Natural Multiple Sclerosis Treatment Systems

Reverse MS Now

Heres just a few things youll learn about how to get back into health. and conquer Multiple Sclerosis. Those not-so innocent yet everyday substances that are currently attacking your body, perpetuating and aggravating your Multiple Sclerosis. What to do and what Not to do to overcome your Multiple Sclerosis effectively and permanently. How to create the energy you need to be able to work full time and feel confident you will be able to take care of your loved ones. How the pharmaceutical and food industry are conspiring to poison you and make you sick (Hint: American medical system is now the leading cause of death in the US). More here...

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Immunopathogenesis of Multiple Sclerosis

Cell Therapies Multiple Sclerosis

Multiple sclerosis is an immunopathological, presumably autoimmune, disease that is clearly influenced by environmental and genetic factors. The development of therapeutic strategies for MS has followed the evolution of pathogenetic concepts (Hemmer et al. 2006 Sospedra and Martin 2005 Hafler 2004), and current models of MS immunopathogenesis offer numerous molecular targets for mAb therapy (Fig. 13.1).

Multiple Sclerosis and Experimental Autoimmune Encephalomyelitis

Multiple sclerosis (MS) is an autoimmune disease of the CNS in which CD4+ T cells of the TH1 and TH17 subsets react against self myelin antigens, resulting in inflammation in the CNS with activation of macrophages around nerves in the brain and spinal cord, destruction of the myelin, abnormalities in nerve conduction, and neurologic deficits. It is the most common neurologic disease of young adults. On pathologic examination, there is inflammation in the CNS white matter with secondary demyelination. Multiple sclerosis is characterized clinically by weakness, paralysis, and ocular symptoms with exacerbations and remissions CNS imaging suggests that in patients with active disease, there is frequent new lesion formation. The disease is modeled by experimental autoimmune encephalomyelitis (EAE) in mice, rats, guinea pigs, and nonhuman primates, and this is one of the best characterized experimental models of an organ-specific autoimmune disease mediated mainly by T lymphocytes. EAE is...

Multiple sclerosis

Multiple sclerosis is an inflammatory demylinating disease directed at the brain and spinal cord characterized by lesions that are due to the perivascular infiltration of monocytes and lymphocytes into the brain parenchyma, brain stem, optic nerve, and spinal cord. There is evidence that its etiology might be viral in origin but the data are inconclusive. The resulting demyelination leads to impaired nerve signaling and subsequent impairment in vision, sensation, movement, and cognition. Multiple sclerosis lesions tend to be focal, and therefore the symptoms are often discretely tied to a particular body region, and multiple symptoms may occur in a single patient. Multiple sclerosis primarily affects adults, with a typical age of onset between 20 and 50 years. An estimated 300 000 individuals in the USA are afflicted with multiple sclerosis. While a relationship between multiple sclerosis risk and latitude exists in North America, Australia, and New Zealand, this is not consistent....

Additional Readings Websites

CAM website of the Rocky Mountain Multiple Sclerosis Center Bourdette D, Yadav V, Shinto L. Multiple sclerosis. In Oken BS, ed. Complementary Therapies in Neurology An Evidence-Based Approach. New York Parthenon Publishing Group, 2004, 291-302. Burnfield A. Multiple Sclerosis A Personal Exploration. London Souvenir Press, 1997. Forsythe E. Multiple Sclerosis Exploring Sickness and Health. London Faber and Faber, 1988. Kalb RC. Multiple Sclerosis The Questions You Have The Answers You Need. New York Demos Medical Publishing, 2004. Polman CH, Thompson AJ, Murray TJ, et al. Multiple Sclerosis The Guide to Treatment and Management. New York Demos Medical Publishing, 2006. Schapiro RT. Managing the Symptoms of Multiple Sclerosis. New York Demos Medical Publishing, 2003. medicine use among adults United States, 2002. Adv Data 2004 343 1-20. Berkman CS, Pignotti MG, Cavallo PF, et al. Use of alternative treatments by people with multiple sclerosis. Neurorehab Neural Repair...

Other Tests Available in an Eye Department

Cal changes that take place in the retina when the eye is exposed to light. It can indicate retinal function in the same way that the electrocardiogram indicates cardiac function. The visually evoked potential is a measure of minute electrical changes over the back of the scalp, which occur when the eyes are stimulated with a flashing light. This test has been shown to be useful in detecting previous damage to the optic nerve in patients with suspected multiple sclerosis.

Studies in MS and Other Conditions

No well-conducted studies have shown that aspartame causes MS or worsens symptoms in most people with the disease. Through www.ms-cam.org, the CAM website of the Rocky Mountain Multiple Sclerosis Center, we conducted a survey of aspartame use among a large group of people with MS. We had 3,075 people with MS respond to this survey. A minority (15 percent) of those who responded experienced problems that they attributed to aspartame use. Headache was the most common complaint, which was noted by about one third (36 percent) of those who noticed symptoms related to aspartame. Among MS symptoms, those that were reported to be worsened most commonly by aspartame were fatigue, thinking problems, weakness, and numbness. Nearly two-thirds of people reported that their aspartame-related symptoms began within minutes or hours of using the sweetener. Overall, these findings indicate that the majority of people with MS do not have problems with aspartame and that the most common symptom provoked...

Additional Readings Journal Articles

Capell E, Gardella M, Leandri M, et al. Lowering body temperature with a cooling suit as symptomatic treatment for thermosensitive multiple sclerosis patients. Ital J Neurol Sci 1995 16 533-539. Feys P, Helsen W, Liu X, et al. Effect of peripheral cooling on intention tremor in multiple sclerosis. J Neurol Neurosurg Psych 2005 76 373-379. Flensner G, Lindencrona C. The cooling-suit a study of ten multiple sclerosis patients' experience in daily life. J Adv Nursing 1999 29 1444-1453. Guthrie TC, Nelson DA. Influence of temperature changes on multiple sclerosis critical review of mechanisms and research potential. J Neurol Sci 1995 29 1-8. Ku YT, Montgomery LD, Wenzel KC, et al. Physiologic and thermal responses of male and female patients with multiple sclerosis to head and neck cooling. Am J Phys Med Rehab 1999 8 447-456.

Additional Readings Books

Dietary Supplements and Multiple Sclerosis A Health CA Therapeutic Research Faculty, 2005. Polman CH, Thompson AJ, Murray TJ, Bowling AC, Noseworthy JH. Multiple Sclerosis The Guide to Treatment and Management. New York Demos Medical Publishing, 2006. Swank RL, Dugan BB. The Multiple Sclerosis Diet Book. New York Doubleday, 1987. Ulbricht CE, Basch EM, eds. Natural Standard Herb and Supplement Reference Evidence-Based Clinical Reviews. St. Louis Elsevier-Mosby, 2005. Anon. Omega-3 oil fish or pills Consumer Reports 2003July 30-32. Bates D, Cartlidge NEF, French JM, et al. A double-blind controlled trial of long chain n-3 polyunsaturated fatty acids in the treatment of multiple sclerosis. J Neurol Neurosurg Psychiatry 1989 52 18-22. Bates D, Fawcett PRW, Shaw DA, et al. Polyunsaturated fatty acids in treatment of acute remitting multiple sclerosis. Br Med J 1978 2 1390-1391. Bates D, Fawcett PRW, Shaw DA, et al. Trial of polyunsaturated fatty acids in non-...

TNFa and Semimature DCs

In this regard, TNFa may play a role, since it has been shown that injection of DCs cultivated in presence of TNFa acted in a tolerogenic fashion 14 . In these experiments, DCs were able to block autoimmunity in a murine model of multiple sclerosis (EAE). This suppressive effect was mediated by the induction of IL-10-producing regulatory T cells. The subsequent phenotypic analysis revealed that the DCs expressed regular amounts of MHC class II and T cell co-stimulatory molecules, i.e., according to the authors these DCs displayed a mature phenotype as judged by their surface-marker expression. In contrast, these DCs failed to secrete IL-1 , IL-6, TNFa and in particular IL-12. The importance of IL-12 production for full maturation of DCs and acquisition of an immunostimulatory phenotype is further substantiated by results showing that IL-10 as well as cAMP are potent agonists of IL-12p70 secretion. In fact, DCs treated with these agents are resistant to terminal maturation and induce T...

