Cerebellar contribution to motor and cognitive performance in multiple sclerosis: An MRI sub-regional volumetric analysis

2016 ◽  
Vol 23 (9) ◽  
pp. 1194-1203 ◽  
Author(s):  
Alessandro D’Ambrosio ◽  
Elisabetta Pagani ◽  
Gianna C Riccitelli ◽  
Bruno Colombo ◽  
Mariaemma Rodegher ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cognitive Performance ◽  
Motor Performance ◽  
Statistical Parametric Mapping ◽  
Progressive Multiple Sclerosis ◽  
Volumetric Analysis ◽  
Linear Regression Models ◽  
Hyperintense Lesion ◽  
Brain Volumes ◽  
Cerebellar Volume

Objective: To investigate the role of cerebellar sub-regions on motor and cognitive performance in multiple sclerosis (MS) patients. Methods: Whole and sub-regional cerebellar volumes, brain volumes, T2 hyperintense lesion volumes (LV), and motor performance scores were obtained from 95 relapse-onset MS patients and 32 healthy controls (HC). MS patients also underwent an evaluation of working memory and processing speed functions. Cerebellar anterior and posterior lobes were segmented using the Spatially Unbiased Infratentorial Toolbox (SUIT) from Statistical Parametric Mapping (SPM12). Multivariate linear regression models assessed the relationship between magnetic resonance imaging (MRI) measures and motor/cognitive scores. Results: Compared to HC, only secondary progressive multiple sclerosis (SPMS) patients had lower cerebellar volumes (total and posterior cerebellum). In MS patients, lower anterior cerebellar volume and brain T2 LV predicted worse motor performance, whereas lower posterior cerebellar volume and brain T2 LV predicted poor cognitive performance. Global measures of brain volume and infratentorial T2 LV were not selected by the final multivariate models. Conclusion: Cerebellar volumetric abnormalities are likely to play an important contribution to explain motor and cognitive performance in MS patients. Consistently with functional mapping studies, cerebellar posterior–inferior volume accounted for variance in cognitive measures, whereas anterior cerebellar volume accounted for variance in motor performance, supporting the assessment of cerebellar damage at sub-regional level.

scholarly journals A comprehensive assessment of cerebellar damage in multiple sclerosis using diffusion tractography and volumetric analysis

2011 ◽  
Vol 17 (9) ◽  
pp. 1079-1087 ◽  
Author(s):  
VM Anderson ◽  
CAM Wheeler-Kingshott ◽  
K Abdel-Aziz ◽  
DH Miller ◽  
A Toosy ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Upper Limb ◽  
Mean Diffusivity ◽  
Volumetric Analysis ◽  
Motor Deficit ◽  
Superior Cerebellar Peduncle ◽  
Radial Diffusivity ◽  
Linear Regression Models ◽  
Clinical Scores ◽  
Cerebellar Peduncle

Background: White matter (WM) and grey matter (GM) brain damage in multiple sclerosis (MS) is widespread, but the extent of cerebellar involvement and impact on disability needs to be clarified. Objective: This study aimed to assess cerebellar WM and GM atrophy and the degree of fibre coherence in the main cerebellar connections, and their contribution to disability in relapsing–remitting MS (RRMS) and primary progressive MS (PPMS). Methods: Fourteen patients with RRMS, 12 patients with PPMS and 16 healthy controls were recruited. Cerebellar WM and GM volumes and tractography-derived measures from the middle and superior cerebellar peduncles, including fractional anisotropy (FA), mean diffusivity (MD), and directional diffusivities, were quantified from magnetic resonance imaging (MRI). Patients were assessed on clinical scores, including the MS Functional Composite score subtests. Linear regression models were used to compare imaging measures between 12 RRMS, 11 PPMS and 16 controls, and investigate their association with clinical scores. Results: Patients with PPMS showed reduced FA and increased radial diffusivity in the middle cerebellar peduncle compared with controls and patients with RRMS. In PPMS, lower cerebellar WM volume was associated with worse performance on the upper limb test. In the same patient group, we found significant relationships between superior cerebellar peduncle FA and upper limb function, and between superior cerebellar peduncle FA, MD and radial diffusivity and speed of walking. Conclusion: These findings indicate reduced fibre coherence in the main cerebellar connections, and link damage in the whole cerebellar WM, and, in particular, in the superior cerebellar peduncle, to motor deficit in PPMS.

