MS Fatigue & Cognitive Dysfunction Associated
With Frontal Cortex & Basal Ganglia

  1. Reduced metabolism in Cerebral Cortex correlates with MRI changes and Cognitive Dysfunction in patients with Disseminated Sclerosis
    Ugeskr Laeger 2001 Jul 2;163(27):3788-92

  1. Reduced Glucose metabolism in the Frontal Cortex and Basal Ganglia in Multiple Sclerosis Fatigue
    Neurology 1997 Jun 48:6 1566-71

  2. The Basal Ganglia: a substrate for Fatigue in Multiple Sclerosis
    NeuroRadiology 2008 Jan;50(1):17-23


Reduced Glucose Metabolism In The Frontal Cortex And Basal Ganglia In Multiple Sclerosis Fatigue

Roelcke U., Kappos L., Lechner-Scott J., Brunnschweiler H., Huber S., Ammann W., Plohmann A., Dellas S., Maguire RP., Missimer J., Radü EW., Steck A., Leenders KL.
Neurology 1997 Jun 48:6 1566-71
Paul Scherrer Institute, PET Program, Villigen, Switzerland
PMID# 9191767

To investigate the PathoPhysiology of Fatigue in MS, we assessed Cerebral Glucose Metabolism (CMR-Glu) in 47 MS patients using PET and 18F-Fluorodeoxyglucose.

Applying the Fatigue Severity Scale (FSS), we first compared MS patients with Severe Fatigue (MS-FAT, n = 19, FSS > 4.9).

And, MS patients Without Fatigue (MS-NOF, n = 16, FSS < 3.7) on a pixel-by-pixel basis using Statistical Parametric Mapping (SPM95).

Second, we compared FSS values of all 47 patients covering the whole range of this scale with CMRGlu using an analysis of covariance (SPM95).

In addition, we determined global CMRGlu by region-of-interest analysis. Sixteen healthy subjects served as control subjects (CON).

Global CMRGlu was significantly lower in both MS groups compared with CON (CON 43.3 +/- 6.9 mumol/100 mL/min, MS-FAT 34.7 +/- 4.4, MS-NOF 35.4 +/- 4.5) but was not related to Fatigue severity.

    Comparing the two MS groups, SPM95 analysis revealed:
  1. Predominant CMRGlu reductions BiLaterally in a PreFrontal area
    • Involving the Lateral and Medial PreFrontal Cortex and
    • Adjacent White Matter
  2. In the PreMotor Cortex, Putamen, and
  3. In the right Supplementary Motor Area of MS-FAT
  4. There were CMRGlu reductions in the White Matter extending from the Rostral Putamen toward the Lateral Head of the Caudate Nucleus.

FSS values were inversely related to CMRGlu in the right PreFrontal Cortex. CMRGlu in the Cerebellar Vermis and Anterior Cingulate was relatively higher in MS-FAT than in MS-NOF patients.

CMRGlu of both regions showed positive correlations with FSS values.

Our data suggest that Fatigue in MS is associated with Frontal Cortex and Basal Ganglia dysfunction that could result from DeMyelination of the Frontal White Matter.


The Basal Ganglia: A Substrate For Fatigue In Multiple Sclerosis

Téllez N, Alonso J, Río J, Tintoré M, Nos C, Montalban X, Rovira A
NeuroRadiology 2008 Jan;50(1):17-23
Unitat de NeuroImmunologia Clínica, Hospital Universitari Vall d’Hebron, Pg. Vall d’Hebron 119–129, 08035, Barcelona, Spain
PMID# 17955232

The origin of Fatigue in Multiple Sclerosis (MS) remains uncertain. However, the use of nonconventional Magnetic Resonance techniques has increased our understanding of this problem.

We aimed to study the relationship between Fatigue in MS and the presence of focal dysfunction in the Basal Ganglia and Frontal White Matter.

Included in the study were 41 patients with Relapsing/Remitting MS with mild disability and 20 healthy controls.

Fatigue was assessed by the Fatigue Severity Scale (FSS) and the Modified Fatigue Impact Scale (MFIS).

Patients were classified as "Fatigued" when they expressed a subjective feeling of fatigue, and the FSS score was >/= 5.0 and/or the MFIS score was > 38.

Patients with no subjective Fatigue were classified as "NonFatigued" when the FSS score was < 4.0.

Proton Magnetic Resonance Spectra were obtained from two different regions: the Frontal White Matter and the Lentiform Nucleus. The relationships between Fatigue and NAA/Cr, NAA/Cho and Cho/Cr ratios were analysed.

A significant decrease in NAA/Cr in the Lentiform Nucleus region in patients with Fatigue was observed.

No differences between the groups were found in the Frontal White Matter.

Although confirmatory studies are needed, our results would support the idea that a specific dysfunction or involvement of the Basal Ganglia might partly contribute to the development of MS-related Fatigue.

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