Focal appearance of cerebellar torpedoes associated with discrete lesions in the cerebellar white matter

Summary Cerebellar torpedoes, unique fusiform swellings of Purkinje cell axons within the granular layer, have been known to occur sparsely associated with diffuse cerebellar changes. This report describes, in three human autopsy cases with focal necrotic lesions in the cerebellar white matter, torpedoes which were essentially confined to the cerebellar cortex overlying the lesions. Purkinje cells in the same region showed no recognizable change, but were obviously decreased in number. The location of the necrotic lesions was such that they may well have severed Purkinje cell axons projecting into the deeply located cerebellar nuclei from the torpedo-carrying cortex. These findings indicate that damage to Purkinje cell axons, even if it occurs far away from the cell bodies, may have a critical influence upon the metabolism of Purkinje cells and play an important role in the formation of torpedoes.     

An autopsied case of idiopathic late cortical cerebellar atrophy--comparison with other cortical cerebellar atrophy

A 68-year-old man without familial history developed ataxic gait and sensory disturbance in the lower extremities. At the age of 74, neurological examination revealed marked cerebellar ataxia of all limbs, dysarthria, sensory disturbance of glove and stocking type in the extremities, and slight neurogenic muscular atrophy. There were no mental deterioration and dysautonomia. He died of pneumonia at the age of 74. Neuropathological findings. The cerebellum was decreased in size. Microscopically, there were severe disappearance of Purkinje cells in the cerebellar vermis and hemispheres. The molecular layer, granular cell layer, and cerebellar white matter were preserved. Neurons of the inferior olivary nuclei were also spared. In the spinal cord, there was myelin pallor in the posterior column predominant in Goll's fascicule and moderate atrophy of neurons in the anterior horn. Degeneration of the posterior roots was greater than that of the anterior roots. No abnormal findings were found in the extrapyramidal system, cranial nerves, and cerebrum. We compared this case clinicopathologically with other diseases with cortical cerebellar atrophy; alcoholic cerebellar degeneration, phenytoin intoxication, neuroleptic malignant syndrome, and subacute paraneoplastic cerebellar degeneration. In conclusion, idiopathic late cerebellar cortical atrophy (LCCA) was different clinicopathologically from the other diseases. Especially, LCCA showed the characteristic topography of Purkinje cells loss sparing the molecular and granule cell layers.     

An autopsied case of progressive supranuclear palsy presenting with cerebellar ataxia and severe cerebellar involvement

A Japanese male patient presented with gait disturbance at the age of 69 years. His principal symptom was cerebellar ataxia for several years. He was initially diagnosed as having olivopontocerebellar atrophy because dysarthria and ataxia gradually developed, and head CT scan showed apparent atrophy of the cerebellum and brainstem and dilatation of the fourth ventricle. Later, he showed vertical gaze palsy, dysphagia, retrocollis, parkinsonism, axial dominant rigidity and grasp reflex, and therefore, the diagnosis was modified to progressive supranuclear palsy (PSP). Progressive atrophy of the frontotemporal lobe, cerebellum and brainstem, and dilatation of the lateral, third and fourth ventricles were evident on MRI. Gastrostomy and tracheotomy were performed 9 and 10 years after onset, respectively, and the patient died after 11 years disease duration. At autopsy the brain weighed 1000 g and showed atrophy of the frontotemporal lobe, cerebellum and brainstem. Neurofibrillary tangles, mainly globose‐type revealed by Gallyas‐Braak silver staining, were extensively observed in the cerebral cortex and subcortical grey matter. Numerous glial fibrillary tangles, including tuft‐shaped astrocytes and coiled bodies, and extensive argyrophilic threads were also recognized, particularly in the frontal lobe, basal ganglia, cerebellar white matter, brainstem and spinal cord. The Purkinje cell layer showed severe neuron loss with Bergmann's gliosis, and the dentate nucleus showed severe neuron loss with grumose degeneration. Tau‐positive/Gallyas‐positive inclusions in the Purkinje cells and the glial cells of the Purkinje cell layer were observed. Pathological findings of the present patient were consistent with the diagnosis of PSP, but the olivopontocerebellar involvement, particularly in the cerebellum, was generally more severe, and the quantity of tau‐positive/Gallyas‐positive structures were more abundant than in typical PSP cases. The existence of a distinct, rare PSP subtype with severe olivopontocerebellar involvement, “PSP‐C“, which tends to be clinically misdiagnosed as spinocerebellar degeneration in the early disease stage, is noteworthy. The present case corresponded to this rare subtype of PSP.     

