Natural Multiple Sclerosis Treatment Book
In the classic sense, multiple sclerosis (MS) is a disease of the central nervous system (the brain and spinal cord) that most commonly affects young adults. Sclerosis means hardening MS means that there are multiple areas of hardened tissue in the brain and spinal cord. The word disease means a loss of a feeling of ease (i.e., dis-ease), or otherwise stated, a loss of a sense of well-being. This is a meaningful definition for MS patients faced with a bewildering variety of other specific symptoms. Often, patients afflicted with MS have difficulty describing just how they feel. Although the MS patient appreciates and understands this concept, many healthy persons, including physicians, unfortunately, often do not.
Studies have shown that adults with multiple sclerosis (MS) display the expected V P profile, with Verbal IQ 5 to 12 points better (e.g., Heaton, Nelson, Thompson, Burks, & Franklin, 1985 Maurelli et al., 1992). The subtests that require the least amount of motor coordination are
There is speculation that fertility is reduced in patients with MS and that the rate of spontaneous abortion is increased in the first trimester of pregnancy. There is no evidence or expectation that MS directly affects the unborn child. However, from the information collected in the North American Research Committee on Multiple Sclerosis (NARCOMS) database, the interferonbeta treatments for MS (Betaseron, Avonex, and Rebif) do pose an increased risk of birth defects in the unborn child.
The National Multiple Sclerosis Society (NMSS) chapters and other groups have played an important part in education of patients and their families about MS. The MS Society chapters have regularly supported educational lectures for MS patients and their families. These sessions sometimes double as group therapy. When supervised by a professional, they are of real value to participants. Certainly, meeting other patients and exchanging experiences can help put the disease in perspective. It is important to recognize that the clinical course of illness varies greatly from one person to another. Young people may be intimidated when they meet severely affected individuals, regardless of the age or duration of illness. Therefore, potential participants in these sessions may wish to get more information about who will be present at a particular group session they are considering attending and whether it will be led by a knowledgeable professional.
Another drawing by Charcot showing loss of normal myelin around a small blood vessel. This blood vessel is a venule with five or six long, beanlike nuclei oriented more or less vertically in the middle of the drawing. Also seen are spaghetti-like axons without myelin, which appear smaller than the other axons with their myelin intact. This observation led to multiple sclerosis being termed a demyelinating disease. Figure 5. Another drawing by Charcot showing loss of normal myelin around a small blood vessel. This blood vessel is a venule with five or six long, beanlike nuclei oriented more or less vertically in the middle of the drawing. Also seen are spaghetti-like axons without myelin, which appear smaller than the other axons with their myelin intact. This observation led to multiple sclerosis being termed a demyelinating disease.
The increasing understanding of the mechanisms that lead to immunologi-cal tolerance to self and the role that HLA and non-HLA alleles play in antigen recognition by autoaggressive T cells may also lead to novel therapeutic strategies. Several clinical studies have sought to restore immunological tolerance to self by the administration of modified self peptides, such as the administration of altered peptide ligands of myelin proteins in multiple sclerosis. Immature dendritic cells hold great promise as highly efficient tools to induce immuno-logical tolerance to defined self proteins or peptides as demonstrated in murine allograft rejection models. They may induce tolerance by inducing antigen-specific anergy of autoreactive T cells and or by the induction of regulatory T lymphocytes that inhibit the activation of autoaggressive T cells.
A general name for a group of neurological diseases involving myelin sheath abnormalities, of which multiple sclerosis (MS) is the most common.The myelin surrounding an axon may develop normally and be lost later, but leaving the axon preserved.Alternatively, there may be some defect in the original formation of myelin as a result of an error of metabolism. Multiple sclerosis is thought to be autoimmune in nature.
This is the second of two chapters on V-P IQ discrepancies. Chapter 8 explored Verbal-Performance IQ discrepancies as related to brain damage. The patterns obtained by patients with left versus right lesions provided some insight into the greater sensitivity of the V-P IQ difference for patients with right damage (V P of 9 points) compared to those with left damage (P V of only 3K points), and examined the relationship between patient variables and V-P discrepancy in adults with brain damage. This chapter focuses on Verbal-Performance discrepancies in various types of clinical profiles, such as learning disabilities, delinquency, bilingualism, autism, mental retardation, psychiatric disorders, alcoholism, multiple sclerosis, and dementia. The chapter will conclude with the presentation of clinical case reports that exemplify V-P discrepancies within a profile.
