Fatigue And Sleep Disturbance In Multiple Sclerosis
Kaynak H, Altintas A, Kaynak D, Uyanik O, Saip S, Agaoglu J, Onder G, Siva A
Eur J Neurol 2006 Dec;13(12):1333-9
Istanbul University, Cerrahpasa School of Medicine, Department of Neurology, Istanbul, Turkey
Considering the association of sleep disturbance and Fatigue in Multiple Sclerosis (MS), we investigated the presence of sleep disturbances that may be related to Fatigue by using objective and subjective measures.
We included 27 MS patients with Fatigue, 10 MS patients without Fatigue and 13 controls. The Pittsburgh sleep quality index score showed significant differences between patient groups and controls.
Beck Depression inventory scores were significantly higher in Fatigued than Non-Fatigued patients.
Comparison of patient groups and controls revealed significant differences for time in bed, sleep efficiency index, sleep continuity index, wake time after sleep onset, total arousal index and periodic limb movement arousal index.
Our study confirms that MS causes sleep fragmentation in terms of both macro and microstructure. Fatigue in MS could be partially explained by disruption of sleep microstructure, poor subjective sleep quality and depression.
Focal Thinning Of The Cerebral Cortex In Multiple Sclerosis
Sailer M, Fischl B, Salat D, Tempelmann C, Schonfeld MA, Busa E, Bodammer N, Heinze HJ, Dale A
Brain 2003 Aug;126(Pt 8):1734-44
Otto-von-Guericke-University Magdeburg, Leipzigerstrasse 44, 39120 Magdeburg, Germany
Brain Atrophy as determined by quantitative MRI can be used to characterize disease progression in Multiple Sclerosis. Many studies have addressed White Matter (WM) alterations leading to Atrophy, while changes of the Cerebral Cortex have been studied to a lesser extent.
In vivo, the Cerebral Cortex has been difficult to study due to its complex structure and regional variability. Measurement of Cerebral Cortex thickness at different disease stages may provide new insights into Gray Matter (GM) pathology.
In the present investigation, we evaluated in vivo Cortical thickness and its relationship to disability, disease duration, WM T2 hyper-intense and T1 HypoIntense lesion volumes.
High-resolution MRI Brain scans were obtained in 20 patients with clinically definite Multiple Sclerosis and 15 age-matched normal subjects.
A novel method of automated surface reconstruction yielded measurements of the Cortical thickness for each subject's entire Brain and computed cross-subject statistics based on the Cortical anatomy.
Statistical thickness difference maps were generated by performing t-tests between patient and control groups and individual thickness measures were submitted to analyses of variance to investigate the relationship between Cortical thickness and clinical variables.
The mean overall thickness of the Cortical ribbon was reduced in Multiple Sclerosis patients compared with controls [2.30 mm (SD 0.14) versus 2.48 mm (SD 0.11)], showing a significant main effect of group (controls versus patients).
In patients, we found significant main effects for disability, disease duration, T2 and T1 lesion volumes.
The visualization of statistical difference maps of the Cortical GM thickness on inflated Brains across the Cortical surface revealed a distinct distribution of significant focal thinning of the Cerebral Cortex in addition to the diffuse Cortical Atrophy.
Focal Cortical thinning in Frontal [2.37 mm (SD 0.17) versus 2.73 mm (SD 0.25)] and in Temporal [2.65 mm (SD 0.15) versus 2.95 mm (SD 0.11)] Brain regions was observed, even early in the course of the disease or in patients with mild disability.
Patients with longstanding disease or severe disability, however, presented additionally with focal thinning of the Motor Cortex Area [2.35 mm (SD 0.19) versus 2.74 mm (SD 0.15)].
We conclude that in vivo measurement of Cortical thickness is feasible in patients suffering from Multiple Sclerosis.
The data provide new insight into the Cortical pathology in Multiple Sclerosis patients, revealing focal Cortical thinning beside an overall reduction of the Cortical thickness with disease progression.
