MULTIPLE SCLEROSIS (MS)
Neurological Associates Pain
1255 37th Street,
Vero Beach, FL 32960
|The information below has
been instigated by the fact that we get a lot of calls and are asked about
how to treat MS. This information is to facilitate communication and to
Multiple Sclerosis (MS) is an
autoimmune disease due to a combination of stressful factors such as early
infancy or childhood viral infections stimulating the immune system, later in
life complicated by recurrent stress leading to recurrent attacks of rogue and
dysfunctional immune system coding. It is more likely to develop in patients of
northern European lineage. It is more prevalent in colder climate countries.
Females are almost twice as likely to suffer from MS. It has four main forms:
relapsing-remitting, seen in 4/5 of patients, primary progressive which starts
at somewhat older age and is seen almost equally in both sexes, secondary
progressive which may follow the relapsing-remitting form, and relatively benign
form with a few attacks (relapses) followed by years or decades of no new
attacks unless the patient is exposed to a major stress - more common in
females. According to a European data base center (NEMJ, 11/16/2000), the
primary progressive form takes a median time of around one year to start showing
disability. This is in contrast to a median time of 11 years in
MS is not diagnosed by the process of
exclusion. It is diagnosed by careful history taking, thorough neurological
examination, and tests such as MRI (not CAT Scan), physiological tests such as
evoked potentials (BAER, SER, VER) and laboratory tests, such as serum and CSF
immunological changes. Monitoring the T-cell lymphocyte function test may help
in prognostication and treatment of MS.
The diagnostic tools in order of
1. A careful history taking which if
taken in detail will provide vital information in regard to how the very first
attack in childhood or early teenage years started as a viral infection
(measles, infectious mononucleosis, whooping cough, etc). The same history gives
a detail of the nature of the disease and helps with prognostication in regard
to the fact that the patient may have had multiple attacks which may have been
mistaken for the patient being hysterical or malingerer or Munchausen’s Syndrome
(blaming the patient for being a liar), etc.
2. A careful neurologic examination
which specifically, quite frequently reveals evidence of thoracic spinal cord
and/or brain stem involvement with sensory loss over the face, chest, trunk, or
3. MRI. Unfortunately, there are a lot
of false positive and false negative MRI’s. The MRI shows typical changes in MS,
but the damages to the white matter of the brain and spinal cord can be quite
variable. Other diseases may mimic MRI changes seen in MS. For example, patients
who have had early childhood viral infections may show multiple areas of
abnormal density which may be the result of nothing but the original viral
infection. Other patients may have had a head injury which may show
abnormalities similar to MS. MRI should be taken for its value in regard to its
limitations, but it is a useful test in research studies to find out if more
plagues are evolving. In this regard, it also helps with the study of
medications trials for MS.
4. The next series of informative tests
are evoked potential tests. These are totally harmless and are done in the form
of visual, auditory, or somatosensory evoked potentials. The tests simply gently
stimulates the nerves to the eye, inner ear, or to the spinal cord, and record
the delay of conduction of the impulse from periphery to the brain. In at least
1 out of 5 patients with MS, evoked potentials may be quite abnormal in face of
no abnormality on MRI.
5. Another test that seems to be out of
vogue now-a-days is the spinal fluid evaluation. The lumbar puncture and the
spinal fluid can be quite important in diagnosis and in prognostication of the
disease, and more importantly in differential diagnosis. It can reveal other
diseases that mimic MS. It can reveal the severity or lack of severity of the MS
reflecting itself in the tests on the spinal fluid such as infections.
Obviously, in this day and time, only less than 10% of such patients require
spinal tap, but if there is doubt about diagnosis and there is need for more
definitive diagnosis, this test should not be ignored.