Parkinsonism was reported after a wasp sting resulting in a progressive syndrome of frequent freezing, rigidity, and bradykinesia, in addition to dystonia in the left arm (98). The patient was reported to have had emotional lability and bilateral frontal release signs. The brain MRI showed marked destruction of the striatum and pallidum bilaterally, and enlargement of the lateral and third ventricles. There were circulating antibodies against the basal ganglia and cerebral cortex. The patient responded to immunosuppressive therapy with plasma exchange and intravenous immunoglobulin. Multiple sclerosis (MS) has also been reported to cause parkinsonism (99). One patient presented mainly with gait difficulty, with slowness, short steps, and unsteadiness. She also developed rest tremor, hypomimia, and hypophonia. There were other features suggestive of multiple sclerosis in the form of diplopia, brisk reflexes, and sensory loss. The patient improved with steroids. So far in the literature...
The MHC is the most important genetic region in relation to common human diseases such as autoimmunity and infection. Because of this biomedical importance, the MHC was completely sequenced by 19994, well ahead of the human genome draft sequence. Driven by pathogen variability, the MHC is under enormous pressure to evolve and adapt quickly. Over time, it has become the most polymorphic region in the human genome with some genes such as HLA-B (which has been associated with Behcet's disease), having over 400 alleles. However, even subtle changes in the self non-self recognition pathways can lead to genetic miscommunication and result in autoimmune diseases such as Diabetes, Multiple Sclerosis and Behcet's disease. Figure 2 shows a summary of chromosome 6 including the extended MHC which is located on the short arm at 6p21.31-22.1. The high gene and SNP densities of the MHC are clearly visible.
MMP inhibitors have also been considered a treatment for neurodegenerative or neuroinflammatory diseases. Interest has focused on multiple sclerosis (NS) in which the active phase of the disease is characterized by degradation of the blood-brain barrier, demyelination, and axonal loss. Studies have shown elevated levels of MMPs in the cerebrospinal fluid of MS patients, in particular gelatinase B (36), and MMPs have been shown to degrade myelin basic protein, releasing encephalogenic fragments (37,113).
Recovery of neurological deficits by the transplantation of bone marrow cells. In rodent models of stroke, Parkinson's disease, multiple sclerosis, trauma, and neurodegeneration, direct intracerebral grafting or systemic administration of bone marrow cells helped promote functional recovery (Table 1). Rats subjected to MCAO performed significantly better in motor and somatosensory behavior tests when treated with intravenous or intracarotid administration of MSCs 1 d or 7 d after ischemia (67,87). Similarly, direct transplantation of MSCs into the ischemic hemispheres of mice or rats 1-7 d after MCAO improved functional recovery from the rotarod, limb placement, or modified neurologic severity score tests (65,66).
Stream into the neural parenchymal tissue (79) it was believed for many years that these barriers naturally extend to blood-borne cells. However, inflammatory processes do occur in the brain and retina and there is evidence that the normal central nervous system (CNS) is subject to regular patrol by lymphocytes, most likely of the activated or blast form since resting T cells do not normally enter the CNS parenchyma (80). This is supported by evidence that in autoimmune conditions, such as multiple sclerosis or uveitis, autoreactive T cells do indeed enter the CNS or eye, respectively. A paradigm has emerged that low numbers of lymphocytes, albeit activated, access and patrol the CNS parenchyma for potential pathogens (81). If, as evidence to date would indicate, DCs are excluded from the normal neural retina (and brain parenchyma), which cell type within the neural retina acts to present Ag to patrolling activated T cells If, as outlined earlier, it is accepted that DCs act as the...
Carp virus A transmissible virus obtained from cases of human multiple sclerosis. Depresses the number of circulating poly-morphonuclear neutrophils within 16-48 h of inoculation into adult mice. The effect lasts at least 11 months during which time the mice remain normal. The virus passed through membranes of 50nm average pore diameter but not of 25nm. Replicates in PAM cells, a line of mouse fibroblasts. The effect in mice was neutralized by serum from patients with multiple sclerosis. However, the mouse test has proved difficult to reproduce and is unreliable. It is possible that these results are an artifact and the virus does not exist.
