Multiple Sclerosis (MS)

The basic pathologic derangement in MS is the stripping of the myelin sheath surrounding neurons in the CNS. Demyelination, coupled with an inflammatory response, leads to the formation of characteristic MS lesions, or plaques, that are found primarily in the brain, spinal cord, and optic nerves.(1) Neuronal axons, although stripped bare of their myelin sheath, are usually well preserved.(2)

Although MS was first described over 130 years ago, the exact cause(s) still remain a mystery, and there is no known cure. The term "multiple sclerosis" refers to two characteristics of the disease: the numerous affected areas of the brain and spinal cord producing multiple neurologic symptoms that accrue over time, and the characteristic plaques or sclerosed areas that are the hallmark of the disease. MS is usually diagnosed in patients between the ages of 20 and 45 years (although cases in children have been reported),(3) with peak incidence occurring in the fourth decade.(4)

MS is, in general, a disease of temperate climates. In both hemispheres, its prevalence increases with distance from the equator. The highest known prevalence (250 per 100,000) occurs in the Orkney Islands, located north of the mainland of Scotland. Multiple sclerosis is also common in Scandinavia and throughout northern Europe.(5) Prevalence seems to be higher in Caucasians than other racial groups. MS is extremely rare in Japan and in black Africans; however, Japanese Americans and African Americans are at a significantly higher risk for developing the disease, with respective prevalence rates estimated at one-fourth and one third that of Caucasians.

The familial recurrence rate of MS is approximately 10 percent, with siblings being the most commonly reported relationship.(6) Even though this is true, it is unlikely that a simple genetic model for inheritance of MS is valid. It is probably polygenic in nature, each with a relatively small contribution to overall risk, but may provide susceptibility when presented with an as yet unknown etiologic trigger.

In the autoimmune theory, MS results from an autoimmune attack against self-myelin or self-oligodendrocytes antigens. The actual mediator of myelin destruction has not been established, but this activity has been attributed to the action of macophages, T-killer cells, lymphokines, antibodies, or a combination of these elements.(7) T-helper cells appear to be key initiators of myelin destruction. These cells are activated in the periphery, possibly after viral infection, and recognize myelin-associated proteins (myelin basic protein, proteolipid protein, myelin oligodendrocyte glycoprotein, and myelin-associated glycoprotein) as antigens. This cellular recognition creates an inflammatory cascade where the T-helper (CD4) cells are activated. Activated T cells are able to cross the blood brain barrier and produce the autoimmune response that leads to the destruction of myelin. It is also probable that cytokines regulate many of the cellular interactions that occur in MS. A large number of proinflammatory cytokines have been detected in the brain, cerebrospinal fluid (CSF), and peripheral blood of MS patients. Tumor necrosis factor alpha and interferon gamma may contribute directly to tissue damage by injuring oligodendrocytes or the myelin membrane.(8)

Although the exact mechanism has not been found, there are several ways in which a virus could play a role in the pathogenesis of MS, including either a direct attack on myelin and/or oligodendrocyte, or stimulation of an autoimmune response, leading to demyelination.(9),(10) Higher antibody titers against many viruses (measles, herpes simplex, varicella, rubella, Epstein-Barr, and influenza-C) have been found in the blood and CSF of patients with MS. Recently, HHV-6, or human herpes virus-type 6, has been reported to be commonly expressed in MS plaques. To date, however, no virus has been isolated consistently.

As with many of the autoimmune disorders, a look to environmental influences may play a key role in uncovering the contributing initiators to the disease process. This could include environmental toxins such as heavy metals, endotoxins from various infections, stress response, genetics, nutrients status or any combination of the above. Need to emphasis the environmental component at the very least mention mercury toxicity as a controversy.