The disease should be treated as aggressively as is
safe. The common practice of "wait and see" is asking for more permanent damages
due to MS. At the present time, there are plenty of medications that can be used
in a rational fashion, suppressing the disease and proportionately reducing the
damages caused in the central nervous system by MS. The treatment should be
tailored to the type and severity of the MS individually. Four-fifths of the
patients suffer from the intermittent (relapsing-remitting) type of MS. The
prognostic factors are influential to the outcome of the treatment. Early
treatment is imperative in all forms of MS. The response to treatment is
individualized. However, the relapsing-remitting type of MS which shows a
tendency for few and far in between attacks of flare-up of the disease,
especially in a young female, and in a patient who has not been exposed to
multiple stressors (such as husband with poor understanding of the disease, or
intake of alcohol, or frequent viral infections), is more likely to respond
positively to the treatment and to have less residuals from it.
On the other hand, male patients in the late youth or
middle ages, with frequent attacks of illness, and with a tendency to be exposed
to stress either due to the work environment or due to financial reasons will
have a worse prognosis.
In the relapsing-remitting MS patients, there has been
a tendency for starting the treatment with IV corticosteroid (Prednisolone)
followed by oral corticosteroid by mouth. The usual schedule is 4-5 days of IV
Prednisolone followed by a few weeks of corticosteroid by mouth. First of all,
there is no proof that this form of treatment will do better than the newer
forms of treatments.
Secondly, repetitive treatment with corticosteroids has
a tendency to cause suppression of the function of the adrenal glands and
secondarily, make the patient more susceptible to suffer from frequent
infections, and severe chronic fatigue syndrome (CFS). So, in these patients it
may make sense to start IV Prednisolone for 4 days, then to follow with newer
medications listed below.
There is a tendency to limit the treatment
to corticosteroid therapy for a few weeks with no subsequent treatment until the
next attack. This may leave the patient unprotected. As soon as possible, the
patient should be treated with one of the Interferon or copolymer type of
Early treatment with Interferon and or Glatiramer
acetate (GA, aka Copolymer- 1 or Cop-1) is far more effective than
corticosteroid treatment. Immune therapy plays a major role in the treatment of
MS. Beta Interferon is an effective form of treatment, but causes too many side
effects. In our experience, only less than 25% of the patients could
successfully continue the treatment with Beta Interferon. It has a harsh effect
on the immune system, resulting in practically intolerable inflammation, fever
and other immune system dysfunction's in the majority of patients. Among the
patients who can tolerate Beta Interferon, the relapse rate is decreased by up
to 30%, which is a major improvement for prevention of reoccurrences in MS.
Glatiramer acetate (GA / Copaxone) inhibits the
myelin - reactive T-cells by blocking human leukocyte antigen (HLA), as well as
antagonizing the T-cell receptor. GA (Cop-1) exerts a strong inhibitory role in
the proliferation of myelin basic protein (MBP).
Interferon Beta 1a (Avonex) is well tolerated, and is
quite effective in improving the MS pathology, reducing the progression of
neurological impairment and reducing the relapse rate. It is better tolerated
than Beta Interferon. Copolymer- 1 is also effective in the treatment of
remitting relapsing attacks of MS. The combination of Cop-1 and Avonex is even
more effective in the treatment of more progressive and destructive MS patients.
The combination works better due to the fact that Cop-1 acts as a complimentary
agent; whereas Avonex interferes with antibody formation, the Copolymer-1
(Cop-1) as drone or a decoy to protect the brain from the destructive effect
antibody against brain tissue.
IV immunoglobulin treatment is quite effective in the
management of MS. The published articles in MED- LINE from January 1981 through
January 1995 reported the effect of IVIG in 189 patients. Ninety-eight (52%) of
the patients responded with improvement with the help of IVIG. Since January
1995, there have been other large studies. Five hundred fifty MS patients were
treated with IVIG, showing reduction and prevention of recurrence of the
disease. Achiron, in multiple trials of IVIG treatment, found this form of
treatment very effective in reducing the relapses (exacerbations) of MS.