Multiple sclerosis and Tay-Sachs disease are degenerative disorders of the myelin sheath. In multiple sclerosis (MS), the oligodendrocytes and myelin sheaths of the CNS deteriorate and are replaced by hardened scar tissue, especially between the ages of 20 and 40. Nerve conduction is disrupted with effects that depend on what part of the CNS is involved double vision, blindness, speech defects, neurosis, tremors, and numbness. Patients experience variable cycles of milder and worse symptoms until they eventually become bedridden. Most die from 7 to 32 years after the onset of the disease. The cause of MS remains uncertain most theories suggest that it results from an immune disorder triggered by a virus in genetically susceptible individuals. There is no cure.
The work-up for treatment by sacral neuromodulation must include careful assessment of past history with special emphasis on drugs influencing bladder function. A physical examination may be given to assess neurologic status, togther with a perineal examination with urodynamic investigation to assess bladder and sphincter function. To rule out any other lower urinary tract pathological conditions, urine culture can be performed to exclude urinary tract infection. Cytology and cystoscopy are helpful in ruling out carcinoma cystitis, and when indicated, imaging of the upper tract may be performed. It is recommended to perform MRI of the entire spinal cord to screen for neurologic diseases such as multiple sclerosis, a neoplasm, syringomyela, lipoma, etc.
Despite the various different diagnostic criteria, the rates for PSP and MSA across all studies are not too dissimilar. One obvious observation is that studies with very large populations, e.g., New Jersey (6) or United Kingdom (15), produce lower prevalence estimates whereas very small populations produce high rates. The effect of varying population size and hence intensity of case finding is most elegantly demonstrated by the Russian Doll Method method employed by Nath and colleagues (15). This general pattern is also well noted with prevalence studies for multiple sclerosis
1) Neurologic illness or injury, most commonly traumatic or medical spinal cord injury, demyelinating disease including multiple sclerosis, supraspinal disease such as stroke, Parkinson disease, tumor, degenerative disease or dementia. The neurogenic mechanism of OAB may be related to various changes in both peripheral and central neural pathways, such as
The first publications showed an improvement in bladder hyperactivity among spinal cord lesion patients 63, 154 . Bosch and Groen 20 showed that treatment of refractory urge incontinence by chronic S3 nerve stimulation was feasible in selected multiple sclerosis patients. The fact that no irreversible changes to the bladder or nerves occur is an advantage of this treatment option over destructive alternatives. However, the unpredictable evolution of the disease and particularly cognitive alterations are con-treindicated in case of rapid evolution. In a case series, Chartier-Kastler et al. 41 reported 9 women with spinal diseases (including vascular myelitis, multiple sclerosis and traumatic spinal cord injury) undergoing neuromodulation. All patients reported an improvement of 75 in their visual analog scale at last follow-up (mean follow-up 43 months). In another case series, Hohenfellner et al. 83 evaluated patients with neurogenic bladder (complete or incomplete spinal cord...
The spatial-simultaneous grouping of subtests (excluding Matrix Reasoning, because none of the studies were based on the WAIS-III) has also been found to be of clinical significance for a different sample with motor coordination problems patients with multiple sclerosis (Heaton et al., 1985 Maurelli et al., 1992). All five WAIS-R Performance subtests (versus only two of six Verbal tasks) discriminated significantly between normal adults and patients having multiple sclerosis. But only Block Design, Object Assembly, and Picture Completion significantly discriminated between two samples of multiple sclerosis patients, one with relapsing-remitting symptoms, the other having chronic-progressive multiple sclerosis. Interpretation of the simultaneous subtests requires some caution. Although performance on the tasks has been positively associated with a field-independent cognitive style (Good-enough & Karp, 1961), there is some evidence, based partly on WAIS Block Design data, that the two...
Tremor recording machine used by Charcot to separate cases of typical rest tremor from those with postural tremor and action-induced tremor. Early studies focused on the differentiation by tremor type of multiple sclerosis and Parkinson's disease, but this apparatus was later used to study the various formes frustes of Parkinson's disease as well. In the insert, tremor recordings are shown for resting posture (AB) and action (BC) in patients with different tremor patterns. From Dictionnaire Encyclop dique des Sciences M dicales, 1883. Fig. 1. Tremor recording machine used by Charcot to separate cases of typical rest tremor from those with postural tremor and action-induced tremor. Early studies focused on the differentiation by tremor type of multiple sclerosis and Parkinson's disease, but this apparatus was later used to study the various formes frustes of Parkinson's disease as well. In the insert, tremor recordings are shown for resting posture (AB) and action (BC) in...
