (MELAS). Here we document an autopsy case with this rare neuropathology. Most MELAS cases are diagnosed antemortem by A3243G transition of mitochondrial DNA. While cerebral damage including necrotic foci in the cerebral cortex are common findings in MELAS, prominent white matter involvement best characterizes this MELAS case. There were numerous necrotic foci, varying in size and chronological stage, in the cerebral white matter. In the areas of the white matter without necrotic foci, there was diffuse fibrillary gliosis with the loss of axons and oligodendrocytes. The gliosis was dominant in the deep white matter, sparing the U‐fiber. The cerebral cortex showed diffuse cortical atrophy with few scattered necrotic foci. Distribution of the cerebral lesions does not coincide with the territory of blood supply. The vascular wall presented only slight to mild hyalinosis. We assumed a common pathogenesis to the cortical lesions and the white matter change. The pathogenesis of the present diffuse cerebral lesions may not be just secondary to circulatory disturbance but partly due to metabolic abnormality.     

Severe cerebral atrophy in progressive supranuclear palsy: a case report

A 60-year-old woman with a history of hypertension and chronic headache initially presented with irritative personality change and mild but steadily progressive dementia and oral tendency, left-sided hemiplegia, intense nuchal stiffness, and swallowing difficulty in the later stage. She died of bronchopneumonia at the age of 76. The brain showed marked loss of nerve cells with gliosis in the cerebral cortex and fibrillary gliosis in the white matter in addition to the typical pathological findings of progressive supranuclear palsy (PSP): extensive subcortical neurofibrillary tangles (NFTs) and loss of nerve cells with gliosis accentuated in the globus pallidus, Luys body and substantia nigra. In many case reports on PSP, the cerebral cortex is described as normal or within normal limits [Jellinger 1971, Steele et al. 1964], and to our knowledge, there is no reported case of severe cortical atrophy as seen in this case. The differential diagnosis of this case is also discussed.     

A case of membranous lipodystrophy (Nasu) with diffuse cerebral white matter involvement and cerebellar atrophy on brain CT and MRI

A 37-year-old female was admitted to our hospital because of progressive dementia and gait disturbance. She was healthy until 34 years of age when she had difficulty in walking and memory disturbance with personality changes. At age 36, she developed urinary incontinence and dementia. The neurological examination demonstrated euphoric mental state, emotional incontinence, severe dementia, paraplegia, dysmetria, choreic movements in both arms and urinary incontinence. Diffuse hyperreflexia and bilateral Babinski signs were observed. Routine laboratory examination showed slightly increased erythrocyte sedimentation rate and alkaline phosphatase. Electroencephalogram revealed diffuse irregular slow waves. X-ray film of the ulnar bone revealed osteoporotic and cystic lesions. The biopsy of the left tibial bone showed a specific membranous cystic structure. Computerized tomography (CT) of the brain showed symmetric, diffuse low density areas in the cerebral white matter and severe atrophy of the cerebellum. T2-weighted magnetic resonance imaging (MRI) revealed diffuse high intensity areas in the cerebral white matter. The present case is characterized by diffuse changes in cerebral white matter and cerebellar atrophy, which have been never reported in Nasu-Hakola disease. The diffuse cerebral white matter changes shown by CT and MRI appear to indicate that this patient is the first case of leukodystrophy of sudanophilic type since the original case reported by Nasu et al.     

A severe case of dentatorubro-pallidoluysian atrophy (DRPLA) with microcephaly, very early onset of seizures, and cerebral white matter involvement

We report a severe case of Dentatorubro-pallidoluysian atrophy (DRPLA) presenting with microcephaly, developmental delay, severe epilepsy, and progressive mental deterioration with a very early onset of disease. The case is notable for the early detection of white matter changes by brain MRI. Neuroradiological findings from the case were compared to those of previously reported patients with disease onset before 10 years of age.     

Portal‐systemic shunt encephalopathy presenting with diffuse cerebral white matter lesion: An autopsy case

We report herein an autopsy case of portal‐systemic encephalopathy (PSE) presenting with diffuse tissue rarefaction in the cerebral deep white matter. Clinically, the patient showed recurrent episodes of unconsciousness, abnormal behavior and urinary incontinence, as well as flapping tremor. Cognitive impairment and peripheral neuropathy developed following recurrent episodes. Although conventional arterial portography revealed a small portal‐systemic collateral vessel of a left gastro‐renal venous shunt, abdominal CT and liver biopsy showed no evidence of liver cirrhosis and serum ammonia level showed a mild increase. T2‐weighted MRI demonstrated symmetrical signal hyperintensities in the deep white matter. Neuropathological findings showed Alzheimer type II astrocytes in the deep layers of the cerebral cortices and severe tissue rarefaction with no or slight reactive astrocytosis in the subcortical and deep white matter. These white matter changes have been reported infrequently in patients with PSE. The present case suggests that chronic PSE without liver cirrhosis may develop diffuse white matter lesions.     

Myopathy with cerebral white matter abnormality--a case report]

A 45-year-old man noticed mild numbness of the feet at the age of 40 years and difficulty in standing up from squatting position at 43 years. His birth and developmental milestones were normal and the family history was unremarkable. He was alert and intelligent with global IQ of 91. There was mild muscle weakness as well as atrophy in bilateral hips and thighs. The serum creatine kinase level was 542 U/l. On computed tomography, the hamstrings were preferentially involved. The biopsied specimens from the right quadriceps femoris and peroneal muscles showed myogenic changes with evidence of necrotic and regenerating process. Dystrophin, dystrophin-associated glycoproteins and merosin were normally expressed. From the clinical and pathologic findings, he was diagnosed as having myopathy. The electroencephalogram was normal but the P300 latency was prolonged. T2-weighted head magnetic resonance imaging showed diffuse high intensity in the cerebral white matter. Myopathy with cerebral white matter abnormality in adult patients has not yet been reported. Asymptomatic cerebral white matter abnormality should be considered in adult patients with myopathy.     