An autopsied case of alcoholic cerebellar degeneration with spastic paraplegia and neuropathy

A 45 year-old-female was admitted to Kanagawa Rehabilitation Center because of marked spastic paraplegia. There was no family history of neurological diseases. She had been drinking a great excess of alcohol since twenty years of age. Though she noticed the unsteadiness of gait several years prior to the admission, she had not been examined. On admission neurological examination revealed pyramidal weakness of both legs, and slight sensory impairment in distal part of the lower extremities. But she had neither difficulty in speech nor abnormal findings in the upper extremities. Her mentality was well preserved. Though computed tomography revealed cerebellar cortical atrophy, no signs of cerebellar impairment could not be found except spastic paraplegia. Blood chemistry failed to reveal liver dysfunction. There was no pernicious anemia. These symptoms were almost stationary until her death. At the age of 53, she died of gastric cancer. Postmortem examination disclosed marked degeneration of cerebellum and spinal cord. Cerebellar cortical degeneration, which was characterized by involvement of all layers of the cortex, showed unique distribution. The lingula, central lobule, culmen, superior portion of declive, anterior lobules and anteromedial half of simple lobule were severely degenerated, while other lobules were spared excluding moderate degeneration in inferomedian portion of the hemisphere. These cortical degeneration was prominent much more in vermis than in hemisphere. There was a mild myelin pallor in the lamellar white matter and slight fibrous gliosis. In the dentate nucleus, there were moderate neuronal loss with gliosis.(ABSTRACT TRUNCATED AT 250 WORDS)     

An autopsied case of dentato-rubro-pallido-luysian atrophy with atypical pathological lesions]

In this paper, atypical pathological findings in a genetic diagnosed case of dentato-rubro-pallido-luysian atrophy (DRPLA) with mild degeneration in the common lesions of the disease is reported. The patient was 59-year-old woman with 31-year history of involuntary movement, ataxia and psychiatric disorders. Her CAG repeat number of DRPLA gene was 68/14. Besides the spongy degeneration in the third and fourth layers of the occipital cortex, severe degenerations were observed in the cerebellar cortex and white matter, inferior olive, posterior funicular nuclei of the medulla oblongata, posterior and lateral funicles of the spinal cord, and Clarke's nucleus. A wide spread distribution of the intracellular polyglutamine aggregation was also showed including both common and uncommon lesions. Genetic diagnosis disclosed a DRPLA case with lesions different from the conventional cases.     

A case of subdural empyema with transient cerebral white matter lesions

We reported a fourteen years old male with subdural empyema followed by consecutive magnetic resonance imaging (MRI) examination. He was admitted to our hospital, complaining incomplete paresis of the left upper extremities, headache and high fever. The first MRI T2-weighted image at admission revealed an abnormal high intensity in the right frontal subdural space, indicating an abscess. Antibiotics therapy and a burr hole operation were effective and he made a remarkable recovery. One month later, the third MRI T2-weighted image showed an abnormal high intensity in the deep white matter of the right frontal lobe, which had not been detected in the subsequent MRI after the operation. On the other hand, the meningeal enhancement on the second Gd-DTPA enhanced MRI was more thickened than the previous meningeal enhancement. This abnormal high intensity on MRI had disappeared two month later, when the meningeal enhancement had grown thin. These data suggested the meningeal enhancement was relative to the transient high intensity which was considered to represent brain edema. We concluded that careful observation and serial MRI examination might be necessary in patient with subdural empyema even after disappearance of all symptoms.     

Transient encephalopathy with reversible white matter lesions: a case report

We report on a boy with bilateral optic nerve hypoplasia and mild psychomotor retardation. At 1 year and 9 months of age, he was admitted to hospital with a cluster of febrile convulsions and unconsciousness. Magnetic resonance imaging (MRI) revealed widespread areas of high signal intensity on diffusion-weighted imaging of the deep cerebral white matter and corpus callosum. This imaging disappeared at five days of illness. No atrophy or abnormalities were noted on the 6-month follow-up MRI. Despite full recovery after the acute episode, the patient showed retarded developmental progress. We discuss the differential diagnosis for this case.     

Cognition and white matter lesions

Although it is recognized that ischemic stroke is a potent risk factor for vascular dementia, the influence of white matter lesions (WML) on cognitive function is less clear. In community-based MRI studies that have administered mental status tests to subjects who were free of clinically evident neurologic disease, a weak relationship between WML and generalized cognitive function has been reported. In studies that have administered neuropsychological test batteries, a stronger and more specific association has been recognized between WML and deficits in executive function, most likely due to the involvement of frontal-subcortical pathways. Cognitive deficits may be related to the total volume of the WML, with a threshold perhaps needing to be surpassed before such deficits are evident, but it is likely that the location of the WML also plays a role, with that threshold varying in association with the distribution of the lesions. Potential confounders of the results of previous studies include small, strategically located subcortical infarctions that may be masked by more extensive WML and other comorbid neurologic disorders, particularly Alzheimer's disease. Future studies should be prospective, utilize standardized methods for structural and functional brain imaging, and administer comprehensive neuropsychological assessments in order to more rigorously investigate the relationship between evolving WML and declining cognitive functions.     