scholarly journals Cerebrospinal fluid mtDNA concentration is elevated in multiple sclerosis disease and responds to treatment

2017 ◽  
Vol 24 (4) ◽  
pp. 472-480 ◽  
Author(s):  
Cyra E Leurs ◽  
Petar Podlesniy ◽  
Ramon Trullas ◽  
Lisanne Balk ◽  
Martijn D Steenwijk ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Disease Progression ◽  
Progressive Multiple Sclerosis ◽  
Neurologic Disease ◽  
Brain Volumes ◽  
Multiple Sclerosis Disease ◽  
Relapsing Remitting ◽  
Relapsing Remitting Multiple Sclerosis ◽  
Digital Polymerase Chain Reaction

Background: Mitochondrial dysfunction is increasingly recognized as an important feature of multiple sclerosis (MS) pathology and may be relevant for clinical disease progression. However, it is unknown whether mitochondrial DNA (mtDNA) levels in the cerebrospinal fluid (CSF) associate with disease progression and therapeutic response. Objectives: To evaluate whether CSF concentrations of mtDNA in MS patients can serve as a marker of ongoing neuropathology and may be helpful to differentiate between MS disease subtypes. To explore the effect of disease-modifying therapies on mtDNA levels in the CSF. Methods: CSF mtDNA was measured using a digital polymerase chain reaction (PCR) CSF mtDNA in two independent MS cohorts. The cohorts included 92 relapsing-remitting multiple sclerosis (RRMS) patients, 40 progressive multiple sclerosis (PMS) patients (27 secondary progressive and 13 primary progressive), 50 various neurologic disease controls, and 5 healthy controls. Results: Patients with PMS showed a significant increase in CSF mtDNA compared to non-inflammatory neurologic disease controls. Patients with higher T2 lesion volumes and lower normalized brain volumes showed increased concentration of mtDNA. Patients treated with fingolimod had significantly lower mtDNA copy levels at follow-up compared to baseline. Conclusion: Our results showed a non-specific elevation of concentration of mtDNA in PMS patients. mtDNA concentrations respond to fingolimod and may be used to monitor biological effect of this treatment.

A Septuagenarian With Progressive Hemiparesis

2021 ◽  
pp. 48-50
Author(s):  
Roman Kassa ◽  
B. Mark Keegan
Keyword(s):  
Multiple Sclerosis ◽  
Late Onset ◽  
Progressive Multiple Sclerosis ◽  
Oligoclonal Bands ◽  
Hyperintense Lesion ◽  
Fluid Analysis ◽  
Hemiparetic Gait ◽  
Magnetic Resonance Imaging Mri ◽  
Disease Modifying Agents ◽  
The Right

A 78-year-old man with no pertinent medical history sought care for an 18-month history of progressive right lower extremity weakness, gait impairment, and falls. On neurologic examination, he had a hemiparetic gait. He had normal higher cognitive function and cranial nerve function. Motor examination showed decreased bulk over the right hand with no fasciculations, mild spasticity over the right leg, and right hemiparesis with an upper motor neuron pattern. Deep tendon reflexes were brisk throughout his limbs, and he had an extensor plantar reflex on the right side. He had impaired vibratory sense at the toes, with otherwise normal sensory and coordination examinations. Magnetic resonance imaging (MRI) of the brain showed ovoid periventricular and punctate subcortical and deep white matter T2 hyperintense foci. Some of these had corresponding T1 hypointensity. MRI of the cervical spine showed 1 eccentrically located T2 hyperintense lesion over the right lateral aspect of C2. Cerebrospinal fluid analysis showed no pleocytosis, an increased protein concentration of 66 mg/dL, and 4 unique oligoclonal bands. A diagnosis of primary progressive multiple sclerosis, very late onset, was made. With any diagnosis of late-onset multiple sclerosis, a decision about whether multiple sclerosis disease-modifying agents are indicated should be carefully considered. Our older patient had a progressive disease course, and neuroimaging studies did not reveal evidence of active disease. Based on this, a decision was made to monitor him clinically and radiologically. Management of spasticity with regular daily stretching exercises was discussed with him. A first clinical manifestation of multiple sclerosis can occur at a later-than-typical age. Most studies consider an onset at age 50 years or older to be late-onset multiple sclerosis, whereas first symptoms occurring at age 60 years or older are commonly referred to as very late–onset MS.