The demyelination of MS causes disruptions in the transmission of nerve impulses, which leads to neurologic symptoms reflecting the area of the brain affected. Generally, the effect is a prolonged refractory period that impairs conduction; however, positive conduction abnormalities also may occur, including ectopic impulse generation, or abnormal "crosstalk" between demyelinated axons. Conduction block may account for the fluctuations in function that vary from hour to hour and from day to day in MS and for the worsening that follows elevation in core body temperature. Ectopic impulse generation or "crosstalk" might give rise to Lhermitte’s symptom (a momentary electric-like sensation evoked by neck movement or coughing), paroxysmal symptoms, or paresthesia.(11)

The course of MS can take several paths, and progression of the disease is roughly divided into four categories. The first is the most benign, and is characterized by unpredictable recurrent attacks of neurologic dysfunction. The duration of these attacks varies, and recovery ranges from complete to partial, or no recovery. There is no progression of symptoms between attacks. This is known as relapsing-remitting MS. This is the course most frequently seen in the early stages of the disease. The second clinical pattern is known as secondary progressive MS (or relapsing/progressive). This is similar to the relapsing-remitting pattern; however, there is disease progression between exacerbations. This gradual progression of disability may begin shortly after disease onset, or may be delayed years or even decades. The third pattern, primary progressive MS, is characterized by a slow, steady onset of symptoms, with relatively few attacks, and disability that worsens over time. The most uncommon clinical course is progressive relapsing MS. This is where patients who appear to have primary progressive MS will experience superimposed relapses. In all patients, attack frequency tends to decrease over time, independent of worsening disabilities.(12)

The clinical course of MS is highly variable; however, when progression of disability is followed 15 years after diagnosis, generally 20 percent of patients will have no functional limitation, 70 percent will be limited or unable to perform major activities of daily living, and 75 percent will be unemployed. Researchers found that 75 percent of patients with MS were cognitive impaired on at least one portion of a computerized neurophsycological test.(13) Progressive resistance training can provide therapeutic improvements in patients with multiple sclerosis.(14)

National Multiple Sclerosis Society, 2005.

• Two-three times as many women as men have MS.
• Worldwide, MS may affect 2.5 million individuals.

The Multiple Sclerosis Foundation, 1999.

• 350,000-500,000 people in the United States are estimated to have multiple sclerosis.
• 8,000 new cases are reported each year.
• MS is seen more often in the Caucasian population.
• Most are diagnosed between the ages of 30 to 50.
• 20% have benign MS with no permanent disability.
• 30% have intermittent symptoms with long periods of stability.
• 40% have a slowly progressive form of the illness.
• 10-20% have steady progression from onset.
• 30% of those diagnosed with chronic-progressive MS stabilize after two years.
• 75% diagnosed with MS never need a wheelchair.
• 40% diagnosed experience no disruptions of their normal activities.
• Average lifespan of the MS patient is at least 75% of normal.
• MS occurs more often between 40 and 60 degrees north and south latitudes.

Primary symptoms include visual complaints (double vision, blurriness), gait problems, Paresthesia, pain, spasticity, weakness, ataxia, speech difficulties, psychological changes (depression is particularly common), cognitive changes, fatigue, bowel and bladder dysfunction, sexual dysfunction, Llermitte’s sign and tremors. Some secondary symptoms include recurrent UTI, urinary calculi, decubiti, muscle contractures, respiratory infections and poor nutrition. Tertiary symptoms include such events as personal or social problems, financial or vocational problems and emotional problems.

• Recurrent urinary tract infections
• Urinary calculi
• Decubiti
• Muscle contractures
• Respiratory infections
• Poor nutrition

Treatment of acute exacerbations

Treatment depends upon the severity of the attack, with mild attacks possibly requiring no treatment. As attacks become progressively worse, and functional ability is affected, treatment is usually started with corticosteroids. In milder cases, oral prednisone is used in a variety of dosing regimens. Intravenous methylprednisolone is the most commonly used agent in the treatment of severe, acute exacerbations.(16) The mechanism of action for corticosteroids in MS is unknown; however, it is speculated that steroids improve recovery by decreasing edema in the area of demyelination.(17) Methylprednisolone doses usually range from 500 to 1,000mg daily, administered intravenously. The duration of therapy is variable, and may range from three days to three weeks. Most frequently, if improvement is seen, it will occur within the first three to five days; therefore, parenteral therapy may continue for up to five days, followed by an oral steroid taper. Oral steroid regimens typically begin with 60 to 80mg of prednisone for three to seven days; then, the dosage is tapered over seven days or longer depending on the patient’s symptoms.(18)

Prevention of relapse and progression

Interferon b-1b, in addition to significantly reducing annual MS exacerbation rates by about one-third, was the first agent to potentially slow the progression of MS.(19) The dosage is 8 million units, every other day, administered subcutaneously.

