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Case Report
Persistent hiccups after acute supratentorial stroke:
Report of seven cases and review of literature
Imarhiagbe F. Aiwansoba, Okoh B. Ewere, Ugiagbe R. Ashinedu1, Okaka E. Ibiene2
Departments of Medicine, Neurology Unit, 1Gastroenterology Unit, 2Nephrology Unit, UBTH, Benin City, Nigeria
ABSTRACT
Persistent hiccups are hiccups that last for at least 48 h, and may occur following a legion of causes including
strokes. They have been described following infarctive and hemorrhagic strokes. Hiccup is a respiratory
reflex action that occurs following the sudden contraction of the diaphragmatic and intercostals muscles with
closure of the glottis; and putatively believed to be a form of myoclonus (very brief repeated contractions of
striated muscles) that occurs from irritation of the medullary mediated reflex arc that has supratentorial inputs.
This underpins the association of hiccups with suprabulbar lesions like strokes, apparently following repeated
excitatory inputs from the higher centers. Hiccups are ordinarily self-limiting, but persistent hiccups are advisedly
treated with pharmacologic agents, of which baclofen, a GABA B agonist muscle relaxant has proven to be
remarkably efficient. It is believed that the action of baclofen interrupts the hiccup reflex arc. Nonpharmacologic
remedies like vagus nerve stimulation have also been found to be effective and may be complementary. This
case series highlights the use of baclofen in persistent hiccups following supratentorial infarcts.
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DOI:
10.4103/0331-3131.133101
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Key words: Acute, baclofen, hiccup, persistent, stroke
INTRODUCTION
H
iccup or singultus derives its name from the “hic”
sound made from the contraction of the diaphragm
and intercostal muscles followed by a closed glottis, and
is a respiratory reflex action.[1,2] Singultus has a Latin
provenance, from “singult,” meaning catching one’s
breath while sobbing.[1] Its exact role is unknown and
usually it is innocuous when brief but can however
become a source of concern and increased morbidity
when it is persistent or intractable. It is classified as
acute if it occurs for less than 48 h, persistent if it lasts
up to 48 h or more, and intractable if it lasts up to 2
months.[1,3] The causes of hiccup are many and include
electrolyte derangement, nutritional deficiencies,
gastrointestinal disorders and instrumentation,
cardiovascular disorders, renal impairment, central
nervous system (CNS) disorders and drugs; however,
the cause may be unknown.[3-6] It is known that most
cases of pathological hiccups are due to either irritation
Corresponding Author: Dr. Frank A. Imarhiagbe,
Department of Medicine, Neurology Unit, University of Benin
Teaching Hospital (UBTH), Benin City, Nigeria.
E-mail: [email protected]
Annals of Nigerian Medicine / Jul-Dec 2013 / Vol 7 | Issue 2
of peripheral or central nervous system component of
the hiccup reflex arc, a reflex arc that is as yet poorly
defined.[1,2] The hiccup reflex arc has an afferent limb
made up of the phrenic, vagus and sympathetic chain;
a modulating center that is putatively thought to be
located between the medulla and the cervical spine,
with central processing that is believed to be mediated
by neurotransmitters like GABA and dopamine; and an
efferent limb mediated through the phrenic and other
accessory nerves to the inspiratory muscles.[2,6]
Hiccup may follow several CNS disorders, from strokes
to inflammatory to neoplastic conditions, or as side
effects of some CNS acting drugs.[1] The association
of hiccup with CNS disorder derives in part from the
fact that hiccup is seen as a form of myoclonus and
the belief that there exist a brainstem neural pathway
with supratentorial inputs for hiccup.[4,7,8] Majority of
the reports of hiccup following CNS disorders have
been linked with medullary lesions, which suggest the
presence of a hiccup center in the medulla.[9-11] It bears
reiteration that persistent hiccups can be a source of
increased morbidity after stroke and should advisedly
be treated as early as possible.
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Imarhiagbe, et al.: Persistent hiccups after acute supratentorial stroke
Persistent hiccups after stroke are not so rare.[5] In this
case series, we report seven cases of persistent hiccups
after acute supratentorial stroke in a stroke unit in SubSaharan Africa that responded well to baclofen, a GABA
B agonist muscle relaxant.
