Multiple sclerosis

Association of multiple sclerosis and intracranial hypertension

Authors: Newman NJ, Selzer KA, Bell RA.

Three patients fulfilled the diagnostic criteria for both multiple sclerosis and pseudotumor cerebri. Although coincidence is possible, intracranial hypertension may be a manifestation of demyelinating disease.

Multiple Sclerosis and Intracranial Hypertension Presenting as Paroxysmal Kinesigenic Dyskinesia

Author:  Dr. Daniel E Jacome

Background: Paroxysmal movements in the form of tonic spasms, dystonia, choreoathetosis and hemidyskinesia have been reported in patient with multiple sclerosis (MS). Intracranial hypertension with headache and papilledema resembling idiopathic intracranial hypertension (IIH) exceptionally occurs in patient with MS. Conversely, IIH may rarely present as movement disorder in children.

Aims of the study: Report an unusual patient with MS and intracranial hypertension anteceded by movement disorder.

Methods: Clinical examinations and ancillary diagnostic testing.

Results: A 54 year old patient presented one year earlier to her diagnosis of MS with symptoms of paroxysmal kinesigenic diskinesia (PKD). Her initial neurologic examination and brain MRI were normal. A year later her examination became abnormal and her MRI showed demyelination. Her cerebrospinal fluid contained oligoclonal bands and the opening pressure was markedly elevated, in the absence of headache and papilledema.

Conclusion: PKD may antecede MS and acephalgic intracranial hypertension without papilledema in exceptional patients.

Repulsive Guidance Molecule-a and Demyelination: Implications for Multiple Sclerosis

Authors: Kubo T, Tokita S, Yamashita T.

Drug development for neurodegenerative and neuroinflammatory diseases such as multiple sclerosis and traumatic brain injury is challenging. One promising strategy is to target a molecule with multiple biological actions affecting divergent pathophysiological disease phases simultaneously since these diseases arise from multiple pathological phases. In recent years, we pursued this strategy with a focus on multiple sclerosis and spinal cord injury and found that repulsive guidance molecule-a (RGMa) inhibits regeneration of injured CNS axons following spinal cord injury. We also found that RGMa enhances CD4(+) T cell activation facilitating CNS demyelination in an animal model of MS, mouse experimental autoimmune encephalomyelitis (EAE), which supports the idea that RGMa has distinct pathological actions. The multiple functions of RGMa in the CNS and the immune system would provide a therapeutic opportunity to concurrently block the autoimmune reactions and axon injury in neurodegenerative and neuroinflammatory diseases. In this article, we introduce the therapeutic potential of targeting RGMa as a novel intervention for MS and spinal cord injury.

Increased Risk of Multiple Sclerosis after Traumatic Brain Injury: A Nationwide Population-based Study

Authors: Kang JH, Keller J, Lin HC.

Previous data show conflicting results regarding the association between MS and prior brain trauma. This study aims to investigate the risk for MS following a traumatic brain injury (TBI) using a population-based dataset. This study used data from the National Health Insurance Research Database. In total, 72,765 patients with TBI were included as the study cohort, and 218,295 randomly selected subjects were matched with the study cohort by sex and age as controls. We traced each patient individually for a six-year period from their index health care utilization to identify those who received a subsequent diagnosis of MS. We used the Kaplan-Meier method and the log-rank test to compare the difference in six-year MS-free survival rates between the two groups. Stratified Cox proportional hazard regressions were computed to compare the risk of developing MS for these two cohorts. The incidence rate of MS was 10.51 (95% CI: 7.60-14.16) per 100,000 person-years in patients with TBI and 6.63 (95% CI: 5.30-8.20) per 100,000 person-years in patients without TBI. After censoring cases who died from non-MS causes, stratifying for hospitalization of cases as a proxy for severity, and adjusting for monthly income and geographic region of the community in which the patient resided, the HR of MS for patients with hospital-treated TBI injuries was 1.97 (95% CI=1.31-2.93, p<0.01) that of patients without TBI during the six-year follow-up period after index healthcare use. Our study concludes that patients with TBI are at higher risk for subsequent MS over a six-year follow-up period.

The possible role of cranio-cervical trauma and abnormal CSF hydrodynamics in the genesis of multiple sclerosis

Authors: Damadian RV, Chu D.

UPRIGHT Multi-Position MR scanning has uncovered a key set of new observations regarding Multiple Sclerosis (MS), which observations are likely to provide a new understanding of the origin of MS. The new findings may also lead to new forms of treatment for MS. The UPRIGHT MRI has demonstrated pronounced anatomic pathology of the cervical spine in five of the MS patients studied and definitive cervical pathology in the other three. The pathology was the result of prior head and neck trauma. All eight MS patients entered the study on a first come first serve basis without priority, and all but one were found to have a history of serious prior cervical trauma which resulted in significant cervical pathology. The cervical pathology was visualized by UPRIGHT MRI. Upright cerebrospinal fluid (CSF) cinematography and quantitative measurements of CSF velocity, CSF flow and CSF pressure gradients in the upright patient revealed that significant obstructions to CSF flow were present in all MS patients. The obstructions are believed to be responsible for CSF "leakages" of CSF from the ventricles into the surrounding brain parenchyma which "leakages" can be the source of the MS lesions in the brain that give rise to MS symptomatology. The CSF flow obstructions are believed to result in increases in intracranial pressure (ICP) that generate "leakages" of the CSF into the surrounding brain parenchyma. In all but one MS patient, anatomic pathologies were found to be more severe in the upright position than in the recumbent position. Similarly, CSF flow abnormalities were found to be more severe in the upright position than in the recumbent position in all but one MS patient. Images of the MS patient anatomic pathologies and CSF flow abnormalities are provided with comparison images from normal examinees in Figures 1-15.

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