CLINICAL ELECTROENCEPHALOGRAPHY

8 1998 VOL. 29 NO. 3

Reversible HypercaIcemic Cerebral Vasoconstriction
with Seizures and Blindness: A Paradigm for Eclampsia?
Peter W. Kaplan

Key words
Cortical Blindness
Eclampsia
Hypercalcemia
Magnesium
Pencdic Lateralized Epileptiform Discharges
Seizures
~

INTRODUCTION
Hypercalcemia can cause drowsiness, lethargy, weakness, confusional states and coma but rarely causes
seizures.l4 Reversible diffuse or focal neurologic deficits
can occur, often associated with electroencephalographic
(EEG) correlates.5nA patient with reversible blindness due
to ischemia and seizures with hypercalcemia is presented
with pathophysiologic comparison to eclampsia.
Case Report
A 66-year-old woman developed hypercalcemia from
multiple myeloma and ingestion of calcium-containing
antacids. Serum calcium was 13.6 mg/dL, total protein
10.9 mg/dL; albumin 3.4 mg/dL; magnesium 2.2 mg/dL;
and ionized calcium 1.80 mg/dL. On neurological examination she appeared awake, but was having auditory and
visual hallucinations despite being oriented to time, place
and person. She had conjugate gaze, full extraocular
movements, reactive pupils, normal fundi, and visual fields
that were full to examination by confrontation. Strength,
tone, sensation and reflexes were intact with down-going
plantar responses.
Despite hydration and treatment with pamidronate (a
calcium-lowering agent), serum calcium remained elevated
between 11512. 5 mg/dL. Following a generalized tonicclonic seizure, computerized head tomography (CT), and
cerebrospinal fluid studies showed no abnormality; the
patient was given intravenous phenytoin with a level of
11.0 pg per ml. The next day she was confused, and
examination still showed full extraocular movements, reactive pupils and normal fundi, but there was no reaction to
visual threat, sight for objects or movement. Repeat head
CT scan again showed no abnormality, but EEG revealed
an occipital high-voltage spike-and-slow- wave complex
seen approximately every 1% - 2 seconds throughout the
recording (Figure 1). Pattern-reversal visual evoked poten-

tial studies showed no responses bilaterally. Single Photon
Emission Computerized Tomography (SPECT) showed
multiple perfusion defects in the right occipital, left parietal
and frontal regions (Figure 2). With the further lowering of
serum calcium to 6.4 mg/dL, hallucinations resolved, and
the patient had no further seizures.
By hospital day 21 she was alert and oriented, and her
vision had returned although with a residual right hemianopsia. Magnetic Resonance Imaging (MRI) showed an
increased T, signal in the occipital lobes consistent with
cerebral infarction.
This patient presented with marked hypercalcemia,
confusion, hallucinosis, and a tonic-clonic seizure. Her
clinical state evolved, and she became cortically blind with
occipital spike-slow-wave complexes on EEG, and evidence of occipital hypoperfusion on SPECT despite a normal head CT scan. Following a marked reduction in serum
calcium, occipital spike-slow-wave activity stopped and
vision returned. This is the first well-documented case of
hypercalcemic reversible ischemia with bioccipital epileptiform discharges and cortical blindness. In one previous
case, hypercalcemia without seizures resulted in cerebral
vasospasm and infarction of both the right parietal
parasagittal cortex and the occipital r e g i ~ n . ~
Differentiating cause and effect in a patient with visual
loss, occipital epileptiform activity and hypercalcemia may
be difficult. Many mechanisms can be involved in producing this association: a) hypercalcemia may produce cerebral vasospasm resulting in cerebral infarctiong; b) hypercalcemia may cause focal or generalized seizures with
encephal~pathy~'~;
c) hypercalcemia may produce hypertensive encephalopathy", with raised intracerebral pressure and cerebral ischemia. To complicate matters, there
may also be interplay between these pathopsychological
mechanisms: For example, vasospasm may itself produce reversibleQor permanent ischemia which, in turn,
Peter W Kaplan, M B F R C P, is Chairman, Department 01 Neurology,
Johns Hopbns Bayview Medical Cenler, Associate Prolessor of Neurology,
Johns Hopkns University,Baltimore, Maryland
Requests for repnnts should be addressed to Peter W Kaplan. M B
F R C PI Johns Hopkins Bayview Medical Center, 4940 Eastern Avenue,
Bahmore. MD 21224

