Postmortem cerebellar and brainstem alterations in episodic ataxia type 1 and 2: Expanding the clinicopathological spectrum
Jeroen J. de Vries1, Maria João da Costa Caiado2,3, Wilfred F.A. den Dunnen2
1 Expertise Center for Movement Disorders, Department of Neurology, 2 Department of Pathology and Medical Biology, Division of Pathology, University Medical Center Groningen, and 3 Department of Molecular Pharmacology, University of Groningen, Groningen, The Netherlands
DOI 10.5414/NP301727
Abstract
Background: Episodic ataxias (EAs) are rare autosomal-dominant channelopathies presenting with recurrent attacks of ataxia and variable neurological features. While MRI studies suggest mild cerebellar atrophy in some patients, detailed neuropathological descriptions are lacking. Materials and methods: We examined postmortem brains and spinal cords from two genetically confirmed patients: EA1 (KCNA1 Val174Phe mutation) and EA2 (CACNA1A A253Y mutation). Routine histology and immunohistochemistry were performed. Results: In EA1, the cerebellar vermis and hemispheres showed narrowing of the folia, segmental Purkinje cell loss, Bergmann gliosis, and scattered torpedoes. The dentate nucleus contained focal lipofuscin-laden macrophages and Rosenthal fibers. Concurrently, α-synuclein pathology (Braak stage 3) was also present, along with sparse age-related tau tangles and minimal vascular amyloid. In EA2, only focal Purkinje cell loss was detected, but novel p62-positive axonal and dendritic inclusions were observed in the cerebellar cortex and inferior olive. No additional α-synuclein, tau, or amyloid pathology was found. A concurrent glioblastoma was identified as the immediate cause of death. Conclusion: These are the first detailed autopsy reports of EA1 and EA2. Both revealed cerebellar pathology, with EA1 showing more pronounced Purkinje cell degeneration, while EA2 demonstrated previously undescribed p62-positive inclusions. These findings expand the clinicopathological spectrum of EAs and highlight the value of postmortem studies in elucidating underlying disease mechanisms.
Author Details
Authors
Departments
- 1 Expertise Center for Movement Disorders, Department of Neurology,
- 2 Department of Pathology and Medical Biology, Division of Pathology, University Medical Center Groningen, and
- 3 Department of Molecular Pharmacology, University of Groningen, Groningen, The Netherlands
Address
Wilfred F.A. den Dunnen, MD, PhD, Associate Professor in Neuropathology, Department Pathology and Medical Biology, University Medical Center Groningen, PO Box 30.001, 9700 RB Groningen, The Netherlands
Email:
[email protected]
Citation
Jeroen J. de Vries, Maria João da Costa Caiado, and Wilfred F.A. den Dunnen.Postmortem cerebellar and brainstem alterations in episodic ataxia type 1 and 2: Expanding the clinicopathological spectrum. ; : 0-8. doi: 10.5414/NP301727.