Clinicians must carefully screen and monitor patients chosen to receive this therapy. Adverse reactions are seen in the majority of patients, and include local redness and swelling at the injection site and flu-like symptoms. These symptoms may be mild or severe, and may include depression. Although depression is commonly seen in MS, it may be further provoked by interferon beta-1b.

Interferon b-1a is given intramuscularly at a dose of 30mcg once weekly for two years. Interferon b-1a has been shown to be beneficial for MS symptoms.(20) Interferon b-1b may hold advantages over interferon b-1a in that although the adverse event profile is similar, it only needs to be administered once weekly rather than three times a week, and there are fewer local tissue reactions seen. Patients have about a one-third annual decrease in relapse rate as well as disease progression.

Glatiramir, formerly known as copolymer-1, is administered subcutaneously at a dose of 20mg daily. Effects are similar to the interferons in annual relapse rate; however, the side effect profile is milder than the interferons, and it does not seem to induce formation of neutralizing antibodies like the interferons.

Other therapies have been used, and have shown to produce some decreases in the progression of MS; however, due to toxicities, can generally not be tolerated for extended periods of time. Cyclophosphamide, azathioprine, and methotrexate are among the agents that have been tested. Further study needs to be done to confirm benefit. Other drugs used in the treatment of MS include those employed in the management of symptoms such as optic neuritis, gait difficulties and spasticity, tremor, bowel and bladder symptoms, major depression, and sensory symptoms.

Although there is probably a genetic component to MS susceptibility, an environmental factor is also clearly involved. Exposure to sunlight is one of the most likely environmental factors. The degree of sunlight exposure catalyzes the production of vitamin D3 in skin, and the hormonal form of vitamin D3 is a selective immune system regulator, which may play a role in inhibiting this autoimmune disease. Thus, under low-sunlight conditions, less vitamin D3 is produced, causing insufficient production of 1,25-dihydroxyvitamin D3, which increases the risk for MS. Although the hypothesis that vitamin D3 is an immunoprotective environmental factor against MS is circumstantial, it is compelling and worthy of consideration.

Two global anomalies in MS rates can also be explained by this theory. Switzerland has high MS rates at low altitudes and low MS rates at high altitudes, Norway has high MS rates inland and lower MS rates along the coast. Ultraviolet (UV) light intensity is greater at high altitudes, resulting in a greater synthesis of vitamin D3, which explains the lower MS rates at higher altitudes. Coastal Norwegians consume a diet high in fish, and fish oils are rich in vitamin D3. Furthermore, experimental work with animals provides strong support for the importance of vitamin D3 in reducing the risk and susceptibility for MS.

The authors feel that there could be therapeutic potential in using 1,25-dihydroxyvitamin D3 or its analogs in MS patients. Migration studies combined with current research could possibly make MS preventable by early intervention using 1,25-dihydroxyvitamin D3 with genetically susceptible individuals.(22) Findings from a study indicate that vitamin D could have an impact on the course of MS.(23)

Other research, which tends to support the above hypothesis, included the fact that MS patients have a high prevalence of vitamin D deficiency and reduced bone mass. One study reported a prevalence of vitamin D deficiency with secondary hyperparathyroidism in female MS patients which could be a significant cause of low bone mineral density contributing to the increased risk of fracture in these patients. Researchers suggest that routine supplementation of vitamin D may correct the vitamin D deficiency in female MS patients.(24) Researchers found that vitamin deficiency effects the DRB1 gene, which is associated with MS, and suggests vitamin D supplementation during pregnancy and early childhood to reduce the risk of a child developing MS later in life.(25)