A main reason for the shortage of transplant organs is the fact that the tissues of the donor and the recipient need to match for successful transplantation. Tissues are matched when they have a similar pattern of cell surface proteins. Cell surface proteins are in fact glycoproteins due to the carbohydrates (sugars) attached to their surface. The carbohydrate acts as a flag designating the cell as belonging to the individual. The cellular gly-coprotein pattern may specify an individual within a species or specify a species. If a particular sugar is missing from the surface of a cell, the immune system may recognize this cell as foreign and try to kill it. An attack on self tissue may lead to autoimmune diseases, where the autoimmune reaction can be directed against a specific tissue such as the brain in multiple sclerosis or the digestive tube in Crohn disease. In other cases, the overly active immune system may attack many cells and tissues so that various organs are affected such...
Parkinsonism owing to multiple sclerosis Tremor-dominant parkinsonism following injury Parkinsonism following some insult in utero, or immediate postnatal period in association with tremor, cognitive dysfuncion, behavioral abnormalities, headaches, and strabismus Hemiatrophy in association with hemiparkinsonism dystonia, but without postural instability Tends to remain unilateral for 535 yr after onset of parkinsonian symptoms Early age at onset, history of birth injury, slow progression of the disease are very typical features. Parkinsonism in presence of tumors, hemorrhage typically contralateral to the lesion and sometimes ipsilateral to the lesion Parkinsonian features in presence of other symptoms of multiple sclerosis
Monoclonal expansion of T-cells may be indicative for antigen-driven process either in blood or in tissue. Since each monoclonal TCR can be molecularly defined (see above), a molecular probe specific for the respective CDR3 region can be designed and the individual T-cell clone can either be traced in different compartments or longitudinally over time in a patient. This methodology has been used to tag clonal T-cell populations in autoimmune myositis (25), or in patients with multiple sclerosis (MS) suggesting that expansion of certain TCR VB families may be associated with disease onset or progression (26, 27). Similarly, if a monoclonal T-cell response can be linked to MHC peptide recognition, it allows to visualize monoclonal TCRs with defined specificity in situ, e.g. in a patient with melanoma responding to peptide vaccination An TCR VB16+ Melan-A MART-1 reactive T-cell clone could be demonstrated in a vitiligo lesion associated with destruction of melanin-positive cells (i.e....
Cryptic epitopes may also be generated in vivo via specific protease activity that more efficiently destroys a dominant epitope in the thymus than in the periphery, preventing the deletion of autoreactive cells in the thymus and increasing the chances that antigen-processing events in the periphery could stimulate these cells and contribute to tissue damage in a pro-immune context. This has been demonstrated in the murine experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis. In this model, the efficient cleavage of a myelin basic protein (MBP) epitope by AEP destroys the dominant T-cell epitope recognized by encephalitogenic T-cell clones 19 . In the presence of AEP inhibitors in antigen-presenting cells, presentation of the epitope is enhanced. The authors propose that since AEP is highly expressed in thymic antigen-presenting cells, destructive processing by this enzyme limits presentation of this epitope in the thymus and allows encephalitogenic T-cell clones...
A surrogate marker should accurately reflect disease activity, track course of illness, or index treatment outcome. To fulfill the requirement of a surrogate marker or endpoint, the marker should be directly in the causative pathway to disease outcome (Fleming and DeMets, 1996). Such biomarkers could be important in diagnostic practice, but most will have their major value in tracking the course of disease or monitoring effects of therapeutic interventions. Examples of surrogate markers include CD4 cell counts and measures of viral load in HIV research, and the number of hyperintense plaques on MR brain scan in multiple sclerosis. In AD, there are as yet no accepted biomarkers as surrogate outcomes, although measures of brain atrophy show promise. The basis of dementia in AD is neuronal loss and decreased synaptic contacts, which are the proximate causes of dementia (Gomez-Isla et al., 1996, 1997). If there were a treatment that prevented or even slowed neuronal death and atrophy, how...
In July 2001, the National Institutes of Neurological Disorders and Stroke convened the Stroke Program Review Group (SPRG) 87 to advise on directions for basic and clinical stroke research for the following decade. Although much progress had been made in dissecting the molecular pathways of ischemic cell death, focusing therapy to a single intracellular pathway or cell type had not yielded clinically effective stroke treatment. Integrative approaches were felt to be mandatory for successful stroke therapy. This meeting emphasized the relevance of dynamic interactions between endothelial cells, vascular smooth muscle, astro- and microglia, neurons, and associated tissue matrix proteins, and gave rise to the concept of the neurovascular unit. This modular concept emphasized the dynamics of vascular, cellular, and matrix signaling in maintaining the integrity of brain tissue within both the gray and white matter, and its importance to the pathophysiology of conditions such as stroke,...