An autopsied case of Parkinson's disease manifesting Shy-Drager syndrome]

We report an autopsied case of Parkinson's disease manifesting Shy-Drager syndrome. At the age of 63 years, the patient noticed an onset of progressive orthostatic dizziness, which was followed by constipation, dysuria, and sexual impotence. When he was 66 years old, syncopal attack for a few minutes, tremor in the bilateral hands, and memory disturbance developed. On admission, his blood pressure was 142/72 mmHg in supine position, which fell to 58/42 mmHg on standing with appropriate increase of heart rate. Neurological examination revealed hallucination, memory disturbance, masked face, muscular rigidity, bradykinesia, mild postural tremor, and autonomic dysfunction including severe orthostatic hypotension, hypohydrosis, constipation, dysuria, and sexual impotence. Electroencephalogram showed diffuse slowing. Brain CT demonstrated absence of severe atrophy of the cerebellum, and brain stem. Pharmacological study revealed denervation hypersensitivity to the intravenously administrated noradrenaline. A diagnosis of Shy-Drager syndrome was made, and he was treated with anti parkinsonian drugs. However, no improvement was observed in his clinical symptoms. Seven months later, he died of pneumonia. Neuropathological examination revealed marked neuronal cell loss and gliosis in the substantia nigra and locus ceruleus. Lewy bodies were seen in those pigmented nuclei, dorsal vagal nucleus, hypothalamus and nucleus basalis of Meynert. No abnormality was found in the intermediolateral nucleus of the spinal cord. This is the first report on a Japanese patient who presented clinically Shy-Drager syndrome and pathologically typical Parkinson's disease. In this patient, from the pharmacological and pathological findings, sympathetic ganglia were supposed to be the responsible lesion for orthostatic hypotension.     

Extensive demyelinating changes in the peripheral nerves of Crow-Fukase syndrome: a pathological study of one autopsied case

Summary Pathological changes of the peripheral nervous system in one autopsied case of Crow-Fukase syndrome (POEMS syndrome) was systemically examined. Distally accentuated myelinated axon loss was observed in the peripheral nerve trunks, ventral and dorsal spinal roots, but was not observed in the fasciculus gracilis. Segmental demyelination and remyelination associated with focal excessive myelin outfolds were the most characteristic features, the distribution of which was more prominent in the proximal nerve trunks and the spinal nerve roots. Endoneurial edema was present, and focal perivascular T lymphocyte accumulation was occasionally observed in the spinal nerve roots and proximal nerve trunks. Neurons in the sympathetic ganglia, dorsal root ganglia and ventral horns were well preserved.Supported by grants from the Ministry of Welfare and Health of Japan     

Caudal regression syndrome associated with the white matter lesions and chromosome 18p11.2 deletion

Caudal regression syndrome (CRS) is a rare combination of congenital abnormalities characterized by caudal vertebral agenesis/dysgenesis that is usually associated with congenital anomalies of spinal cord, gastrointestinal and genitourinary organs. Although the exact teratogenic mechanism is not known, same environmental, e.g., hyperglycemia and genetic factors appears to play a crucial role in this fetopathy. Herein, we report an unusual case of CRS associated with unspecific white matter lesions and 18p-syndrome manifested by congenital ptosis, hypothyroidism, facial dysmorphy and chromosome 18p11.2 deletion.     

Wilson's disease with myoclonus and white matter lesions

White matter lesions (WML) and epilepsy have been occasionally seen in Wilson's disease. No cases of generalized myoclonus have been reported so far. We present a patient with psychiatric symptoms starting at age 16, followed by tremor, generalized dystonia and severe generalized myoclonus. In addition to classical findings, the MRI showed also extensive WML in temporal, parietal and frontal regions, preserving interhemispheric fibers. Necropsy revealed marked alterations of white matter, cortex and basal ganglia. We subsequently review the literature concerning WML and myoclonus in Wilson's disease.     

Postinfectious encephalitis with multifocal white matter lesions

Two cases of multifocal white matter lesions occurring after viral illness are reported. Evoked potentials study and cranial magnetic resonance imaging (T2-weighted image) showed early abnormalities while CT scan was initially normal. Patients improved dramatically with steroid therapy. It would seem that because of a considerable responsiveness to steroids this affection should be differentiated from other types of encephalitis. Relations with multiple sclerosis are discussed.     