Demyelinating Disease

TNF-a inhibition should not be initiated in patients with a history of demyelinating disorders such as multiple sclerosis (MS). Post-marketing surveillance has reported rare incidences of demyelinating disorders or exacerbations of pre-existing multiple sclerosis in patients receiving etanercept. In addition, early studies examining the use of a TNF- inhibitor, lenercept, in the treatment of multiple sclerosis found increased numbers of MS exacerbations compared to placebo as well as MS exacerbations that occurred earlier compared to placebo. Physicians should be wary of new-onset neurological symptoms in patients receiving eta-nercept treatment, and a good neurological history should be obtained before commencing therapy.

The Complement System

No immunoglobulins or T-cell subsets can be detected within or around plaques of AD cases, which indicates that humoral or classical cellular immune-mediated responses are not involved in cerebral P-amyloid plaque formation or Ap plaque induced inflammatory events in AD 67 , unlike in other brain disorders such as multiple sclerosis 46 and HIV-dementia 199 . No (increased) expression of the most relevant intercellular adhesion molecules (ICAM-1, VCAM-1, E-selectin) is seen on endothelial cells of capillaries in AD brains 70 , whereas in MS and HIV dementia the expression of E-selectin and VCAM-1, necessary for adhesive interactions between leukocytes and endothelial cells of brain capillaries and for leukocyte recruitment to inflammatory foci in the neuropil, coincides with monocyte macrophage infiltration. In addition, many of the large variety of inflammatory mediators, including acute phase proteins, protease inhibitors, complement factors, cytokines, and chemokines seen in AD...

Vitamins Minerals and Other Nonherbal Supplements

Multiple sclerosis decreased relapse rate through dietary supplementation with calcium, magnesium and vitamin D. Med Hypoth 1986 21 193-200. 3. Fleming JO, Hummel AL, Beinlich BR, et al. Vitamin D treatment of relaps-ing-remitting multiple sclerosis (RRMS) a MRI-based pilot study. Neurology 2000 54 A338. 4. Wingerchuk DM, Lesaux J, Rice GPA, et al. A pilot study of oral calcitriol (1,25-dihydroxyvitamin D3) for relapsing-remitting multiple sclerosis. J Neurol Neurosurg Psych 2005 76 1294-1296. 5. Kira J, Tobimatus S, Goto I. Vitamin B metabolism and massive-dose methyl vitamin B therapy in Japanese patients with multiple sclerosis. Int Med 1994 33 82-86. 6. Loder C, Allawi J, Horrobin DF Treatment of multiple sclerosis with lofepramine, L-phenylalanine, and vitamin B12 mechanism of action and clinical importance roles of the locus coeruleus and central noradrenergic systems. Med Hyp 2002 59 594-602. 7. Wade DT, Young CA, Chaudhuri KR, Davidson DLW. A...

Adjunctive Therapies For Neurodegenerative Disorders

Glatiramer acetate (GA, Copaxone, copolymer-1) is an FDA-approved immunomodulatory drug for the treatment of multiple sclerosis (MS). GA immunization induces Th2 regulatory T lymphocytes secreting anti-inflammatory cytokines in mice and humans. These T cells migrate to the brain and provide bystander suppression against neuroinflammation. GA was shown to be an effective immunomodulatory treatment for neuroprotection in animal models of experimental autoimmune encephalomyelitis, optic nerve crush, PD, and AD (Kipnis et al., 2000 Benner et al., 2004 Weber et al., 2004 Frenkel et al., 2005 Wolinsky, 2006). In addition, clinical trials are ongoing in the use of GA in the treatment of ALS (Gordon et al., 2006). A newly completed study in our own lab tested the effects of GA immunization on neuropath-ological outcomes in rodent models of HIVE. GA administration resulted in significant neuroprotection accompanied by increased levels of IL-10 and BDNF (Gorantla et al., submitted)....

Antioxidant Vitamins Generally Vitamins A C and E

Among all categories of dietary supplements, antioxidant vitamins were among those used most frequently by a large group of people with MS who were surveyed through a study at the Rocky Mountain Multiple Sclerosis Center (the full results of this survey may be seen at www.ms-cam.org). Antioxidant vitamins include

Principles And Applications Of Bioregenerative

Structure and function of the central and peripheral nervous systems pathogenesis, pathology, clinical features, and conventional treatment of nerve disorders, including nerve injury, Alzheimer's disease, Parkinson's disease, Huntington's disease, and multiple sclerosis and application of regenerative engineering approaches to the treatment of nerve disorders.

Differential Diagnosis

It is important to exclude any potentially treatable causes such as infections with HIV becoming increasingly important. Rarer examples are Whipple's disease, chronic bacterial meningitis, Lyme disease, neurosyphilis and a number of viral encaphalitides (herpes simplex, subacute sclerosing panencephalitis (SSPE), progressive rubella panencephalitis, progressive multifocal leukoencephalopathy). Dementia is also a feature in patients with multiple sclerosis, brain tumor, paraneoplastic disease and metabolic disorders (deficit of vitamin Bi2 or nicotinic acid, hypothyroidism, chronic hypoglycemia, hypo- and hypercalcemia, Cushing's syndrome, Addison's disease, renal impairment leading to uremic encephalopathy and hepatic disturbances). Further, a number of inherited metabolic diseases are associated with cognitive problems (Wilson's disease, metachromatic leukodystrophy, adrenoleukodystrophy, neuronal ceroid-lipofuscinosis, membranous lipodystrophy, Gaucher's disease, Niemann-Pick...

Traditional Views Of The Cp

How infected leukocytes or activated T lymphocytes cross the CP is unknown, but it is intuitively obvious that their crossing can have disastrous consequences. The CP might be involved in the CNS entry of activated, myelin-directed autoreactive T lymphocytes during multiple sclerosis (MS). Activated T-lymphocyte infiltration into the brain results in the formation of demyelination plaques that underlie the clinical symptoms of MS. Because these plaques are frequently located in the periventricular area, the CP may constitute a preferential way for T lymphocytes to reach these structures. T lymphocytes and T-lymphocyte chemo-attractants are found in the CSF from MS patients.

Optic or Retrobulbar Neuritis

On examination, a relative afferent pupil defect on the affected side might be the only objective evidence of disease. It is essential to test the pupil before dilating it with eye drops. The fundus is often normal initially (retrobulbar neuritis), although there can be slight swelling of the optic disc (optic neuritis). After two or three weeks the optic disc starts to become pale. The visual prognosis is generally good. Most patients make a complete or nearly complete recovery after 6-12 weeks. The attack is unilateral in 90 of cases, although there is a risk that the other eye can be affected at a later date and recurrent attacks in one or both eyes can cause permanent damage to the vision. Fortunately, it is extremely rare for a patient to be made blind by multiple sclerosis.

Additional Resources Books

An investigation into the management of the spasticity experienced by some patients with multiple sclerosis using acupuncture based on traditional Chinese medicine. Compl Ther Med 1996 4 58-62. Xi L, Zhiwen L, Huayan W, et al. Preventing relapse in multiple sclerosis with Chinese medicine. J Chin Med 2001 66 39-40.

Herbs Contain Many Different Chemicals

Many chemicals with beneficial activity against disease have been identified in herbs. It is estimated that 25 percent of prescription drugs and 60 percent of over-the-counter drugs are derived from plants. Well-known examples of these drugs are digitalis, which is derived from the foxglove plant, and quinine, which is derived from South American Peruvian bark. Steroids, which are used to treat multiple sclerosis (MS) attacks, have a very specific chemical structure. Chemicals with steroid-like structures and biologic effects have been identified in Asian ginseng (ginsenoside) and in licorice (glycyrrhizic acid).

