Forn C, Barros-Loscertales A, Escudero J, Belloch V, Campos S, Parcet MA, Avila C
NeuroImage 2006 Jun;31(2):686-91
Universitat Jaume I, Campus Riu Sec, Dept. Psicologia, Fac. Ciencies Humanes i Socials, e-12071 Castello, Spain
Cortical reorganization in Multiple Sclerosis (MS) is defined as a compensatory mechanism which requires MS patients to overactivate specific Brain areas in order to perform the task as controls.
To investigate this process with the Paced Auditory Serial Addition Test (PASAT) task, we selected 15 MS patients who performed the PASAT task within-normal limits and 10 healthy controls.
Once selected, we used Functional Magnetic Resonance Imaging (fMRI) to investigate Brain areas involved in PASAT performance in both groups.
Results showed that the task activated the left Frontal (BA6 and 9) and Parietal Cortex (BA7 and 40) in both groups, but MS patients showed a stronger activation in the Left Prefrontal Cortex (BA9, 44 and 45) when compared with controls.
These results confirmed those obtained post hoc by Audoin et al. [Audoin, B., Ibarrola, D., Ranjeva, J.P., Confort-Gouny, S., Malikova, I., Ali-Cherif, A.M., Pelletier, J., Cozzone, P., et al., 2003].
Compensatory Cortical activation observed by fMRI during Cognitive task at the earliest stage of MS, and we interpreted this as showing true cortical reorganization..
Hum. Brain Mapp. 20, 51-58
Multiplex Analysis Of Expression Of Three IFN-ß-Induced Genes In Antibody-Positive MS Patients
Pachner AR, Narayan K, Pak E
Neurology 2006 Feb 14;66(3):444-6
University of Medicine and Dentistry of New Jersey, Medical School, Newark, NJ 07103, USA
Some Interferon-beta (IFN-ß)-treated patients with Multiple Sclerosis develop AntiBody-mediated decreased bioactivity with resultant loss of therapeutic effect.
The authors developed real-time multiplex reverse transcriptase PCR to measure expression of three IFN-ß-inducible genes to directly assess IFN-ß bioactivity in patients with Neutralizing AntiBodies (NAbs). The three genes responded in tandem.
Correlation of NAb level with bioactivity at low/moderate NAb levels was poor, indicating that for such patients, direct measurement of IFN-ß bioactivity is most reliable.
Efficacy Of Botulinum-A Toxin Bladder Injections For The Treatment Of Neurogenic Detrusor Overactivity In Multiple Sclerosis patients: An objective and subjective analysis
Schulte-Baukloh H, Schobert J, Stolze T, Sturzebecher B, Weiss C, Knispel HH
NeuroUrol Urodyn 2006 Feb 8;25(2):110-115
Academic Teaching Hospital of Charite University Hospital, Department of Urology, St. Hedwig Hospital, Berlin
We studied the use of Botulinum-a toxin (BTX-A) injections into the Bladder as an alternative approach in patients with Neurogenic Detrusor overactivity due to Multiple Sclerosis (MS) with drug-refractory OverActive Bladder (OAB) symptoms.
Sixteen MS patients-11 women, 5 men; mean age 48.6 years-with refractory OAB symptoms were included in a one-center prospective study.
For outcome analysis, we used a Bladder diary, a complete Urodynamic study, and validated questionnaires for subjective assessment.
We injected 300 U of BTX-A (Botox(R)) into the Bladder and into the external sphincter muscle to reduce the probability of posttreatment urine retention.
There was an increase in residual volume from 81.3 +/- 23.8 to 126.3 +/- 32.9 ml after 4 weeks. In one woman, transient self-catheterization was unavoidable.
Four weeks and 3 and 6 months after BTX-A injection, the significant results were as follows:
Daytime frequency was reduced by 29%, 44%, and 30%, respectively. Nocturia diminished by 33%, 72%, and 40%.
Use of pads was be reduced by 38% after 4 weeks and by 64% after 3 months.
Urodynamically, reflex volume and maximal cystometric Bladder capacity increased by 73%, 77%, and 58% (at 6 months, the increase was not significant) and by 36%, 27%, and 36% (not significant).
Maximal Detrusor pressure decreased by 35%, 22%, and 57%.
Subjective outcome indicated significant improvement of symptoms at 4 weeks and 3 months, but not at 6 months. Patient satisfaction with the therapy was very high.
BTX-A Detrusor injections are very effective in the treatment of drug-resistant OAB symptoms in MS patients as reflected in Urodynamic measurements and in patient satisfaction.
Build up of residual urine remains a problem of which patients must be informed.
NeuroUrol. Urodynam. (c) 2006 Wiley-Liss, Inc.
Haensch CA, Jorg J
J Neurol 2006 Feb;253 Suppl 1:i3-i9
HELIOS Klinikum Wuppertal, Dept. of Neurology, Heusnerstr 40, 42283, Wuppertal, Germany
Multiple Sclerosis (MS) is the most frequent chronic Neurological Disease affecting young persons in developed countries. MS is, however, considered as a secondary cause, of Central origin, for Autonomic Dysfunction.
The most common Autonomic symptoms in MS are disorders of Micturation, Impotence, Sudomotor and GastroIntestinal disturbances, Orthostatic intolerance as well as sleep disorders.
The majority of the patients suffer at some period of the disease from Lower Urinary Tract symptoms and sexual dysfunction. Awareness and treatment of these conditions is vital to improving health and quality of life in patients with MS.
