Interferons are used in clinical medicine
for a number of medical conditions including:
A
wide range of cancers
Chronic
hepatitis
Multiple
sclerosis
Chronic
granulomatous disease
AIDS-related
disorders
Rarely considered are the effects of large doses of this immune
cytokine on brain function. For example, the conventional treatment
of chronic hepatitis is interferon-alpha-2b. Despite poor results
in controlling the disease and the existence of safer, more
effective natural treatments, physicians continue to use this
toxic treatment. Of major concern are the neurologic effects
of the treatment.
Acute Problems
It is known that interferons have two patterns of injury to
the brain. One is acute and occurs within hours of treatment,
often lasting for the first one to three weeks of the treatment.
This usually includes fever, chills, headache and fatigue.
Chronic Problems
This is followed by a chronic phase in which more serious injuries
to the nervous system result. Chronic symptoms can include malaise,
lethargy, somnolence, headaches, low-grade fevers, anorexia
(loss of appetite) and more serious symptoms such as psychomotor
symptoms, cognitive problems, psychiatric behaviors and even
delirium and coma.
Brain Toxicity
The severity of symptoms depends on the dose of the interferon
and manner of administering the medication. Continuous infusion
of high-dose interferons is associated with more severe neurologic
problems. It is known that chronic brain toxicities occur at
all doses but more so after doses higher than 18 million to
20 million units a day. Most common is severe fatigue.
Even lower doses have been associated with a lack of drive
and disinterest in participating in normal activities, a process
called psychomotor retardation. This occurs in anywhere from
47 percent to 80 percent of patients. Changes in the ability
to think clearly (cognitive changes) are frequently seen in
patients treated with as little as 9 million units of interferon
per week. The difficulty with thinking reaches a peak at one
to three months. This can include a decreased attention span,
difficulty concentrating, defective short-term memory and mental
clouding.
Studies have described frequent periods of silence and vacant
staring, occurring even in mid-sentence. Objective testing for
recall and cognitive function have shown an incidence of 17
percent to 50 percent in patients receiving standard doses of
interferons. Most of these cognitive difficulties do improve,
yet there are reports of persistent impairments lasting up to
two years following cessation of treatment.
In some patients the effect is so severe on the brain that
patients sleep up to 20 hours a day and during waking periods
experience disorientation and confusion. Speech difficulties
(expressive dysphasia) and problems with balance have also been
reported. On rare instances, these neurological effects have
progressed to a demented state. Hallucinations have also been
reported.
It is important to appreciate that the patients in the first
two categories to be described had no previous psychiatric history.
Renault and co-workers, who examined many of these patients,
divided the neurobehavioral effects into three syndromes: organic
personality syndrome, organic affective syndrome and delirium
effects. Patients with organic personality syndrome frequently
experience uncontrollable overreaction to minor frustrations,
are very irritable and have a short temper.
Depression Common
Those with the organic affective syndrome often describe feelings
of depression and hopelessness. They cry easily and have difficulty
interacting socially with others. Patients experiencing delirium
have a clouding of their thinking, have short-term memory problems
and have frequent mood changes. Many become severely agitated,
abusive, withdrawn and may exhibit suicidal thoughts, delusions
of being persecuted and phobias. Patients having delirium symptoms
often had co-existing liver disease, history of psychiatric
disorder or previous brain injury.
Severe Reactions in Cancer Treatment
The most severe effects have been seen in patients treated
for cancers. In these patients death due to encephalopathy (widespread
brain injury) and associated seizures have been described. This
may be a result of combined toxicities of radiation, chemotherapy
and interferon.
Interferon-gamma is less toxic than the alpha or beta-interferons.
With higher doses one can see chronic neurotoxicities, which
can include dizziness, slowed thinking, confusion, crying spells,
and even symptoms resembling Parkinson's disease.
How Interferon Ruins Your Brain
The mechanism of this injury to the brain appears to involve
the brain's special immune cell called the microglia. Normally,
these cells remain dormant in the brain. That is, they are sleeping.
Microglia cells can be activated by numerous factors, including
mercury, aluminum, iron, overvaccination, and brain trauma,
strokes, infections (viruses, bacteria, rickettsia) and cytokines
such as interferons.
Once activated, microglia can move about the brain secreting
very toxic compounds, which include two excitotoxins (glutamate
and quinolinic acid). These excitotoxins dramatically increase
free radical generation in the brain as well as oxidation of
lipids (called lipid peroxidation). These radicals damage synaptic
connections, interfere with neurotransmitters and can even kill
neurons. In addition, these activated microglia generate other
toxic compounds such as prostaglandins (PGE2), which increase
brain inflammation.
If the microglia activation is short lived, the damage to the
brain is minimal and recovery takes place. Yet, should the activation
continue, which would occur with high-dose and long-term use
of interferons, the damage could be substantial and irreversible.
Protecting the brain with high-dose and varied antioxidants
as well as certain metabolic stimulants can substantially reduce
this damage. Certain nutrients, such as malate, pyruvate, DHA,
ascorbate, magnesium and methylcobalamin inhibit excitotoxicity.
Physicians Frequently Miss Side Effects
Physicians often ignore patient complaints of neurological
difficulties during interferon treatments, assuming they are
benign and reversible. As stated in the beginning, natural alternatives
have been shown to be much more effective and dramatically safer
than interferon treatments.
By
Russell L. Blaylock, M.D.