Department of Neurology,
Niederösterreichisches
Landeskrankenhaus
für Neurologie und
Psychiatrie Klostemeuburg, Austria
Lithium carbonate, usually helpful in the
treatment of cluster headache, showed a
paradoxical effect in a patient now being seen
for over one year. Chronic cluster headache
developed after she had been taking lithium for
more than eight years for psychiatric
indications. Only by total discontinuation of
lithium therapy could a complete remission of
the headaches be brought about. This effect was
observed repeatedly. It is suggested that a
chronic effect of lithium at the receptor sites
of the central trigeminovascular pathways plays
a role.
It has been clinically established that
lithium carbonate can rapidly improve chronic or
episodic cluster headaches. The dose is the same
as for psychiatric disorders. Though much has
changed in the pathophysiological concepts of
cluster headache in recent years, its mechanism
has remained obscure.
A female patient is described in whom
lithium therapy, started for depressive episodes
eight years previously, repeatedly triggered
chronic cluster headaches. To our knowledge,
this is the first case in which lithium showed
such a paradoxical effect
CASE REPORT
A 45-year-old female patient was refered by
a neurologist for chronic cluster headache
occurring during lithium carbonate therapy. Only
discontinuation of oral lithium brought about
symptom-free periods but lithium had to be
prescribed again for recurring severe
depressions.
On admission the otherwise healthy woman
complained of severe facial pain starting rather
abruptly with a painful burning sensation in the
inner right nose and at the corner of the right
eye spreading perorbitally followed by slight
swelling and reddening of the upper eyelid,
ciliary injection, increased lacrimation and
occasionally increased rhinorrhea on the right
side. Such attacks occurred either spontaneously
or by sneezing,
yawning or
eating spiced food, especially with vinegar.
Within the past two years these painful
sensations had been experienced only
occasionally, but in the preceding four weeks
had reached an unbearable intensity. They now
occurred in closely packed groups, especially in
the morning.
For eight years the patient had been
regularly treated with oral lithium carbonate
for endogenous depressions. Since the beginning
of the therapy no severe depressive episodes had
been experienced and no hospitalization had been
necessary. Before that, the patient, having had
many depressive phases since her 18th year, had
been frequently admitted to psychiatric
institutions.
No neurological abnormality and no signs of
lithium intoxication were noted clinically.
Lithium blood cells were 0.8 meq/l. All routine
laboratory tests were normal. ACT of the head
was unremarkable. Carotid arteriography showed
no intracranial pathology, nor did the neck
arteries show any irregularities. Rhinological
and ophthalmological examinations were normal.
Thyroid function was normal. The EEG showed some
diffuse dysrhythmic activity without paroxysmal
activation. Electroneurographic studies of the
peroneal and median nerves showed no slowing of
motor or sensory nerve conduction velocity.
Transcutaneus ultrasonic doppler flow
examination of the supratrochlear artery were
registered in the symptom-free interval and
during a provoked attack. A marked flow
acceleration on the affected side was recorded
in the attack phase thus impying increased flow
in the ophtalmic artery.
Within the following weeks no therapeutic
response was seen with pizotifen,
dihydroergotamine, indomethacine, or pindolol.
Inhalation of pure oxygen gave no lasting or
definite relief. Also amitriptyline, diazepam or
placebo showed no effect. Finally, lithium had
to be discontinued and this brought about a
completely symptom-free state. Provocation by
sneezing or
yawning had
no effect. Also small amounts of ethanol could
not evoke an attack. Because of recurring severe
depressive episodes with suicidal ideas, lithium
was started again, resulting in new clusters of
painful headaches within two days. The daily
lithium dose was then reduced to correspond to a
blood level of 0.4 meq.IL and carbamazepine was
added in a daily dose of 600 mg. With this
medication the patient stated that the cluster
headaches reoccurred but less intensely. In the
follow-ups no significant change was reported by
her within one year.
DISCUSSION
Lithium carbonate is known to bring about
almost immediate relief from cluster headache.
It is often superior to other drugs but, because
of its narrow therapeutic range, has been
recommended mainly in cases resistant to
conventional prophylactic agents. The
therapeutic benefit can be long-lasting, but
Ekbom noted "a tendency to diminishing
effectiveness of the drug after a few
months."
The present case met the diagnostic criteria
for chronic cluster headache. We do not assume
the cluster headache in this patient to be an
equivalent symptom of the depression, as the
effect of lithium has been shown to be
independent of its antidepressant action. In
addition, ultrasonic Doppler flow probes in our
patient showed an increased flow in the
ophthalmic artery of the affected side during an
attack. Though conflicting evidence has been
reported on the diagnostic reliability and
pathophysiological significance of such
findings, identical ultrasonic changes have in
one series been shown to be of value in the
differential diagnosis between migraine patients
and patients with cluster headache. Moreover,
recent work has shown that pathological changes
of blood flow in cluster headache are secondary
events due to primary neuronal processes within
the central or peripheral trigeminal
pathways.
Though we are unable to give a full
explanation of this seemingly contradictory
effect of lithium, any interpretation must take
into account that the patient received lithium
many years prior to her headache symptoms.
Possibly chronic lithium intake evoked changes
on a molecular level at the local
trigemino-vascular receptors that led not only
to a wearing-off, but to a paradoxical effect.
Of the known long-term effects of lithium at
synaptic levels, the most relevant phenomenon
may be that chronic lithium intake is known to
reduce synaptic tryptophan-hydroxylase activity,
thereby causing a disequilibrium of tryptophane
and serotonin. This effect is not seen in
patients with newly started lithium carbonate
therapy.
It is evident that additional factors must
be considered: first, because the symptoms are
strictly unilateral; and, second, because in a
long-term follow-up of lithium patients
undergoing careful clinical, laboratory, and
neurophysiological testing, no symptoms similar
to those in this case have been found.
2. Ekbom K: Lithium in the treatment of
chronic cluster headache. Headache 17:39-40,
1977.
3. Mathew NT: Clinical subtypes of cluster
headache and response to lithium therapy.
Headache18:26-30,1978.
4. Ad Hoc Committee on the Classification of
Headache. JAMA 179:717-718,1962. 5. Kudrow L:
Thermographic and Doppler flow asymmetry in
cluster headache. Headache 19:204-208,
1979.