CASE REPORTS
Case 1 [Figure 1]
A 64-year-old university lecturer, male, right handed,
with acute right frontal infarct; admission CNS score of
9 (moderately severe stroke); admission blood pressure
of 200/100 mmHg; admission serum creatinine of
114.9 μmol/l and blood sugar of 5.9 mmol/l and was
managed as per the stroke unit protocol for acute
stroke care. He did well but was however noticed
to have persistent hiccups after 72 h of admission
without nasogastric tube or percutaneous endoscopic
gastrostomy (PEG) tube in place or oral feeding. He
was initially commenced on 5 mg of baclofen, which
was increased later to 10 mg via nasogastric tube after
24 h of onset of hiccups and symptoms abated and
resolved within 48 h of commencement of baclofen and
he was discharged to outpatient clinic with a modified
Rankin score of 2 (disabled but independent) after 15
days on admission.
Figure 1: Cranial computed tomography, showing right frontal infarct
Case 2 [Figure 2]
An 81-year-old retiree, male, right handed, with
acute right parietal infarct; admission CNS score of 9
(moderately severe stroke) and admission blood pressure
of 130/90 mmHg; serum creatinine of 70.2 μmol/l;
blood sugar of 4.9 mmol/l with electrolytes and urea
being unremarkable. He was managed as per the unit
protocol for acute stroke care and did well. He was
however noticed to have persistent hiccups after 6 days
on admission without nasogastric or PEG tube or oral
feeding. He was commenced on 10 mg of baclofen via
nasogastric tube after 24 h of onset of hiccups and
symptoms resolved within 48 h. He was discharged
home with a modified Rankin score of 2 (disabled but
independent) after 10 days on admission.
Figure 2: Cranial computed tomography, showing right parietal infarct
Case 3 [Figure 3]
A 54-year-old polytechnic lecturer, male, right handed,
with left temporooccipital infarct and admission CNS
score of 6.5 (moderately severe stroke); admission
serum creatinine of 44.2 μmol/l and blood sugar of
7.6 mmol/l. He had normal urea and electrolytes and
admission blood pressure of 170/100 mmHg. He had
persistent hiccups after 25 days on admission with
a nasogastric tube in place. He responded to 10 mg
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Figure 3: Cranial computed tomography, showing left temporocipital infarct
baclofen after 4 days with resolution of hiccups. He
was discharged with a modified Rankin score of 4
(severely disabled and could only stand with support)
after 48 days on admission.
Annals of Nigerian Medicine / Jul-Dec 2013 / Vol 7 | Issue 2
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Imarhiagbe, et al.: Persistent hiccups after acute supratentorial stroke
Case 4 [Figure 4]
A 69-year-old retiree, male, right handed, with left
parietal infarct, admission CNS score of 10 (consistent
with mild stroke) and blood sugar of 7.8 mmol/l;
admission blood pressure of 110/60 mmHg, serum
creatinine of 79.6 μmol/l and electrolytes and urea
within the normal limits. He was managed as per the
stroke unit protocol for acute stroke and was noticed
to have persistent hiccups after 12 days on admission.
He did well and was commenced on 10 mg baclofen
per oral after 48 h of onset of hiccups and symptoms
resolved after 72 h. He was discharged after 21 days
with a modified Rankin score of 1 (near full recovery,
only has symptoms without any disability).
Figure 4: Cranial computed tomography, showing left parietal infarct
Case 5 [Figure 5]
A 55-year-old civil servant, male, right handed, with
left parietofrontal infarct; CNS score of 6.5 (moderately
severe stroke) and admission blood pressure of
180/100 mmHg; serum creatinine of 79.6 μmol/l and
blood sugar of 6.2 mmol/l. He was noticed to have
persistent hiccups after 21 days on admission and
electrolytes and urea were unremarkable. He was
initially offered 10 mg of baclofen per oral which was
increased to 15 mg after 48 h and symptoms abated and
eventually resolved within 72 h of commencement of
the drug. He received treatment as per the stroke unit’s
protocol for acute stroke care and was discharged after
38 days on admission with a modified Rankin score
of 4 (severely disabled and could only stand with
support) after 48 days on admission.