Another interesting study reported that a group of young multiple sclerosis patients were treated with a combination of vitamin D, calcium, and magnesium for a period of one to two years. This protocol resulted in a decreased rate of relapse. The results were patients experienced less than one half the number of exacerbations that were expected from case histories. This regimen with nutritional supplements may offer a new means of controlling the rate of exacerbations in MS, at least for younger patients. In addition to highlighting the importance of vitamin D, these results lend support to a theory of MS, which states that calcium and magnesium are important in the development, structure and stability of myelin.(26)

Research in Japan compared 24 MS patients with 73 patients with other neurological disorders and 21 healthy controls. MS patients did not have low vitamin B12 levels, however, a significant decrease in the unsaturated vitamin B12 binding capacities was found in patients with MS when compared with other groups. A massive dosing of methylcobalamin (methyl-B12), providing 60 mg every day for 6 months was administered to 6 patients with chronic progressive MS, which is a disease that usually has a morbid prognosis that produces widespread demyelination in the central nervous system. Although the motor disability in these patients did not improve clinically, the abnormalities in both the visual and brainstem auditory evoked potentials improved more frequently during the therapy than in the pre-treatment period. These authors suggest a massive dose methylcobalamin therapy may be useful as an adjunct to immunosuppressive treatment for chronic progressive MS.(29)

Dr. Nieper believed that calcium EAP functioned as a cell membrane sealant that protected cell membranes from toxins and immune system aggression without inhibiting the transport of nutrients into the cell. Electron microscopy conducted at a German university apparently confirmed this, and subsequently, the German government accepted calcium EAP as a treatment for multiple sclerosis. From 1986 to 1987, a restrospective study on 151 of Dr. Nieper’s patients was conducted, in which 82% of the patients indicated their response to the Calcium EAP therapy was either stabilization or improvement.(30)

In 1999, a survey of patients with MS who had utilized intravenous calcium EAP was undertaken.(31) The survey was conducted by the Brewer Science Library, which is the repository for Dr. Nieper’s collected writings. The results of that survey are as follows.

Of the 293 individuals surveyed who tried the intravenous calcium EAP, 235 reported noticing improvement on an average of 13 out of the 36 possible symptoms listed on the survey. As to the most often improved symptoms, 162 patients experienced less numbness, 142 felt less fatigue, 130 experienced an improvement in balance, and 119 reported greater ease in walking. Overall, 71% of those surveyed rated themselves as being "stabilized" or "mildly to markedly" improved. On the other hand, 99 individuals reported some deterioration in from 1 to 10 symptoms and 24 reported deterioration in more than 11 symptoms. (These statistics include individuals who experience improvements in some areas but deterioration in other areas.)

Statistics from a subgroup of 117 patients with chronic progressive multiple sclerosis were also reported. 95 of those individuals reported improvement in 13 or more symptoms while 53 reported deterioration in 7 or more symptoms. (Again, some patients reported both improvements and deteriorations.)

Another study found that calcium deficiency was related to the progression of multiple sclerosis.(32)

It has also been noted that extracellular magnesium is required for nitric oxide release from cells, so that a magnesium deficiency may result in increased nitric oxide production in the cell and reduced release from the cell. The excess levels of trapped nitric oxide combine with superoxide to form peroxinitrite, which is an extremely powerful free radical that can cause myelin damage in patients with MS.(35)

Another theory about the association between low zinc levels and MS notes the following points. It is well known that multiple sclerosis has a much higher incidence among females than males. Also, menstruating women have increased copper absorption and half-life, which causes them to accumulate more copper than males. Moreover, rapidly growing girls have an increased demand for zinc, but their rapidly decreasing production of melatonin results in impaired zinc absorption, which is exacerbated by the high copper levels. Low zinc levels result in deficient CuZnSuperoxide dismutase (CuZnSOD), which in turn leads to increased levels of superoxide-induced free radical damage.(38)

More recently, a review of published studies on the relationship between omega-6 and omega-3 fatty acids in patients with multiple sclerosis was conducted. The reviewers reported finding a trend suggesting that the addition of omega-6 and omega-3 polyunsaturated fatty acids to the diet of patients with multiple sclerosis resulted in a reduction of the severity and frequency of relapses and in a mild overall benefit in a two year period.(40)

However, in a study of phospholipids in MS patients, the levels of almost all of the omega-6 fatty acids were found to be normal whereas the levels of all omega-3 fatty acids were found to be below normal.(41) The results of this research suggest that MS patients might be more critically deficient in omega-3 fatty acids than omega-6.