Meier DS, Guttmann CR
NeuroImage 2006 Aug 15;32(2):531-7
Brigham and Women's Hospital, Center for Neurological Imaging, 221 Longwood Avenue, RF 396, Boston, MA 02115, USA
A mathematical model was applied to new lesion formation in Multiple Sclerosis, as apparent on frequent T2-weighted MRI.
The pathophysiologically motivated two-process model comprises two opposing nonlinear self-limiting processes, intended to represent degenerative and reparatory processes, respectively, investigating T2 activity from a dynamic/temporal rather than a spatial/static perspective.
Parametric maps were obtained from the model to characterize the MRI dynamics of lesion development, answering the questions of:
- How long new T2 lesion activity persists
- How much residual damage/HyperIntensity remains
- How the T2 dynamics compare to those of contrast-enhancing MRI indicating active inflammation
997 MRI examinations were analyzed, acquired weekly to monthly from 45 patients over a 1-year period.
The model was applied to all pixels within 332 new lesions, capturing the time profiles with excellent fidelity (r = 0.89 +/- 0.03 average correlation between model and image data).
From this modeling perspective, the observed dynamics in new T2 lesions are in agreement with two opposing processes of longitudinal intensity change, such as inflammation and degeneration versus resorbtion and repair.
On average, about one third of a new lesion consisted of transient signal change with little or no residual HyperIntensity and activity of 10 weeks or less.
Global lesion burden as MRI surrogate of disease activity may therefore be confounded by large amounts of transient HyperIntensity.
T2 activity also persisted significantly beyond the period of contrast enhancement, thereby defining MRI sensitivity toward a subacute phase of lesion development beyond Blood-Brain Barrier patency.
Concentric patterns of dynamic properties within a lesion were observed, consistent with concentric histological appearance of resulting MS plaques.
Axonal Conduction And Injury In Multiple Sclerosis: The Role Of Sodium Channels
Nat Rev NeuroSci 2006 Dec;7(12):932-41
Yale School of Medicine, Department of Neurology and Center for NeuroScience and Regeneration Research, New Haven, Connecticut 06510, and the Rehabilitation Research Center, Veterans Affairs Medical Center, West Haven, Connecticut 06516, USA
Multiple Sclerosis (MS) is the most common cause of Neurological disability in young adults.
Recent studies have implicated specific Sodium ChannelSodium Channel isoforms as having an important role in several aspects of the pathophysiology of MS.
Including the restoration of Impulse Conduction after DeMyelination, Axonal Degeneration and the mistuning of Purkinje Neurons that leads to Cerebellar dysfunction.
By manipulating the activity of these channels or their expression, it might be possible to develop new therapeutic approaches that will prevent or limit disability in MS.
Long-term Protection Of Central Axons With Phenytoin In Monophasic And Chronic/Relapsing EAE
Black JA, Liu S, Hains BC, Saab CY, Waxman SG
Brain 2006 Dec;129(Pt 12):3196-208
Yale University School of Medicine, Department of Neurology and Center for NeuroScience and Regeneration Research, New Haven, CT, USA
Axonal Degeneration is a major contributor to NonRemitting deficits in Multiple Sclerosis, and there is thus considerable current interest in the development of strategies that might prevent Axonal Loss in NeuroInflammatory Disease.
DysRegulation of Sodium Ion homeostasis has been implicated in mechanisms leading to Axonal Degeneration, and several studies have shown that blockade of Sodium Channels can ameliorate Axon damage following Anoxic, Traumatic and Nitric Oxide-induced CNS injury.
Two Sodium Channel Blockers, Phenytoin and Flecainide, have been reported to protect Axons in Experimental Autoimmune Encephalomyelitis (EAE) for 30 days, but long-term protective effects have not been studied.
We demonstrate here that oral administration of Phenytoin provides long-term (up to 180 days) protection for Spinal Cord CorticoSpinal Tract (CST) and Dorsal Column (DC) Axons in both monophasic (C57/BL6 mice) and Chronic/Relapsing (Biozzi mice) murine EAE.
Untreated C57/BL6 mice exhibit a 40-50% loss of CST and DF Axons at 90 and 180 days post-EAE induction via Myelin-Oligodendrocyte Glycoprotein (MOG) injection.
