Multiple sclerosis as a whole-brain inflammatory and neurodegenerative disease

Multiple Sclerosis

"WHOLE-BRAIN" DISEASE

Multiple Sclerosis

Description, Population and Challenges

Multiple sclerosis or MS is a most afflicting and challenging condition. It is a common, inflammatory and neurodegenerative disease of the central nervous system or CNS (Borazanci et al., 2009 p 229; Litzinger & Litzinger, 2009 p HS3). It is called a "whole-brain" disease for its powerful immune response against CNS antigens, such as myelin peptide antigens. The exact cause remains unknown, although linked to this abnormal response, the disruption of the blood-brain barrier or BBB, and the transfer of activated leukocytes from peripheral circulation to the CNS. What triggers it is still unclear and speculative, although attributed to genetic and environmental factors in the development of the disease. MS is not a single disease but represents various clinical conditions with different causes and responses to immunosuppressive agents. The four major types are relapsing-remitting or RRMS, primary progressive or PPMS, secondary progressive or SPMS, and progressive relapsing or PRMS. Approximately 80-85% of all MS cases are RRMS. Women are clearly more vulnerable than men at a ratio of 1:6, commonly occurring between ages 28 and 33. RRMS is characterized by clinical relapses, full or partial recovery, and intervals of clinical stability and absence of progression. A relapse is an episode of inflammatory and demyelinating lesions. Progression consists of an inflammatory arm and a neurodegenerative arm (Borazanci et al. pp 230-236, Litzinger & Litzinger HS4-5).

Those afflicted with RRMS develop SPMS at 50% (Borazanci et al., 2009 p 237). This type is characterized by progression with or without occasional relapses, minor remissions and plateaus. PPMS can develop in women and men equally. They are usually older and suffer from myelopathy with less brain lesions. Other rare forms include benign MS and PRMS. A person with benign MS can fully function for 15 years from the start of the disease with little or no progression after the first attack. PRMS is a rare form and characterized by acute relapses with or without recovery and intervals. This indicates progression of underlying cause (Bonazanci et al. pp 238-240).

Available evidence suggests the maternal origin of MS (Bonazanci et al., 2009 p 240; Litzinger & Litzinger, 2009 HS6). The direct transmission of mitochondrial genes or indirect transmission of autosomal genes, genetic imprinting, and the interaction between genes and female-specific environmental factors are among the genetic explanations. These factors may be hormonal, intrauterine or perinatal. These explanations are, however, still inconclusive (Bonazanci et al. pp 241-242). Other factors are immune system malfunction, diet, vitamin deficiencies and allergic reactions (Litzinger & Litzinger, 2009 HS6). The common line of all hypotheses is the resulting inflammatory responde and sclerosis of the neuton (Litzinger & Litzinger HS7-8).

Neuroimaging has greatly boosted the diagnosis and assessment of MS (Bonazanci et al., 2009 p 243). It has improved understanding and knowledge about its natural history, pathogenesis, the extent of brain and spinal cord lesions, therapeutic response to treatment agents, and complications to therapies. Other imaging techniques are serial MRI of the brain, proton magnetic resonance spectroscopy, magnetization transfer MRI, diffusion MRI, functional MRI, perfusion MRI, and tractography. Current immunomodulatory and immunosuppressive agents for the last two decades are IFN-? preparations, glatiramer acetate, mitoxantrone and natalizumab. A significant number of patients have responded favorably to these therapies with tolerable side effects. Adverse effects or a breakthrough of disease activity has been reported in some MS cases, however. From these adverse effects and toxicities, potential future therapies are currently being studied. These include daclizumab, almetuzumab, rituximab, doxycycline and minocycline, fingolimod, cladribin, teriflunomide, laquinimod, Vitamin D and Fumaric Acid (Bonazanci et al. pp 244-246).

On the whole, management of MS is limited to treating exacerbations, symptoms, reduced functions and the use of disease-modifying drugs or DMDs (Litzinger & Litzinger, 2009 HS8-9). It includes a short course of corticosteroids, physical or occupational therapy and DMDs on a long-term basis. These DMDs have been shown to reduce the severity and frequency of clinical attacks. The FDA-approved DMDs are Avonex, Betaseron, Copaxone, Rebif, Novantrone and Tysabri (Litzinger & Litzinger HS9).

Research Projects

Pain in RRMS

RRMS is the most common type of MS. A comparison of the multidimensional aspects of pain between those afflicted and those free of RRMS to measure the presence of pain and its aspects (Newland, 2009 p 262) the multidimensional aspects included intensity, pattern, location, descriptors and interference. The investigation was conducted in a seven-day period with 40 women with RRMS and 40 healthy women without it. Findings revealed that the women with RRMS had a significantly higher presence of pain, present pain intensity, average pain intensity, pain interference and pain in different locations than in the healthy women without RRMS (Newland pp 263-265).

