Relapses and Pseudo-relapses
The relapse in early relapsing-remitting MS has a typical pathology
irrespective of its location. The first visible event is the
orderly, local, mass death of oligodendrocyctes, the cells which
support myelin. The myelin associated with these cells then degenerates.
Degenerating myelin activates an inflammatory process. When this
is over, young oligodendrocytes mature and make new myelin. The
clinical counterpart to this pathology (unless it occurs in a
silent area) is a loss of function which worsens over several
hours to two days. The loss of function remains in place until
the inflammation is over and remyelination begins. It will thus
be seen that the relapse has a definite pattern and timescale.
Some people experience strange
new sensations on beginning antibiotics and are often afraid
that these are relapses. While relapses can occur during the
first few months of antibiotics, probably initiated by virus
infections, these sensations do not fulfil the timescale criteria
of true relapses and tend to change their form within a week.
Sometimes, in fact, they herald a return of function. What causes
these 'pseudo-relapses' I do not know, but I suspect it is rebudding
of neurones which make trial-and-error connections. Synaesthesia
(crossover of the senses) can sometimes result; as an example,
the seeing of flashes of light when hearing a loud noise. They
can be quite troubling even when improvement is taking place.
Repair takes place at a cellular level; function has to be re-learned
at a much higher level.
Peripheral Nerve Inflammation and Central Pain:
Reflex Sympathetic Dystrophy
A number of people with chronic infection with Chlamydia pneumoniae,
whether or not they have MS, may, on treatment, experience a
deep, grinding bone pain; it has a crushing quality. It does
not correspond to any recognised area supplied by a sensory nerve,
and it can travel along a limb, one moment being in the shoulder
and the next in the fingers. It can suddenly go, and just as
suddenly return. In its more severe form it is accompanied by
a redness of the limb, dilation of the superficial veins and
an increase in sweating in the limb. Use of the limb may be limited.
There is often an exaggerated perception of skin stimuli; a light
breeze over the limb may be felt as painful. Fortunately it seems
This pain is typical of damage to a large peripheral nerve; it
is called Reflex Sympathetic Dystrophy. It is caused by injuries
- often quite minor - to a nerve; it may occur after a virus
infection, particularly shingles.
In chronic Chlamydia pneumoniae infection Reflex Sympathetic
Dystrophy may be caused by acute inflammation associated with
the destruction of a local bacterial collection.
The mechanism of the pain is not fully understood, but is thought
to involve stimulation of the thalamus, an area of grey matter
deep in the brain. The pain is thus generated in the brain. It
is common in those with a chronic Chlamydia pneumoniae
infection, and many people develop it during bacterial killing.
Its severity seems to depend on bacterial load and placement.
Fortunately it is usually mild and often does not last long,
though the limb can remain red or mottled for some months. In
my experience complete resolution is the rule.
Severe thalamic pain of central origin can also occur in MS and
is usually long-lasting. Pain as described above which goes after
a month or so, and which is related to a bacteria-killing agent
(when metronidazole, for instance, is added to protein-synthesis
inhibitors) is more likely to be due to transient inflammation
in a peripheral nerve rather than a relapse.
Other transient phenomena seen during chronic infection with
Chlamydia pneumoniae include painful tics. Muscle fasciculations
may also occur.
In addition to their antimicrobial
capabilities, doxycycline and minocycline are powerful immunomodulants
which inhibit microglial activation in the central nervous system.
They have numerous other inhibitory effects on the immune system,
including downregulation of proinflammatory cytokines. This is
well reviewed by Tauber and Nau: [http://www.bentham.org/cmp/samples/cmp%201-1/Nau.pdf] Doxycycline inhibits the inflammatory
response to bacterial infections: [Bernardino AL, Kaushal D, Philipp
MT J Infect Dis. 2009 May 1;199(9):1379-88.] Doxycycline also inhibits the action of matrix
Long term treatment of chronic
C. pneumoniae infection with doxycycline is thus accompanied
by an attenuation of the immune system's activity. It may be
expected that withdrawal of immumodulatory antibiotics may give
rise to worsening of symptoms, with flu-like symptoms and loss
of energy. One may speculate that symptoms of this nature which
occur within a few weeks of stopping doxycycline are due to increased
destruction of dead bacterial remnants by a strengthened immune
Symptoms like this are unlikely
to be due to regrowth of bacteria, which after all had taken
years, even decades, to produce significant disease.
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page updated 28th Aug