Information About CAM and MS

For CAM in general, the information available to the general public is vast but of variable quality. For CAM that is relevant to MS, the amount of information is limited and the quality also is variable. To attempt to understand the type of information that is available on CAM and MS, we conducted an informal survey of the popular literature on CAM at the Rocky Mountain Multiple Sclerosis Center. At two local bookstores, we found 50 CAM books written for a lay audience. Two-thirds of these books had sections on MS. In some books, MS was incorrectly defined as a form of muscular dystrophy. Other books made the erroneous and potentially dangerous statement that, because MS is an immune disorder, it is important to take supplements that stimulate the immune system. In fact, MS is an immune disorder, but it is characterized by an excessively active immune system thus, immune-stimulating supplements actually may be harmful. On average, the CAM books recommended five or six therapies for...

Cooling Therapy

Capell E, Gardella M, Leandri M, et al. Lowering body temperature with a cooling suit as symptomatic treatment for thermosensitive multiple sclerosis patients. Ital J Neurol Sci 1995 16 533-539. 2. Flensner G, Lindencrona C. The cooling-suit a study of ten multiple sclerosis patients' experience in daily life. J Adv Nurs 1999 29 1444-1453.

Website Focused on CAM and MS

This book was written to provide objective, MS-relevant CAM information to people with MS. Also, because the area of CAM is changing rapidly, we developed a website devoted to CAM and MS at the Rocky Mountain Multiple Sclerosis Center. This site, www.ms-cam.org, is updated regularly and has interactive features. This site has several missions

Moving from the Protein to the Biological Activity The Post Genome

Er than miniaturizing assays to increase throughput and reduce costs, we have transformed more and more complex biology to 96-well formats. For example, in our field of multiple sclerosis, we have pioneered a way to study remyelination of neurons in 96-well assays - a technology involving several cell types, a 21-day incubation period, and complex image analysis. It was this technology that led to the identification of several new proteins involved in neuronal repair - of which osteopontin is the forerunner (Fig. 17.5). In the immunology field we were the first to link the FACS cell sorter to our robotics system - and now routinely examine the cytokine production profile of cells (Besson et al. 2003). Whenever possible, we have used human cell or cell-based assays that reflect as closely as possible the mechanism of human physiology and pathology 'in vitro'. Out of our collection of 2,000 proteins and using approximately 10 assays, a large quantity of data points need to be collected....

Inflammation In Alzheimer Dementia

It should be emphasized that the theory of inflammation as a primary disease-aggravating hallmark, opposed to a secondary or even a disease-ameliorating factor, remains a hypothesis. One should be aware that our current knowledge of microglia is still incomplete, speculative, and mainly based upon in vitro observations rather than in vivo studies (33). Indeed, B or T cells and immunoglobulins (Igs) are not readily detectable in the Alzheimer's dementia brain and are found only in very small amounts in relation to amyloid plaques (without IgM IgA) (34). Likewise, although the presence of leukocytes has been demonstrated, their role in Alzheimer's dementia has not been established (35). As such, the evidence for an antigen-driven acquired immune response in Alzheimer's dementia, with T cells eliminating amyloid and B cells producing Ap-specific antibodies, is not as overt as in well-established neuro-inlfammatory diseases (e.g., multiple sclerosis 36).

The secondary narcolepsycataplexy

Association of cataplexy with EDS with another disorder of the brain was first reported in the early 1900. These associations includes tumors, localized most frequently to the diencephalon or to the brain stem, other diencephalic lesions (e.g. , large arterio-venous malformation, or lesions secondary to ischemic events), multiple sclerosis with plaques in the diencephalon, head injury, encephalitis, etc. In young children, Niemann-Pick disease type C, characterized by hepatosplenomegaly, progressive ataxia, dystonia, dementia and vertical supranuclear opthalmoplegia, is often associated with cataplexy early in life, as pointed out by Challamel et al. 63 . Cat-aplexy was noted much earlier in these children with Niemann-Pick, than in a group of prepubertal children 35 with a mean age of onset of 6years 63-66 . The other cause of very early onset of secondary cataplexy is craniopharyngioma. This tumor is one of the most common brain tumors in children and account for 9 of all pediatric...

Early Preclinical Work Leading to the Development of Gabapentin

Gabapentin was conceived as part of a drug discovery program to treat neurological diseases, including epilepsy, spasticity, multiple sclerosis, and other central nervous system (CNS) disorders. This program began in the early 1970s at the German company, Goedecke, A.G., in Freiburg, Germany, which was a part of Warner-Lambert (now incorporated into Pfizer). The history of this project included chemical attempts to inhibit g-amino-butyric acid (GABA) degradation in brain with compounds that inhibited the catalytic pyridoxylphosphate of GABA-transaminase. It had already been known for some time that GABA was a key inhibitory neurotransmitter, and that experimental chemical impairment of GABA systems could cause seizures in experimental animals. The GABA transaminase project at Goedecke had progressed a compound to phase I clinical trials, but these were halted because of safety concerns. The chemical matter developed within the GABA transaminase project had no direct relationship to...

Intervention with Adhesion Molecules

Cyte migration, haemostasis, and tumour biology (Hynes 2002). T cells in the blood circulation adhere to endothelium by interaction of alpha-beta integrins on their surface (Lobb and Hemler 1994). In 1993 it was established that T-cell migration into brain parenchy-mal tissue is mediated by a distinct subset of these integrins, the integrin molecule (Baron et al. 1993), interacting with counter-receptors on endothelial cells. Observations like this lead to the idea of inhibiting T-cell migration in diseases where T cells are key mediators, like multiple sclerosis (MS), which is the most common inflammatory autoimmune disease of the central nervous system (Gold and Hohlfeld 2007). Antibodies against 4 integrin on T cells were shown to inhibit the MS animal model, experimental autoimmune encephalomyelitis (EAE) (Yednock et al. 1992). A humanized antibody was developed (natalizumab, Tysabri, formerly Antegren), which binds to the a4 subunit of human a and a4 37 integrin, for the...

In Search and Discovery of Potential New Therapeutic Indications

The search for additional indications for modafinil naturally focused on diseases associated with wake deficits and somnolence. The effects of the drug in an animal model of sleep-disordered breathing suggested that modafinil might be effective in reducing sleepiness associated with sleep apnea,50 and this was subsequently demonstrated in the clinic.51-53 Other disorders where somnolence or sedation was concomitant with the disease, e.g., Parkinson's disease,54-56 myotonic dystrophy,57-60 fibromyalgia,61 amyotrophic lateral sclerosis,62 multiple sclerosis,63 cerebral lymphoma,64 or resulting from the side-effects of other medications such as antidepressants,65 antipsychotics,66 dopaminergic D2 agonists,67,68 opioids,69 or valproic acid,70 have also proven to be amenable to treatment with modafinil. Likewise modafinil has been applied with equal success to treating the fatigue coexisting with other serious diseases, including multiple sclerosis,71,72 pain,73 and acquired...

Acquired immune deficiency syndrome dementia

A number of autoimmune neuroinflammatory disorders (see 6.09 Neuromuscular Autoimmune Disorders) affect either the central or peripheral nervous system. Many of these disorders are exceptionally rare such as Moersch-Woltman syndrome (stiff-man), Lambert-Eaton myasthenic syndrome, and myasthenia gravis (MG). While uncommon, these disorders tend to be highly debilitating as they directly alter neuromuscular transmission. The most common of these disorders is MG which affects an estimated 60 000 people in the USA. The primary pathology underlying MG appears to be the production of autoantibodies directed against the alpha subunit of the neuromuscular nicotinic acetylcholine receptor. Through direct interference and complement-mediated lysis of the postsynaptic muscle membrane, the autoantibodies cause disruption in the motor endplate that leads to a weakness in skeletal muscle throughout the body. The autoimmune disorder systemic lupus erythematosus (SLE) and the neuroinflammatory...