The respondents were MS patients in clinics in the Midwestern United States, older than 18 and diagnosed with MS for more than 6 months before the study (Newland, 2009 p 262). The PASAT method, a component of the MS Functional Composite testing, was used for cognitive screening. Pain is the main complaint of women with RRMS. The presence of demyelinated lesion in the spinal cord, which directly injures the nerves of the brain and the spinal cord, mainly explains the pain. It is also due to the inflammatory process occurring during relapses. Despite daily analgesics, the pain remains more intense in them than in healthy women without RRMS. Over-the-counter analgesics may, therefore, not be effective in relieving RRMS (Newland pp 263-265).

Findings of the investigation revealed that women with RRMS experience pain differently from healthy women (Newland, 2009 p 266) without RRMS. RRMS women also said the pain interfered with their daily lives more than it did in healthy women. Nurses, therefore, need to monitor their pain more assiduously and address it effectively. Further study should explore the presence of pain, pain intensity and pain interference among MS subtypes. It should also design specific interventions for pain management in persons with RRMS (Newland pp 267-268).

Migraine-like Headache in MS

Another study showed that patients with MS suffer from a migraine-like headache caused by plaques in the brainstem or in other locations (Gee et al., 2005 p 670). This was in response to the need for more clinical case studies and experimental evidence to bolster the connection. A total of 4369 MRI scan reports between December 1992 and June 2002 at the Department of Radiology was reviewed to confirm the diagnosis of MS and document the headache complaints of 277 patients, 207 of whom were women. Of the total, 66% had RRMS, 17% with PPMS and 17% with SPMS. Of the total, 55% complained of headache, 61% of which were reported to be migraine-like. Those with a plaque within the midbrain or periaqueductal gray matter areas showed a four-fold increase in the migraine-like headaches. MS patients with three or more lesion locations tend to have the headaches two times more (Gee et al. pp 671-74).

Observations pointed to the midbrain as the key link between MS and the migraine-like headache (Gee et al., 2005 p 675). The periaqueductal gray matter can be affected by the demyelinating process as much and as extensively as the white matter. The study concluded that the presence of a midbrain plaque in MS patients increases the likelihood of migraine-like headaches (Gee et al. pp 671-75).

Community Programs

Putting People First

A reformed adult social care system in England is a response to the demographic challenges posed by an increasingly aging society and its dependence on social care (Department of Health, 2010 p 1). Increased life expectancy brings about more complex conditions, including dementia and MS. By 2022, 20% of the British population shall be over 65. By 2027, those over 86 years old shall have increased by 60%. They want and expect services rendered with dignity and respect. Older people and those physically and mentally disabled demand all the aspects and the full range of rights and privileges of equal citizenship (Department of Health p 1). These summarize the intent of the reformed social care system.

The key elements of the social care system are local authority, agreed and shared outcomes, and system-wide transformation (Department of Health, 2010 p 3). Local authority shall have authentic working partnership with the local National Health Service and related statutory agencies and private sector providers. Together, they shall target a new, high-quality care system that is fair, accessible and responsive to individual needs. Agreed and shared outcomes will guarantee that the beneficiaries live independently, stay health or recover quickly from illness, assert maximum control over their lives, sustain their family units without enlisting children for caring roles, and economic and social participation as active citizens. And a system-wide transformation shall conduct regular join strategic needs assessment and commission in order to provide incentives and stimulate the provision of high standards of care, dignity and maximum choice and control for service users (Department of Health pp 2-4).

This reformed adult social care system is also designed to promote the rights and needs of older and disabled people and those with mental health needs (Department of Health, 2010 p 5), including those with MS. Its priorities are intergenerational programs for older but active citizens, which support independent living. These include housing, access to work, education, training and leisure, transition planning for younger disabled people and local action for the stigma of mental health problems (Department of Health p 8).

Stem Cell Treatment

The use of stem cells may be a new way to address the management of MS and other neurodegenerative and neuroimmunological disorders (Karussis & Kassis, 2007 p 1201).

This is done by directing the migration of stem cells into the affected inflammatory areas to induce local immunomodulation and neuroprotection. Neuroprotection will accelerate or enhance the remyelinating mechanisms through the activation, growth and production of resident stem cells. The trans-differentiation of myelin-producing cells or neurons already theoretically exists in evidence. Fusion mechanisms may occur instead of trans-differentiation but they may still be beneficial in inducing the rejuvenation of partially damaged CNS cells (Karussis & Kassis pp1190-1195).

Adult stem cells are most appropriate for human use as they incur less dangers and more responsive to ethical standards (Karussis & Kassis, 2007 p 1200-1201). The best compromise seems to be bone marrow-derived mesenchuman stem cells for the said purposes and for ease of use. These cells can induce strong peripheral immunomodulating effects if directly administered into the cerebrospinal fluid for best advantage (Karussis & Kassis pp 1196-1201). Stem cell therapy is recommended when warranted by sufficient controlled clinical trials in MS.

Multiple sclerosis or MS is a most afflicting and challenging condition. The unknown origin, the lack of exact cure and the suffering caused by MS on people justify massive attention and action of all kinds. #