scholarly journals Enlarged perivascular spaces are not associated with vascular co-morbidities, clinical outcomes, and brain volumes in people with secondary progressive multiple sclerosis

2020 ◽  
Vol 6 (4) ◽  
pp. 205521732096450
Author(s):  
Lindsey Wooliscroft ◽  
Erin Boespflug ◽  
Andrea Hildebrand ◽  
Kathleen Shangraw ◽  
Elizabeth Silbermann ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Outcomes ◽  
Progressive Multiple Sclerosis ◽  
Secondary Progressive Multiple Sclerosis ◽  
Perivascular Spaces ◽  
Centrum Semiovale ◽  
Informative Marker ◽  
Brain Volumes ◽  
Secondary Progressive ◽  
Disability Status

Background In secondary progressive multiple sclerosis (SPMS) significance of enlarged perivascular spaces (ePVS) is unknown. Objectives, Methods: Analysis of associations between vascular co-morbidities, clinical outcomes, and volumetrics with categorical ePVS scores in midbrain, basal ganglia (BG), and centrum semiovale (CSO) in SPMS(n-46). Results, Conclusion: In BG, advancing age (Z = 2.68) and lower Expanded Disability Status Scale (Z = −2.04) were associated with increasing ePVS score. In CSO, advancing age (Z = 2.66) and male gender (Z = 2.45) were associated with increasing ePVS score. No associations between ePVS score and vascular co-morbidities or volumetrics existed; ePVS may not be an informative marker for SPMS.

The role of cerebellar abnormalities in neuromyelitis optica – a comparison with multiple sclerosis and healthy controls

2014 ◽  
Vol 21 (6) ◽  
pp. 757-766 ◽  
Author(s):  
Katrin Weier ◽  
Arman Eshaghi ◽  
Stefano Magon ◽  
Michaela Andelova ◽  
Ernst-Wilhelm Radue ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Spinal Cord ◽  
Neuromyelitis Optica ◽  
Brain Magnetic Resonance Imaging ◽  
Cervical Cord ◽  
Healthy Controls ◽  
Brain Volumes ◽  
Secondary Degeneration ◽  
Cerebellar Volume ◽  
And Gender

Background: In relapsing–remitting multiple sclerosis (RRMS), the cerebellum is a known predilection site for atrophy. Neuromyelitis optica (NMO) is characterized by extensive lesions in the spinal cord and optic nerve; however, cerebellar involvement has been less studied. Secondary degeneration of the spinocerebellar tract could impact the cerebellum in NMO. Objective: We aimed to investigate whether spinal cord and cerebellar volume measures differ between patients with NMO and RRMS. Methods: Volumetric analyses of the cerebellum (TCV), the upper cervical cord (UCV) as well as the whole brain (NBV) of age- and gender-matched patients with NMO ( n=30; 56% AQP4 +ve) and RRMS ( n=25) were performed on 3T brain magnetic resonance imaging (MRI) and compared with 34 healthy controls (HC). Results: UCV was significantly reduced in NMO patients (6.3 cm3) as compared with HC (6.7 cm3), while patients with MS had reduced brain volumes compared with HC (NBV=1482 cm3; p<0.001; TCV=188 cm3; p=0.042), but UCV close to normal values. Patients with RRMS and NMO differed in NBV ( p=0.001; lower in RRMS) and by trend (towards reduction in RRMS) in cerebellar volume ( p=0.06). Conclusions: While atrophy seems to be diffuse in MS patients, a rather focussed pattern with predominant involvement of the UCV was observed in NMO patients.