Experimental Autoimmune Encephalomyelitis EAE

EAE is a primarily CD4+ T cell-mediated demyelinating disease of the CNS, and it is widely used as an animal model for human multiple sclerosis (MS). EAE can be induced in susceptible animal strains by immunization with various myelin proteins or immunodominant peptide epitopes derived from myelin basic protein (MBP), proteolipoprotein (PLP), or myelin oligodendrocyte glycoprotein (MOG) peptide emulsified in complete Freund's adjuvant (CFA) together with pertussis toxin treatment (Gonatas etal., 1986 Wekerle, 1991). THl-type responses appear to be responsible for EAE pathogenesis, while TH2 responses seem to be protective (Adorini and Sinigaglia, 1997 Liblau et al., 1995). The adjuvant and pertussis might be necessary to skew the systemic cytokine profile to TH1 phenotype, affect the blood-brain barrier, and support prolonged inflammation.

Dementia Due to Other General Medical Conditions

Dementia also may be caused by other diseases with primarily central nervous system pathology, such as multiple sclerosis, amyotrophic lateral sclerosis, and various conditions (e.g., progressive subcortical gliosis, focal lobar atrophy) with mainly frontal lobe-type behavioral manifestations. Extracerebral pathology, both intracranial (brain tumor, subdural hematoma, hydrocephalus) and extracranial (hypothyroidism, hypercalcemia, hypoglycemia) processes, also can cause dementia via mechanical and biochemical effects on brain function. Accurate diagnosis usually depends on recognition of the characteristic clinical and laboratory features of the underlying illness. The battery suggested in Table 5-4 in Chapter 5 (Dementia and Alzheimer's Disease) is designed to have relatively high sensitivity for this purpose.

Scientific Foundations

Man undergoing plasmapheresis treatment for multiple sclerosis. In this treatment, blood is removed from the patient and the harmful agents that attack the nerve cells are filtered out before returning the blood to the body. Annie Griffiths Belt Corbis. Since that time, the National Multiple Sclerosis Society has divided MS into four types for the purposes of identification and treatment relapsing-remitting, secondary-progressive, primary-progressive, and progressive relapsing. Relapsing-remitting involves unpredictable relapses and attacks followed by remission (periods of no attacks). When symptoms go away between remission periods, it is called benign MS. It is the second most common type of MS. Secondary-progressive patients first go through a relapsing-remitting phase, which is followed by less severe attacks (but total remission does not occur). It is the most common type of MS.

Clinical Trial Issues

Further, scales used to measure disease severity or progression are imperfect. One needs a standardized scale that can be used to provide a quantitative measure of a patient's clinical status and course or stage of progression. Scales currently in use have limitations - the Kurtzke Expanded Disability Status Scale (EDSS) and the Multiple Sclerosis Functional Composite score used in MS, for example.

Neurodegenerative Diseases

Neurodegenerative diseases (see 6.08 Neurodegeneration) include AD Parkinson's disease amyotrophic lateral sclerosis (ALS) demyelinating diseases, e.g., multiple sclerosis neuropathies, e.g., diabetic, HIV, and chemotoxin-induced Down's syndrome (DS) prion diseases, e.g., Creutzfeldt-Jakob disease tauopathies, e.g., Pick's disease, frontal temporal dementia with Parkinsonism (FTDP) trinucleotide repeat or polyglutamine (polyQ) diseases, e.g., Huntington's disease (HD) spinocerebellar ataxias (SCA) dentatorubral-pallidolysian atrophy (DRPLA) Friedreich's ataxia multiple systems atrophy (MSA) stroke and traumatic brain injury.

Specificity to Alzheimers Disease

Upregulation of clusterin and abnormal staining of lesions for apoE is not limited to AD. Brain levels of clusterin seem to be elevated in many conditions involving injury or chronic inflammation of the brain. Elevated levels of the mRNA for clusterin are seen in the hippocampus in Pick's disease as well as in AD.4 Abnormal staining for clusterin has been seen in dystrophic neurites and some NFTs in the Parkinson's dementia complex of Guam (Fig. 7.1). It has also been seen in humans in ischemic Purkinje cells which showed the shrunken and pyknotic appearance characteristic of irreversible damage.45 Intense staining for clusterin has been seen in hypertrophic astrocytes in cases of multiple sclerosis, stroke and AIDS encephalitis. In these cases, however, the distribution of clusterin did not appear to correlate with that of the MAC,46 a correlation which does appear to occur in AD.9

Conventional Medical Therapy for MS

Because of the positive effects of the FDA-approved medications, all people with MS should be strongly considered for treatment with one of these drugs. A 1998 statement by the National Multiple Sclerosis Society emphasized the importance of treatment. The statement recommended that treatment with these medications should be started soon after an MS diagnosis is made and should be considered in all people with MS, regardless of age, rate of relapses, and level of disability.

Acupuncture and Traditional Chinese Medicine

Spoerel WE, Paty DW, Kertesz A, et al. Acupuncture and multiple sclerosis. CMA Journal 1974 110 751. 3. Smith MO, Rabinowitz N. Acupuncture treatment of multiple sclerosis Two detailed clinical presentations. Am J Acupuncture 1986 14 143-146. 4. Miller RE. An investigation into the management of the spasticity experienced by some patients with multiple sclerosis using acupuncture based on traditional Chinese medicine. Compl Ther Med 1996 4 58-62. 5. Steinberger A. Specific irritability of acupuncture points as an early symptom of multiple sclerosis. Am J Chinese Med 1986 14 175-178. 7. Wang Y, Hashimoto S, Ramsum D, et al. A pilot study of the use of alternative medicine in multiple sclerosis patients with special focus on acupuncture. Neurology 1999 52 A550. 8. Xi L, Zhiwen L, Huayan W, et al. Preventing relapse in multiple sclerosis with Chinese medicine. J Chin Med 2001 66 39-40. 9. Yi S, Xiaoyan L. A review on traditional Chinese medicine in prevention and treatment of multiple...

Clusterin Expression and Localization in the Brain

Clusterin mRNA and protein levels increase in a variety of human neurologic disorders, including Alzheimer's disease (AD),7-9,16,17 multiple sclerosis,18 acquired immune deficiency syndrome (AIDS),18 Pick's disease,9 epilepsy19 and gliomas19 (see chapter 7 for complete review). Clusterin expression is also increased in a variety of experimentally-induced brain injury rodent models representing ischemia,20,21 synaptic repair,22,23 epilepsy,8,24,25 or hormonal alterations26,27 (see chapter 3 for complete review). Human CSF clusterin is increased in patients with evidence for de-myelination, but at normal levels in patients with neurodegenerative and meningeal disease.28,29

Studies of MS and Other Conditions

The effects of prayer and spirituality on multiple sclerosis (MS) have not been rigorously studied. One frequently described case of MS that appeared to respond dramatically to prayer and faith involved Rita Klaus. Klaus was a nun who was diagnosed with MS in 1960, at the age of 20. Because of the effects of her illness, she was given dispensation of her vows and left the convent. She eventually married and had three children. At the Rocky Mountain Multiple Sclerosis Center, we conducted a survey of spirituality and prayer in more than 1,000 people with MS. The vast majority of the respondents (90 percent) stated that they believed in God. Within this group, more people (43 percent) believed that God did not play a role in their having MS than believed that God did play a role (28 percent). Of those who believed God played a role in their having MS, a very small percentage (3 percent) thought that MS was a punishment from God. The majority (90 percent) of those who thought that God...

