Cerebellar Cognitive Affective Syndrome in Machado Joseph Disease: Core Clinical Features

Abstract

The cerebellum is no longer considered a purely motor control device, and convincing evidence has demonstrated its relationship to cognitive and emotional neural circuits. The aims of the present study were to establish the core cognitive features in our patient population and to determine the presence of Cerebellar Cognitive Affective Syndrome (CCAS) in this group. We recruited 38 patients with spinocerebellar ataxia type 3 (SCA3) or Machado–Joseph disease (MJD)-SCA3/MJD and 31 controls. Data on disease status were recorded (disease duration, age, age at onset, ataxia severity, and CAG repeat length). The severity of cerebellar symptoms was measured using the International Cooperative Ataxia Rating Scale and the Scale for the Assessment and Rating of Ataxia. The neuropsychological assessment consisted of the Mini-Mental State Examination, Clock Drawing Test, Wechsler Adult Intelligence Scale, Rey–Osterrieth Complex Figure, Wisconsin Card Sorting Test, Stroop Color–Word Test, Trail-Making Test, Verbal Paired Associates, and verbal fluency tests. All subjects were also submitted to the Hamilton Anxiety Scale and Beck Depression Inventory. After controlling for multiple comparisons, spatial span, picture completion, symbol search, Stroop Color–Word Test, phonemic verbal fluency, and Trail-Making Tests A and B were significantly more impaired in patients with SCA3/MJD than in controls. Executive and visuospatial functions are impaired in patients with SCA3/MJD, consistent with the symptoms reported in the CCAS. We speculate on a possible role in visual cortical processing degeneration and executive dysfunction in our patients as a model to explain their main cognitive deficit.

Patients with autosomal dominant spinocerebellar ataxia have more risk of falls, important balance impairment, and decreased ability to function

“…Interestingly, higher risk of falls was not evidenced in SCA6 patients, probably because they present a pure presentation with late onset of symptoms. It must be borne in mind that each SCA type has different neurological signs and symptoms associated with ataxiafor instance, neuropathy and ophthalmoparesis in SCA2 and SCA3, pyramidal signs in SCA1, and dystonia, and other extrapyramidal signs in SCA3 [19][20][21][22] . Therefore, we hypothesized that there will be differences in balance impairment and ability to function in different SCA types.…”

Cognitive Impairment in Native Chinese with Spinocerebellar Ataxia Type 3

“…[7]. Several studies have reported cognitive and psychiatric deficits in patients with SCA3, mainly in the domains of verbal and visual memory, verbal attention, verbal fluency, executive functioning, as well as visuospatial and visuoconstructive abilities [6,8,9]. Nevertheless, none of these cognitive impairments was found to correlate with CAG repeat length in SCA3 [10].…”

Pattern of Peripheral Nerve Involvement in Machado-Joseph Disease: Neuronopathy or Distal Axonopathy? A Clinical and Neurophysiological Evaluation

“…It is caused by an unstable CAG trinucleotide repeat within the coding region of a gene located on chromosome 14q, which leads to an elongated polyglutamine tract in the ataxin-3 protein. MJD is also characterized by variable clinical and pathological features, and recent clinical data has demonstrated a high frequency of extracerebellar symptoms in MJD, which include cognitive and psychiatry disturbances, olfactory dysfunction and sleep disorders [3,4,5,6,7,8]. …”