Grey matter damage and overall cognitive impairment in primary progressive multiple sclerosis

2011 ◽  
Vol 17 (11) ◽  
pp. 1324-1332 ◽  
Author(s):  
C Tur ◽  
S Penny ◽  
Z Khaleeli ◽  
DR Altmann ◽  
L Cipolotti ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cognitive Impairment ◽  
Information Processing ◽  
Executive Function ◽  
Cognitive Performance ◽  
Verbal Memory ◽  
Visual Information ◽  
Grey Matter ◽  
Progressive Multiple Sclerosis ◽  
Primary Progressive Multiple Sclerosis

Objectives: To identify associations between cognitive impairment and imaging measures in a cross-sectional study of patients with primary progressive multiple sclerosis (PPMS). Methods: Neuropsychological tests were administered to 27 patients with PPMS and 31 controls. Patients underwent brain conventional magnetic resonance imaging (MRI) sequences, volumetric scans and magnetization transfer (MT) imaging; MT ratio (MTR) parameters, grey matter (GM) and normal-appearing white matter (NAWM) volumes, and WM T2 lesion load (T2LL) were obtained. In patients, multiple linear regression models identified the imaging measure associated with the abnormal cognitive tests independently from the other imaging variables. Partial correlation coefficients (PCC) were reported. Results: Patients performed worse on tests of attention/speed of visual information processing, delayed verbal memory, and executive function, and had a worse overall cognitive performance index, when compared with controls. In patients, a lower GM peak location MTR was associated with worse overall cognitive performance ( p < 0.001, PCC = 0.77). GM mean and peak height MTR showed the strongest association with the estimated verbal intelligence quotient (IQ) decline ( p < 0.001, PCC = -0.62), and executive function ( p < 0.001, PCC = 0.79). NAWM volume was associated with attention/speed of visual information processing ( p < 0.001, PCC = 0.74), while T2LL was associated with delayed verbal memory ( p = 0.007, PCC = -0.55). Conclusions: The finding of strong associations between GM MTR, NAWM volume and T2LL and specific cognitive impairments suggests that models that predict cognitive impairment in PPMS should include comprehensive MRI assessments of both GM and WM. However, GM MTR appears to be the main correlate of overall cognitive dysfunction, underlining the role of abnormal GM integrity in determining cognitive impairment in PPMS.

Cognitive dysfunction in primary progressive multiple sclerosis: a neuropsychological and MRI study

2009 ◽  
Vol 15 (9) ◽  
pp. 1055-1061 ◽  
Author(s):  
M Ukkonen ◽  
T Vahvelainen ◽  
P Hämäläinen ◽  
P Dastidar ◽  
I Elovaara
Keyword(s):  
Multiple Sclerosis ◽  
Cognitive Performance ◽  
Cognitive Dysfunction ◽  
Neuropsychological Tests ◽  
Brain Lesion ◽  
Progressive Multiple Sclerosis ◽  
Primary Progressive Multiple Sclerosis ◽  
Cognitive Domains ◽  
Primary Progressive ◽  
Mri Study

Although cognitive dysfunction is known to occur in multiple sclerosis (MS), only few studies have reported cognitive performance in patients with primary progressive MS (PPMS). To find out the pattern of cognitive performance in PPMS, 28 PPMS patients underwent an extensive battery of neuropsychological tests. The results were compared to those of healthy controls ( n = 20) and patients with secondary progressive MS (SPMS, n = 28). Furthermore, the results of neuropsychological tests in PPMS were correlated to magnetic resonance imaging findings. Our study showed that the PPMS patients have deficits in several cognitive domains when compared to age-matched and education-matched controls, but the cognitive impairment in the PPMS and SPMS patients appeared to be similar. Cognitive deficits in PPMS patients correlated with diffuse brain lesion, T1- and T2-lesion load, but no correlations were found with atrophy.

