Asymmetrical temporal lobe atrophy with massive neuronal inclusions in multiple system atrophy

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Abstract

This report concerns a rare association of asymmetrical temporal lobe atrophy with multiple system atrophy (MSA). A 53-year-old Japanese woman developed cerebellar ataxia and parkinsonism and was diagnosed as olivopontocerebellar atrophy (OPCA). This patient showed forgetfulness and subsequent disorientation even in the early stage of the disease. She fell into a decorticate state at the age of 64, and died a year later. The autopsy showed MSA with asymmetrical atrophy of temporal lobes, intraneuronal globular inclusions mostly confined to the hippocampus, amygdaloid nucleus, and most abundant in the granule cells in the dentate fascia. These inclusions were intensely argyrophilic and expressed marked immunoreactivity to ubiquitin, but not to neurofilament (NF), tau and paired helical filaments (PHF). Ultrastructurally, they were composed of scattered short filamentous structures of 15 to 30 nm in diameter, ribosome-like granules, mitochondria and lipofuscin. The lack of immunoreactivity against tau, NF and PHF suggests that the inclusions are distinct from Pick bodies. To our knowledge, MSA in association with asymmetrical temporal lobe atrophy with the present neuronal inclusions has not been reported. This case is distinct from MSA combined with atypical Pick’s disease in the distribution and immunohistochemical properties of neuronal inclusions, and may present a new variant of MSA since the neuronal inclusions are similar, in many respects, to those of neuronal inclusions reported in MSA. Globular inclusions are also discussed in variants of Pick’s disease, amyotrophic lateral sclerosis and Alzheimer’s disease.

Introduction

Multiple system atrophy (MSA) includes olivopontocerebellar atrophy (OPCA), striatonigral degeneration (SND) and Shy–Drager syndrome [1]. The clinicopathological unity of these syndromes is supported by the presence of characteristic argyrophilic cytoplasmic inclusions in the oligodendroglia and neurons [2], [3], [4], [5], [6], [7], [8], [9]. Rarely, this disease may be associated with Alzheimer’s disease [10], progressive supranuclear palsy [11], or atypical Pick’s disease [12]. This study documents the case of a patient with MSA who displays asymmetrical temporal lobe atrophy with neuronal intracytoplasmic inclusions having some features of Pick bodies.

Section snippets

Case report

A 53-year-old woman, the proprietress of ‘ryokan’ (Japanese inn) developed an unsteady gait, dysarthria, and impairment of memory. The dysmnesia gradually became worse. She often forgot the telephone number of booking visitors and was unable to continue her work as proprietress. At age 55 years, she was diagnosed as having OPCA by one of the authors (K.I.). The patient developed depressive state and neurogenic bladder that gradually progressed. She was admitted to Kanagawa Rehabilitation Center

Subject and methods

The brain was fixed in 20% formalin solution for a week and the representative sections including large hemispheric sections of the cerebrum and cerebellum were embedded in paraffin wax. The routine stains employed were hematoxylin-eosin, Klüver–Barrera for myelin, Holzer for glial fiber, Bodian and Bielschowsky silver impregnation, and Gallyas silver development.

For electron microscopy, a small fragment of Ammon’s horn was taken from the formalin-fixed brain (postmortem delay of 6 h). The

Neuropathologic findings

The brain weight was 920 g. Marked atrophy of the cerebellum and pons was present (Fig. 3a). On coronal sections, the putamen was atrophic and showed brown discoloration. The substantia nigra was totally depigmented. In addition, the right anterior temporal lobe and hippocampus appeared considerably atrophic, and in contrast, the left one was spared, being asymmetrical (Fig. 3b).

Microscopically, the cerebellar hemispheres showed considerable loss of Purkinje cells and thinning of the granular

Discussion

In the present case, there was severe neuronal loss and gliosis in the olivopontocerebellar system involving the cerebellar cortex, and in the striatonigral system. In addition, oligodendroglial argyrophilic inclusions [2], [3], [4], [8], [9], [13] were widely distributed throughout the brain. So, this case was easily diagnosed as MSA [1], [14].

Interestingly, the patient developed dysmnesia and subsequent disorientation even in the early stage of the disease. The cerebrum showed asymmetrical

References (27)

  • M.I. Papp et al.

    Glial cytoplasmic inclusions in the CNS of patients with multiple system atrophy (striatonigral degeneration, olivopontocerebellar atrophy and Shy–Drager syndrome)

    J Neurol Sci

    (1989)
  • J.G. Graham et al.

    Orthostatic hypotension and nicotine sensitivity in a case of multiple system atrophy

    J Neurol Neurosurg Psychiatry

    (1969)
  • Y. Nakazato et al.

    Oligodendroglial microtubular tangles in olivopontocerebellar atrophy

    J Neuropathol Exp Neurol

    (1990)
  • N. Arai et al.

    Immunohistochemical study of glial cytoplasmic inclusion in multiple system atrophy

    Brain Nerve

    (1991)
  • H. Abe et al.

    Argyrophilic glial intracytoplasmic inclusions in multiple system atrophy: immunocytochemical and ultrastructural study

    Acta Neuropathol

    (1992)
  • K. Kobayashi et al.

    Cytoskeletal protein abnormalities in patients with olivopontocerebellar atrophy — an immunocytochemical and Gallyas silver impregnation study

    J Neuropathol Appl Neurobiol

    (1992)
  • A. Mochizuku et al.

    Argentophilic intracytoplasmic inclusions in multiple system atrophy

    J Neurol

    (1992)
  • M.I. Papp et al.

    The distribution of oligodendroglial inclusions in multiple system atrophy and its relevance to clinical symptomatology

    Brain

    (1994)
  • Y. Nakazato et al.

    Oligodendroglial microtubular tangles in multiple system atrophy

    Neuropathology

    (1996)
  • K. Kosaka et al.

    Striatonigral degeneration combined with Alzheimer’s disease

    Acta Neuropathol

    (1981)
  • K. Renkawek et al.

    Striatonigral degeneration with neurofibrillary tangles

    Acta Neuropathol

    (1993)
  • D.S. Horoupian et al.

    Striatonigral degeneration, olivopontocerebellar atrophy and ‘atypical’ Pick disease

    Acta Neuropathol

    (1991)
  • H. Abe

    Multiple system degeneration. Clinical and pathological observation of 15 cases of multiple system atrophy (Oppenheimer)

    Yokohama Med Bull

    (1992)
  • Cited by (0)

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