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Q1998 VOL. 29 NO. 3

may act as a trigger for focal epileptiform discharges.
dence to suggest that cortical damage in eclampsia is proAlternatively, parieto-occipital seizures themselves may
duced by v a s o ~ p a s m , ~which
~ . ' ~ is reversed by intravenous
result in permanent neurologic sequelae and induce cortimagnesium sulfate infusion. In subarachnoid hemorrhage,
cal blindness.lo From a different perspective, up to 20% of
calcium channel blockers such as nimodipine have been
patients with occipital EEG epileptiform foci may have
used to minimize vasospasm, and the effect of magnevisual field deficits."
sium sulfate might therefore be as a calcium antagonist,
In this patient, a likely sequence of events was a rise
preventing cerebral va~oconstriction~~
and subsequent
in serum calcium resulting in a confusional state, superimepileptogenic cortical injury. One can speculate that one
posed on occipital ischemia which resulted in visual hallucomponent of the cerebrovascular pathology of eclampsia
cinations. A combination of this ischemia (as documented
represents an increased vascular sensitivity or reactivity of
watershed zones to local calcium ions that can be counby SPECT scanning and subsequent MRI changes in the
teracted in eclampsia with magnesium infusion. There are
occipital lobes) in concert with hypercalcemia resulted in
data to suggest that magnesium ions block N-methyl-Dbioccipital foci in the form of periodic epileptiform disaspartate channels that mediate calcium entry into
charges (vide infra).
cells.19mThis case may therefore provide some parallels
The mechanism of vasospasm involves a hypercaland insight into the interplay of calcium and magnesium
cemic-induced actin-myosin coupling with activation of
vascular smooth muscle in the arteriolar c i r c ~ l a t i o n . ~ ~cations,
~ ~ ~ ~ ~vasospasm in parieto-occipital watershed zones
with the onset of seizures. There are few other parallels in
Cerebral vasospasm may then produce patchy ischemia
humans to eclampsia.
but it favors watershed zones, typically in the parietooccipital regions, resulting in cortical b l i n d n e s ~The
.~
vasospastic cause of the ischemia allows for potentially
SUMMARY
reversible deficits.
Although hypercalcemia may cause drowsiness,
Structural abnormalities such as strokes or ischemic
lethargy, weakness, confusion and coma it rarely causes
zones when associated with a seizure are known to result
seizures or cerebral infarction. The patient presented had
in periodic lateralized epileptiform discharges (PLEDs) on
a clinical evolution from hallucinosis to a generalized
EEG. In this case, the occipital regions are those most
tonic-clonic seizure, and subsequent cortical blindness
affected and in the face of a tonic-clonic seizure, these
with occipital cerebral ischemia as evidenced by SPECT
posterior regions may engender irritative zones producing
and MRI scans. EEG revealed occipital PLEDs. With
bioccipital epileptiform discharges, possibly with reversible
reversal of hypercalcemia, there was a return of vision,
ictal functional impairment. Cortical blindness with permaresolution of EEG epileptiform activity, although with some
nent visual loss has clearly been documented following
residual occipital infarction. This case, in concert with a litseizures,l0 although other causes include migraine, hypererature review of hypercalcemia, reveals examples of
tensive encephalopathy and eclampsia, all of which may
occipital and watershed ischemia, blindness, seizures and
be reversible.
hypertension, a pattern markedly similar to that of eclampsia. Furthermore, medications such as magnesium sulHypercalcemia has been reported to selectively induce
fate, believed to reverse cerebrovasospasm responsible
seizures originating in the occipital Iobes12 and to induce
for the eclamptic neurologic findings, may counter the
cerebral hyperten~ion.~
Eclampsia also typically affects
effects of hypercalcemia at a cellular level, lending support
the parieto-occipital region, causes cerebral hypertension,
to a calcium-mediated injury in eclampsia.
reversible occipital ischemia and seizures. There is evi-

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