Spinocerebellar ataxia type 3 presenting simultaneously with motor neuron disease and cerebellar ataxia

Ataxia espinocerebelar tipo 3 apresentando-se simultaneamente com doença do neurônio motor e ataxia cerebelar

A 66-year-old man reported an eight-year history of progressive ataxia and one-year of weakness, fasciculation and muscle atrophy (Figure 1). Examination disclosed hypermetric saccades, diffuse fasciculations and absent deep tendon reflexes. Family history was remarkable for autosomal dominant ataxia (Figure 2). MRI showed cerebellar atrophy. Genetic testing confirmed SCA3 (66 allelic expansion on ATXN3 gene). EMG disclosed diffuse denervation and confirmed motor neuron disease (MND).

Figure 1.
Index patient with spinocerebellar ataxia type 3 and motor neuron disease presenting with forearm flexor muscle atrophy (1A), split hand sign noted as a preferential wasting of first dorsal interossei (1B) and thenar muscles abductor pollicis brevis (1C). Brain MRI showed global diffuse atrophy, more marked on middle and superior cerebellar peduncles, as on cerebellum (1D-E), and cervical spine MRI showed diffuse cervical spinal cord atrophy with no signal changes (1F).

Figure 2.
Heredogram. Family with spinocerebellar ataxia type 3 (SCA3).

Spinocerebellar ataxias (SCAs) may manifest as MND, particularly SCA2. Although SCA3 usually manifest as peripheral nerve involvement in a neuronopathy pattern and anterior horn degeneration, marked MND is uncommon1^,2. SCA3 with simultaneous sporadic amyotrophic lateral sclerosis should also be considered and may be related to accumulation of transactivation-responsive DNA-binding protein 43 (TDP-43) in the lower motor neurons3.

References

• 1. Pinto S, De Carvalho M. Machado-Joseph disease presenting as motor neuron disease. Amyotroph Lateral Scler 2008 Jun;9(3):188-91. https://doi.org/10.1080/17482960701702603
  » https://doi.org/10.1080/17482960701702603
• 2. Moro A, Munhoz RP, Arruda WO, Raskin S, Moscovich M, Teive HA. Spinocerebellar ataxia type 3: subphenotypes in a cohort of brazilian patients. Arq Neuropsiquiatr 2014 Sep;72(9):659-62. https://doi.org/10.1590/0004-282x20140129
  » https://doi.org/10.1590/0004-282x20140129
• 3. Toyoshima Y, Takahashi H. TDP-43 pathology in polyglutamine diseases: with reference to amyotrphic lateral sclerosis. Neuropathology. 2014 Feb;34(1):77-82. https://doi.org/10.1111/neup.12053
  » https://doi.org/10.1111/neup.12053

• Ethical statement:
  Our Ethics Committee has approved this report. Patient provided informed consent for this publication.

Publication Dates

• Publication in this collection
  11 June 2021
• Date of issue
  Sept 2021

History

• Received
  02 May 2020
• Reviewed
  09 Oct 2020
• Accepted
  08 Dec 2020