Coffee and Other Caffeine Containing Herbs and Supplements

The largest study to date was conducted by the Rocky Mountain Multiple Sclerosis Center the results of this study have been published in a preliminary form (1) and may be viewed at www.ms.cam.org, the CAM website of the Rocky Mountain MS Center. This study was an online survey that involved nearly 2,000 people with MS. Those who appeared to have MS fatigue were questioned about the various conventional and unconventional therapies that they had tried. For the respondents, about 50 percent believed that some form of caffeine was helpful for their fatigue. Another MS study that included caffeine involved a therapy known as Prokarin the results of this study are difficult to interpret for several reasons, including the fact that Prokarin contains caffeine as well as histamine (see the chapter on Prokarin).

Practical Information

Pathways Exercise Video for People with Limited Mobility is a video showing yoga poses designed for people with MS. Information about the southern California yoga and MS program may be obtained from the southern California chapter of the National Multiple Sclerosis Society at www.nationalmssociety.org CAL home or 2440 S. Sepulveda Boulevard, 115, Los Angeles CA 90064 (800-344-4867 or 310-479-4456). General information on yoga is available from several yoga organizations

Hyperbaric Oxygen

Hyperbaric oxygen treatment of multiple sclerosis. A randomized, placebo-controlled, double-blind study. N Engl J Med 1983 308 181-186. 2. Kleijnen J, Knipschild P. Hyperbaric oxygen for multiple sclerosis review of controlled trials. Acta Neurol Scand 1995 91 330-334. 3. Bennett M, Heard R. Hyperbaric oxygen therapy for multiple sclerosis. Cochrane Database Syst Rev 2004 (1) CD003057. 4. Neubauer RA, Neubauer V Gottlieb SF The controversy over hyperbaric oxygenation therapy for multiple sclerosis. J Amer Phys Surgeons 2005 10 112-115.

Placebos and the Placebo Effect

As would be expected, a placebo effect occurs in studies of people with multiple sclerosis (MS). A notable response to placebos has been observed in studies of therapy for MS itself, as well as for MS-related symptoms. In older MS studies, from 1935 to 1950, a variety of ineffective therapies produced 60 to 70 percent improvement. More recently, trials with chemotherapy drugs in MS showed a placebo effect on the rate of MS attacks. In recent research studies using interferon beta-1b (Betaseron), the first U.S. Food and Drug Administration (FDA)-approved immune therapy for MS, the number of MS attacks was determined for people taking Betaseron and for another group taking placebo. The placebo-treated group had a 28 percent decrease in the rate of MS attacks. Similarly, the placebo group showed decreased attack rates of 33 percent in trials using intramuscular interferon beta-1a (Avonex), 13 percent in trials with subcutaneous interferon beta-1a (Rebif), and 43 percent in trials with...

Music Therapy

Active music therapy in the treatment of multiple sclerosis patients a matched control study. J Music Ther 2004 61 225-240. 2. Lengdobler H, Kiessling WR. Group music therapy in multiple sclerosis initial report of experience. Psychother Psychosom Med Psychol 1989 39 369-373. 3. Wiens ME, Reimer MA, Guyn HL. Music therapy as a treatment method for improving respiratory muscle strength in patients with advanced multiple sclerosis a pilot study. Rehabil Nurs 1999 24 74-80.

Placebos and Psychoneuroimmunology

The placebo effect during a double blind trial of recombinant alpha2 interferon in multiple sclerosis patients immunological and clinical findings. Neurosci 1988 39 189-196. 4. Brown RF, Tennant CC, Dunn SM, et al. A review of stress-relapse interactions in multiple sclerosis important features and stress-mediating and -moderating variables. Mult Scler 2005 11 477-484. 5. Mohr DC, Hart SL, Julian L, et al. Association between stressful life events and exacerbation in multiple sclerosis a meta-analysis. Br Med J 2004 328 731-735.

Magnets and Electromagnetic Therapy

Pulsing electromagnetic field therapy of multiple sclerosis by the Gyuling-Bordas device double-blind, cross-over and open studies. J Bioelec 1987 6 23-35. 3. Richards TL, Lappin MS, Acosta-Urquidi J, et al. Double-blind study of pulsing magnetic field effects on multiple sclerosis. J Alt Complement Med 1997 3 21-29. 4. Lappin MS, Lawrie FW, Richards TL, et al. Effects of a pulsed electromagnetic therapy on multiple sclerosis fatigue and quality of life a double-blind, placebo controlled trial. Alt Ther 2003 9 38-48.

Hippotherapy and Therapeutic Horseback Riding

Hammer A, Nilsagard Y, Eorsberg A, et al. Evaluation of therapeutic riding (Sweden) hippotherapy (United States). A single-subject experimental design study replicated in eleven patients with multiple sclerosis. Physiother Theory Prac 2005 21 51-77. 2. MacKay-Lyons M, Conway C, Roberts W. Effects of therapeutic riding on patients with multiple sclerosis a preliminary trial. Proceedings of the 6th International Therapeutic Riding Congress 1988 8 173-178.

Diets and Fatty Acid Supplements

Multiple sclerosis twenty years on low fat diet. Arch Neurol 1970 23 460-474. 2. Swank RL, Dugan BB. Effect of low saturated fat diet in early and late cases of multiple sclerosis. Lancet 1990 336 37-39. 4. Miller JHD, Zilkha KJ, Langman MJS, et al. Double-blind trial of linoleate supplementation of the diet in multiple sclerosis. Br Med J 1973 1 765-768. 5. Bates D, Fawcett PRW, Shaw DA, et al. Polyunsaturated fatty acids in treatment of acute remitting multiple sclerosis. Br Med J 1978 2 1390-1391. 6. Paty DW, Cousin HK, Read S, et al. Linoleic acid in multiple sclerosis failure to show any therapeutic benefit. Acta Neurol Scand 1978 58 53-58. 7. Dworkin RH, Bates D, Millar JHD, et al. Linoleic acid and multiple sclerosis a reanalysis of three double-blind trials. Neurology 1984 34 1441-1445. 8. Bates D, Fawcett PRW, Shaw DA, et al. Trial of polyunsaturated fatty acids in non-relapsing multiple sclerosis. Br Med J 1977 10 932-933. 10. Bates D, Cartlidge NEF, French JM, et...

Matter of Perspective

Alexander Burnfield, an English psychiatrist who has MS, wrote a book entitled Multiple Sclerosis A Personal Exploration. With reference to evening primrose oil, he states I started taking it before the research was published and, being only human, take it just in case I get worse if I stop. This is, I know, an unscientific and emotional response, and the logical-doctor part of me is quite shocked (16). Dr. Elizabeth Forsythe, also an English physician with MS, wrote Multiple Sclerosis Exploring Sickness and Health. With reference to diet and MS, she states It is what you feel in your own body and mind that is the most important thing, and it is very easy for doctors and patients to forget that. I believe that a little of what you fancy does do you good (17).

Unmet Medical Needs

Concerns have been raised in regard to current screening paradigms used in AED discovery, e.g., the NINDS in vivo panel, that are viewed as generating AEDs of similar efficacy (and limitations) to those already in use.29,43 In the 10 years encompassing the 1990 Decade of the Brain, eight new AEDs were introduced, none of which appears to have had any impact on the treatment of intractable epileptic patients.43 This same period also saw a doubling of the finding for epilepsy research from 40 million to 80 million and, in 1999, a major White House initiative, 'Curing Epilepsy - Focus on the Future,' focused on translational research initiatives to use the evolving knowledge of basic brain function at the genomic and proteomic levels to develop new models that would lead to new treatments for epilepsy, new AEDs as well as possible cures and prevention of the disorder(s). Like many of the debatably successful outcomes from the Decade of the Brain,44 the transition of research findings to...

