This case illustrates that ALS can be associated and even begin with a movement disorder, namely cerebellar ataxia. In the first visit the patient presented with a pancerebellar syndrome plus already some upper motor neuron signs. This observation, the subsequent clinical evolution, and the lack of other plausible aetiology for the cerebellar ataxia, makes us believe that ALS with the genetic mutation in SOD1 gene is the final diagnosis and explains all the features presented by the patient.
ALS was traditionally deemed a pure motor disorder, however neuroimaging and pathologic studies have demonstrated a multisystem involvement, including structures related to movement disorders, like the basal ganglia and cerebellum. Specifically, in SOD1 mutations, dentate nucleus and spinocerebellar tracts degeneration have been documented.8,9 In a meta-analysis by Gellersen et al, specific patterns of gray matter loss in the cerebellum of ALS patients were gathered, demonstrating that atrophy clustered in vermal and paravermal regions, alongside the inferior cerebellum and hemispheric lobules V, VI and VIII.10 Furthermore, cerebellar atrophy has also been highlighted in ALS-FTD spectrum disease, in which has been shown that specific patterns of atrophy correlate with motor, cognitive and neuropsychiatric symptoms. 11
Despite being recognized that cerebellar involvement is a consistent feature of ALS, the “ALS-ataxia continuum” remains still debatable in comparison to the strong evidence of the “ALS-FTD continuum” – more studies beyond the ALS-FTD spectrum disease are needed, including sporadic and other genetic ALS cases, like with SOD1 mutation.12 In a recent case report publication, it was highlighted the co-occurrence and potential multifactorial role of a pathogenic variant in SOD1 gene plus a variant of uncertain significance in Cp gene, in a patient presenting with late-onset cerebellar ataxia with an unilateral ALS profile.13 This raises the possibility of other co-occurrent mutations having a role in these complex phenotypes.
In summary, cerebellar pathology has been demonstrated in ALS and probably has an important role modulating some of the cardinal features of this motor neuron disease. The reason why rarely patients develop cerebellar ataxia and the majority do not still remains to be elucidated.