Depressive and Memory Symptoms as Presenting Features of Spinocerebellar Ataxia
2006; American Psychiatric Association Publishing; Volume: 18; Issue: 3 Linguagem: Inglês
10.1176/appi.neuropsych.18.3.420
ISSN1545-7222
AutoresAaron McMurtray, D. G. Clark, M. K. Flood, S. Perlman, M. F. Mendez,
Tópico(s)Mitochondrial Function and Pathology
ResumoBack to table of contents Previous article Next article CLINICAL RESEARCH REPORTSFull AccessDepressive and Memory Symptoms as Presenting Features of Spinocerebellar AtaxiaAaron M. McMurtray M.D.David G. Clark M.D.Mary K. Flood R.N., C.N.S., P.N.H.Susan Perlman M.D.Mario F. Mendez M.D., Ph.D.Aaron M. McMurtray M.D.Search for more papers by this authorDavid G. Clark M.D.Search for more papers by this authorMary K. Flood R.N., C.N.S., P.N.H.Search for more papers by this authorSusan Perlman M.D.Search for more papers by this authorMario F. Mendez M.D., Ph.D.Search for more papers by this authorPublished Online:1 Jul 2006AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail T he autosomal dominant spinocerebellar ataxias (SCA) are a heterogeneous group of disorders that differ in the extent of neuropathological involvement of cerebellum, brainstem, and basal ganglia. It is well established that these disorders can be manifested in neuropsychiatric symptoms, 1 but it is less understood how frequently these symptoms occur on presentation and the extent to which they differ among SCA subtypes. Moreover, the differences in presenting neuropsychiatric symptoms between SCA types may reflect differences in the underlying neuropathology of the disorder. We report the frequency depressive and memory symptom complaints, the two most common neuropsychiatric symptoms in SCA, 1 among a large cohort of SCA patients presenting to a large university-based ataxia center. We reviewed the intake neuropsychiatric assessments for the four common SCA subtypes with distinctive underlying differences in neuropathology. The findings of this study highlight the importance of a neuropsychiatric evaluation of patients who present with a potentially inheritable ataxic disorder. METHOD This study reviewed 76 subjects presenting to a large university-based ataxia program. The patients underwent extensive initial evaluations, including intake neurological and psychiatric assessment, neurological examinations, laboratory tests (routine tests and thyroid function tests, B 12 level, and VDRL), and magnetic resonance imaging (MRI) of the brain. If the patients met clinical criteria for a spinocerebellar ataxia, further genetic testing was obtained. All patients diagnosed with SCA1, SCA2, SCA3, or SCA6, the common SCA subtypes, were included in this study. An intake neuropsychiatric assessment identified memory and depressive complaints. These two symptoms are the most common neuropsychiatric symptoms in SCA. An ataxia specialist screened the patients and their caregivers for neuropsychiatric symptoms, especially depressive and memory problems. The patients were screened for the following symptoms of depression: depressed mood, anhedonia, and lack of interest in usual activities. 2 They were screened for the following symptoms of memory difficulty: difficulty remembering recent events or problems incorporating new information. RESULTS This study included a total of 12 SCA1, 22 SCA2, 20 SCA3, and 22 SCA6 patients ( Table 1 ). Depressive symptoms were significantly greater in SCA3 (60%) compared to the other SCA types (SCA1 [25%], SCA2 [23%], and SCA6 [27%]) ( Figure 1 ). In contrast, memory symptoms were less frequent, although not at significance level, in SCA6 (23%) compared to the other SCA subtypes (SCA1 [42%], SCA2 [45%], and SCA3 [50%]; χ 2 =3.63, df=3, p=0.057). TABLE 1. Characteristics of 76 Patients with Spinocerebellar AtaxiaTABLE 1. Characteristics of 76 Patients with Spinocerebellar AtaxiaEnlarge tableFIGURE 1. Depressive and Memory Symptoms in Major Spinocerebellar Ataxia *Significantly higher rate of depressive complaints than found in other spinocerebellar ataxia subtypes (χ 2 =8.02, df=3, p<0.005) We performed an additional analysis comparing the presence of initial neuropsychiatric symptoms with two measures of disease severity, disease duration, and CAG repeat length ( Table 1 ). No significant associations occurred after Bonferroni correction for multiple comparisons. DISCUSSION Patients with a spinocerebellar ataxia may have depression or memory difficulty on initial presentation with their disorder. 