Progressive cerebral atrophy in multiple system atrophy

Nine patients with multiple system atrophy (MSA) were studied based on MRI findings of cerebral hemispheric involvement. The age at onset was 56.4+/-8.6 (mean+/-S.D.) years, duration of illness at the first MRI study 2.1+/-1.1 years, duration of illness at the last study 9.7+/-2.6 years, and the follow-up duration 7.6+/-2.3 years. Controls were 85 neurologically intact persons (60.2+/-11.1 years age). In the MRI study, measurements of the ratio of each area to the intracranial area were performed for the cerebral hemisphere, frontal, temporal and parietal-occipital lobes. A significant progression of atrophy to under the normal limit was observed in the cerebrum, frontal and temporal lobes. Besides the typical pathological lesions in MSA, five autopsied patients revealed frontal lobe atrophy with mild gliosis, mild demyelination and glial cytoplasmic inclusions (GCIs). One of these patients showed remarkable frontal lobe atrophy with degenerative changes in the cerebral cortex. We observed the involvement of the cerebral hemisphere, especially the frontal lobe.     

Multiple system atrophy with remarkable frontal lobe atrophy

The autopsy findings of a multiple system atrophy (MSA) patient with remarkable frontal lobe atrophy are described. The patient was a 65-year-old woman with a 13-year history of untreatable parkinsonism, dysautonomia and progressive motor aphasia. The brain weight was 810 g, and there was remarkable atrophy of the cerebrum predominantly in the frontal lobe, striatum, pons and cerebellum. Microscopic examination revealed a preserved cortical structure with laminar gliosis in the sixth layer of the precentral and superior frontal gyri of the frontal lobe, and postcentral gyrus and inferior parietal lobule of the parietal lobe. The second layer of the cortices of these regions were also revealed to be in a spongy state, and mild cell loss was seen in the fifth and six layers. The frontal lobe white matter showed a mild loss of myelinated fibers and axons, and mild gliosis. Glial cytoplasmic inclusions (GCIs) were abundantly observed in the deep layer of the cortex in the regions mentioned above, and were more abundant in the white matter of the frontal and parietal lobes, callosal body, and internal, external and extreme capsules. There was severe degeneration in the olivopontocerebellar and striatonigral systems, and GCIs in widespread regions of the brain. No Pick bodies, Lewy bodies, ballooned neurons, senile plaques, or significant amounts of neurofibrillary tangles were detected. There were no vascular changes. Thus, this was a verified MSA patient with progressive aphasia and remarkable frontal lobe atrophy. We indicate a possible involvement of the cerebral lobes in MSA. Received: 5 August 1998 / Revised, accepted: 21 October 1998     

Progression of brain atrophy in multiple system atrophy

In this study, we aimed to determine the progression of brain atrophy in the parkinson variant of multiple system atrophy (MSA-P). Voxel-based morphometry was applied to two consecutive high resolution MR images of 14 patients with probable MSA-P in comparison to 14 patients with Parkinson's disease (PD). The time interval between baseline and follow-up investigations (1.0 +/- 0.5 SD years in MSAP and 1.4 +/- 0.6 SD years in PD patients) was introduced as covariate in the statistical analysis. Additionally, correlation analyses were performed between the progression maps and clinical data. We observed marked progression of brain atrophy in the MSA-P cohort, the regions including striatum, mesencephalon, thalamus and cerebellum, but also cortical regions such as the primary sensorimotor cortex, supplementary motor area, lateral premotor cortex, medial frontal gyrus, middle frontal gyrus, orbito-frontal cortex,insula, posterior parietal cortex and hippocampus. Short disease duration was correlated with progression of atrophy in the striatum whereas longer disease duration was correlated with increasing atrophy in the cortical areas and cerebellar hemispheres. The UPDRS-III score was not significantly correlated with any brain region. Our data suggest that cortical atrophy is prominent in MSA-P and early degeneration of the basal ganglia drives late onset cortical atrophy.     

Cerebral atrophy in multiple system atrophy by MRI

Cranial magnetic resonance images (MRI) of the cerebral areas of 40 patients with multiple system atrophy (MSA) and of 61 age-matched controls were analyzed. The cerebral area of MSA patients was 131. 95+/-15.89 cm(2) (mean+/-S.D.), which was significantly smaller than that of normal controls at 149.01+/-10.93 cm(2) (P<0.0001). All 23 MSA cases subjected to the MRI study over a 1-year period showed progressive cerebral atrophy, and the atrophy rate was 2.46+/-1. 66%/year. There were no significant differences within the MSA subtypes or between gender. The progression of cerebral atrophy in MSA correlated more with duration (r=-0.634) than age (r=-0.421). We conclude that MRI findings throughout the course of MSA suggest progressive cerebral atrophy, which is common in all subtypes and reflects duration of the disease rather than age.     

Hypothalamic atrophy

A patient, who has been followed for thirteen years, developed the first symptoms of progressive hypothalamic atrophy at the age of 39. The diagnosis was confirmed by pneumoencephalography five years after onset. Hypothalamic dysfunction was manifested clinically by loss of libido, impotence, obesity, polydypsia, somnolence, and rage attacks. Assessment of endocrinologic function demonstrated low serum levels of testosterone, FSH, and LH, a diabetic glucose tolerance curve, decreased basal and hypoglycemic stimulated levels of HGH, and progressively increasing levels of serum prolactin. Repeated pneumoencephalography revealed an initial, and then progressive, enlargement of the third ventricle which was later associated with generalized, but proportionately less severe, atrophy of the cerebellum and cerebral hemispheres. Analysis of the physiologic and endocrinologic mechanisms underlying these abnormalities suggests diffuse hypothalamic damage, especially in the ventromedial area. The decreased somnolence and increased libido and potency which accompanied therapy with levodopa suggest damage to dopaminergic and noradrenergic pathways. Slowly progressive hypothalamic atrophy, confirmed by pneumoencephalography, but without specific etiology, has not been reported previously. This article describes such a patient followed over thirteen years, and the efficacy of therapy with levodopa in ameliorating certain aspects of his disease.     