Medical Examination Under Section 4 of the RTA

Whether the examination is carried out by a forensic physician in London or an emergency room physician in San Francisco, the aim of the examination is to exclude any medical condition other than alcohol or drugs as the cause of the driver's behavior. The differential diagnosis is wide and includes head injury, neurological problems (e.g., epilepsy, stroke, cerebral tumour, and multiple sclerosis), metabolic problems (e.g., hypoglycemia), hepatic or renal failure, and mental illness. The procedure should include introductory details, full medical history, and clinical examination. In Scotland, forensic physicians use form F97. Appendix 6 contains a form that has been found useful. Similar forms are not available in the United States, but there is nothing to prevent any emergency department in the United States from drafting and providing a similar document. Even if no special form is provided, most of the relevant material will have been (or at least should be) recorded in the...

Inhibitors of Leukocyte Migration

A new therapeutic agent, called fingolimod (FTY720), works by binding to and blocking sphingosine 1-phosphate (S1P) receptors on lymphocytes. S1P is required for the egress of lymphocytes from lymphoid organs (see Chapter 3), and blocking its action leads to the sequestration of lymphocytes in lymph nodes. Fingolimod inhibits allograft rejection in animal models. This drug is not yet used for clinical transplantation, but it is approved for treatment of multiple sclerosis, an autoimmune disease of the central nervous system.

Teitelbaum R Arnon and M Sela Weizmann Institute of Science Rehovot Israel 2007 Elsevier Ltd All Rights Reserved

8.14.3.3.4 Study of primary progressive multiple sclerosis 178 8.14.4.2 Immunological Effects of Glatiramer Acetate in Multiple Sclerosis Patients 181 8.14.4.2.2 T-cell response to glatiramer acetate in naive multiple sclerosis patients 181 8.14.4.2.3 T-cell response to glatiramer acetate in treated multiple sclerosis patients 181

Proinflammatory Cytokines

Solid tumours 15 , this cytokine has been implicated as the initiating signal for a variety of cellular and metabolic events seen in critically ill patients. TNF-a may circulate predominantly as a complex with its soluble receptors, making detection of the bioactive ligand more difficult. Increased levels of these soluble TNF-a receptors are seen in response to diverse inflammatory stimuli including sepsis, cancer and AIDS 16 . Nevertheless, elevated TNF-a levels are detected in many disease states including bacterial infections, cancer, sepsis and AIDS 17 . TNF-a is a metabolic hormone acting both in a paracrine fashion, and, in some istances, as an endocrine hormone 18 . Systemically, TNF-a has been suggested to act in the brain to cause anorexia and subsequent body weight loss 19 . The metabolic effects of TNF-a seem to promote redistribution of body protein and lipid stores. The result is a net loss of peripheral tissue protein with a concomitant increase in hepatic uptake 20 ....

Complementary and Alternative Medicine and MS

Berkman CS, Pignotti MG, Cavallo PF, et al. Use of alternative treatments by people with multiple sclerosis. Neurorehab Neural Repair 1999 13 243-254. 6. Marrie RA, Hadjimichael O, Vollmer T. Predictors of alternative medicine use by multiple sclerosis patients. Mult Scler 2003 9 461-466. 7. Stuifbergen AK, Harrison TC. Complementary and alternative therapy use in persons with multiple sclerosis. Rehab Nursing 2003 28 141-147. 8. Nayak S, Matheis RJ, Schoenberger NE, et al. Use of unconventional therapies by individuals with multiple sclerosis. Clin Rehabil 2003 17 181-191. 9. Shinto L, Yadav V, Morris C, et al. Demographic and health-related factors associated with complementary and alternative medicine (CAM) use in multiple sclerosis. Mult Scler 2006 12 94-100. 11. Hooper KD, Pender MP, Webb PM, et al. Use of traditional and complementary medical care by patients with multiple sclerosis in South-East Queensland. Int J MS Care 2001,3 13-28. 12. Page SA, Verhoef MJ, Stebbins RA, et...

Annexin 1 And Inflammation

Annexin 1 is up-regulated in multiple sclerosis and in an experimental model of the disease (experimental autoimmune encephalomyelitis-EAE) intracerebroven-tricular administration of annexin 1 proved to be neuroprotective. Annexin 1 is present in both macrophages and astrocytes localised in the lesions (Bolton et al., 1990 Huntinga et al, 1998). In experimental autoimmune neuritis (EAN), a model for human Guillain-Barre syndrome, increased annexin 1 expression was also observed in macrophages and T-cells in the inflamed sciatic nerve (Gold et al.,1999).

Important Precautions About ementary and Alternative Medicine and

This book provides much detailed information about specific types of complementary and alternative medicine (CAM). This information is intended to assist people in assessing CAM therapies for multiple sclerosis (MS). In addition to this specific information, some general ideas are important to understand and may be helpful in the CAM decision-making process

Internuclear Ophthalmoplegia

Whereas double vision is a common symptom in multiple sclerosis, it is unusual to see an obvious defect of the ocular movements. Sometimes it can be seen that one eye fails to turn inwards when the patient is asked to look to the opposite side, and yet when the patient is made to converge the eyes on a near object, the medial rectus moves normally. This failure of the muscle action with certain co-ordinated eye movements only (i.e., limitation of adduction),while the opposite abducting eye shows nystagmus, is termed internuclear ophthalmoplegia. It is characteristic of multiple sclerosis when seen in young people (when the internuclear ophthalmoplegia is usually bilateral and is caused by a demyelinating lesion in the pons) but usually has a vascular cause in the elderly (when it is usually unilateral).

Future Strategies And Developments In Mrbased In Vivo Metabolic Imaging

Modification of spectra with metabolite-nulling sequences allow for improved evaluation of lipids and other macromol-ecules, with improved resolution of peaks at 0.9 ppm, and 1.3 ppm, and 2.1 ppm. These correlated to spectra of methyl groups, methylene, and terminal methylene groups, respectively. Findings have been evaluated in the setting of acute stroke and multiple sclerosis. Mader et al. (165) found significant evaluation in macromolecular peaks in the setting of acute MS plaques in contrast to normal-appearing white matter and chronic MS lesions, perhaps representing the residues from cytosolic protein that may become elevated during the course of disruption.

Peroxisomal Disorders

The first manifestations of ALD may be psychiatric or behavioral hence, diagnosis may be delayed. In the classic forms, progressive dementia ensues with disturbances of gait manifest by spastic paraplegia. Other features include cerebel-lar signs of clumsiness and incoordination, dysarthria, dysphagia, and neurosensory loss. Visual loss occurs because of optic atrophy or bilateral occipital white matter lesions. Seizures, when present, are multifocal in origin. Features may appear asymmetric in onset. Pace of deterioration is variable. Adrenomyeloneuropathy or AMN is a phenotypic variant and may occur in families with boys with classic adrenoleukodys-trophy. This variant involves additionally, distal polyneuropa-thy. Females, because of their allelic heterogeneity and variant X-inactivation, may appear unaffected or display variable symptoms from mild to more significant. Features may mimic multiple sclerosis.

Functional Coimaging

Attempts have been made to visualize inflammation by means of cobalt radioisotopes. Both in vivo and in vitro experiments have shown that Ca2 accumulates in the damaged nerve cell body and degenerating axons by two mechanisms (1) a passive influx caused by a shortage of ATP following ischemia, resulting in the disappearance of the membrane potential, and (2) neuronal and glial uptake by divalent cation-permeable kainate-activated non-N-methyl-D-aspartate glutamate receptor-operated channels in the membrane (5257). 57Co (SPECT) and 55Co (PET), both as Ca2+-analogs, can reflect Ca2+-influx in ischemically or neurotoxically damaged cerebral tissue. In this way, both 57Co SPECT and 55Co PET have been shown capable of visualizing focal neurode-generative changes, reactive gliosis, endangered brain tissue, and or ongoing neuronal tissue decay, including inflammatory lesions in various brain diseases, for example, multiple sclerosis, trauma, tumors, and stroke (58-64). Moreover, the time...

