An autopsy case of Degos' disease with ascending thoracic myelopathy]

Degos' disease is a rare multisystem vasculopathy of unknown etiology. We report a 44-year-old man who presented himself with gait and sensory disturbances mainly due to thoracic transverse myelopathy four years after the appearance of many characteristic umbilicated papules over the trunk and extremities. He did not complain of abdominal pain or discomfort. Laboratory, electrophysiological and imaging studies did not show any characteristic change, except for the increase of protein contents and cell counts in the cerebrospinal fluid. We tried methylprednisolone pulse-dose therapy (1,000 mg/day x 3 days) five times, but this patient's neurological condition worsened stepwise after it, although the appearance of new skin lesion was suppressed. Intravenous infusion of ozagrel sodium and cyclophosphamide (1,000 mg/day) were also ineffective, and this patient died of respiratory failure after showing oculomotor paresis and comatose state. Necropsy revealed Degos' disease-specific vasculopathy in the central nervous system and the gastrointestinal tract, where occlusions of small-sized arteries and veins due to the intimal thickening were evident. The tissue necrosis was macroscopically remarkable in the brainstem and the thoracic spinal cord. The efficacy of steroid therapy for this disease should be investigated more carefully.     

Motor neuron disease with predominantly upper extremity involvement: a clinicopathological study

We report two autopsy cases of motor neuron disease (MND) patients with an unusual type of muscular atrophy predominantly affecting the shoulder girdle and the upper extremities with proximal dominance. Both patients are considered to be clinically categorized into the El Escorial suspected form of amyotrophic lateral sclerosis (ALS). At autopsy, they showed marked loss of spinal anterior horn cells accompanied by astrogliosis positively immunostained with anti-glial fibrillary acidic protein antibody at the cervical level. At the lumbosacral level, anterior horn neurons were relatively well preserved and Bunina bodies, ubiquitin-positive skein-like inclusions and Lewy body-like inclusions were observed in the remaining neurons. In one patient, brain stem motor neurons (nerves V, VII, XII) and motor cortex, including Betz cells, were also affected and the corticospinal tracts were degenerated at the level of the thoracic and lumbar spinal cord. Pathological findings of this patient are consistent with those of ALS. In the other patient, the motor cortex, brain stem motor nuclei and the corticospinal tracts were well preserved, which is pathologically compatible with progressive spinal muscular atrophy. These patients with such a peculiar pattern of progressive muscular atrophy should be placed in a subgroup of ALS. Received: 14 January 1999 / Revised, accepted: 6 April 1999     

An autopsy case of dementia with motor neuron disease accompanying Alzheimer's disease lesion]

We report the case of a 60-year-old man with autopsy-proven dementia with motor neuron disease (D-MND) and Alzheimer's disease lesion. The patient presented with clumsiness of his right hand at the age of 55 years old and subsequently developed dysarthria, weakness and atrophy of his upper limbs. He was unaffectionate towards his family, repeated the same phrase, and showed severe disorientation of time and place. Neurological examination on admission showed not only diffuse lower motor neuron signs, such as weakness, atrophy, fasciculation and areflexia in both upper limbs, but also dementia (HDS-R 9/30). He died of respiratory insufficiency. Neuropathological examination showed mild atrophy of the frontal and temporal lobes and anterior spinal roots. Microscopic examination of cortical sections revealed degenerative changes with simple atrophy and gliosis, and these changes were predominant in layers 1 and 2 of the frontal and temporal cortices. Using immunohistochemical staining, ubiquitin-positive but tau-negative inclusions were frequently found in neurons of the hippocampal granular cell layers and temporal lobes. Many senile plaques and neurofibrillary tangles were present in all sections of the brain. Our final diagnosis was dementia with motor neuron disease accompanying Alzheimer's disease lesion, because of hypoperfusion in the parietal lobe as well as the frontal lobe demonstrated by SPECT, and the presence of many senile plaques and neurofibrillary tangles in the cerebral cortex. Overlapping of pathologically-proven D-MND and Alzheimer's disease lesion is extremely rare, and this case may improve our understanding of the process of neurodegeneration.     