Spinal muscular atrophy combined with sporadic olivopontocerebellar atrophy

The combination of spinal muscular atrophy (SMA) with a variety of neural and extraneural defects, particularly pontocerebellar hypoplasia, has been reported. To date, all of the reported SMA with pontocerebellar hypoplasia was from infants; however, here we report a SMA with sporadic olivopontocerebellar atrophy (sOPCA) in an adult patient. The 68-year-old male patient displayed various clinical symptoms including progressive proximal muscle weakness, muscle atrophy and muscle fasciculation with a long course of disease. EMG demonstrated that amyotrophy was due to the impairment of lower motor neurons. The clinical symptoms and the EMG were consistent with the diagnosis of SMA. The presence of cerebellar ataxia, limb tremors, muscle atrophy and weakness in the patient led to the diagnosis of sOPCA that was confirmed by the MRI results. To our knowledge, this is the first case report of combination of SMA with sOPCA in an adult. It is yet unclear whether there is a common pathogenesis between the two diseases.     

Hemiplegic atrophy

Summary Anterior tibial muscle biopsies of the hemiplegic side of 16 patients with a cerebrovascular accident in the middle cerebral artery region were analyzed qualitatively and quantitatively by enzyme histochemistry and electron microscopy.Patients grouped according to the time lapsed as from the occurrence of the accident (1–17 months) demonstrated a progressive decrease in the fiber diameter and changes in fiber type distribution with predominant type II atrophy and type I predominance. Nuclear internalization, myopathic alterations, and perifascicular fatty infiltrations were observed constantly.In the affected fibers the ultrastructural findings were myofibrillar alterations with the formation of rods and cytoplasmic bodies. There was accumulation of lipofuscin, glycogen, and lipid droplets. Microvascular changes were observed frequently.Biopsies from the asymptomatic legs were either normal or showed age-related muscle alterations.Correlation was noted between the clinical and functional status of the patients and the morphological aspects seen in muscle biopsies.     

Monomelic atrophy

Weakness of distal muscles of one upper limb which progresses over 1 year and then appears to arrest ("monomelic amyotrophy") has been reported mainly in Japan and India. We report 5 cases of a similar syndrome occurring in Canada. In our cases the wasting affected the forearm muscles of one upper limb (sparing brachioradialis and extensor carpi radialis). There was minimal wasting and electromyographic changes in the opposite upper limb. The CT myelogram showed unilateral wasting of the cervical cord.     

Evolution of sporadic olivopontocerebellar atrophy into multiple system atrophy

OBJECTIVE: To determine the percentage of sporadic olivopontocerebellar atrophy (sOPCA) patients who later develop multiple system atrophy (MSA). METHODS: Observations of the course of 51 sOPCA patients 20 years of age or older initially evaluated in an ataxia clinic over 14 years and followed at 3- to 6-month intervals for 3 months to 10 years (median 2.5 years, interquartile range 5 months to 4 years). RESULTS: Seventeen patients evolved to develop MSA, whereas the remaining 34 manifested only progressively worsening cerebellar ataxia. The features of the MSA cases included autonomic failure and parkinsonism in 10 patients, autonomic failure without parkinsonism in six, and parkinsonism without autonomic failure in one. Using survival analysis methods, the authors estimated that 24% of subjects in this population will evolve to MSA within 5 years of the onset of sOPCA symptoms (95% CI 10% to 36%). An older age at onset of symptoms and a shorter time from onset of symptoms to first presentation in a neurology specialty clinic were both highly predictive of evolution to MSA. Six of the 17 patients who evolved to MSA died 4 months to 5 years after they had met diagnostic criteria for MSA. The estimated median survival time from time of transition was 3.5 years. In contrast, death occurred in only one of the 34 patients with sOPCA who did not evolve to MSA. Autopsy examination of all six patients with MSA who died confirmed the diagnosis. CONCLUSIONS: Approximately one-fourth of sporadic olivopontocerebellar atrophy patients will evolve to multiple system atrophy within 5 years, and this transition carries a poor prognosis for survival. Older age at onset of ataxia and earlier presentation in a neurologic specialty clinic predicted transition to MSA.     

X-linked spinal and bulbar muscular atrophy without proximal atrophy

We report on a case of genetically proven X-linked spinal and bulbar muscular atrophy (X-SBMA) with prominent distal muscle atrophy and without proximal muscle involvement. The patient was a 35-year-old man who had a history of slow progressive hand and distal leg muscle weakness and wasting for 10 years. Motor nerve conduction velocities were normal with reduced compound muscle action potential amplitudes of hand and foot muscles. Sensory action potential amplitudes were small. Needle EMG revealed a chronic partial denervation with reduced interference in hand and distal leg muscles but with normal heading in all tested proximal muscles. Genetic studied showed an expansion of CAG repeat in the first exon of the androgen receptor gene, which suggests diagnosis of X-SBMA. The importance of genetic studies in this patient with unusual clinical presentation is emphasized.     

Infantile cerebellar atrophy

We describe a family whose members have a dominantly inherited, early-onset, nonprogressive syndrome that includes spontaneous upbeating nystagmus and mild gait ataxia. Magnetic resonance imaging showed localized atrophy of the cerebellar vermis. Several families described in the literature resemble our family but differ in mode of inheritance, age at onset, rate of progression, or clinical findings. We believe this family represents a unique type of inherited early-onset atrophy of the cerebellar vermis.