PART
VIII:
NEUROLOGICAL
SYMPTOMS
As a result of the neurological
damage explained earlier, many neurological symptoms and signs are classical in
a floxing. Symptoms is more or less what you feel whereas signs is what your
doctor can see either by personal exploration or through medical tests.
The fluoroquinolones are toxic
antibiotics that act directly on the nerves. When the intensity of the toxicity
is sufficiently high, the floxed person starts to feel many symptoms. But do
not forget that the damage reaches to the whole nervous system and each cell
takes its share. The neurological symptoms of a severe floxed person, that can
amount to more than 50, is only the tip of the iceberg.
You know that the nerves control
all organs of the body. For instance, your intestines will malfunction but all
the multiple chemical sensitivities that you will develop, the reactions to
foods, the dry intestine, the feeling unwell are not as easily attributed to a
neurological failure as tremors or numbness of your fingers. So in the
following sections we only treat very obvious simptoms of quinolone toxicity,
the most common ones, knowing in advance that they are normally only a small
part of the health damage, and not the most critical one.
Peripheral neuropathy caused by
quinolones affects a variety of peripheral nerve cells and fibers, including
sensory (temperature, touch, vibration...), motor (muscles, by altering the neuromuscular
junction as we have explained before), and autonomic fibers (those that you do
not control, like orthostatic pressure, erection). Most quinolone induced
peripheral neuropathies affect all fiber types to some extent. However, a
single fiber type may be predominantly or exclusively affected in some cases
producing very particular neuropathies. In some floxed persons, peripheral
neuropathies involve single peripheral nerves (single=mono neuropathies), or
numerous individual peripheral nerves, the so-called mono-neuritis multiplex
syndrome. In addition, peripheral nerve disorders may involve the brachial
plexus, lumbosacral plexus, or a single root, that is to say, the low spine,
resulting in signs and symptoms in one limb, with pains that can be excruciating
(in the hamstrings, ankle, lower leg, knee, hip, etc). Most cases of floxing
conform to a poly-neuropathy syndrome, which usually implies both sensory and
motor fiber involvement in a relatively symmetric fashion and typically with a
distal-to-proximal gradient of involvement (more intense the more distant from
the trunk). These conditions are termed sensory-motor poly-neuropathies, and
they represent the most common form of peripheral neuropathy. They also cause a
diminished quality of life.
Although we do not know for sure,
it is plausible that quinolones might induce pathologic reactions in the
nerves: wallerian degeneration, axonal degeneration, and segmental
demyelination. In wallerian degeneration, the axon degenerates distal to a
focal injury that interrupts the continuity of the axon. This reaction often
occurs in focal mono-neuropathies that result from nerve infarction as a result
of an ischemic vasculitic process. The toxicity plus the ischemia interfere
with nerve metabolism. They affect the longest neurons first, since long
neurons have greater metabolic demands than short ones. Symptoms therefore may
begin in the feet, then progress up the legs and then affect the hands. It is a
typical pattern of severe reactions. In intermediate reactions the neuropathy
does not usually progress up.
Axonal (rod) degeneration starts
at the most distal (distant from the trunk) extent of the axon. Axonal
degenerative poly-neuropathies are usually symmetric (although frequently with
different pain intensities in both sides), and are the most common in floxings.
Floxed persons also predominantly show signs of segmental demyelination that
refers to focal degeneration of the myelin sheath with sparing of the axon.
This reaction can be seen in focal mono-neuropathies but also in generalized
sensory-motor or predominantly motor neuropathies. Toxic segmental
demyelinating poly-neuropathies might be the result of the immunological
reaction.
In those peripheral nerve
disorders that are characterized by either wallerian degeneration or axonal
degeneration, prognosis (likely outcome) is less favourable due to the fact
that the axon must regenerate and re-enervate muscle, the sensory organ, blood
vessels, and other structures before clinical recovery is noted. That may be
why the new warning (October 2004) in the package insert of quinolones mentions
“irreversible condition” with respect to neuropathy. Recovery may be more rapid
with segmental demyelination because remyelination is accomplished more
quickly, in turn re-establishing normal conductivity of the axon and return of
function.
Whereas it is difficult for us to
get a proper disagnosis about our nerve injuries, it is easy for the floxed
person to feel and describe the multiple symptoms of his/her peripheral neuropathy.