The increased understanding of the pathophysiological mechanisms in Autonomic Dysfunction in MS, along with technological and pharmaceutical developments has advanced our ability to treat the multiple aspects complicating Autonomic failure in MS.
Treatment Of Severe Spacticity In Multiple Sclerosis By Continuous Intrathecal Baclofen
Peric P, Antic B, Dincic E, Obradovic D, Arsic S
Vojnosanit Pregl. 2006 Feb;63(2):187-91
Vojnomedicinska akademija, Klinika za neurohirurgiju, Beograd, Srbija i Crna Gora
Successful treatment of severe Spasticity represents an imperative of symptomatic therapy of Multiple Sclerosis (MS).
Due to a significant improvement of physical, psychic and social rehabilitation of MS patients, as well as a long-term cost savings for the additional treatments of conditions arising from uncontrolled severe Spasticity.
Continuous Intrathecal administration of Baclofen (ITB), using a subcutaneously implanted programmable infusion pump, is a minimally invasive, reversible method for the treatment of severe diffuse Spasticity of the Spinal origin.
The first two cases in our country, treated by ITB due to severe Spasticity caused by MS, were reported.
Despite the local complications of surgical wound healing above the implanted components of the ITB-system in one patient, the optimal reduction of Spasticity the with complete elimination of spastic pain was obtained in both patients.
Our initial experiences confirmed ITB as a safe and effective therapeutical option for the treatment of intractable Spasticity in patients with MS.
Major prerequisites for this were adequate patient selection and good control of the basic disease.
The use of the minimal invasive implantation technique and the experience in choosing of the adequate ITB-system components, could successfully prevent the occurrence of local complications related to the impaired healing of the ITB-system implantation site.
J Neurol 2005 Nov;252 Suppl 5:v3-9
University Hospital Georg-August-University, Dept. of NeuroPathology, Robert-Koch-Str. 40, 37075, Gottingen, Germany
Multiple Sclerosis is a chronic inflammatory DeMyelinating disease of the Central Nervous System manifested morphologically by inflammation, Demyelination, Axonal loss and Gliosis.
The inflammatory lesions are characterized by massive infiltration by a heterogeneous population of cellular and soluble mediators of the Immune System, including T-Cells, B-Cells, Macrophages and Microglia.
As well as a broad range of Cytokines, Chemokines, AntiBodies, Complement and other toxic substances. The appearance of such lesions is associated with clinical relapses.
Recent detailed ImmunoPathological studies of early, acute lesions revealed profound heterogeneity in the patterns of DeMyelination and the factors of the Immune System involved.
During remission, resolution of inflammation is the main factor which leads to clinical improvement of patients.
However, the Immune System can play a beneficial role at this stage, promoting ReMyelination perhaps by production of Growth Factors such as BDNF.
In contrast, the progressive irreversible Neurological deficit in Multiple Sclerosis is associated with NeuroDegenerative processes resulting in Axonal and Neuronal loss.
The mechanisms behind damage to Axons in Multiple Sclerosis lesions are poorly understood.
However, the close proximity of areas with prominent Axonal loss and areas containing inflammatory infiltrates (e. g., T-Cells, Macrophages) suggest that Axonal damage is closely associated with inflammation.
Different soluble or cellular mediators of the Immune response have been shown to damage Axons in experimental systems, and these may be responsible for NeuroDegeneration in human disease.
AntiBodies To Native Myelin Oligodendrocyte Glycoprotein Are Serologic Markers Of Early Inflammation In Multiple Sclerosis
Lalive PH, Menge T, Delarasse C, Della Gaspera B, Pham-Dinh D, Villoslada P, von Budingen HC, Genain CP
Proc Natl Acad Sci USA 2006 Feb 14;103(7):2280-5
University of California, Department of Neurology, San Francisco, CA 94143
Myelin Oligodendrocyte Glycoprotein (MOG) is an integral membrane protein expressed in CNS Oligodendrocytes and outermost Myelin lamellae.
Anti-MOG Abs cause Myelin destruction (DeMyelination) in animal models of Multiple Sclerosis (MS); however, such pathogenic Abs have not yet been characterized in humans.
Here, a method that specifically detects IgG binding to human MOG in its native, membrane-embedded conformation on MOG-transfected mammalian cells was used to evaluate the significance of these Auto Abs.
Compared with healthy controls, native MOG-specific IgGs were most frequently found in Serum of Clinically Isolated Syndromes (P < 0.001) and Relapsing/Remitting MS (P < 0.01), only marginally in Secondary/Progressive MS (P < 0.05), and not at all in Primary/Progressive MS.
We demonstrate that Epitopes exposed in this cell-based assay are different from those exposed on the refolded, ExtraCellular domain of human recombinant MOG tested by solid-phase ELISA.
In marmoset monkeys induced to develop MS-like CNS inflammatory DeMyelination, IgG reactivity against the native membrane-bound MOG is always detected before clinical onset of disease (P < 0.0001), unlike that against other Myelin constituents.
We conclude that
- Epitopes displayed on native, glycosylated MOG expressed in vivo are early targets for pathogenic Abs;
- These Abs, which are not detected in solid-phase assays, might be the ones to play a pathogenic role in early MS with predominant inflammatory activity; and
- The cell-based assay provides a practical Serologic marker for early detection of CNS Autoimmune Demyelination including its preclinical stage at least in the primate MS model.