Atypical motor neuron disease with features of a multisystem degeneration: a non-familial case with prominent sensory involvement

A 66-year-old male with no family history of neurological disease developed symmetrical paraesthesia, numbness and flaccid weakness of the hands and feet. Both the weakness and sensory loss became progressively more severe, and spread to involve the forearms and lower legs. Limb muscle wasting and tongue fasciculation only became apparent late in the disease course, and death eventually occurred from respiratory failure eight years after the onset of symptoms. Postmortem examination revealed most of the typical histological features of motor neuron disease, but in addition there was degeneration of the spinocerebellar tracts and spinal cord posterior columns, with degeneration and loss of their associated neuronal perikarya in Clarke's nuclei and dorsal root ganglia. The clinical and pathological features of this case suggest that it is a non-familial but atypical form of motor neuron disease, and support the concept that this disease represents part of a spectrum of neuronal degenerative processes rather than a circumscribed disorder limited to motor neurons.     

Motor neuron disease and malignancies: results of a population-based study

Summary Eight cases of malignancies with concurrent motor neuron disease (MND), derived from an unselected population representing all cases of MND diagnosed during a 15-year period in two Italian provinces, were studied to verify the existence of paraneoplastic forms of the disease. No statistically significant association between the two diseases was found. Therefore, from our findings the occurrence of a neoplasm in a patient affected by MND can be considered a chance association.This work was partly supported by CSI — Piemonte (Consorzio per il Sistema Informativo)     

The sensory neuropathy of Friedreich's ataxia: an autopsy study of a case with prolonged survival

Summary Observations have been made on a patient with Friedreich's ataxia who died 52 years after the onset of symptoms. The pathology of the brain and spinal cord was typical of this disorder. Apart from loss of dorsal root ganglion cells, severe loss of secondary sensory neurons was observed, including the nucleus dorsalis in the spinal cord, the spinal and principal trigeminal nuclei and, in particular, the mesencephalic trigeminal nucleus in the brain stem. Morphometric studies on the first sacral nerve root and on the sural nerve at levels from midthigh to ankle revealed a distally accentuated axonal loss that predominantly affected larger myelinated nerve fibres. Regenerative activity was seen, mainly in the spinal root and proximally in the sural nerve. Relative myelin thickness, assessed by g ratios, tended to be reduced. As teased fibre studies showed only limited evidence of demyelination/remyelination and of axonal regeneration, this therefore suggests the presence of hypomyelination. The results confirm the presence of a distal axonopathy and provide no evidence that this is preceded by axonal atrophy.Supported by the Friedreich's Ataxia Group     

A case of syringomyelia with proximal dominant muscle weakness and without superficial sensory disturbance]

A 43-year-old woman had noticed muscular weakness in her arms for four years before her admission. Muscle weakness and atrophy were prominent in the bilateral deltoid muscles, but muscular strength was almost unimpaired in the bilateral forearms and intrinsic muscles. There was no sign of sensory impairment except vibratory sensation. EMG revealed neuropathic NMU. X-P of the cervical spine showed enlargement of the spinal canal diameter, and MRI of the spinal cord revealed a large syrinx. On the basis of metrizamide CT and cranial MRI, a diagnosis of syringomyelia with Chiari malformation (type I) was made. Despite the presence of a large syrinx extending from C 1 to Th 11, the only detectable neurological sign was proximal weakness of the upper extremities simulating myopathy.     

A case of motor neuron disease with progressive aphasia and dementia]

We report a 71-year-old woman showing rapidly progressive non-fluent aphasia and dementia accompanied by motor neuron disease (MND). There was no family history of dementia or motor neuron disease. There was 10 months history of dysarthria and dysphagia. On examination, she showed profound difficulty in articulation. Her comprehension was impaired in that she was unable to obey three-stage command. Her written language was also impaired with phonological spelling errors, syntactic errors, and perseveration. Neuroradiological investigations showed atrophic changes and hypoperfusion of left temporal and bilateral parietal region revealed by MRI and SPECT, respectively. Her subsequent decline was rapid. It might be likely that aphasia is much more common in dementia with bulbar MND than is currently recognized because bulbar palsy might mask the language disorder.     