Lamotrigine

I n summary, carbamazepine remains an established first line option in the treatment of trigeminal neuralgia. There is good evidence supporting gabapentin and pregabalin for the treatment of post herpetic neuralgia and painful diabetic neuropathy, and growing evidence for lamotrigine and oxcarbazepine in neuropathic pain. Carbamazepine may also be used in neuropathic pain if the pain is predominantly electric shock-like or if it is caused by multiple sclerosis. Large trials have identified that topiramate is not analgesic in painful diabetic neuropathy, and the efficacy of topiramate in other types of pain remains to be established. Thus, it is reasonable to use gabapentin, pregabalin and carbamazepine first (in the case of liver disease carbamazepine should be avoided) and then to move to lamotrigine or oxcarbazepine, if there is no response or the patient is unable to tolerate side effects. In the case of trigeminal neuralgia, baclofen provides an additional option 8 .

Journal Articles

Homeopathy in multiple sclerosis. Complement Ther Nurs Midwifery 2003 9 5-9. HH-yperbaric oxygen treatment is a form of oxygen therapy. It is claimed to be an effective treatment for a large number of diseases, including multiple sclerosis (MS). Unfortunately, many of the claims about this therapy are not supported by research evidence.

Treatment Method

A unique therapeutic use of electrical energy has been employed recently to treat tremors in people with multiple sclerosis (MS), Parkinson's disease, and other neurologic disorders. In this treatment, an electrode is implanted in a brain region that controls body movements. Electrical stimulation of the electrode may significantly improve the tremor.

Imaging

Using imaging, it may be possible to develop approaches such that changes in function can be correlated between animals and humans. Many of these applications of imaging may facilitate the development of biomarkers. The ability to do multiparametric analysis noninvasively provides the opportunity for identifying a much broader number of biomarkers, in which their relevance to the intact organ can be realized. Imaging approaches are very important in the diagnosis of disease states and its progression. With suitable validation, it may be possible to develop imaging data for these surrogate markers to a level better than the available clinical endpoint. The example of multiple sclerosis (MS) will be discussed in this chapter.

Marijuana

Cannabinoids for treatment of spasticity and other symptoms related to multiple sclerosis (CAMS study) multicentre randomised placebo-controlled trial. Lancet 2003 362 1517-1526. 2. Zajicek J, Sanders HP, Wright DE, et al. Cannabinoids in multiple sclerosis (CAMS) study safety and efficacy data for 12 months follow up. J Neurol Neurosurg Psych 2005 76 1664-1669. 3. Wade DT, Makela P, Robson P, et al. Do cannabis-based medicinal extracts have general or specific effects on symptoms in multiple sclerosis a double-blind, randomized, placebo-controlled study on 160 patients. Mult Scler 2004 10 434-441.

CAM Use in MS

Several studies have evaluated CAM use in MS. One of the earliest studies was conducted in Massachusetts and California in the 1990s (5). Approximately 60 percent of people had used CAM, and, on average, people used two to three different types of CAM. We conducted a similar survey, in 1997, at the Rocky Mountain Multiple Sclerosis Center and found that approximately two-thirds of those who responded to the survey used CAM.

Toxins

Over the years, it has been proposed that many toxins may cause multiple sclerosis (MS) or worsen its symptoms. Recent reports have associated MS with aspartame use and mercury from dental amalgam, both of which are discussed elsewhere in this book. It also has been claimed that MS is provoked by cosmetics or by chemicals in the environment in the form of pollution, aerosol sprays, low levels of formaldehyde, and fumes from solvents. In food, it has been claimed that additives and low levels of residual fertilizers and pesticides may be important. On the basis of concerns about toxic causes for MS and other diseases, an entire field known as clinical ecology has emerged.

Medicine CAM

Multiple sclerosis (MS) is a common disease of the nervous system. Most people with MS use some form of conventional medical treatment. In addition, many people with MS also use complementary and alternative medicine (CAM), which refers to unconventional medical practices that are not part of mainstream medicine. Despite the fact that CAM is used frequently and MS is a common neurologic disorder, it may be difficult to obtain accurate and unbiased information specific to the use of CAM for MS.

Enzyme Therapy

Enzymes are a type of protein used by the body to perform chemical reactions. Enzymes break down food in the digestive tract and carry out essential chemical functions in the rest of the body. It is claimed that treatment with enzymes is beneficial for many diseases, including multiple sclerosis (MS).

Automata Based Models

Later on, one has to acknowledge the Weisbuch and Atlan model (WA) 25 , which was subsequently followed by many other models. Such a model was proposed on the basis of Jerne's theory to study the special case of auto-immune diseases, like multiple sclerosis, in which the immune system attacks the cells of the

Overview

Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS) are the best known neurodegenerative diseases, but also included in the category of neurodegeneration are demyelinating diseases (e.g., multiple sclerosis, Charcot-Marie-Tooth, neuromyelitis optica), neuropathies (e.g., diabetic, human immunodeficiency virus (HIV), chemotoxic), Down's syndrome, prion diseases (e.g., CreutzfeldtJakob disease), tauopathies (e.g., Pick's disease, frontal temporal dementia with parkinsonism (FTDP)), additional trinucleotide repeat or polyglutamine (polyQ) diseases (e.g., spinocerebellar ataxias, dentatorubral-pallidolysian atrophy, Freidreich's ataxia), multiple systems atrophy, stroke, and traumatic brain injury. The current chapter focuses on AD, PD, HD, and ALS multiple sclerosis and stroke are covered elsewhere in this volume (see 6.09 Neuromuscular Autoimmune 6.10 Stroke Traumatic Brain and Spinal Cord Injuries).

Gagtcaagg

Ca2+ to covalently bound EF-hand motifs, to a separate EF-hand subunit, but also to two Ca2+-binding sites of novel type located close to the catalytic center. The two dimeric calpains designated as m and m are ubiquitous. Other tissue-specific calpains, by contrast, are monomeric and may not contain the endogenous EF-hand motifs. However, as they still contain the non-EF-hand Ca2+-binding sites, they are still likely to be controlled by Ca2+. Calpains are regulatory proteases that do not demolish protein substrates completely rather, they remove from them limited peripheral portions, frequently leading to their activation. The two ubiquitous dimeric calpains have been involved in a long list of cell dysfunction states related to disturbances of Ca2+ homeostasis which could have lead to abnormal calpain activation. Alzheimer's disease, cataract, and multiple sclerosis have frequently been mentioned a particularly interesting and well documented case is that of excitotoxic neuronal...

Men10755

Pixantrone (17) is an azaanthraquinone, evolved from mitoxantrone in a search for drugs with lower cardiotoxicity.96 It was selected from a series of analogs on the basis of high cytotoxic activity, significant in vivo antitumor efficacy (especially against lymphomas and leukemias) over a wide dose range, and a lack of delayed cardiotoxicity compared with other anthracenediones.97 It is a DNA intercalating agent and topo II inhibitor,98 but it is not clear if this is its only mechanism of action, since its DNA damaging effects do not correlate with cytotoxicity.99 While pixantrone is not as potent as mitoxantrone it is also less cardiotoxic at equieffective doses, less myelosuppressive, and shows better in vivo activity in leukemia and lymphoma models.96 The drug appears to be most useful in the treatment of non-Hodgkin's lymphoma100 a recent multicenter Phase II trial used a dose of 85 mg m _ 2 in a 3-weekly protocol, gave 9 33 remissions with a median relapse time of 17 + months,...