Sterol is found in all plant-based foods, and sterolin is a glucoside moiety joined to the sterol chemical structure. Both sterols and sterolins were identified as early as 1922. In the natural state, these plant "fats" are bound to the fibers of the plant, making the sterols and sterolins difficult to be absorbed during the normal transit of digested food through our gut. Seeds are the richest source of the sterols and sterolins, but are usually removed during processing by the food industry.

Plant sterols and sterolins have been reported to be effective adjunctive agents in the management and treatment of disease states such as high cholesterol levels, benign prostatic hyperplasia, pulmonary tuberculosis, and stress-induced immune suppression and HIV among others.(42),(43),(44),(45), (46) Some of the most promising uses of these plant "fats" is in the management of autoimmune disorders such as lupus, multiple sclerosis, rheumatoid arthritis, and myasthenia gravis. Of note is that the sterols should be combined with sterolin in order to be an effective agent for the immune system.(47)

Sterols and sterolins have been reported to modulate the function of T-cells, significantly enhancing the proliferation of the CD-4 TH-1 cells and increasing the production of the interleukin 2 (IL2) and gamma-interferon (FN-g and IFN-y).(48) These results indicate that sterols and sterolins are adaptogenic in that they modulate the immune and stress response.

Care should be taken if an individual is taking immunosuppressive agents. Based on pharmacology, If an individual is taking hypocholesterolemic agents concurrently with plant sterols and sterolins, a dosage adjustment in the pharmaceutical medication may be necessary.

Reishi extracts have been reported to significantly increase the life-span of fruit flies by significant amounts (16-17 percent) in several studies, and also enhancing endurance and cellular oxygenation.(50) Reishi has been reported to inhibit superoxide activity and hydroxyl radical activity in vitro, supporting its role as an antioxidant.(51) The constituents with antioxidant activity have been reported to include the triterpenes.(52)

Reishi extracts have been reported to inhibit tumor growth in laboratory animals.(53),(54) In one study, an isolated polysaccharide from reishi (b-1, 3-glucan) was administered to laboratory mice and was reported to produce tumor inhibiting rates of greater than 90 percent, with complete tumor regression of over 75 percent of the mice.(55) A study of 48 patients with advanced stage carcinomas (including renal, gastric and breast cancers) were administered an extract of reishi mushroom (1:10w/v) before chemotherapy.(56) Immunocompromised patients showed increased levels of CD4/CD8 ratio and T-cell counts and lowered levels of T-suppresor cell counts. Radio- and chemotherapy intolerance reportedly was reduced in the cancer patients on the reishi extract and leukopenia from the treatments improved. The patients also showed improved vigor and appetite. Reishi also decreased the immunosuppresion seen in whole body ¡-irradiated mice, showing a greater degree of recovery vs. the control group.(57)

Reishi extracts have also reported hypoglycemic activity both in laboratory animals and in human subjects.(58) A small 2-month open label trial of eight diabetic patients reported that an extract of reishi produced hypoglygemic effects comparable to that of insulin and oral hypoglycemic agents.(59)

Polysaccharides in reishi have been reported several clinical studies to have antiherpetic properties, and has been used in treating herpes(60) and postherpetic neuralgia, decreased pain dramatically in two patients with postherpetic neuralgia recalcitrant to standard therapy and two other patients with severe pain due to herpes zoster infection.(61) The triterpenoid constituents in reishi have reported anti-HIV-1 and anti-HIV-1-protease activity in vitro.(62)

