Cognition in SCA21 reflects developmental and adult onset cerebellar cognitive affective syndrome.

Sir, We read with interest the article by Delplanque et al. (2014) entitled: ‘TMEM240 mutations cause spinocerebellar ataxia type 21 with mental retardation and severe cognitive impairment’. The striking feature of the clinical presentation was not only the cerebellar ataxia and cerebellar volume loss on imaging, but also the cognitive and neurobehavioural impairments that were pervasive, and— in the younger onset cases—severe enough to warrant the designation of severe mental retardation. The neuropsychological examinations of the SCA21 kindreds disclosed moderate impairments in attention, executive function, short-term, working and episodic memory abilities and, marked impairments in action planning, abstract reasoning, language and visuospatial functions. The authors also report neuropsychiatric phenomena including impulsivity, aggression and apathy etc. Despite the centrality of the cognitive and neurobehavioural features in this report of the genetic basis and clinical manifestations of SCA21, the authors do not reflect on the importance of their observations for our understanding of the wider role of the cerebellum beyond motor control, of which this case series represents a prime example. A framework now exists within which cognitive impairments in widespread cerebellar neurodegenerative disorders may be understood. The cerebellar cognitive affective syndrome (CCAS; Schmahmann and Sherman, 1998) is characterized by impairments in executive, visuospatial and linguistic functions as well as changes in affect. The emotional and behavioural symptoms that characterize the affective changes were further defined within the domains of attentional control, emotional control, autism spectrum, psychosis spectrum, and social skill set (Schmahmann et al., 2007). These neurobehavioural phenomena are viewed as manifestations of dysmetria of thought, loss of the universal cerebellar transform applied not only to sensorimotor processing, but also to intellectual function, emotion and autonomic control (Schmahmann, 1991, 2010). Further, the relatively greater impact on cognitive and emotional development in the early onset cases is thought to reflect the loss of sustaining connections between cerebellum and associative and paralimbic regions of the cerebral cortex that are essential for normal development. In the absence of obvious pathology in cerebral cortical and subcortical regions, and in the presence of the primary anatomical locus of pathology in the cerebellum in SCA21, it is reasonable to consider that the bulk of the cognitive deficits in this disorder are consistent with developmental or adult onset CCAS. A wide range of cognitive deficits are now recognized in patients with spinocerebellar ataxias and other hereditary ataxias, including impairments in executive function, visual doi:10.1093/brain/awu382 BRAIN 2015: 138; 1–3 | e364