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Marked laterality of olivopontocerebellar pathology in an autopsied patient with MSA: Implications for degeneration and α-synuclein propagation
  1. Misato Ozawa1,2,
  2. Rie Saito1,
  3. Takuya Konno3,
  4. Reiji Koide2,
  5. Shigeru Fujimoto2,
  6. Osamu Onodera3,
  7. Akiyoshi Kakita1
  1. 1 Department of Pathology, Brain Research Institute, Niigata University, Niigata, Japan
  2. 2 Division of Neurology, Department of Medicine, Jichi Medical University, Shimotsuke, Japan
  3. 3 Department of Neurology, Brain Research Institute, Niigata University, Niigata, Japan
  1. Correspondence to Dr Rie Saito, Department of Pathology, Brain Research Institute, Niigata University, Niigata, Japan; riesaito{at}bri.niigata-u.ac.jp

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Introduction

Multiple system atrophy (MSA) is a sporadic adult-onset neurodegenerative disorder characterised by autonomic dysfunction, cerebellar ataxia and parkinsonism, each due to degeneration of the autonomic, olivopontocerebellar (OPC) and striatonigral (SN) systems with accumulation of α-synuclein (Syn) protein. Approximately, 35% of patients with MSA show asymmetric symptoms1; however, histopathological laterality of lesion severity is rarely evident at autopsy, perhaps due partly to the fact that degeneration of the OPC and SN systems is by then usually far advanced. This makes it difficult to determine how the degeneration progresses in patients with MSA. Here, we report an autopsied patient with MSA characterised by marked degeneration laterality and α-Syn accumulation, suggesting a possible mode of protein propagation and consequent neuronal and glial loss.

Results

A Japanese man in his late 70s developed walking difficulty, pollakiuria and constipation, which gradually worsened. Three years later, he was admitted to a hospital. He had no family history of neurological disorders. Neurological examination revealed left-predominant limb ataxia and slight parkinsonism. Orthostatic hypotension or other autonomic symptoms showed no apparent laterality. The finger flexion reflex and hyper-reflexia of the upper and lower limbs were also positive on the left side. Brain MRI showed left-side predominant atrophy of the cerebellum and middle cerebellar peduncle (MCP) (figure 1 A-1,2), and hot cross bun sign in the pons (figure 1 A-3). The clinical diagnosis was MSA cerebellar type (MSA-C). Thereafter, recurrent syncope developed, and wheelchair assistance became necessary a year after diagnosis. The patient died suddenly six years after disease onset and was autopsied, at which time the brain weighed 1095 g.

Figure 1

Brain MRI and neuropathological findings in the olivopontocerebellar (OPC) system. Brain MRI images at 3 years after onset (A-1, 2, 3). Severe atrophy of the cerebellum and brainstem on the T1-weighted sagittal image (A-1). Left predominant atrophy of the middle cerebellar …

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Footnotes

  • X @Osamu_ON

  • Contributors MO, RS and AK designed research project, performed pathological analysis and drafted the manuscript for intellectual content. TK collected clinical data. RK, SF and OO discussed the results and commented on the manuscript text. The authors read and approved the final manuscript.

  • Funding This study was funded by Japan Society for the Promotion of Science (20K1659523H00434) CNS Degenerative Diseases, Research on Policy Planning and Evaluation for Rare and Intractable Diseases, Health, Labour and Welfare Sciences Research Grants (23FC1008).

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.