Hyperbaric oxygen has not proven to be effective in
treatment of MS. Total lymphoid radiation is too harsh and harmful, and should
not be considered for treatment of MS. TNF (tumor necrosis factor) and anti-CD4
antibodies are being studied by Compston in Cambridge, England. Results are not
Certain forms of chemotherapy such as 4-aminopyridine
(4AP) treatment are helpful in more severe MS patients. The chemotherapy with
4AP is not similar to chemotherapy for cancer. In MS, chemotherapy should be
applied in conservative doses, avoiding hair loss and bone marrow suppression.
Weiner and colleagues, have been reporting their
experience with oral vaccination (ingestion of myelin antigens) and have noted
some promising results in their preliminary study. This form of treatment is
assumed to selectively stimulate T-cells secreting anti-inflammatory Cytokines.
MS usually causes severe pain in over 60% of patients.
The pain itself is a strong stressor instigating flare-up (relapse) of MS.
Treatment with anticonvulsants such as Tegretol (non-generic), Klonopin®
(non-generic), and Depakote help in the management of severe pain. Analgesic
antidepressant treatment with Trazodone or Desipramine (not Amitriptyline),
opioid antagonists, Tramadol (Ultram) are the minimum requirements.
MS can lead to sensitization of spinal cord, causing
myoclonic seizures. Treatment of choice is Klonopin (non-generic). Spasticity
should be managed by Zanaflex, Baclofen (oral or pump).
The stress of bed rest and inactivity on one hand, and
the stress of too much work and isometric exercise are very harmful to any
immune system disease (e.g., Lupus, MS, Arthritis, CRPS, etc).
The stress of tremors, spasticity, and chronic fatigue
syndrome (CFS), should be aggressively counteracted: for CFS, treatment with
proper analgesic antidepressants at night time to prevent insomnia is essential:
Trazodone 50-250 mg at bed time, or Desipramine or Doxepin (at 25 to 200 mg
doses) is usually well tolerated. If the CFS is quite disabling in spite of the
above-mentioned treatments, supplemental doses of Effexor 37.5 to 75 mg in the
morning are helpful.
In more advanced stages the immune system modulated by
the sympathetic system becomes exhausted, and leads to hypertension. After
several months the hypertension changes to hypotension (especially orthostatic
hypotension) causing dizziness, CFS, and unsteadiness. The hypertension responds
best to alpha blockers such as Hytrin. The hypotension responds best to
treatment with Promantine (Midodrin). The hypotension responds best to treatment
with Promantine (Midodrin).
Treatment with Amitriptyline (Elavil) should be
avoided: it may aggravate hypotension, CFS, as well as causing weight gain
average of 6-7 Kg in the first year).
SSRI antidepressants may partially and temporarily help
CFS, but in the long run suppress any sexual desire in over ˝ - Ľ
of patients causing stress, marital problems, and agitation. SSRI should
not be treatment of choice for MS. Treatment with Effexor is helpful to relieve
1. MANAGEMENT OF MS SIDE EFFECTS
The treatments should not be just
limited to counteracting the plague formation of multiple sclerosis, but it
should also address the disabling complications of MS. Here are some of the
Pain. Over 60% of MS patients suffer
from pain. This has been one of the most disabling and most ignored
complications. Treatment with Carbamazepine (Tegretol brand-name) is quite
effective for sharp or stabbing or electric shock type of pain. If the patient
has a burning type of pain, then the treatment of choice would be Gabapentin
(Neurontin). Valproate (Depakote) is also helpful for treatment of pain or
severe headache. If the patient has deep pain in the bones and muscles, then the
treatment of choice would be increasing activity, mobilizing the patient, and in
addition, treating the patient with analgesic, such as Tramadol (Ultram).
Analgesic antidepressants are treatment
of choice in practically every MS patient with pain. The antidepressants are not
given because the patient is depressed, or has any kind of psychiatric disease.
It is given because it prevents the pain. It also usually provides good sleep.