Sensory symptoms: Sensory symptoms include
sensory loss, a sense of numbness, tingling, prickling, and pins-and-needles
sensations, pain, thermal sensation, vibratory sense and intolerance to light
touch. Damage to large sensory fibers lessens the ability to feel vibrations
and touch, resulting in a general sense of numbness, especially in the hands
and feet. People may feel as if they are wearing gloves and stockings, or
having the foot in a cast. In most generalized poly-neuropathies, these symptoms
begin in the most distal (far from the trunk) extent of the longest sensory
fibers, like the toes and feet and then crawl their way up to the knee point in
which the disorder also starts at the fingertips spreading the process to the
upper extremities. In addition to sensory loss, patients frequently complain of
paresthesias and dysesthesias, often characterized by a sense of numbness. Pain
is a serious symptom for many floxed persons. It may be described as a dull
aching sensation, an intense burning sensation or, occasionally, as
intermittent lancinating pulses of pain (called ‘throbbing’ in this report). Intractable
and high level pain is very common during acute reactions and also in long
term, chronic severe reactions to quinolones.
Motor-muscle: Muscle weakness is the most
common symptom of motor nerve damage. All severe reactions present with a loss
of muscle mass that cannot be regained regardless of how much exercise or
workouts are done. Oddly, many people take a long time to realize that they are
lossing strength or wasting muscle because visually it is not so apparent.
Other symptoms may include painful cramps and fasciculations (uncontrolled
muscle twitching visible under the skin, or at least felt), muscle loss, bone
degeneration, and changes in the skin, hair, and nails (these more general
degenerative changes also can result from sensory or autonomic nerve fiber
loss). Impairment of motor function typically begins with weakness in the toes,
and as the poly-neuropathy progresses, ascends up the distal lower extremities
to the level of the knees, at which time motor involvement in the hands may be
observed.
In the toxic segmental
demyelinating poly-neuropathies, proximal muscle (quads) weakness resulting
from root (polyradiculoneuropathy) involvement may be observed. Axonal
degenerative poly-neuropathies tend to produce weakness along with muscle
atrophy, but atrophy is much less conspicuous in segmental demyelinating
poly-neuropathies because in these disorders the axon remains in continuity
with the muscle, preventing denervation atrophy. Therefore, your doctor can
measure the perimeter of your thighs and tell you that he/she finds both the
same size, even though you feel your more painful one nearly useless, soft,
idle and deprived of strength. A common
symptom (but not universal) in severe floxing poly-neuropathy is weakness in
dorsiflexion of the big toe. That disability is somehow a measure of the
initial severity of the mono-neuropathy of the distal peroneal, tibial and
flexor groups of the lower leg, and progresses up for severe reactions to
weakness of quads or even gluteus in the worst cases.
Motor toxicities have a much
deeper influence on the health of floxed persons than is normally acknowledged.
Motor nerve injuries caused by quinolones provoke a lack of function of the
related muscles, and they become atrophied. The atrophy causes the limb to work
improperly and other muscles and nerves are overstressed, causing further
pains, sometimes very intense and for many years. The bad news is that some of
these motor nerves have a limited capacity of healing, and normally they also
have deadlines for healing (around 2 years) after which time they cannot
recover and the injuries and pain cannot be reversed, apparently.
Autonomic nerves: Some floxed persons report
symptoms that indicate that autonomic fibers are also affected. Symptoms of
autonomic nerve damage are diverse and depend upon which organs or glands are
affected. Autonomic nerve dysfunction can become life threatening when the
heart begins beating irregularly (extremely common in floxed persons) or there
is difficulty with breathing. Other common symptoms of autonomic nerve damage
include an inability to sweat normally (floxed persons notice reduced or absent
sweating in the legs and hands, and at the same time excessive sweating
confined to the head and neck region), a partial loss of bladder control and an
inability to control muscles that expand or contract blood vessels to maintain
safe blood pressure levels. A loss of control over blood pressure can cause
dizziness, light-headedness, or even fainting when a person moves suddenly from
a seated to a standing position (orthostatic hypotension).