3 , 4 In this large series of patients evaluated in a university-based ataxia center, depressive symptoms were significantly more frequent in those with SCA3 compared with all other SCA patients. The greater depressive complaints in SCA3 may be due to dysfunction of frontal-subcortical circuits in the basal ganglia, structures that are uniquely involved in SCA3 as opposed to the other subtypes. The presence of early neuropsychiatric features in SCA emphasizes the need for careful behavioral screening and assessment of these patients. Patients with SCA are usually seen in neurological programs where their disturbances in gait, coordination, and movements may take precedence over evaluations for depression or memory difficulty. The patients in this study were initially screened for these difficulties, resulting in subsequent referrals for treatment of depression or for neuropsychological testing, as indicated. This study further indicates that the presence of early neuropsychiatric symptoms can be diagnostic clues to the particular subtype of SCA. In addition to cerebellar degeneration, differences in other neuropathological involvement between SCA subtypes may account for differences in neuropsychiatric manifestations. In SCA1 there is variable olivopontocerebellar atrophy (OPCA), with more prominent involvement of the dentate nuclei. 5 – 7 In SCA2 there is OPCA with nigral degeneration and less prominent involvement of the dentate nuclei. 1 In SCA3 there is a lack of OPCA, but significant pathology in the dentate nuclei, substantia nigra, subthalamic nuclei, striatum and globus pallidus. 8 Finally, in SCA6 the pathology is uniquely restricted to the cerebellum. 9 The involvement of the basal ganglia in SCA3 may account for the increased frequency of depressive symptoms in this subtype. A number of neurological disorders that involve the basal ganglia and its connections, such as Huntington's disease and Parkinson's disease, also result in similar depressive symptoms. The greater frequency of depressive complaints in SCA3 patients, as in these other neurological disorders, may result from disruption of reciprocal connections between the frontal lobes and the striatum within the basal ganglia. 1This study is a preliminary report of screening for initial neuropsychiatric symptoms in spinocerebellar ataxia. One limitation of this study is the focus on initial symptoms. This report, however, emphasizes the importance of patient or caregiver report of the experience of neuropsychiatric difficulty; experiences which may lead them to seek clinical consultation. Second, the study is limited to the common neuropsychiatric symptoms, rather than a more extensive survey of behavioral symptoms. Finally, there is no comparison group consisting of patients diagnosed with a non-SCA chronic movement disorder. This report, however, focuses on a comparison across different subtypes of SCA. In sum, early neuropsychiatric symptoms are common in SCA, particularly depressive symptoms in SCA3. This preliminary report shows that the likelihood of presentation with neuropsychiatric symptoms varies depending on the SCA type and its underlying neuropathology. Neuropsychiatric symptoms, such as depressive and memory symptoms, are common presenting symptoms in SCA and should be evaluated in all patients presenting with a progressive ataxia.Received November 7, 2005; accepted November 21, 2005. Drs. McMurtray, Clark, and Mendez are affiliated with the Department of Neurology, University of California at Los Angeles (UCLA), and the Veterans Affairs Greater Los Angeles Healthcare System. Drs. Flood and Perlman are affiliated with the University of California at Los Angeles, Los Angeles, California. Address correspondence to Dr. McMurtray; Neurobehavior (166AF), Veterans' Affairs