Lesion enhancement diminishes with time in primary progressive multiple sclerosis

2010 ◽  
Vol 16 (3) ◽  
pp. 317-324 ◽  
Author(s):  
Z. Khaleeli ◽  
O. Ciccarelli ◽  
K. Mizskiel ◽  
D. Altmann ◽  
DH Miller ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Spinal Cord ◽  
Progressive Multiple Sclerosis ◽  
Primary Progressive Multiple Sclerosis ◽  
Linear Regression Models ◽  
Mixed Effect ◽  
Gadolinium Dtpa ◽  
Primary Progressive ◽  
Inflammatory Phase ◽  
Brain And Spinal Cord

Fewer gadolinium-enhancing lesions are seen in established primary progressive multiple sclerosis (PPMS) compared with other subtypes. Previously, we found unexpectedly high enhancement levels in early PPMS (42%), suggesting an early inflammatory phase. The objective of this study was to investigate whether this level of enhancement was maintained, and whether it influenced clinical progression, over 5 years. Forty-five patients with PPMS, within 5 years of onset, were scored on the Expanded Disability Status Scale (EDSS), Multiple Sclerosis Functional Composite (MSFC) and its subtests (including the timed walk test [TWT]) 6-monthly for 3 years, and at 5 years. T1-weighted brain and spinal cord images after triple dose gadolinium—DTPA, and T2-weighted brain sequences were also acquired. A mixed effect logistic model evaluated change in the percentage of patients with enhancing lesions. Ordinal logistic and multiple linear regression models identified predictors of progression, adjusted for T2 lesion load. The percentage of patients with enhancing lesions in the brain and spinal cord declined over 5 years ( p = 0.03). Among patients with enhancement, more enhancing lesions at baseline predicted greater decline in mobility on the TWT over 5 years ( p = 0.02). In conclusion, a proportion of patients with PPMS may undergo an early inflammatory phase, which has some impact on subsequent mobility.

scholarly journals Dual-task cost in people with multiple sclerosis: A case–control study

2018 ◽  
Vol 81 (7) ◽  
pp. 384-392 ◽  
Author(s):  
Jolien Lemmens ◽  
Sofie Ferdinand ◽  
Annick Vandenbroucke ◽  
Stephan Ilsbroukx ◽  
Daphne Kos
Keyword(s):  
Multiple Sclerosis ◽  
Cognitive Performance ◽  
Dual Task ◽  
Motor Performance ◽  
Hand Function ◽  
Cognitive Capacity ◽  
Fine Motor ◽  
Dual Task Cost ◽  
Task Conditions ◽  
Fine Motor Performance

Introduction Limitations in fine motor functioning and cognitive performance are frequently reported in multiple sclerosis. Studies about dual-task costs in multiple sclerosis generally explore walking and postural performance. This study aims at exploring dual-task costs when simultaneously performing fine motor and cognitive tasks. Method Eighty people with multiple sclerosis and 80 matched controls performed the nine-hole peg test and the months backward test under single and dual-task conditions. Differences in performance over time were analysed with the paired t-test; differences in dual-task costs between groups were analysed with independent t-tests. Results People with multiple sclerosis and controls showed a significant decrease in fine motor and cognitive performance in dual-task conditions compared to single-task conditions ( P < 0.01). People with multiple sclerosis with limited hand capacity showed larger dual-task costs for cognitive performance compared to other hand capacity groups ( P < 0.05). Individuals with multiple sclerosis with lower cognitive capacity showed larger dual-task costs for fine motor performance ( P < 0.01). Conclusion Both people with multiple sclerosis and controls experience dual-task costs. People with multiple sclerosis with limited hand function showed an increased dual-task cost of cognitive performance and individuals with limited cognitive capacity showed a higher dual-task cost for fine motor performance. Therefore, occupational therapists should focus on cognitive or fine motor aspects during dual-task training dependent on individuals' capacities.

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