A number of neurodegenerative disorders present with a combination of psychiatric, cognitive, and neurological symptoms. Consistent with the existence of the concept of nonmotoric cerebellar functions, preliminary evidence points to cognitive and psychiatric disturbances in patients with diseases affecting the cerebellum. Various neuropsychiatric manifestations are associated with hereditary ataxias.1 Spinocerebellar ataxia type 2 has been described in Cubans, the population being the largest homogenous group of patients with ataxia yet described. It is associated with development of schizophrenic psychosis and cognitive dysfunction, but there is no reported case of mood disturbances especially in childhood populations associated with spinocerebellar ataxia 2.2 We report a case of spinocerebellar ataxia type 2 presenting with acute mood disturbance in an adolescent.
R.K., a 16-year-old Hindu female patient from a lower socioeconomic stratum of rural India, presented to the outpatient department of Centre for Child and Adolescent Psychiatry at Central Institute of Psychiatry, Ranchi, India, with a 2-year history of insidious onset, slowly deteriorating illness characterized by difficulty in walking, unsteady gait, and dysarthric speech. This was combined with a 3-month history of acute onset illness following poor performance in school that was characterized by slowly deteriorating academic interest, irritable mood with periods of excessive and abnormal excitement, and dullness occurring over a period of time. At times there was also crying, expressing suicidal ideations, and making grandiose claims with poor sleep and appetite. Physical examination, including detailed neurological examination, revealed signs suggestive of cerebellar dysfunction including dysarthric speech, slow saccadic movements, cogwheel rigidity of lower limbs, brisk deep tendon reflexes, dysmetria, dysdiadokokinesia, titubation and ataxic gait. There was no nystagmus, intention tremor, hypotonia, or abnormal fundoscopy findings. There was no history of urinary incontinence or progressive loss of body functions. Past history was unremarkable for epilepsy or any major medical ailment.
Mental status examination revealed an irritable patient with psychomotor agitation, over productive speech, elated affect, delusion of grandiosity and persecution, impaired judgment and grade 1 insight. There was family history of karyotypically documented spinocerebellar ataxia type 2 in the patient’s mother, detected at the age of 37, and similar features in her maternal aunt and maternal grandmother. She was subsequently admitted to the inpatient department, and investigation reports revealed cerebellar atrophy on brain MRI and sensory neuropathy involving bilateral lower limbs on nerve conduction studies. Karyotyping with detailed chromosomal analysis using polymerase chain reaction revealed 28 CAG repeats on one allele and 43 on the other (upper limit of normal = 31) at chromosome 12q24. This confirmed the diagnosis of spinocerebellar ataxia type 2, and on the basis of psychiatric evaluation, an impression of mania with psychotic symptoms with a differential diagnosis of mixed affective episode was made and the patient was managed subsequently with quetiapine, up to 100 mg/day, and sodium valproate, 600 mg/day, as a mood stabilizer. The patient showed gradual improvement over 4 weeks after which she was discharged with the same regimen.
Spinocerebellar ataxias are a group of autosomal disorders affecting the spinal cord and the cerebellum. Spinocerebellar ataxia types 1, 2, 3, 6, 7 and spinocerebellar ataxia 17 are caused by CAG triplet repeat expansions in different genes. An earlier age of onset and more aggressive disease in subsequent generations (anticipation) are due to expansions of the CAG triplet repeat.3 Researchers examining hereditary ataxia using largely undefined psychiatric diagnostic schemes found presence of psychiatric disorders in approximately 23% of subjects, 12% of their neurologically normal family members, and 3% of the neurologically normal individuals from families without neurological disease.4 This is the first known reported case of affective disorder in a patient with spinocerebellar ataxia type 2. Development of psychiatric symptomatology in these cases poses a serious clinical implication for early detection and intervention as this might lead to decompensation of the functional status of the patient if left untreated. Also motor symptoms might be mistaken for side effects of medications which requires use of safer agents.
Spinocerebellar ataxia type 2 is an autosomal dominant neurodegenerative disease caused by a pathological expansion of a CAG repeat on chromosome 12q24. The age of onset ranges from 2 to 65 years old, though this disease starts in early adulthood which is not the case with our patient. The disease is characterized by development of progressive cerebellar ataxia of trunk and limbs with impairment of gait, slow saccadic eye movements, dysathria, parkinsonian rigidity, optic disk pallor, mild spasticity, and retinal degeneration. Development of mood symptoms in our case requires discussion. Although our case had psychotic symptoms, MRI did not reveal any striatal involvement, which goes against the hypothesis of development of psychosis in cerebellar dysfunction.5 Alternatively, development of mood symptoms can be explained on the basis of the hypothesis put forth by Schmahmann6 called the “Cerebellar Cognitive Affective Syndrome,” which implies that a universal cerebellar transform facilitates automatic modulation of behavior around a homeostatic baseline, and the behavior being modulated is determined by the specificity of anatomic subcircuits, or loops, within the cerebrocerebellar system. Damage to the cerebellar component of the distributed neural circuit subserving sensorimotor, cognitive, and emotional processing disrupts the universal cerebellar transform, leading to significant emotional disturbances in such cases.6 Isolated cerebellar dysfunction is associated with development of rapid cycling unipolar mania, depression, and bipolar disorder.7 Significant cerebellar dysfunction in our case might explain development of mood symptoms, though it would be difficult to negate that the development of mood disorder might be primary and unrelated to cerebellar dysfunction although posing a serious question regarding continuation of mood stabilizer for the long term in our case.
Also, certain psychiatric disorders also exhibit genetic anticipation including schizophrenia and bipolar affective disorder. The degree of expansion often correlates with genetic anticipation. This has led researchers in psychiatric genetics to search for unstable DNA sites as susceptibility factors for schizophrenia and bipolar affective disorder. Initial studies of genome-wide trinucleotide repeats suggested possible association of large CAG/CTG repeat tracts with schizophrenia and bipolar affective disorder. More recently, three loci have been identified that contain large, unstable CAG/CTG repeats that occur frequently in the population. These repeats localize to an intron on 13q21, spinocerebellar ataxia 8 that is believed to be responsible for a form of spinocerebellar ataxia. Preliminary evidence suggests that large repeat alleles at spinocerebellar ataxia 8 that are nonpenetrant for ataxia may be a susceptibility factor for major psychosis.8 The co-occurrence of the two disorders lends further support to the hypothesis of trinucleotide repeat expansions as being a common vulnerability factor which supports development of mood symptoms in our case.
This case illustrates the importance of considering the possibility of psychiatric symptoms in patients who present with neurodegenerative disorders. In particular, clinicians should be quick to evaluate unexpected cognitive or neurological symptoms that may be interpreted mistakenly as psychiatric in origin or as side effects of psychotropic medications.
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