Greater Los Angeles Healthcare, 11301 Wilshire Blvd., Los Angeles, CA 90073; [email protected] (E-mail).Copyright © 2006 American Psychiatric Publishing, Inc.References1. Mendez MF, Cummings JL, eds: Dementia: A Clinical Approach, 3 rd ed. Philadelphia, Elsevier Publishing Company, 2003 Google Scholar2. American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders (4 th Ed, text revision). Washington, DC, APA, 2000 Google Scholar3. Kish SJ, El-Awar M, Stuss D, et al: Neuropsychological test performance in patients with dominantly inherited spinocerebellar ataxia: relationship to ataxia severity. Neurology 1994; 44:1738–1746Google Scholar4. Geschwind DH: Focusing attention on cognitive impairment in spinocerebellar ataxia. Arch Neurol 1999; 56:20–22Google Scholar5. Kish SJ, Schut L, Simmons J, et al: Brain acetylcholinesterase activity is markedly reduced in dominantly-inherited olivopontocerebellar atrophy. J Neurol Neurosurg Psychiatry 1998; 51:544–548Google Scholar6. Kish SJ, El-Awar M, Schut L, et al: Cognitive deficits in olivopontocerebellar atrophy: implications for the cholinergic hypothesis of Alzheimer's disease. Ann Neurol 1988; 24:200–206Google Scholar7. Gilman S, Sima AAF, Junck L, et al: Spinocerebellar ataxia type 1 with multiple system degeneration and glial cytoplasmic inclusions. Ann Neurol 1996; 39:241–255Google Scholar8. Sudarsky L, Coutinho P: Machado-Joseph disease. Clin Neurosci 1995; 3:17–22Google Scholar9. Gomez CM, Thompson RM, Gammack JT, et al: Spinocerebellar ataxia type 6: gaze evoked and vertical nystagmus, Purkinje cell degeneration, and variable age of onset. Ann Neurol 1997; 42:933–950Google Scholar FiguresReferencesCited byDetailsCited ByA Systematic Review of the Spectrum and Prevalence of Non‐Motor Symptoms in Adults with Hereditary Cerebellar Ataxias6 September 2022 | Movement Disorders Clinical Practice, Vol. 7Consensus Paper: Strengths and Weaknesses of Animal Models of Spinocerebellar Ataxias and Their Clinical Implications10 August 2021 | The Cerebellum, Vol. 21, No. 3Psychiatric-Like Impairments in Mouse Models of Spinocerebellar Ataxias8 January 2022 | The Cerebellum, Vol. 22Rating scales and biomarkers for CAG-repeat spinocerebellar ataxias: Implications for therapy developmentJournal of the Neurological Sciences, Vol. 424Hippocampal mitochondrial dysfunction and psychiatric-relevant behavioral deficits in spinocerebellar ataxia 1 mouse model25 March 2020 | Scientific Reports, Vol. 10, No. 1Non‐motor symptoms in patients with autosomal dominant spinocerebellar ataxia5 August 2020 | Acta Neurologica Scandinavica, Vol. 142, No. 4Conversion of individuals at risk for spinocerebellar ataxia types 1, 2, 3, and 6 to manifest ataxia (RISCA): a longitudinal cohort studyThe Lancet Neurology, Vol. 19, No. 9Nonmotor symptoms in spinocerebellar ataxias (SCAs)27 August 2019 | Cerebellum & Ataxias, Vol. 6, No. 1Twenty-five years since the identification of the first SCA gene: history, clinical features and perspectives for SCA11 August 2018 | Arquivos de Neuro-Psiquiatria, Vol. 76, No. 8Karyopherin α-3 is a key protein in the pathogenesis of spinocerebellar ataxia type 3 controlling the nuclear localization of ataxin-323 February 2018 | Proceedings of the National Academy of Sciences, Vol. 115, No. 11Bidirectional Connections between Depression and Ataxia Severity in Spinocerebellar Ataxia Type 3 Patients15 May 2018 | European Neurology, Vol. 79, No. 5-6International Review of Psychiatry, Vol. 29, No. 5Fragile X-associated tremor/ataxia syndrome: phenotypic comparisons with other movement disorders14 July 2016 | The Clinical Neuropsychologist, Vol. 30, No. 6Depression and clinical progression in spinocerebellar ataxiasParkinsonism & Related Disorders, Vol. 22Psychiatric disorders, spinocerebellar ataxia type 3 and CAG expansion13 June 2015 | Journal of Neurology, Vol. 262, No. 7Journal of the Neurological Sciences, Vol. 347, No. 1-2Neurogenetic disordersPsychiatry and Clinical Neurosciences, Vol. 62, No. 5 Volume 18Issue 3 Summer, 2006Pages 420-422 Metrics PDF download History Published online 1 July 2006 Published in print 1 July 2006
Referência(s)