An autopsy case with lower motor neuron disease showing a transient-appearance of anti-GM1 antibody and an improvement of conduction block after gamma-globulin administration]

We report a 63-year-old man who died of respiratory failure. He was well until 1992 (57 years of his age), when he had an onset of progressive weakness of the bilateral upper limbs. He showed no improvement with TRH administration in other hospital. On January 12, 1994, he admitted to our department because of the progressive muscle weakness. Neurologic examination revealed a muscular atrophy associated with severe weakness and hyporeflexia in both upper limbs, and fasciculation were seen in his tongue. Electrophysiological studies revealed mild conduction block in the left medial nerve, and F-waves were not evoked in the left ulnar nerve and bilateral median nerves. After an administration of 25 g/day of human gamma-immunoglobulin for 5 days, conduction block as well as F-wave abnormalities in the left median and left ulnar nerve were improved, yet no improvement of muscle weakness was seen. The anti-GM1 IgG titer was transiently elevated in the patient's serum after gamma-immunoglobulin therapy. On September 8, 1994, subtotal gastrectomy was performed because of the early stage gastric cancer. Histological examination showed poorly differentiated adenocarcinoma (signet-ring cell carcinoma). His muscle weakness had been gradually extended to the lower limbs and he couldn't walk himself on January, 1998. On March, 1998, he developed tetraplegia, mild dysphagia, dysuria and the respiratory disturbance. On April 12, 1998, he admitted to our department for the second time. Neurologic examination revealed a muscular atrophy and fasciculation associated with severe weakness in all of his limbs, tongue and musclus masseter. Neither deep tendon reflex nor pathologic reflex was evoked in his upper and lower extremities. His ocular movements and sensations were well preserved. He died of respiratory failure on May 1, 1998. The patient was presented in a neurological CPC. Neurological and laboratory findings suggested a spinal progressive muscular atrophy (SPMA). However, there were several unusual points as a typical SPMA in this case, that is, an improvement of the electrophysiological abnormalities by gamma-globulin treatment, as well as transient elevation of anti-GM1 antibody. The clinical neurologists have arrived at the conclusion that the patient had lower motor neuron syndrome associated with anti-ganglioside antibody and cause of death was ascribed to the respiratory failure. We discussed whether this case was SPMA or multifocal motor neuropathy. Postmortem examination revealed numerous diverticulums in the ascending colon and lymphothyroiditis. No recurrent carcinoma was detected. Neuropathologically, both severe atrophy of the anterior spinal roots, and severe gliosis and neuronal loss in the anterior horn of the spinal cord were observed. Onuf nuclei were not affected. Neurogenic muscular atrophy was detected in the tongue, diaphragm, and limb muscles. Motor neurons of the brainstem were relatively preserved, but skein-like inclusions as detected by anti-ubiquitin antibody, were present in the facial and hypoglossal nuclei. Neither motor cortex nor cortico-spinal tracts were affected. Demyelination, remyelination or cellular infiltrations were not apparent in the right median nerve and sciatic nerves. The neuropathologic features were compatible with SPMA.     

Rapidly progressive aphasia and motor neuron disease: a clinical, radiological, and pathological study of an autopsy case with circumscribed lobar atrophy

This report concerns an autopsy case of rapidly progressive aphasia and motor neuron disease. The patient was a Japanese woman who was 75 years old at the time of death. The family history did not reveal hereditary burden. She developed language disturbances and difficulty in swallowing at age 74. Neurological examination 1 month after the disease onset revealed motor aphasia without dementia and bulbar sign, followed by muscle weakness of the four extremities. Neuroradiological examination revealed progressive atrophy of the anterior part of the left temporal lobe. She died of respiratory difficulty 10 months after the disease onset. Macroscopically, neuropathological examination showed circumscribed atrophy of the left perisylvian region and, histologically, neuronal loss in the cerebral cortex, including the primary motor area, substantia nigra, brain stem motor nuclei, and anterior horns of the spinal cord, in addition to obvious degeneration of the pyramidal tracts and presence of Bunina bodies. Ubiquitin-immunoreactive neuronal inclusions were present in the hippocampal dentate granular cells and frontotemporal cortical layer II neurons. Based on these clinicopathological findings and a review of the literature, we concluded that our case is the first reported case of amyotrophic lateral sclerosis with dementia that clinically showed rapidly progressive aphasia. Received: 1 March 1999 / Revised, accepted: 11 May 1999     

An autopsy case of frontotemporal dementia with severe dysarthria and motor neuron disease showing numerous basophilic inclusions

We report a clinicopathological study of a patient suffering from frontotemporal dementia (FTD) with severe dysarthria and concomitant motor neuron disease (MND). The patient was a 52‐year‐old woman with almost simultaneous emergence of severe dysarthria and FTD. The severe dysarthria subsequently evolved into anterior opercular syndrome. Motor neuron signs then emerged, and the patient developed akinetic mutism approximately 2 years after the onset of the disease. The patient died of pneumonia after a 7‐year clinical illness. Pathologically, severe and widespread degeneration in the frontal and temporal lobes, including the anterior opercular area, limbic system, basal ganglia, spinal cord and cerebellum, and frequent ubiquitin‐ and tau‐negative basophilic inclusions were observed. The pyramidal tracts and anterior horns of the cervical cord also showed marked degeneration. Cases showing basophilic inclusions reported so far have been divided into two groups: early onset FTD and MND with basophilic inclusions. Our case presented clinicopathological features of both FTD and MND, which suggests that cases showing basophilic inclusions may constitute a clinicopathological entity of FTD/MND.     