Acute paraplegia with vanishing white matter lesions

Young adults presenting with an acute myelopathy often represent a diagnostic challenge. We present the case of a 20-year-old man who demonstrated many of the diagnostic issues involved in the evaluation of this syndrome.     

Imaging of white matter lesions

Magnetic resonance imaging (MRI) is very sensitive for the detection of white matter lesions (WML), which occur even in normal ageing. Intrinsic WML should be separated from physiological changes in the ageing brain, such as periventricular caps and bands, and from dilated Virchow-Robin spaces. Genuine WML are best seen with T2-weighted sequences such as long TR dual-echo spin-echo or FLAIR (fluid-attenuated inversion recovery); the latter has the advantage of easily separating WML from CSF-like lesions. Abnormal T2 signal in MRI is not specific, and can accompany any change in tissue composition. In the work-up of WML in small vessel disease, magnetic resonance angiography can be used to rule out (concomitant) large vessel disease, and diffusion-weighted MRI to identify new ischaemic lesions (amidst pre-existing old WML). The differential diagnosis of WML includes hereditary leukodystrophies and acquired disorders. The leukodystrophies that can present in adult age include metachromatic leukodystrophy, globoid cell leukodystrophy, adrenomyeloneuropathy, mitochondrial disorders, vanishing white matter, and cerebrotendinous xanthomatosis. These metabolic disorders typically present with symmetrical abnormalities that can be very diffuse, often with involvement of brainstem and cerebellum. Only the mitochondrial disorders tend to be more asymmetric and frequently involve the grey matter preferentially. Among the acquired white matter disorders, hypoxic-ischaemic causes are by far the most prevalent and without further clinical clues there is no need to even consider the next most common disorder, i.e. multiple sclerosis (MS). Among the nonischaemic disorders, MS is far more common than vasculitis, infection, intoxication and trauma. While vasculitis can mimic small vessel disease, MS has distinctive features with preferential involvement of the subcortical U-fibres, the corpus callosum, temporal lobes and the brainstem/cerebellum. Spinal cord lesions are very common in MS, but do not occur in normal ageing nor in small vessel disease.     

Evolution of white matter lesions

A 3-year follow-up of 273 participants (mean age 60 years) of the Austrian Stroke Prevention Study provides first information on the rate, clinical predictors and cognitive consequences of MRI white matter lesions (WML) in elderly individuals without neuropsychiatric disease. Lesion progression was found in 17.9% of individuals over a time period of 3 years. Diastolic blood pressure and early confluent or confluent white matter hyperintensities at baseline were the only significant predictors of white matter hyperintensity progression. Genetic association studies in the setting of the Austrian Stroke Prevention Study provide first evidence for genetic susceptibility factors for progression of WML. We observed associations with the paraoxonase Leu-->Met 54 polymorphism and with the M235T polymorphism of the angiotensinogen gene. Lesion progression had no influence on the course of neuropsychologic test performance over the observational period, but the statistical power of this analysis was low.     

A suspected case of Wegener granulomatosis accompanied with pachymeningitis and white matter lesions]

A 53-year-old woman was admitted to our hospital because of high fever and abnormal chest radiograph shadows. Chest X-ray on admission showed a nodular shadow in the right upper lung field and a mass shadow with a cavity in the left middle lung field. Laboratory data indicated leukocytosis and elevation of C-reactive protein. Pulmonary suppuration was suspected, panipenem/betamipron was prescribed, but a mass and consolidation developed, and the medication was changed to ciprofloxacin. Convulsive seizures with loss of consciousness appeared after the change to ciprofloxacin. Lumbar puncture revealed pleocytosis with a predominance of mononuclear cells (198/3) and elevated protein(83 mg/dl). Brain CT showed no abnormal image, and acute aseptic meningitis was diagnosed and was treated with cefotaxime, clindamycin, fluconazole, acicrovir and sulfamethoxazole/trimethoprim. However, the treatment did not result in symptomatic improvement, and brain MRI showed intracranial disorders. Serum PR3-ANCA was elevated to 15 U/ml. Taken together with chest X-ray, sinusitis and clinical course, a generalized form of Wegener's granulomatosis was diagnosed. She was given 60 mg/day of prednisolone, 100 mg/day of cyclophosphamide and 9 g/day of sulfamethoxazole-trimethoprim and progressively improved. In this process, enhanced MR images showed thickened dural enhancement of the falx and bilateral anterior regions, which showed improvement on brain MRI at 8 months after starting treatment. We report a rare case of Wegener's granulomatosis accompanied with pachymeningitis and white matter lesions.