In severe floxings other autonomic symptoms include dryness of the eyes
and mouth (another marker of the severity of the floxing) and gastrointestinal
dysfunction (nerves controlling intestinal muscle contractions frequently
malfunction), often manifested by alternating constipation and diarrhea or by
early satiety. Many people also have problems eating or swallowing if certain
autonomic nerves are affected. In intermediate and severe floxings in men,
partial erectile dysfunction or incontinence is one of the first autonomic
symptoms.
More details on autonomic nerve
dysfunction (neuropathy) are treated later on this paper.
Diagnosis. Such a vast array of
presentations of peripheral neuropathy in floxed persons makes precise
diagnosis a challenging task and is the reason that physicians reach different
conclusions depending on the predominance of the axon/myelin, phocal/diffuse,
symmetric/asymmetric, sensory/motor/autonomic involvement, and adding the
difficulty posed by the fact that floxed persons develop all of them to
different degrees.
Doctors may order a set of tests
to evaluate your disorder: nerve conduction studies, needle electrode
examination, brain and spine MRI, lumbar puncture for cerebrospinal fluid
analysis. Blood and urine tests can include glucose tolerance test, vitamin
B12, serum protein, anti-GM1 antibodies and anti-myelin antibodies, plus
investigations of markers of various connective disorders associated with
vasculitis. The ultimate analysis is a nerve biopsy, that when performed with
the most advanced techniques by well-trained physicians can assist in the complete
characterization of the injuries. It is an invasive procedure and few floxed
persons have undertaken it because it is mainly ordered only in severe
reactions and when a diagnosis of vasculitis or immune reaction of another type
is being considered. Less common are precision sensory testings, and studies of
sudomotor function, and autonomic responses to provocative physical maneuvers.
In many cases the electrical
conductivity tests render normal results, as well as MRIs of the brain and
spine, and spinal taps. But it is also very typical that well conducted studies
discover alterations in the sensory and motor status of the nerves in many
parts of the body. Muscles also show decreased responses in electromyographic
(EMG) studies.
Other very common findings are
decreased or altered signals in the nerves that control the hands, especially
the ulnar nerve. You will know that your ulnar nerves are affected if your
small and ring fingers become numb, normally if you exert pressure around your
elbow or when bending your elbows sleeping at night. Some doctors will tend to
diagnose you as having ulnar or carpal tunnel syndrome, but you are really
suffering toxic ulnar neuritis.
Other nerves very commonly
implicated are the nerves of the legs. Pains occur predominantly in the
hamstrings, lateral or medial knees, outer gluteus, calves, quads, groin, and
several areas of the ankle, plus the toes. Many times pains mimic strains,
tendinitis, muscular fiber disruptions, and sprains, but they are toxic
neuritis.
|
Remember: In severe reactions neurological pains can last for
years and impair your quality of life. |
In general, we have multiple
peripheral nerve injuries. They can occur sequentially and in a random fashion
(now the upper left leg, then the right ankle, etc...). As stated before, the
earliest findings are loss of vibratory sensation in the toes, atrophy of
intrinsic foot muscles, and reduced or absent ankle jerks. In severe reactions
there are signs of lower motor neuron injuries: weakness, more generalized
atrophy and fasciculations. Sometimes fasciculations are referred to as
"twitching" and they are a serious symptom of denervation that
normally shows up as motor (axonal) nerve damage that is mainly irreversible
and can only be recovered through new nerve fiber regeneration.
Double or triple mono-neuritis
dominates in intermediate reactions. For instance, the right leg (hamstring and
ankle-Achilles) plus heart arrhythmias and perhaps an elbow epicondylitis.
Multiple neuritis is more typical of severe reactions. For instance, this
includes the right leg, plus heart disorders, plus elbow, shoulder, hips,
wrists, and above all- optic neuritis.
Optic neuritis reflects a injury
of the optic nerve and is a secondary effect of the damage caused by the quinolones
to the small blood vessel complexes of the eye (in fact is an ischemic optic
neuropathy). The optic nerve dysfunction usually manifests with blank spots,
difficulties in focusing, and in severe cases transient complete losses of
vision with a solid white vision in one or both eyes. These blindness episodes
have been reported with ciprofloxacin and last for some minutes, are very
terrifying, appear suddenly, so they are also dangerous depending on the
activity in which the floxed person is engaged. These events of blindness can
happen periodically up to 18 months after the treatment with ciprofloxacin and
at any time in the following years if the floxed person experiences a high
re-exposure to quinolones through poultry ingestion, for instance.