A case of motor neuron disease with presenile dementia showing bilateral degeneration of the pyramidal tract on cranial MRI]

A 58-year-old man developed dysarthria followed by a personality change. Subsequently, he developed muscle weakness and atrophy of the left upper and lower limbs, leading to repeated falls when he tried to walk. Neurological examination showed mild dementia, dysarthria, dysphagia, atrophy and fasciculation of the tongue, and muscle weakness and atrophy of all four extremities, particularly on the left side. Deep tendon reflexes were slightly diminished in the upper limbs and slightly exaggerated in the lower limbs without Babinski's sign. Cranial MRI revealed marked atrophy of the medial portions of the temporal lobes, more striking on the right, and T2-weighted imaging revealed symmetrical high-intensity signals from the posterior limbs of the internal capsules to the cerebral peduncles in the midbrain, extending to the pons on the left. 125I-IMP SPECT showed diffuse reduction of RI uptake in the frontal and temporal lobes, which was more marked on the right. We diagnosed this is a case of motor neuron disease with presenile dementia, which Mitsuyama et al. proposed as a new clinical entity, as well as a rare example of bilateral degeneration of the pyramidal tract on cranial MRI.     

An autopsy case of Degos disease with neurological symptoms--neuropathological observations and increased platelet aggregation]

We reported clinical and neuropathological observations of a 41-year-old man with Degos disease. He first noted painless skin lesions over the upper extremities in January, 1982. Three years later he was diagnosed as Degos disease by skin biopsy, and treatment with aspirin was started. In September, 1985, he complained of paresthesia on his right arm, followed by a series of new neurological manifestations suggesting multifocal spinal cord lesions. On October 28, examination of admission showed papules with central umblication over the whole body except the head, face, palms, soles and scrotum. Neurological examination revealed no weakness, diminished right biceps reflex, exaggerated patellar reflexes and Achilles reflexes, left extensor plantar reflex, hypesthesia and hypalgesia to the level of Th8, mild left spastic gait, and retention of urine. In November, he had paraparesis, loss of vibration sense of lower extremities, hypesthesia and hypalgesia to the level of TH4, and weakness of right upper extremity. In December, he showed tetraplegia, left-sided facial palsy, and hypesthesia and hypalgesia to the level of C5. In January, 1986, he showed right facial palsy, left facial hypesthesia, pseudobulbar palsy. In February, he had bilateral abducens nerve palsy and hiccups. On February 18, he died of intracranial hemorrhages. He had episodic abdominal pain several times during admission. His condition deteriorated progressively in four months after the first manifestation of neurological symptoms, despite the therapy with heparin, urokinase, ticlopidine, dipyridamole, and prednisolone. Laboratory studies showed gradual increase of CSF proteins (from 156 mg/dl to 602 mg/dl) and extremely increased platelet aggregation.(ABSTRACT TRUNCATED AT 250 WORDS)     

An autopsy case of familial juvenile Alzheimer's disease with extensive involvement of the subcortical gray and white matters

Summary An autopsy case of familial juvenile Alzheimer's disease with extensive involvement of the subcortical gray and white matters is reported. A 33-year-old woman showed a progressive dementia and died of cardiac failure at the age of 45. Neurological examination disclosed choreatic movements, myoclonus, rigidity, and generalized convulsion. Gross inspection of the brain showed a diffuse cerebral atrophy and marked degenerations of both the subcortical gray and white matters. Microscopically, numerous and extensive argyrophilic changes such as senile plaques, neurofibrillary tangles, and granulovacuolar degenerations were observed in the brain. The present case was characterized by a severe neuronal loss in the basal ganglia, substantia nigra, dentate nucleus, and thalamus as well as a marked myelin loss and axonal damage in the cerebral white matter. This case suggested a combination of multisystemic degeneration and primary degeneration of the cerebral white matter. The pathological similarity of this case to Creutzfeldt-Jakob disease and Pick's disease is discussed.