Figure 5: Cranial computed tomography, showing left parietofrontal infarct
Case 6 [Figure 6]
A 75-year-old retiree, male, right handed, with right
parietofrontal infarct and admission CNS score of
4 (severe stroke); admission blood pressure of
170/90 mmHg and admission blood sugar of 4.6 mmol/l.
Serum creatinine of 114.9 μmol/l and essentially normal
electrolytes and urea. He had persistent hiccups after
16 days on admission and was managed as per the unit’s
protocol for acute stroke care and responded well to
15 mg of baclofen per oral with resolution of symptoms
after 72 h. He however succumbed after 24 days on
admission.
Case 7 [Figure 7]
An 86-year-old village clan head, male, right handed,
with left frontal infarct and admission CNS of 10 (mild
stroke) and blood pressure of 130/70 mmHg. Admission
blood sugar and serum creatinine were 7.7 mmol/l
and 106.1 μmol/l respectively. Electrolytes and urea
were essentially normal and he was managed as per
Annals of Nigerian Medicine / Jul-Dec 2013 / Vol 7 | Issue 2
Figure 6: T2 magnetic resonance imaging, showing right frontoparietal infarct
the stroke unit’s protocol. He complained of persistent
hiccups after 5 days on admission without nasogastric
or PEG tubes in place, hiccups abated with 10 mg of
baclofen per oral and resolved completely after 4 days
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Imarhiagbe, et al.: Persistent hiccups after acute supratentorial stroke
where other pharmacologic remedies failed.[16,17] This
makes a case for the use of the drug in preference
to others such as metoclopramide, chlorpromazine,
promethazine which are all neuroleptics with the
potential effect of lowering the seizure threshold in
postacute stroke patients.[3,17-20] Other options include
gabapentin, cisapride and proton pump inhibitors
and nonpharmacologic procedures like vagus nerve
stimulation.[21,22]
CONCLUSION
Figure 7: Cranial computed tomography, showing left frontoparietal infarct
of commencement of the drug and was discharged to
the outpatient clinic after 1 week on admission with a
Rankin score of 2 (disabled but independent).
DISCUSSION
The age range of the subjects in this report is consistent
with related studies on acute stroke and it is noteworthy
that all the subjects were males.[12] Though we are not
aware of any previous report of the influence of gender
on hiccup after stroke, an earlier study reported a male
preponderance in hiccups in subjects without stroke.[13]
Remarkably, only infarcts were reported on cranial
computed tomography. This may be partly explained by
the irritative effect of ischemic injury on supra bulbar
centers connected with the lower brain stem areas
involved in the control of hiccup.[8] Hiccups have also
been described after hemorrhagic stroke as has been
after infarctive strokes.[14]
Admission Canadian Neurological Scale score, a
measure of the severity of acute neurological injury
after a stroke may partly explain why 4 out of the
7 patients survived with modified Rankin score of 2
and below, which is consistent with good physical
functional ability after stroke. [15] Out of the other
three patients, two had poor functional recovery
at discharge and one succumbed albeit after the
resolution of hiccups. Of note also is that the response
to baclofen, a GABA B agonist muscle relaxant, was
generally good without any untoward side effects
reported. It is believed that the reduction of dopamine
release by GABA B receptor stimulation is what
interrupts the reflex arc and in one large series on
intractable hiccups, it successfully aborted hiccups
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We conclude that though hiccup is not life-threatening
for the most part, persistent hiccups can increase
morbidity after acute stroke and prompt use of
oral baclofen, in addition to treating any identified
underlying cause(s), is advised.[2,3,20]
ACKNOWLEDGMENTS
We acknowledge doctors and support staff of the stroke unit
and intensive care unit at the University of Benin Teaching
Hospital, Benin City Nigeria.
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Cite this article as: Aiwansoba IF, Ewere OB, Ashinedu UR, Ibiene OE.
Persistent hiccups after acute supratentorial stroke: Report of seven cases
and review of literature. Ann Nigerian Med 2013;7:75-9.
Source of Support: Nil. Conflict of Interest: None declared.
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