This chapter begins by touching on recent criticisms of our approach to profile interpretation and then continues with a discussion of a step-by-step approach to interpreting the WAIS-III profile. Here we will provide a description of the first seven of nine steps of interpretation. In these steps we will lead you through an examination of the most global score (Step 1), to examination of the IQs (Steps 2 to 4) and then the factor indexes (Steps 5 to 7). The final two steps, which deal with determining the strengths and weakness in the profile (Step 8) and how to generate specific hypotheses from the statistically significant subtest strengths and weaknesses (Step 9), are discussed in Chapter 12. To aid in interpreting the global dimensions of the WAIS-III, we refer readers to the empirical research presented in Chapter 9 on characteristic profile patterns associated with learning disabilities (e.g., the ACID grouping), Alzheimer's-type dementia (Fuld profile), psychiatric disorders,...
James Parkinson first described Parkinson disease (PD), a neurodegenerative disorder with an incidence range from 4.9 to 26 per 100,000 and prevalence of approximately 200 per 100,000, in 1817 in his monograph Essay on the Shaking Palsy. Parkinson termed the disease paralysis agitans and reported resting tremor, festinant gait, flexed posture, dysarthria, dysphagia, insomnia, and constipation as the hallmarks of the condition. Charcot subsequently used the term Parkinson's disease, and differentiated the resting tremor of PD from the cerebellar outflow action tremor seen in multiple sclerosis. He also noted that tremor was not always present in all PD cases, and that cognitive decline may also be a part of the disease. In 1893 researchers discovered that the substantia nigra was abnormal in those afflicted with PD. Subsequent examinations of the brains of patients dying with idiopathic PD demonstrated
The cannabinoid receptor agonist, R-( + )-WIN-55,212-2 (12), has shown efficacy in controlling disease progression in animal models of multiple sclerosis (MS). This effect has been attributed to its ability to reduce migration of leukocytes into the central nervous system 90 , in which adhesion molecules are believed to be involved. Compound 12, but not its enantiomer, S-(-)-WIN-55,212-2, strongly inhibited IL-1-induced expression of VCAM-1 on astrocytoma and A-172 glioblastoma cells. Interestingly, S-(-)-WIN-55,212-2 showed no efficacy in models of MS. The inhibitory effect of 12 on VCAM-1 expression is not believed to be mediated via cannabinoid receptors, since both selective cannabinoid receptor antagonists and pertussis toxin failed to affect it. Experimental data suggest that 12 blocks IL-1 signaling by inhibiting the transactivation potential of nuclear factor-kB (NF-kB) 91 .
Since myelopathy is usually the most prominent pathology associated with B12 Differential diagnosis deficiency, other causes of myelopathy should be considered. These can include multiple sclerosis, tumors, compression, vascular abnormalities, and myelitis. Myelopathy and sensorymotor polyneuropathy together should suggest vitamin B12 deficiency.
In recent years it has become apparent that DCs, though absent from the CNS parenchyma (including retina), can infiltrate these tissues during inflammation such as multiple sclerosis or experimental autoimmune encephalomyelitis (97,98), and a similar situation appears to exist in the retina during inflammation (99). There is also some evidence that in vitro MG can differentiate into DCs in the prolonged presence of GM-CSF (98) however, whether this can occur in vivo is presently unclear.
Abnormalities in gastric motility occur in a variety of disorders including diabetes and certain neurologic disorders such as Parkinson's and multiple sclerosis. Enteral feeding through a jejunostomy tube allows delivery of nutrients beyond the malfunctioning stomach (Table 4).
Colonic volvulus is a rotation of the colon around an often elongated mesocolon (Fig. 24.10). The sigmoid colon is most often affected ( 70 ) the cecum and transverse colon are markedly less often affected. Colonic volvulus is a common cause of colonic obstruction in developing countries elongation of the sigmoid due to the fiber-rich diet is thought to play a role etiopathogenically. In the western world, colonic volvulus is often associated with neurological diseases (Parkinson disease, multiple sclerosis, diseases of the spinal cord) and psychiatric disorders. In psychiatric disorders, it is the administration of psychopharmaceuticals with negative side effects on colonic motility that is blamed. Patients with severe constipation are also at risk.
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