MSA is clinically characterized by the variable combination of autonomic failure, parkinsonism, cerebellar ataxia, and pyramidal signs, and includes the previously called striatonigral degeneration (parkinsonian features predominate), sporadic olivopontocerebellar atrophy (OPCA) (cerebellar features predominate), and the Shy-Drager syndrome (autonomic dysfunction predominates). Histologically, all subtypes of MSA show glial cytoplasmic inclusions in oligodendrocytes of the cerebral white matter, which contain alpha-synuclein. Therefore MSA ranks among the synucleinopathies, but the reason explaining the different cellular topography of a-synuclein (neuronal in PD, glial in MSA) is still unknown (90).
The majority of data describing neuropsychiatric disturbances in MSA are case reports. Although these reports demonstrate that neuropsychiatric symptoms occur in MSA, few systematical studies have been published. In one of the largest retrospective chart reviews of pathologically proven MSA, clinical data of 203 patients were reported. Unfortunately, neuropsychiatric assessment was restricted to "bedside impressions" of cognition. Mild intellectual impairment was noted in 22%, moderate impairment in 2%, and only one patient had severe dementia (91).
Several reports have described depressive symptoms in MSA (16,92-95). In a study of 15 patients clinically diagnosed with Shy-Drager syndrome using the BDI, 86% scored in the depressed range (i.e., BDI score 10-15), and 29% scored in the moderately depressed range (BDI score 16-19). The mean BDI score was 14.4. This score is comparable to that reported in a community-based sample of patients with PD, who had a mean BDI score of 12.8, compared to 7.9 in patients with non-neurological chronic disease (diabetes mellitus) and 5.9 in healthy elderly controls (52). Severity of depression did not correlate with disability or ability to perform activities of daily living (ADL) (95). In another study using the BDI, 3 of 15 (20%) patients had a score over 15, and MSA patients had similar severity of depression as PD patients (94). The importance of depression in MSA is underlined by reports showing that MSA patients may initially present with an affective disturbance (92,96). Fetoni et al. compared 12 MSA with 12 PD patients matched for age and motor disability at baseline before and after levodopa therapy using the HAM-D and the BPRS. Only 1 of the 12 MSA patients had a HAM-D score of 18 (indicating a moderate-severe depression). At baseline patients with PD were more depressed and anxious than patients with MSA who, by contrast, showed apathy. After levodopa, depression and anxiety of patients with PD improved significantly, whereas the apathy in patients with MSA did not change (16).
Psychotic symptoms have been described in MSA (97-100), also as part of affective disturbances (101). Of special interest for diagnostic thinking is the observation that paranoid-hallucinatory psychosis with organic character can be initial manifestation of MSA (97,99). The patients described by Ehrt et al. also exhibited visual hallucinations, a symptom typically seen in other synucleinopathies such as DLB and PD. However, in a relatively large clinico-pathologic comparative study, "neuropsychiatric toxicity" was reported to be less common in MSA (n = 38) than PD patients (102). However, this term included confusion or hallucinations or the combination of both, the proportion of dementia was higher in PD than MSA, the number and dosage of dopaminergic drugs in the two groups were not comparable, and the assessments were retrospective and unstructured. Thus, it is not yet proven that visual hallucinations are less common in MSA than PD.
Several studies have reported sleep disorders in MSA (64,103-107). Wright et al. describe a polysomnographically confirmed RBD associated with Shy-Drager syndrome (108). Motor dyscontrol in REM sleep has been described in 90% of patients with MSA (104). Among 93 patients with RBD, 14 patients had MSA, 25 PD, and only 1 had PSP (109). And similarly, in a recent study of 15 patients with RBD, the neuropathological diagnosis was DLB in 12 and MSA in 3 cases (64). In a comparison of unselected patients with MSA (n = 57) with 62 age- and sex-matched PD patients, 70% of patients with MSA complained of sleep disorders compared with 51% of patients with PD, and RBD was present in 48% of the MSA patients (106). Decreased nigrostriatal dopaminergic projections may contribute to RBD in MSA (107).
In summary, MSA patients frequently suffer from depression and sleep disorders, including RBD, and visual hallucinations, also seem to be quite common. Thus, the neuropsychiatry pattern resembles that of DLB and PD, suggesting clinical similarities in disorders with a-synuclein pathology (110). In fact, one patient with a clinical diagnosis of MSA turned out at autopsy to have diffuse Lewy body disease (111), supporting the interrelationship of these disorders.
Although few studies have explored the neuropsychiatry symptoms of parkinsonian disorders other than PD and DLB, some preliminary hypotheses regarding the potential diagnostic value of the neuropsychiatric assessment can be postulated. The a-synucleinopathies DLB and PD, as well as MSA, are characterized by the frequent occurrence of hallucinations and delusions, which may be related to Lewy bodies in the temporal lobe or cholinergic deficits. In addition, depression and anxiety are common, and are possibly related to the additional involvement of monoaminergic brainstem nuclei. Finally, RBD seem to be a marker for these disorders. In contrast, tauopathies such as PSP and CBD are characterized by very high frequency of apathy, possibly related to the marked hypostimulation of orbital and medial frontosubcortical circuits owing to involvement of several basal ganglia nuclei, and disinhibition, possibly secondary to frontal lobe involvement. A high frequency of depression has been reported in CBD, which may be caused in part by involvement of brainstem monoaminergic nuclei. However, depression in parkinsonian disorders probably has a multifactorial etiology, including a wide range of neurological and neurochemical changes in combination, and interaction, with psychosocial factors. Future research should further explore the symptom pattern using standardized diagnostic instruments and the underlying brain pathology of neuropsychiatric features in patients with PSP, CBD, and MSA (see Future Research Issues).
Was this article helpful?