|Year : 2013 | Volume
| Issue : 2 | Page : 75-79
Persistent hiccups after acute supratentorial stroke: Report of seven cases and review of literature
Imarhiagbe F Aiwansoba1, Okoh B Ewere1, Ugiagbe R Ashinedu2, Okaka E Ibiene3
1 Department of Medicine, Neurology Unit, UBTH, Benin City, Nigeria
2 Department of Medicine, Gastroenterology Unit, UBTH, Benin City, Nigeria
3 Department of Medicine, Nephrology Unit, UBTH, Benin City, Nigeria
|Date of Web Publication||23-May-2014|
Imarhiagbe F Aiwansoba
Department of Medicine, Neurology Unit, University of Benin Teaching Hospital (UBTH), Benin City
Source of Support: None, Conflict of Interest: None
| 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.
Keywords: Acute, baclofen, hiccup, persistent, stroke
|How to cite this article:|
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
|How to cite this URL:|
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 [serial online] 2013 [cited 2020 Jul 6];7:75-9. Available from: http://www.anmjournal.com/text.asp?2013/7/2/75/133101
| Introduction|| |
Hiccup 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. , Singultus has a Latin provenance, from "singult," meaning catching one's breath while sobbing.  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. , 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. ,,, It is known that most cases of pathological hiccups are due to either irritation of peripheral or central nervous system component of the hiccup reflex arc, a reflex arc that is as yet poorly defined. , 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. ,
Hiccup may follow several CNS disorders, from strokes to inflammatory to neoplastic conditions, or as side effects of some CNS acting drugs.  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. ,, 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. ,, It bears reiteration that persistent hiccups can be a source of increased morbidity after stroke and should advisedly be treated as early as possible.
Persistent hiccups after stroke are not so rare.  In this case series, we report seven cases of persistent hiccups after acute supratentorial stroke in a stroke unit in Sub-Saharan 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.
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.
Case 3 [Figure 3]
|Figure 3: Cranial computed tomography, showing left temporocipital infarct|
Click here to view
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 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.
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).
Case 5 [Figure 5]
|Figure 5: Cranial computed tomography, showing left parietofrontal infarct|
Click here to view
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.
Case 6 [Figure 6]
|Figure 6: T2 magnetic resonance imaging, showing right frontoparietal infarct|
Click here to view
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]
|Figure 7: Cranial computed tomography, showing left frontoparietal infarct|
Click here to view
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 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 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.  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.  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.  Hiccups have also been described after hemorrhagic stroke as has been after infarctive strokes. 
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.  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 where other pharmacologic remedies failed. , 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. ,,,, Other options include gabapentin, cisapride and proton pump inhibitors and nonpharmacologic procedures like vagus nerve stimulation. ,
| Conclusion|| |
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. ,,
| 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.
| References|| |
|1.||Chang FY, Lu CL. Hiccup: Mystery, nature and treatment. J Neurogastroenterol Motil 2012;18:123-30. |
|2.||Fodstad H, Nilsson S. Intractable singultus: A diagnostic and therapeutic challenge. Br J Neurosurg 1993;7:255-60. |
|3.||Smith HS, Busracamwongs A. Management of hiccups in the palliative care population. Am J Hosp Palliat Care 2003;20:149-54. |
|4.||Lewis JH. Hiccups: Causes and cures. J Clin Gastroenterol 1985;7:539-52. |
|5.||Moretti R, Torre P, Antonello RM, Ukmar M, Cazzato G, Bava A. Gabapentin as a drug therapy of intractable hiccup because of vascular lesion: A three-year follow up. Neurologist 2004;10:102-6. |
|6.||Becker DE. Nausea, vomiting, and hiccups: A review of mechanisms and treatment. Anesth Prog 2010;57:150-6. |
|7.||al Deeb SM, Sharif H, al Moutaery K, Biary N. Intractable hiccup induced by brainstem lesion. J Neurol Sci 1991;103:144-50. |
|8.||Nathan MD, Leshner RT, Keller AP Jr. Intractable hiccups.(singultus). Laryngoscope 1980;90:1612-8. |
|9.||Mandalà M, Rufa A, Cerase A, Bracco S, Galluzzi P, Venturi C, et al. Lateral medullary ischemia presenting with persistent hiccups and vertigo. Int J Neurosci 2010;120:226-30. |
|10.||Park MH, Kim BJ, Koh SB, Park MK, Park KW, Lee DH. Lesional location of lateral medullary infarction presenting hiccups (singultus). J Neurol Neurosurg Psychiatry 2005;76:95-8. |
|11.||Ward BA, Smith RR. Hiccups and brainstem compression. J Neuroimaging 1994;4:164-5. |
|12.||Longo-Mbenza B, Lelo Tshinkwela M, Mbuilu Pukuta J. Rates and predictors of stroke-associated case fatality in black Central African patients. Cardiovasc J Afr 2008;19:72-6. |
|13.||Liaw CC, Wang CH, Chang HK, Liau CT, Yeh KY, Huang JS, et al. Gender discrepancy observed between chemotherapy-induced emesis and hiccups. Support Care Cancer 2001;9:435-41. |
|14.||Weisscher N, Vermeulen M, Roos YB, de Haan RJ. What should be defined as good outcome in stroke trials; a modified Rankin score of 0-1 or 0-2? J Neurol 2008;255:867-74. |
|15.||Kumral E, Acarer A. Primary medullary haemorrhage with intractable hiccup. J Neurol 1998;245:620-2. |
|16.||Kumar A, Dromerick AW. Intractable hiccups during stroke rehabilitation. Arch Phys Med Rehabil 1998;79:697-9. |
|17.||Mirijello A, Addolorato G, D'Angelo C, Ferrulli A, Vassallo G, Antonelli M, et al. Baclofen in the treatment of persistent hiccup: A case series. Int J Clin Pract 2013;67:918-21. |
|18.||Patial RK. Baclofen in the treatment of intractable hiccups. J Assoc Physicians India 2002;50:1312-3. |
|19.||Guelaud C, Similowski T, Bizec JL, Cabane J, Whitelaw WA, Derenne JP. Baclofen therapy for chronic hiccup. Eur Respir J 1995;8:235-7. |
|20.||Johnson BR, Kriel RL. Baclofen for chronic hiccups. Pediatr Neurol 1996;15:66-7. |
|21.||Petroianu G, Hein G, Petroianu A, Bergler W, Rüfer R. Idiopathic chronic hiccup: Combination therapy with cisapride, omeprazole, and baclofen. Clin Ther 1997;19:1031-8. |
|22.||Payne BR, Tiel RL, Payne MS, Fisch B. Vagus nerve stimulation for chronic intractable hiccups. Case report. J Neurosurg 2005;102:935-7. |
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7]