Evening primrose oil was reported to be beneficial in effecting the course of diabetic neuropathy by decreasing microvascular problems associated with diabetes.(66) It has been reported in laboratory studies to have PAF inhibiting activity.(67) Evening primrose was reported safe and effective in relieving problems associated with mastalgia, decreasing both pain and tenderness.(68) Evening primrose oil may also be effective in reducing the disabling effects, number of relapses, severity and duration of relapses in patients with multiple sclerosis.(69)

Recent literature has focused on schisandra’s ability to protect the liver from damaging toxins.(73),(74) Liver regeneration was reported in laboratory animals following partial hepatectomy.(75) Schisandra and its lignans have been reported to prevent liver damage, stimulate liver repair and stimulate normal liver function.(76),(77) These properties are thought to be related to the antioxidant ability of the schisandrins, stimulation of liver glycogen synthesis, protein synthesis, protection of hepatocyte cell membranes and elevation of liver microsomal drug-metabolizing enzyme activities.(78),(79)

Other uses include as an expectorant and cough suppressant and as an antioxidant. Schisandra was reported to have a cardioprotective action during administration of Adriamycin (doxorubicin).(80) In clinical studies, schisandra reportedly reduced elevated serum glutamic-pyruvic transaminase (SGPT) levels in various types of hepatitis. However, SGPT levels rebounded after stopping the herb, especially in chronic persistent hepatitis.(81)

Typical Dosage: 6X or 6C, 30X or 30C
Numbness of fingers; Inability to hold small objects; Weakness in upper limbs

Typical Dosage: 6X or 6C, 30X or 30C
Severe general weakness; Joint stiffness; Chronic, progressive paralysis

Typical Dosage: 6X or 6C, 30X or 30C
Paralytic sensation in the limbs; Heavy legs with vague pain; Uncertain gait; Staggering

Typical Dosage: 30X or 30C
Rigidity in limbs; Weakness and heaviness in limbs

Serotonin has been found to be deficient in the brain and spinal cord of MS patients and it is possible that this may result from a primary dysfunction of the pineal gland. It is believed that pulsed applications of EMFs of extremely low intensity and frequency range "energize" the pineal gland, which is considered a "magnetosensor" organ. In experimental animals application of EMFs increases the concentrations in the brain and pineal gland of 5-HT which is involved in the control of motor behavior and regulation of mood, sleep, cognitive functions, endocrine functions and autonomic regulation.

Dr. Sandyk believes that demyelination is an epiphenomenon of the multiple sclerosis and the clinical manifestations of MS are related predominantly to deficient synaptic neurotransmitter functions rather than to delayed conduction resulting from demyelination.

Dr. Sandyk reports that in patients with Parkinson's disease and multiple sclerosis, the rate of improvement in symptoms has been 100%. In other words, every patient who has been treated with this method has experienced at least some symptomatic improvement, which varies from patient to patient. Overall, it is estimated that 60% to 70% of MS patients experience a marked improvement in symptoms, while the remaining experience a mild to moderate improvement. The most severely affected patients with a long duration of illness respond the least well. Therefore, it is recommended that treatment with EMFs is initiated at early stages of the disease.(83)

Histamine/Procarin: There have been reports of remarkable progress in a substantial number of patients with MS through the use of a therapy utilizing histamine, which is derived in humans from the amino acid histidine. Procarin is a proprietary product that was developed by a registered nurse named Elaine DeLack, in an effort to treat her own case of MS, which began in 1985. Ms. DeLack had learned that some physicians had been treating MS with histamine with some success back in the 1950s. In fact, the first published report on the use if intravenous histamine in the treatment appeared in the Journal of the American Medical Association back in 1944.(84) She began treating herself, but found the benefits from normal routes of delivery to be too transient. Ultimately, she developed Procarin, which is histamine along with natural substances that slow down the breakdown and release of the histamine.

Some physicians, and many patients, feel that Elaine DeLack’s revival of histamine therapy with improved methods of delivery (ie. Procarin) is a very important breakthrough in the treatment of multiple sclerosis. Procarin enables MS patients to easily administer the therapy on an outpatient basis.