Intracranial vascular calcification with extensive white matter changes in an autopsy case of pseudopseudohypoparathyroidism

We herein report an autopsy case of a 69‐year‐old man with pseudopseudohypoparathyroidism. The patient suffered from mental retardation and spastic tetraparesis and had all the features of Albright's hereditary osteodystrophy with a normal response to parathyroid hormone in the Ellsworth–Howard test. Computed tomography demonstrated symmetrical massive brain calcification involving the bilateral basal ganglia, thalami, dentate nuclei and cerebral gray/white matter junctions, which was consistent with Fahr's syndrome. Magnetic resonance imaging revealed extensive white matter changes sparing the corpus callosum. Severe ossification of the posterior longitudinal ligament of the cervical spine was also demonstrated. A neuropathological examination revealed massive intracranial calcification within the walls of the blood vessels and capillaries with numerous calcium deposits. The calcium deposits aligned along the capillaries, and deposits in the vessel wall at the initial stage were confined to the border between the tunica media and adventitia. The vascular calcification in the basal ganglia continuously spread over the surrounding white matter into the cortex. The area of vascular calcification in the white matter was very well correlated with the area of the attenuated myelin staining. Axonal loss, myelin sheath loss and gliosis were observed in the white matter with severe vascular calcification. We should recognize the continuous area of vascular calcification and its correlation with extensive white matter changes as possible causes of neuropsychiatric symptoms in pseudopseudohypoparathyroidism with Fahr's syndrome.     

A case of adrenomyeloneuropathy with localized cerebral white matter degeneration

A male with an atypical adrenomyeloneuropathy is described, who developed spastic paraparesis at the age of 37. Because his gait deteriorated further and he had a bladder dysfunction, he was admitted to National Sanatorium Hyogo Central Hospital at the age of 51. A diagnosis of adrenomyeloneuropathy was supported by increased level of very long chain fatty acids in plasma. He became demented and suffered from grand mal seizures during the last one year of his life. CT scan showed symmetrical hypodense lesions in the centrum semiovale. He died of pneumonia and renal failure at the age of 53. Autopsy revealed symmetrical degeneration throughout the corticospinal tracts from cerebral white matter to lumbar spinal cord. Degeneration of the optic radiation, posterior half of the corpus callosum, thalamus, cerebellar white matter, and gracile tract in high cervical segments were also observed. In these area, there was a loss of myelin and axon with marked gliosis and foamy macrophages, as well as mild perivascular cuffing. In our case, symmetrical and well-defined lesion in cerebral white matter is atypical for adrenomyeloneuropathy, while destruction of the gracile tracts is not a feature of adrenoleukodystrophy. In addition, well-demarcated "pseudosystemic" type of fiber tract degeneration appears to be different from a feature of primary demyelination which has been considered to be an essential alteration of adrenoleukomyeloneuropathy-complex. We propose another hypothesis, therefore, that neurons are primarily altered, thereby leading to the degeneration of myelins in this disease.     

Pathological and biochemical studies on a case of Pick disease with severe white matter atrophy

We report on a male patient with Pick disease who had shown severe white matter atrophy and dilatation of the lateral ventricle in the frontal lobe from an early stage. Upon admission to our hospital 2 years after disease onset, the patient showed apathy, and MRI revealed severe atrophy of the cortex and white matter of the frontal lobe. He died at age 74, 11 years after disease onset. Autopsy revealed severe atrophy of the frontal and temporal lobes, severe loss of white matter in the frontal lobe, dilatation of the lateral ventricles, and cortical thinning. Histopathological examination showed severe loss of myelinated fibers in the frontal white matter and severe neuronal loss with gliosis in the frontal and temporal cortices. Many Pick bodies were seen. Our patient had a rare case of Pick disease predominantly affecting the frontal lobe with severe involvement of the white matter from an early stage. This case suggests that myelinated fibers in the white matter as well as cerebral neurons are primarily affected in Pick disease.     

A clinico-pathologico-biochemical study of four autopsy cases of dentatorubropallidoluysian atrophy: With special reference to choreic movement

We evaluated four autopsy cases of dentatorubropallidoluysian atrophy (DRPLA) which had been diagnosed clinically as Huntington's chorea based on choreic movements, mental symptoms, and family history. These cases showed cerebellar ataxia at an early stage and developed choreic movements including a ballistic element. Pathological examination after autopsy revealed findings of DRPLA in all cases, although each case appeared to be in a different stage. Comparison of the clinical signs with the pathological findings suggests that the cerebellar ataxia observed clinically may have been related to pathological changes in the dentate nucleus of the cerebellum, and choreic movements may have been related to the pallidoluysian system, in particular, the nucleus of Luys. Biochemical analysis using frozen brain tissue revealed a decrease in γ-aminobutyric acid (GABA) in the substantia nigra similar to that seen in Huntington's chorea in three cases. The findings of this study help to clarify the pathological processes that are responsible for the motor disturbances seen in patients with DRPLA.     

Panencephalopathic type of Creutzfeldt-Jakob disease: primary involvement of the cerebral white matter

Eight necropsy cases of a “panencephalopathic” type of Creutzfeldt-Jakob disease (CJD) in the Japanese are reported. The reasons why this type should be discussed separately from other types of CJD are that there is primary involvement of the cerebral white matter as well as the cerebral cortex, and that the white matter lesion of one Japanese human brain with CJD similar to the present group has been successfully transmitted to experimental animals.