Some antidepressants such as Zoloft, Paxil, and Prozac don’t have any
significant analgesic value. In addition, they can aggravate the chronic fatigue
syndrome and in 1 out of 5 patient they can suppress sex desire which would
complicate the marital relationship. The treatment of choice is with
antidepressants such as Trazodone, Desipramine, or Doxepin. These three
antidepressants are quite effective without serious side effects. The use of
Amitriptyline (Elavil) should be avoided because it has a tendency to cause
obesity (up to 8kg in the first year, and then up to 6kg the years after). Also,
it aggravates the CFS, and can cause low blood pressure.
2. NEUROPATHIC PAIN
COMPLEX REGIONAL PAIN SYNDROME
(CRPS/RSD) IN MS
In approximately one fifth of MS
patients, neuropathic pain (pain accompanied by inflammation, hypersensitive
skin, and temperature and circulatory changes) is seen as a complication of MS
leading to sympathetic nerve dysfunction. The treatment of choice is a
combination of antidepressants (such as Trazodone or Doxepin) and
anticonvulsants (Depakote, Trileptal, and Klonopin®) as well as nerve
blocks and epsom salt bath are quite effective.
3. CHRONIC FATIGUE SYNDROME
For the treatment of CFS (which the
Social Security Courts accepted as the most disabling type of chronic disease,
treatment of choice is Effexor. In MS patients who have problems with fatigue
plus anxiety, which is totally expected, plus a tendency for depression,
Buspirone (Buspar) at the dosage of 5-15mg 3 times a day is very effective and
has the least side effects. The MS patients should stay away from benzodiazepine
(BZ) type of tranquilizers and sleeping pills such as Xanax, Ativan, Librium,
Valium, etc. These medications suppress the formation of endo-BZ in the brain,
resulting in severe chronic fatigue, withdrawal anxiety and depression, and
inactivity. They should be replaced with Buspar. The two exceptions are Klonopin®
and Serax which do not suppress the formation of endo-BZ’s.
4. MUSCLE SPASMS
For muscle spasms, spasticity, flexor
spasms, and poor mobilization, the treatment of choice is Zanaflex, and if the
patient can not tolerate Zanaflex, then Baclofen. If the spasticity
progressively deteriorates, then Baclofen infusion pump through the spinal fluid
can provide excellent relief, and can help mobilize the patient. For spinal cord
sensitization (myoclonic jerks, or falling attacks) Klonopin®
(non-generic) is helpful.
The above medications have the
potential of having serious side effects, especially if given in large doses and
in combination with a lot of other medications. The patient has to consult with
his/her doctor, and also has to read about the side effects and educate
herself/himself. The above information is nothing but to help educate the people
about the subject of MS, and it does not at all imply that someone can just read
about it and practice on herself.
Physical therapy is essential to
prevent the patient ending up in a wheelchair or a nursing home.
5. URINARY TRACT COMPLICATIONS
Bladder complications are quite serious. In mild cases,
the treatment with Detrol, or Elmiron can be helpful, but urologist consult is a
must, and the urinary complications should be treated as aggressively as
possible. One of the common causes of death (which happens infrequently in MS)
is kidney infection secondary to MS.
Correction of diet is imperative. MS is
a disease of stress. Certain foods aggravate stress such as chocolate, hot dog,
cold cuts, alcohol, 5'C (candy, chocolate cookie, cake, and cocktail), and any
guts meat i.e., liver, kidney, etc. The patient should never skip a meal because
fasting or skipping meal causes fluctuation of blood sugar and secretion of
adrenaline which contributes to more stress and more weight gain. Also,
inactivity is a major stressor and aggravator in this regard.
Finally, the worst of all treatments
and alternatives is to tell the patient that there is no cure for MS and to do
nothing for the patient. Interestingly, this is a common practice among the
clinicians and should be strongly discouraged.
Avoidance of stress (e.g., marital
problems), proper diet (please
refer to the 4F diet )and exercise are
Acknowledgment : I am most grateful to
Mr. Eric Phillips for his indispensable, and extensive research and preparation
of this report.