Journal of Neurology, Neurosurgery, and Psychiatry, 1980, 43, 464-467

Short report

Hypercalcaemia associated with cerebral
vasospasm causing infarction
G L WALKER, P M WILLIAMSON, R B M RAVICH, AND J ROCHE
From the Royal North Shore Hospital of Sydney, St Leonards, New South Wales, Australia

SUMMARY Central nervous system disorders are not uncommon in patients with hyperparathyroidism and hypercalcaemia. Usually these consist of neuropsychiatric disturbances but acute
encephalopathies and seizures may occur. A rare manifestation is cerebral infarction. A patient
is presented with neuroradiological evidence of infarction caused by cerebral arterial spasm which
appears related to hypercalcaemia due to hypervitaminosis D. Arterial spasm is suggested as
a possible aetiological factor in focal neurological lesions associated with hypercalcaemia.
The psychiatric manifestations of hypercalcaemia
have been discussed by several authors.'17
Included are bizarre con-fusional stat.es with
delirium and hallucinations, lethargy, drowsiness,
impairment of intellectual functions, headache
and systemic symptoms such as nausea and
vomiting. Coma occasionally supervenes. Apart
from mental dysfunction, generalised hyperreflexia is usually the only other neurological sign.
The EEG usually reveals non-specific slow wave
activity8 and the CSF may show an elevated
protein.9
Seizures, both generali-sed'0 and focal"1 and
acute encephalopathy with permanent neurological deficit'2 have been described in association

with minor stroke who were found to have
liypercalcaemia due to parathyroid adenomas,
parathyroid hyperplasia or parathyroid carcinoma.
As yet apparently nio mechanism has been
advanced to explain either the neuropsychiatric
features or the episodes of focal neurolo.gical
disturbance seen during hypercalcaemia. The
following case is presented since it reve-als the
mechanism of how this hypercalcaemic patient
developed cerebral infarction.
Case history

DT, a 52 year old left handed Australian female,
had been well until becoming thyrotoxic in
August, 1977. Thyroidectomy in December, 1977
resulted in hypocalcaemia after operation, for
which she was cormmenced on replacement
therapy consisting of Calcium 1 tablet (400 mg
as a mixed salt) three times daily and calciferol
1-25 mg (50 000 units) three times daily.
Following surgery she remained euthyroid and
clinically well until three weeks prior to admission in July 1978 when she began experiencing
severe headaches with vomiting and polyuria.
Examination on admission revealed mild
dehydration, blood pressure 150/100 mm Hg and
pulse 64 per minute, drowsiness, and moderate
hyperreflexia.
generalised
Address for reprint request: Dr PM Williamson, Department of
Serum calcium was 4-3 mmol/l (normal range
Neurology, Royal North Shore Hospital of Sydney, St Leonards,
NSW Australia 2065.
2 05-2 55). Serum sodium was 143 mmol/l,
postassium 2-7 mmol/l, chloride 87 mmol/l and
Accepted 22 January 1980
464

with hypercalcaemia.
One of the less common neurological features
associated with hypercalcaemia is -cerebral
infarcti-on. In 1962, Fentz13 reported a 12 year
old boy who presented with hypercalcaemia and
mild systemic symptoms followed by acute coma,
hypertension and left hemiparesis. Recovery
occurred within a day but was followed by a
similar episode witth right hemiparesis from
which the patient also recovered. Andersson and
Lindholm14 reported a 67 year old male who
developed left hemiparesis which resolved over
a week. Bostrom and Alveryd'5 reported 12
patients with evidence of major stroke and five

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Hypercalcaemia associated with cerebral vasoplasm causing infarctian

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Figure (a) Initial right common carotoid angiogram (CCA) showing spasm of the internal carotid
artery (ICA) beibre and after origin of the posterior communicating artery. (b) Initial left CCA
showing spasm-.Of the middle cerebral artery (MCA), proximal to the trijuircation, and of the anterior
cerebral artery. (c) Repeat right CCA with minimal spasm of the distal ICA. (d) Repeat left CCA

now within normal limits.