If the intoxication of the quinolones
has been intermediate, these neurological symptoms tend to dissapear in two
years time on average. If the intoxication has been severe, the neurological
disorders linger on for many years without abating, although in the 4th or 5th
year mark the floxed person can experience an improvement. Some injuries of the
eye become almost always permanent if they have not resolved after 2 or 3 years
(see other parts of the report).
Had you given a chance that the
most reputed clinics and doctors in the field of neuropathy would be aware of
the toxicity of quinolones?
THE NEUROLOGY AND NEUROSURGERY FORUM. Escalating Burning
Sensory PN
QUESTION:
I have been diagnosed with Sensory peripheral neuropahty (PN) following the use
of a fluoroquinolone.
My
question is this. It is noted in the insert that: 1). That physicians use
Medrol to counteract an adverse and or allergic reaction. 2). But, it also
states that the use of steriods can predispose someone to Tendon
Rupture/Tendonitis. If that's the case, what role could Medrol play in
escalating Sensory PN? or escalating nerve damage/inflammation. It seems in
many cases people with Burning Sensations after fluoroquinolones are given
Medrol to counteract the reaction and their conditions escalate to more acute
burning!. 3).I don't know what the clinical picture is for Steroid Myopathy but
I didn't think it was Sensory PN? I am trying to determine if the antibiotic
alone did this or the combination of both! 4). Could you explain what the term
Arthralagia Means? I not only have the burning but it feels like my skin is
stretched and there is alot of stiffness/joint pain. 5). Can a paresthesia
cause acute burning pain that does not go away for months?
ANSWER:
Regarding the neuropathy - I realise that isolated reports have been popping up
(especially on this forum) about a toxic neuropathy from fluoroquinolones, but I don't believe this is an established
cause of neuropathy. Plus medication
neuropathies are quite uncommon and difficult to establish cause and
effect. So the first thing I would make sure is that all the treatable/common
causes of neuropathy have been evaluated for - diabetes, thyroid disease,
paraproteinemic neuropathy (with an SPEP and immunofixation), inflammatory
(with ESR / ANA). Sometimes a spinal tap and nerve biosy is necessary to fully
evaluate neuropathies.
Well, although this text is a few
years old, the fact that it belongs to a very reputed hospital specialised in
neurological disorders and the firm and stuborn illiteracy of neurologists
makes it appalling.
Many medical reports state that
chemical and drug induced neuropathies account for about 30% of all
neuropathies. The rest have mechanical-surgical-traumatic, inmunological and
other causative factors. Another of our homemade experiments has been to survey
on a daily basis for more than a year the final diganosis of the neuropathies
of patients at two very popular forums moderated by medical hospitals. Between
1,5% (sure diagnosis) and 2,5% (probably diagnosis) of all neuropathies
consulted there had been caused by quinolones. If we give some credibility to
this rude experiments and extrapolate them, that would mean that roughly
between 5 % and 8% of all neuropathies caused by medicines, would have their
origin in ingestions of fluoroquinolones. All of them non-reported as side
effects, of course. Not valid research again but undeniable little piece of scientific
evidence.
Look to this thread on one of the
many internet forums, where people look for answers to their long lingering
health problems. It mentions two sites, one of them ours:
|
From |
Post |
|
patient A |
Help I am
seriously worried about my worsening medical condition. I have had
headaches every last day for the past 5 months and I'm developing sharp
pains in my right wrist right where the palm meets the arm, also Ive had severe
knee cramps while sleeping, wake up and can't move my legs because the
pain is so bad, but after 5-10 agonizing minutes I work the pain out by
moving my legs at the knees. I also notice a far milder but similar sensation
at my ankles as in my wrist. Again, the knee pain works out with
movement, but the wrist pain is made worse but certain movements. Also i have
notice an occasional "buzzing" or tingling down my lower
back, and in addition I have had random acid relfux attacks even on an
empty stomach.... plus nausea and shortness of breath at rest. |
|
Doctor of the
forum. |
Its not clear
whether your symptoms are neurological or not - typical neurological symptoms
result in weakness, clumsiness or loss of sensation on one side of the body,
loss of ability to see or speak etc |
|
patient B |
Hello! Have you
taken any antibiotics within the past few months? |
|
patient C |