Sánchez-Larsen et al. BMC Neurology (2016) 16:135
DOI 10.1186/s12883-016-0660-x

CASE REPORT

Open Access

Cerebral vasospasm and wernicke
encephalopathy secondary to adult cyclic
vomiting syndrome: the role of magnesium
Álvaro Sánchez-Larsen1* , Tomás Segura1, Susana García-Muñozguren2, Javier Peinado-Ródenas3,
Joaquín Zamarro4 and Francisco Hernández-Fernández1,5

Abstract
Background: Magnesium has a regulatory role in the excitability of cell membranes, and is also a cofactor in the
phosphorylation of thiamine. Hypomagnesemia has been associated with coronary vasospasm, but its role in
cerebrovascular pathology is controversial, and cerebral vasospasm exclusively attributable to hypomagnesemia has
not been reported in humans.
Case presentation: We report the case of a 51-year-old man in whom uncontrollable vomiting, treatment with
omeprazole and thiazide, and renal impairment lead to a severe hypomagnesemia (magnesium below the level of
detection in blood tests), which secondarily caused Wernicke’s encephalopathy and vasospasm in multiple cerebral
arteries (seen with cerebral angiography and CT angiography) that presented with a complete right hemisphere
neurological deficit. These disturbances completely resolved when magnesium levels were normalized and
subsequent neuroimaging tests confirmed the resolution of angiographic changes.
Conclusion: Our case suggests that hypomagnesemia should be considered in the differential diagnosis of patients
with neurological symptoms and predisposing causes.
Keywords: Hypomagnesemia, Wernicke encephalopathy, Cerebral vasospasm, Cyclic vomiting syndrome, Case report

Background
Magnesium is the most abundant intracellular divalent
cation and the fourth most abundant element in the
body. The majority of this mineral is localized in the
bones and soft tissues, only 1 % resides in the extracellular
fluids [1]. Magnesium balance is maintained by means of
intestinal absorption in the small bowel, mostly in the
ileum and distal part of jejunum, and renal excretion. The
kidneys are crucial in magnesium homeostasis. 70 % of
the magnesium filtered is reabsorbed in the thick ascending limb of the loop of Henle. It is estimated that an adult
needs an intake of 255–350 mg daily [1]. Conditions that
can lead to hypomagnesemia include alcoholism, diabetes,
malabsorption (Crohn’s disease, ulcerative colitis, coeliac
* Correspondence: aa.sanchezlarsen@gmail.com
1
Department of Neurology, Complejo Hospitalario Universitario de Albacete,
Albacete, Spain
Full list of author information is available at the end of the article

disease, short bowel syndrome), gastrointestinal loses (biliary or intestinal fistula, large-volume diarrhea or vomiting)
endocrine causes (hyperaldosteronism, hyperparathyroidism, syndrome of inappropriate antidiuretic hormone secretion, hypercalcemia, hypercalciuria), renal disease (renal
failure, dialysis, intrinsic tubular disorders) and medication
use (diuretics, proton pump inhibitors, antibiotics, chemotherapeutic agents) [1].
The principal function of magnesium in the human
body is structural, mainly in bones and teeth. However,
according to its ionic characteristics, it also plays a role
in the regulation of the excitability of neuromuscular
membranes. Magnesium works as a cofactor in many
enzymatic reactions such as ATP kinase reactions or the
activation of thiamine by its phosphorylation to thiamine
pyrophosphate [1, 2]. Magnesium is also an antagonist
of the N-methyl-d-aspartate (NMDA) receptor [1, 3],
and has direct vasodilatory effects due to various mechanisms. Hypomagnesemia is thought to lead to an

© 2016 The Author(s). Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0
International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and
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(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Sánchez-Larsen et al. BMC Neurology (2016) 16:135

increase in vascular smooth muscle tone and reactivity,
its association with acute focal vasospasm in coronary
arteries has been known for decades [4], albeit cerebral
vasospasm exclusively attributable to hypomagnesemia
in humans has not been reported. We report a case of vasoconstriction in multiple cerebral arteries and Wernicke’s
encephalopathy (WE) secondary to hypomagnesemia.