466

G L Walker, P M Williamson, R B M Ravich, and J Roche

bicarbonate greater than 50 mmol/l. Blood urea
was 15-6 mmol/l (normal range 2 0-7-0) and
serum creatinine was 037 mmol/l (normal less
than 0-11). Haemoglo-bin was 12-9 g/dl, white
cell count 11 600 per mm3 with a normal
differential count, and ESR 31 mm in 1 hour.
X-rays of chest and hands and ECG were normal.
Parathyroid hormone assay was not elevated in
relation to the hypercalcaemia.
Treatmenit was commenced with intravenous
normal saline, frusemide, and prednisone. However, on the day after admission (when the
serum calcium was still 3-6 mmol/l) the patient
complained of heaviness in her left leg. Over
the next seven days this progressed to left
hemiparesis involving face, arm and leg, associated with cortical sensory loss and fluent
dyslphasia. Both plantar responses were extensor.
Computerised tomographic (CT) brain scan
performed seven days aftter admission showed
cerebral oedema on the right side with at least
two low density areas, one high in the right
parietal parasagittal cortex and another in the
oocipital region. There was no alteration with
contrast enhancement and the *changes were
considered to be consisten-t wiith multiple vascular
defects. Bilateral carotid arterriography perfor.med the same day showed intense spasm of the
distal right internal carotid artery (figure (a))
and the proximal portions of the left anterior
and middle cerebral arteries (figure (b)). Additional localised areas of spasm were seen in distal
cortical branches, and siignificant slowing of
blood flow transit time through both hemispheres
was present. That day lumbar puncture was performed to exclude subarachno,id haemorrhage as
a cause of vasospasm. This revealed normal pressure, no abnormal cells or xanthochromia and a
normal CSF protein of 0 45 gm/l. The serum
calcium level had remained abnormally elevated
for four days after admission but then became
normal as did all other electrolytes.
Over the next three weeks improvement
o,ccurred and only mild pyramidal and dominant
parietal lobe features remained at the time of

discharge.
A second CT brain scan performed two weeks
after the initial one showed mild residual cerebral
oodema in the right hemisphere and the two
regions previously described now -showed some
contrast enhancement consistent with infarction.
Reipeat carotid arteriography performed at the
same time (figure (c, d)) showed a marked decrease in the degree of arterial spasm present. At
that stage serum calcium was 2-3 mmol/l and
supplementation consisted of calcium 1 gm twice

daily and calciferol 1-25 mg daily. She has continued to improve since, and remains well.

Discussion
In determining the aetiology of the various
neurological manifestations of hypercalcaemia,
nio clear radiological lesion has previously been
demonstrated and no constant pathological process found. Bartter3 suggested precipitation of
calcium phosphate and other salts in the brain
whereas Karpati and Frame'6 suggested that
hypomagnesaemia was responsible. Cerebral
angiography was performed two hours and a
week respectively after the development of
hemiparesis in two patients and was found to
be normal.'3 14 In the large series of Bostrom
and Alverydl5 only six of the 17 patients had a
reasona(ble time relationship between hypercalcaemia and the onset of the neurological features
and also had no serious pre-morbid cerebrovascular history. Only one of these six patients
had cerebral angiography and this was normal.
Cerebral emboli were found at autopsy of another
patient. Multiple intracerebral microthromboses

were shown at autopsy in another patient.'7
In animal experimentation, evidence has been
accumulating that vasoactive substances such as
5-hydroxytryptamine, noradrenaline, and prostaglandins are involved in the pathogenesis of
cerebral vasospasm.'8 All of these substances have
an ultimate effect of increasing the intra-cellular
free calcium in the cerebrovascular smooth
muscle cells.'9 Calcium binds to troponin to
initiate t.he actin-myosin coupling; and it has
been shown that calcium is the final activator
of the contractile protein in vascular smooth

muscle.20 Extracellular calcium is an absolute
requirement for serotonin induced vascular
spasm, and Allen et a121 showed varying degrees
of spasm related to differing concentrations of
the calcium environment.
It is of great interest that Edvinsson et a122
recently showed that nifedipine (a drug which
selectively inhibits calcium influx) reduced the in
vitro spasm of human pial arteries after its
induotion by 5-hydroxytryptamine, noradrenaline,
and aut-ologous blood or plasma.
Performance of cerebral arteriography in more
patients with hypercalcaemia and focal
neurological disturbances will establish whether
arterial spasm is a chance or frequent association.
The authors thank Dr Michael Fearnside for
reading the manuscript, and Mrs Barbara Bevan
for her secretarial assistance.

Hypercalcaemia associated with cerebral vasoplasm causing infraction
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467

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