In contrast, only 4% of DF Axons are lost at 90 days, and only 8% are lost at 180 days in Phenytoin-treated C57/BL6 mice with EAE; only 21-29% of CST Axons are lost at 90 and 180 days in Phenytoin-treated C57/BL6 mice with EAE.
Attenuation of Dorsal Column compound Action Potentials was ameliorated and clinical status was also significantly enhanced with Phenytoin treatment at 90 and 180 days in this model.
In addition, inflammatory cell infiltration into the Dorsal Columns was reduced in Phenytoin-treated mice with EAE compared with untreated mice with EAE.
Similar results were obtained in Biozzi mice with Chronic/Relapsing EAE followed for 120 days post-injection.
These observations demonstrate that Phenytoin provides long-term protection of CNS Axons and improves clinical status in both Monophasic and Chronic/Relapsing models of NeuroInflammation.
ChronoTherapy Using CorticoSteroids For Multiple Sclerosis Relapses
Glass-Marmor L, Paperna T, Ben-Yosef Y, Miller A
J Neurol NeuroSurg Psychiatry 2006 Oct 20
Carmel Medical Center, Israel
The activity of the Immune System displays a Circadian rhythm.
In diseases characterized by aberrant Immune activity, ChronoTherapy - treatment regimen tailored to diurnal body rhythms - may increase medication efficiency, safety, and tolerability.
The goal of this study was to compare the outcomes of IntraVenous CorticoSteroid administration during the day or night, for treatment of acute Multiple Sclerosis (MS) relapses.
Seventeen MS patients were included in the study.
Clinical assessment of disability was performed at trial entry, and at days 7 and 30 from therapy initiation.
Adverse events and preference of nighttime versus daytime therapy were assessed at the end of the treatment course.
After nighttime treatment, clinical recovery was significantly enhanced and the mean number of side effects was significantly lower.
Furthermore, the majority of patients expressed a preference for nighttime versus daytime treatment.
The study suggests a potential benefit for implementation of chronotherapy using Steroid treatment for acute MS relapse, with implications for other Immune- mediated Disorders.
Lenzi D, Conte A, Mainero C, Frasca V, Fubelli F, Totaro P, Caramia F, Inghilleri M, Pozzilli C, Pantano P
Hum Brain Mapp 2006 Nov 1
University of Rome "La Sapienza, Department of Neurological Sciences, Rome, Italy
Functional MRI (fMRI) studies have shown increased activation of Ipsilateral Motor Areas during hand movement in patients with Multiple Sclerosis (MS).
We hypothesized that these changes could be due to disruption of TransCallosal Inhibitory Pathways.
We studied 18 patients with Relapsing/Remitting MS. Conventional T1- and T2-weighted images were acquired and Lesion Load (LL) measured.
Diffusion Tensor Imaging (DTI) was performed to estimate Fractional Anisotropy (FA) and Mean Diffusivity (MD) in the body of the Corpus Callosum (CC).
fMRI was obtained during a right-hand motor task. Patients were studied to evaluate TransCallosal Inhibition (TCI, latency and duration) and Central Conduction Time (CCT).
Eighteen normal subjects were studied with the same techniques. Patients showed increased MD (P < 0.0005) and reduced FA (P < 0.0005) in the body of the CC.
Mean latency and duration of TCI were altered in 12 patients and absent in the others.
Between-group analysis showed greater activation in patients in BiLateral PreMotor, Primary Motor (M1), and Middle Cingulate Cortices and in the Ipsilateral Supplementary Motor Area, Insula, and Thalamus.
A multivariate analysis between activation patterns, structural MRI, and NeuroPhysiological findings demonstrated positive correlations between T1-LL, MD in the body of CC, and activation of the IpsiLateral Motor Cortex (iM1) in patients.
Duration of TCI was negatively correlated with activation in the iM1.
Our data suggest that functional changes in iM1 in patients with MS during a motor task partially represents a consequence of loss of TransCallosal Inhibitory Fibers.
Hum Brain Mapp, 2006. (c) 2006 Wiley-Liss, Inc.