Case presentation
A 51-year-old man, diagnosed with adjustment disorder
due to work problems, and hypertension without other
vascular risk factors, non-smoker, no alcohol or drug
consumption, treated with valsartan/hydrochlorothiazide
and omeprazole. He presented with intermittent episodes of incoercible vomiting over a three month period,
and was finally diagnosed with adult cyclic vomiting syndrome after an extensive study that ruled out organic
origin (normal blood tests, stool test, urea breath test,
abdominal CT scan and ultrasound, echoendoscopy with
biopsies). The patient was admitted to hospital for prerenal kidney failure after several weeks of uncontrollable
vomiting, up to 50 episodes per day. Physical examination
was unremarkable except for intermittent optokinetic nystagmus. Blood tests showed creatinine 4.12 mg/dL, urea
92 mg/dL, creatinine clearance 15 mL/min/S, albumin
4.6 g/dL, Na 142 mmol/L, K 3.3 mmol/L, Cl 90 mmol/L,

Page 2 of 5

Ca 7.6 mg/dL (normal 8.6–10.2), P 4 mg/dL (normal 2.6–
4.5). Intravenous hydration and metoclopramide were
started. 24 h later he presented with a sudden and
complete right-sided cerebral hemisphere deficit (National
Institute of Health Stroke Scale [NIHSS] score of 18),
without seizures, fever or other clinical features, and with
a blood pressure of 146/93 mmHg. Code Stroke was activated, ECG, brain CT scan and transcranial Doppler were
normal and intravenous thrombolysis was decided upon.
There was no improvement after 30 min, and a CT angiography was performed (Fig. 1a–b) showing subtle narrowing of the entire right circulation, and stenoses in
several branches of the right middle cerebral artery,
making it impossible to rule out a distal vessel occlusion.
Rescue therapy with mechanical thrombectomy was proposed, but cerebral angiography (Fig. 1c-d) showed several
segments with stenosis without occlusion in multiple arteries of the right carotid circulation, so no therapeutic
procedure was finally realized. There was no improvement
after 24 h, and the patient then developed a rapid progressive encephalopathy accompanied by visual hallucinations,
ataxia, multidirectional nystagmus and ophthalmoparesis,
symptoms in keeping with WE. Brain MRI was unremarkable (Fig. 1g-h, see also Additional files 1, 2, 3 and 4), with
no ischemic areas or other abnormalities. Further
complete blood tests were conducted, and magnesium

Fig. 1 Vasospasm in cerebral arteries secondary to hypomagnesemia. Coronal (a) and axial (b) CT angiography showing subtle focal changes in
the vascular lumen of the right carotid circulation (a, white arrows) and overall decrease of the vascularization in the territory of the right middle
cerebral artery (b, circled in white). Selective cerebral angiography injecting from the left internal carotid artery (c), without abnormalities, and
from the right internal carotid artery (d), showing overall decrease of the vascularization, focal narrowing (d, white arrows) and segmental
stenosis of several arteries (d, white box). CT angiography carried out 7 days after the previous one (e and f) showing complete resolution of the
vascular changes. Diffusion weighted imaging (DWI) (g) and fluid attenuation inversion recovery (FLAIR) (h) sequences of brain MRI showing no
relevant abnormalities

