Selective Cerebellar Atrophy Associates with Depression and Fatigue in the Early Phases of Relapse-Onset Multiple Sclerosis

Lazzarotto, Andrea; Margoni, Monica; Franciotta, Silvia; Zywicki, Sofia; Riccardi, Alice; Poggiali, Davide; Anglani, Mariagiulia; Gallo, Paolo

doi:10.1007/s12311-019-01096-4

Cited by 19 publications

(26 citation statements)

References 57 publications

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“…While mRN is involved in intra-and inter-limb coordination (Lavoie & Drew, 2002) and probably plays a role in compensating lesions of the corticospinal tract (Belhaj-Saif & Cheney, 2000;Siegel, Fink, Strittmatter, & Cafferty, 2015), pRN has been suggested to be involved in more complex functional networks, including those integrating cognitive-motor functions such as motor learning, error encoding, timing, and control of the ongoing movement (Habas, Guillevin, & Abanou, 2010;Lang et al, 2017;Reid et al, 2009). These observations further point out the association of specific cerebellar lobules with cognitive and affective functions (Koziol et al, 2014;Lazzarotto et al, 2020;Schmahmann & Sherman, 1997). Finally, worth of interest is also the possible role of cerebellar and RN damage in the early development of disabling multiple sclerosis (MS) symptoms such as fatigue and depression (Lazzarotto et al, 2020).…”

Section: Introductionmentioning

confidence: 85%

“…These observations further point out the association of specific cerebellar lobules with cognitive and affective functions (Koziol et al, 2014;Lazzarotto et al, 2020;Schmahmann & Sherman, 1997). Finally, worth of interest is also the possible role of cerebellar and RN damage in the early development of disabling multiple sclerosis (MS) symptoms such as fatigue and depression (Lazzarotto et al, 2020).…”

Section: Introductionmentioning

confidence: 85%

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Early red nucleus atrophy in relapse‐onset multiple sclerosis

Margoni

Poggiali

Zywicki

et al. 2020

Human Brain Mapping

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No study has investigated red nucleus (RN) atrophy in multiple sclerosis (MS) despite cerebellum and its connections are elective sites of MS-related pathology. In this study, we explore RN atrophy in early MS phases and its association with cerebellar damage (focal lesions and atrophy) and physical disability. Thirty-seven relapse-onset MS (RMS) patients having mean age of 35.6 ± 8.5 (18-56) years and mean disease

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Section: Introductionmentioning

confidence: 85%

Section: Introductionmentioning

confidence: 85%

Early red nucleus atrophy in relapse‐onset multiple sclerosis

Margoni

Poggiali

Zywicki

et al. 2020

Human Brain Mapping

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“…Higher lesion load in the left arcuate fasciculus, prefrontal cortex, anterior temporal lobe, and parietal lobe were also found to be associated with depression in MS patients [ 137 ]. Moreover, depression was associated with cortical atrophy of regions located in the bilateral frontal lobes, in particular of the prefrontal cortex, contributing to dysfunctional coping strategies that might promote the development of depressive symptoms [ 138 , 139 ]. Furthermore, a significantly lower Vermis Crus I volume and a reduced olfactory bulb volume were detected in depressed MS patients when compared to non-depressed ones [ 61 , 62 ].…”

Section: Brain Circuits Involved In Psychiatric Symptoms Occurring In Cns Disordersmentioning

confidence: 99%

Insights into the Pathophysiology of Psychiatric Symptoms in Central Nervous System Disorders: Implications for Early and Differential Diagnosis

Menculini

Chipi

Paoletti

et al. 2021

IJMS

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Different psychopathological manifestations, such as affective, psychotic, obsessive-compulsive symptoms, and impulse control disturbances, may occur in most central nervous system (CNS) disorders including neurodegenerative and neuroinflammatory diseases. Psychiatric symptoms often represent the clinical onset of such disorders, thus potentially leading to misdiagnosis, delay in treatment, and a worse outcome. In this review, psychiatric symptoms observed along the course of several neurological diseases, namely Alzheimer’s disease, fronto-temporal dementia, Parkinson’s disease, Huntington’s disease, and multiple sclerosis, are discussed, as well as the involved brain circuits and molecular/synaptic alterations. Special attention has been paid to the emerging role of fluid biomarkers in early detection of these neurodegenerative diseases. The frequent occurrence of psychiatric symptoms in neurological diseases, even as the first clinical manifestations, should prompt neurologists and psychiatrists to share a common clinico-biological background and a coordinated diagnostic approach.

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“…In progressive MS, atrophy of specific cerebellar lobules explains different aspects of motor and cognitive disability [2,3] and cerebellar atrophy is a significant predictor of sustained disability [4]. In the relapsing-remitting (RR) phenotype, a cross-sectional analysis has identified a relationship between cerebellar volume, fatigue and depression [5]. Moreover, several studies, conducted in mixed samples including RRMS patients, suggest a relationship between cerebellar atrophy and motor and cognitive disability [6][7][8][9][10][11][12], with a recent study showing a significant role for baseline cerebellar gray matter (GM) volume as predictor of 1-year Expanded Disability Status Scale (EDSS) score worsening [13].…”

Section: Introductionmentioning

confidence: 99%

Cerebellar pathology and disability worsening in relapsing‐remitting multiple sclerosis: A retrospective analysis from the CombiRx trial

Petracca

Cutter

Cocozza

et al. 2021

Euro J of Neurology

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Background and purpose Cerebellar damage is a valuable predictor of disability, particularly in progressive multiple sclerosis. It is not clear if it could be an equally useful predictor of motor disability worsening in the relapsing‐remitting phenotype. Aim We aimed to determine whether cerebellar damage is an equally useful predictor of motor disability worsening in the relapsing‐remitting phenotype. Methods Cerebellar lesion loads and volumes were estimated using baseline magnetic resonance imaging from the CombiRx trial (n = 838). The relationship between cerebellar damage and time to disability worsening (confirmed disability progression [CDP], timed 25‐foot walk test [T25FWT] score worsening, nine‐hole peg test [9HPT] score worsening) was tested in stagewise and stepwise Cox proportional hazards models, accounting for demographics and supratentorial damage. Results Shorter time to 9HPT score worsening was associated with higher baseline Expanded Disability Status Scale (EDSS) score (hazard ratio [HR] 1.408, p = 0.0042) and higher volume of supratentorial and cerebellar T2 lesions (HR 1.005 p = 0.0196 and HR 2.211, p = 0.0002, respectively). Shorter time to T25FWT score worsening was associated with higher baseline EDSS (HR 1.232, p = 0.0006). Shorter time to CDP was associated with older age (HR 1.026, p = 0.0010), lower baseline EDSS score (HR 0.428, p < 0.0001) and higher volume of supratentorial T2 lesions (HR 1.024, p < 0.0001). Conclusion Among the explored outcomes, single time‐point evaluation of cerebellar damage only allows the prediction of manual dexterity worsening. In clinical studies the selection of imaging biomarkers should be informed by the outcome of interest.

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Selective Cerebellar Atrophy Associates with Depression and Fatigue in the Early Phases of Relapse-Onset Multiple Sclerosis

Cited by 19 publications

References 57 publications

Early red nucleus atrophy in relapse‐onset multiple sclerosis

Early red nucleus atrophy in relapse‐onset multiple sclerosis

Insights into the Pathophysiology of Psychiatric Symptoms in Central Nervous System Disorders: Implications for Early and Differential Diagnosis

Cerebellar pathology and disability worsening in relapsing‐remitting multiple sclerosis: A retrospective analysis from the CombiRx trial

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