Types of Biomarkers

The concept of biological markers of disease is both old and new. Historically, markers for disease have been used to diagnose and monitor disease risk, progression, improvement, and severity.67 Examples are clinical chemistry for many disease states, histological markers such as Papanicolaou smears for cervical cancer, magnetic resonance imaging (MRI) for multiple sclerosis, as well as serum markers associated with cancer states, i.e., prostate-specific antigen (PSA), carcinoembryonic antigen (CEA), and cancer antigen-125 (CA-125).29'65'68-73 Markers that can be assessed from blood and or urine samples are very reliable in determining the clinical status of the disease. In most references, the definitions of biomarkers and its categories are often used interchangeably, but for clarity, the functional categories of biomarkers will be used in this discussion (Figure 3).64'65'67,74 Biomarkers can be categorized as disease biomarkers

John M Land

Biomarkers of disease may reflect tissue damage or disease mechanisms - that is, the pathophysiology of the condition. For many years, neurological diseases could only be described in clinical or neuropathological terms. However, in the last decade, we have come to understand some of the mechanisms underlying some of those diseases associated with the most severe morbidity and mortality - particularly Alzheimer's disease, multiple sclerosis (MS) and Parkinson's disease. In addition, we are increasingly recognizing substances which appear to be specific to the cells found in the brain which could act as biomarkers. Examples include N-acetylaspartate (in neurones), neurone-specific enolase (NSE) and an isoform of S-100 protein found in glial cells.

Supplements and MS

Supplements are one of the most popular forms of CAM used by people with MS. The largest and most detailed survey of dietary supplement use among people with MS was conducted at the Rocky Mountain Multiple Sclerosis Center. Of the respondents to this survey, more than 90 percent had used dietary supplements since being diagnosed with MS, and more than 80 percent were using some type of dietary supplement at the time of the survey. The full results of the survey are available at www.ms-cam.org, the CAM website of the Rocky Mountain Multiple Sclerosis Center.

Acupuncture

It is surprising how few studies have evaluated acupuncture in multiple sclerosis (MS). In 1974, a Canadian study of eight people with MS showed that a few had some mild and brief benefits (2). However, there did not appear to be long-lasting effects. In 1986, a very small study of two people with MS showed that multiple MS symptoms improved (3). A recent preliminary study indicates that acupuncture may improve MS-related bladder difficulties. Two large surveys have evaluated the effects of acupuncture on people with MS. At the Rocky Mountain Multiple Sclerosis Center, we conducted a web-based survey on acupuncture on our CAM website, www.ms-cam.org. The preliminary results have been reported (6) and may be viewed at the website. Among more than 1,000 respondents, about 20 percent had used acupuncture since they were diagnosed with MS. The symptoms that were reported to be improved most frequently were pain and anxiety about two-thirds reported improvement with these symptoms. Other...

Mitoxantrone

Therefore, noninvasive monitoring of the cardiac effects of mitoxantrone is also considered to be of great clinical importance, particularly as this agent is frequently used after a course of anthracyclines has been administered. Furthermore, mitoxantrone has been proposed for the treatment of multiple sclerosis (12).

Hypnosis

Hypnosis for pain and neuromuscular rehabilitation with multiple sclerosis case summary, literature review, and analysis of outcomes. Int J Clin Exp Hypn 1996 44 208-231. 2. Sutcher H. Hypnosis as adjunctive therapy for multiple sclerosis a progress report. Am J Clin Hypn 1997 39 283-290. 3. Sutherland G, Andersen MB, Morris T. Relaxation and health-related quality of life in multiple sclerosis the example of autogenic training. J Behav Med 2005 28 249-256.

Central Cytokines

Glia cells and neurons in various brain areas express proinflammatory cytokines and cytokine receptors 9, 10 . Acute and chronic CNS diseases (e.g., meningitis, encephalitis, multiple sclerosis, Alzheimer's disease, stroke and brain tumours) stimulate CNS cytokine production 11, 12 . Cytokines produced within the blood-brain barrier (BBB) can act directly on neural circuitries controlling energy balance, and intracerebroven-tricular (ICV) administration of proinflammatory cytokines presumably models the clinical features of such diseases, e.g. anorexia. Peripheral immune stimulation may increase de novo proinflammato-ry cytokine synthesis in the brain, and this may contribute to anorexia in some of these conditions 3, 13-15 . Often, however, centrally produced cytokines may not be essential in the anorexia of systemic immune challenges because a crucial cytokine is not expressed in the brain 16 , the cytokine expression pattern does not fit a role in the anorexia 17 , and only...

Treatment Strategies

Psychostimulants such as methylphenidate, pem-oline, and dextroamphetamine have shown great promise in the treatment of fatigued patients with cancer and multiple sclerosis (Krupp et al., 1989a Weinshenker et al., 1992). These drugs have also been used safely and successfully in HIV patients with fatigue (Holmes et al., 1989 Wagner and Rabkin, 2000 Breitbart et al., 2001). Breitbart and colleagues (2001) conducted the first randomized, double-blind, placebo-controlled trial of two psychostimulants for the treatment of fatigue in ambulatory patients with HIV disease. They found that both methylphenidate hydrochloride (Ritalin) and pemoline (Cylert) were equally effective and significantly superior to placebo in decreasing fatigue severity with minimal side effects. Fifteen patients (41 ) of 144 ambulatory HIV patients taking methylphenidate and 12 patients (36 ) taking pemoline experienced clinically significant improvement, as compared to 6 patients (15 ) taking placebo. The...

Exercise

Exercise is not always classified as a form of complementary and alternative medicine (CAM). Instead, it may be viewed as conventional medicine or entirely out of the realm of medicine, as a type of self-care or simply a component of one's lifestyle. Regardless of its formal classification, it is important to consider exercise because it is not always fully discussed during a conventional medical office visit, and it has significant health implications for people with multiple sclerosis (MS).

Intravenous IgG

There are ongoing attempts at more specific treatment, such as inducing tolerance in disease-producing T cells or inducing regulatory T cells specific for self antigens. Multiple sclerosis and type 1 diabetes are two immune diseases in which the target antigens have been defined in both, clinical trials are starting in which the antigens (peptides of myelin basic protein and insulin, respectively) will be administered to patients in ways predicted

Energy Therapies

This book would not have been possible without the support of the Board of Directors, as well as Karen Wenzel, Executive Director, and other staff at the Rocky Mountain Multiple Sclerosis Center. Dr. Ronald S. Murray encouraged development of this project in the early stages. Thomas Stewart, J.D., PA.-C., M.S., played an important role by devoting time and energy to the research and by providing creative input. Patricia Kennedy, R.N., C.N.P, and Lee Shaughnessy read the initial manuscript carefully and made valuable suggestions. Research assistance was provided by Lee Shaughnessy, Dr. Ragaa Ibrahim, and Julie Lawton for the first edition and by Kathy Haruf for the second edition. I thank the users of www.ms-cam.org, the CAM website of the Rocky Mountain Multiple Sclerosis Center. Users of this website have generously participated in our surveys, which allow us to research the types of CAM

Abt724

The worldwide prevalence of ED has been estimated at over 152 million males with projections for 2025 being in excess of 320 million. In older males, ED may have a physical cause, such as disease, injury, drug side effects, injury to nerves, arteries, smooth muscles, and fibrous tissues, or impaired blood flow in the penis. Other common causes of organic ED include the metabolic syndrome, diabetes, kidney disease, chronic alcoholism, multiple sclerosis, atherosclerosis, vascular disease, and neurologically related causes.9 The incidence of ED increases with age with approximately 5 of 40-year-old males and 15-25 of 65-year-old males experiencing aspects of ED. Surgery, including radical prostatectomy and bladder cancer surgery, can injure nerves and arteries near the penis, causing ED. Antihypertensives, antihistamines, antidepressants, and hypnotics can produce ED as a side effect. Psychological factors including stress, anxiety, guilt, depression, low self-esteem, and fear of sexual...

Massage

Hernandez-Reif M, Field T, Field T, et al. Multiple sclerosis patients benefit from massage therapy. J Bodywork Movement Ther 1998 2 168-174. 2. Brouwer B, de Andrade VS. The effects of slow stroking on spasticity in patients with multiple sclerosis a pilot study. Physiother Theory Pract 1995 11 13-21. 4. Forsythe E. Multiple Sclerosis Exploring Sickness and Health. London Faber and Faber, 1988 129.

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