Sánchez-Larsen et al. BMC Neurology (2016) 16:135

levels were found to be below the level of detection
(<0.5 mg/dL, normal 1.5–2.5), mild hypocalcaemia
(6.6 mg/dL) and hypophosphatemia (1.9 mg/dL) were also
observed. Diuretics, omeprazole and dextrose were
stopped, intravenous ondansetron controlled the vomiting, and aggressive intravenous magnesium replacement,
saline and empirical thiamine were commenced, and the
patient was admitted to the intensive care unit to control
potential cardiac arrhythmias. Blood tests after 24 h
showed almost normal calcium levels (8.5 mg/dL) and a
mild hypomagnesemia persisting (1.3 mg/dL). In subsequent blood tests all ions were always in normal ranges.
No cardiac abnormalities were apparent, and following
analytical recovery the patient started to improve and
within 48 h the focal symptoms disappeared, and WE was
completely resolved within two weeks. CT angiography
carried out 7 days after the beginning of symptom onset
(Fig. 1e–f ) showed resolution of the arterial changes.
Subsequent studies excluded renal tubular diseases
(normal magnesium and other ions in 24–hour urine),
endocrine disorders (PTH and 25-hydroxy vitamin D
normal) and in successive neuroimaging controls no
new abnormalities were found. The patient remains
neurologically asymptomatic.

Conclusions
Acute hypomagnesemia can produce different symptoms
depending on the severity of the deficiency. Early signs
of hypomagnesemia are non-specific and include loss of
appetite, lethargy, nausea, vomiting, fatigue and weakness. The association with hypophosphatemia and hypocalcaemia is frequent. Subsequently, lower magnesium
levels can result in tremor, muscle cramps, tetany and
generalized seizures [1]. On the other hand, chronic
magnesium deficiency is not rare these days, however, it
usually remains asymptomatic. This condition has been
associated with anxiety, depression, other psychiatric
disorders and dementia [1]. Hypomagnesemia is a
known cause of Wernicke`s encephalopathy, and frequently these cases are refractory to treatment with
thiamine, as magnesium is a cofactor in thiamine phosphorylation, needed for its activation [2]. Our patient developed WE, without an associated Korsakoff syndrome
as he did not present with amnesia. These symptoms
were completely reversed after two weeks of supplementation with magnesium and thiamine.
As previously mentioned, magnesium plays a key role
in the regulation of the excitability of cell membranes. It
antagonizes the NMDA receptor [1, 3] and cell surface
and intracellular voltage-gated calcium channels [3, 5],
thereby impeding calcium entry to ischemic neurons,
which is crucial for the activation of cellular apoptotic
pathways. Due to these actions, magnesium has been
shown to be a neuroprotective agent in different models

Page 3 of 5

of cerebral ischemia, demonstrating improvement of
prognosis after a cardiac arrest [6], in pre-term infant
hypoxic-ischemic injury [7], during cardiac by-pass
surgery [8] and during carotid endarterectomy [9].
Nonetheless, recent trials that evaluated intravenous
magnesium versus placebo in acute stroke have shown
no benefit to this treatment, nor remarkable adverse
events [10, 11].
According to its cardiovascular functions, magnesium
deficiency has been linked to vascular risk factors such
as hypertension, atherosclerosis and diabetes, as well as
having a statistical association with greater risk of coronary heart disease, myocardial infarction, sudden cardiac
death and stroke [1]. This ion has direct vasodilatory
effects in the cerebral vasculature by antagonizing
endothelin-1, neuropeptide Y and angiotensin II, whilst
at the same time exerting a calcium antagonist effect on
vascular smooth muscle [3, 5]. Several trials reported its
benefit as a vasodilator agent improving symptomatic
vasospasm and delayed ischemia in aneurysmal subarachnoid hemorrhage (SAH) [12, 13], and for years it
was used routinely in the treatment of these problems.
However, recent trials evaluated the effect of intravenous
magnesium for aneurysmal SAH and showed no benefit
in any of their objectives [14, 15]. It is possible that prolonged delay of the administration of magnesium and its
limited passage through the blood–brain barrier after
intravenous supplementation [5, 16] have limited its potential benefit. Furthermore, hypomagnesemia has been
previously described as a cause of human coronary [4,
17] and retinal [18] vasospasm, but cerebral vasospasm
directly attributable to hypomagnesemia has previously
been proven only in animals models [19]. This may be
because cerebral circulation is less sensitive to variations
in magnesium concentrations due to the blood–brain
barrier, and mild or moderate hypomagnesemia may
have no effect on the cerebral vasculature. In the case
of our patient, massive vomiting, renal impairment and
previous treatment with omeprazole and thiazide lead
to a severe hypomagnesemia, which caused secondary
vasoconstriction in multiple cerebral arteries, in
addition to WE. These disturbances were resolved when
serum magnesium levels were normalized, which further confirms the cause-and-effect relationship. It is
also possible that adult cyclic vomiting syndrome,
which has been associated with autonomic vascular
changes [20, 21], could have played a role in the cerebral vasospasm of the patient, albeit previous studies
did not report any cerebrovascular event, so it is difficult to establish a clear association in this case. As to
why our patient developed cerebral vasospasm and not
vasospasm at other locations remains unknown. In the
same way, we cannot give a feasible explanation for why
these changes only occurred in the right hemisphere

Sánchez-Larsen et al. BMC Neurology (2016) 16:135

and not in both. Further studies in this area are needed
to confirm these hypotheses.
In conclusion, hypomagnesemia should be considered
in the differential diagnosis of patients with neurological
symptoms and predisposing causes for magnesium deficit. To the best of our knowledge, we have not found
any other reported cases of cerebral vasospasm attributable to hypomagnesemia in humans in the literature.
This may be an underdiagnosed condition which should
be considered because rapid detection and correction of
serum magnesium levels would completely resolve the
symptoms. Further studies are needed to confirm these
hypotheses.

Additional files
Additional file 1: MRI, axial T1 sequence of the pons, cerebellum and
temporal poles showing no abnormalities. (JPG 265 kb)
Additional file 2: MRI, axial T1 sequence of the pons, cerebellum and
temporal poles showing no abnormalities. (JPG 417 kb)
Additional file 3: MRI, axial T1 sequence of the midbrain, perisylvian
spaces and temporo-occipital regions showing no abnormalities.
(JPG 395 kb)
Additional file 4: MRI, axial T1 sequence of the basal ganglia showing
no abnormalities. (JPG 277 kb)
Abbreviations
NIHSS, National Institute of Health Stroke Scale; NMDA, N-methyl-d-aspartate;
SAH, subarachnoid hemorrhage; WE, Wernicke’s encephalopathy
Acknowledgements
The authors would like to thank the patient and his family for their
cooperation and consent in relation to this study. We also want to thank the
Research Committee of the Gerencia de Atención Integrada of Albacete for
the support given for the publication of this article.
Funding
None funding declared
Availability of data and materials
Data of the clinical history of the patient (discharge summary, blood tests
and radiological tests) will not be shared to maintain his anonymity.
However, these data are available for review by the by the Editor-in-Chief of
this journal.
Authors’ contributions
SGM, FHF, ASL interviewed, diagnosed and treated the patient. JZ, JPR
performed the radiological tests, evaluated the neuroimaging findings and
gave important clinical opinions. ASL drafted the manuscript. FHF, TS
participated in the design of the case report and helped to draft the
manuscript. All authors read and approved the final manuscript.
Competing interests
The authors declare that they have no competing interests.
Consent for publication
Written informed consent was obtained from the patient for publication of
this case report and any accompanying images. A copy of the written
consent is available for review by the Editor-in-Chief of this journal. The
publication of this manuscript was approved by the Clinical Research Ethics
Committee of the Complejo Hospitalario Universitario de Albacete.
Ethics approval and consent to participate
Not applicable

Page 4 of 5

Author details
Department of Neurology, Complejo Hospitalario Universitario de Albacete,
Albacete, Spain. 2Department of Neurology, Grupo Hospitales de Madrid,
Madrid, Spain. 3Department of Radiology, Complejo Hospitalario Universitario
de Albacete, Albacete, Spain. 4Unit of Interventional Neuroradiology,
Department of Radiology, Hospital Universitario Virgen de la Arrixaca, Murcia,
Spain. 5Unit of Interventional Neuroradiology, Department of Radiology,
Complejo Hospitalario Universitario de Albacete, Albacete, Spain.
1

Received: 29 April 2016 Accepted: 2 August 2016

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