Intractable hiccups as the harbinger of a diffuse pontine glioma

Abstract

Hiccups are experienced by people of all ages. While acute hiccups are benign and self-limited, persistent and intractable hiccups can sometimes signal a serious disease. We present a young previously healthy man who complained of only hiccups for 4 months and later developed a severe headache and projectile vomiting. His systemic examination was within normal limits. Brain imaging revealed a diffuse pontine glioma with mild hydrocephalus.

Background

Hiccups occur in people of all ages and can be a source of transient discomfort. Hiccups lasting for more than 48 hours should be investigated, as they can occasionally be the sole presentation of a serious pathology. Hiccups can result from stimulation of the reflex arc at any point; hence a wide variety of conditions can ultimately result in hiccups. The wide differentials can sometimes delay diagnosis and may lead to the development of complications in some patients. Here, we present a case of a young man who had hiccups for 4 months and was ultimately diagnosed with diffuse pontine glioma.

Case presentation

A young man in his early-30s came to emergency complaining of headache for 15 days which was diffuse, insidious in onset, gradually progressive, continuous, severe in intensity for the past 5 days, non-radiating and temporarily relieved on taking analgesics. It was associated with vomiting, around 2–3 episodes per day, which was projectile and associated with nausea. The headache was not associated with lacrimation, photophobia, phonophobia, blurring of vision, seizures, altered sensorium, trauma or weakness of any part of the body. There was no history of fever, cough, neck swelling and decreased hearing.

The patient was apparently well 4 months back when he developed hiccups which progressed from intermittent to continuous over a month. They were interfering with the patient’s sleep and eating as well. It was not associated with coughing, heartburn, difficulty in swallowing, weight loss, abdominal pain, stress, decreased vision, focal weakness or sensory loss. He could not identify any precipitating and relieving factors. He visited multiple doctors but with limited to no relief. His personal history was significant for tobacco intake. He had no significant history or medication history.

On arrival, he was conscious and oriented to time, place and person. Pulse rate was 78 /min, blood pressure 149/75 mm Hg, oxygen saturation 95% on room air, respiratory rate 18/min and random blood sugar was 93 mg/dL. His higher mental functions were intact, speech and gait were normal, and there was no facial asymmetry. All four limbs had a normal tone, a power of 5/5, intact sensations and normal 2+reflexes. Pupils were 3 mm, bilaterally equal and reacting to light. Plantar reflexes were bilaterally flexor. Cranial nerve examination was normal. The rest of the systemic examination was within normal limits.

Investigations

A non-contrast CT of the head revealed an ill-defined hyperdense lesion involving the midbrain and pons with surrounding perilesional oedema and blood attenuation contents within (figure 1). It was causing effacement of basal cisterns and fourth ventricle causing mild upstream hydrocephalus. There was mild dilatation of bilateral lateral ventricles and third ventricle with mild periventricular ooze (figure 2A, B).

Figure 1.

Non-contrast CT scan of the brain showing an ill-defined hyperdense lesion in the brainstem (pink arrow).

Figure 2.

(A) Non-contrast CT scan of the brain showing dilated lateral ventricles (yellow arrow) with periventricular ooze (green arrow). (B) Non-contrast CT scan of the brain showing dilated third ventricle (pink arrow).

Postoperatively a contrast enhanced MRI of the brain with time of flight angiogram was done, which was suggestive of diffuse infiltrating pontine mass with extensions—likely pontine glioma with internal bleed (figure 3).

Figure 3.

T2-weighted magnetic resonance image of sagittal section of the brain showing the diffuse infiltrating pontine mass (yellow arrow).

Treatment

The patient was admitted under neurosurgery, and an endoscopic third ventriculostomy was done. The patient was discharged on the eighth day and was planned for radiotherapy. The tumour and 1–2 cm of adjacent brain tissue was treated with 54 Gy over 30 fractions, with the total duration of radiotherapy being 6 weeks.

Outcome and follow-up

The patient’s hiccups began to resolve after the initiation of radiotherapy and after 1 month of radiotherapy, the patient’s hiccups had subsided considerably.

Discussion

People of all ages experience hiccups. The medical terminology for hiccups is singultus, which means ‘catching one’s breath while sobbing’. Hiccups are spontaneous myoclonic contractions of the diaphragm and sometimes the intercostal musculature, which leads to a rapid intake of air. This is interrupted by glottic closure within a few milliseconds, which produces the characteristic ‘hic’ sound. They seem to serve no physiological role in adults.^{1 2}

The reflex arc of hiccups was proposed by Bailey in 1943, which comprises afferent, central and efferent components. The afferent arm comprises the sensory component of the vagus, phrenic, the pharyngeal part of the glossopharyngeal nerve and sympathetic nerve fibres from the thoracic outflow T6–T12. The central component comprises the C3–C5 spinal cord segments, medulla oblongata, reticular formation and the hypothalamus. The efferent arm comprises the phrenic nerves, external intercostal nerves (T1–T11) and the scalenus anticus nerve. The recurrent laryngeal nerve is responsible for the closure of the glottis.³ Glottic closure serves as a crucial protective reflex in patients with tracheostomy.⁴ This reflex arc involves multiple neurotransmitters—GABA, dopamine, serotonin, glutamate, glycine, histamine, epinephrine and acetylcholine.⁵

Hiccups are classified based on duration into acute, persistent and intractable. An acute attack of hiccups subsides within 48 hours. Hiccups lasting more than 2 days are called ‘persistent hiccups’, and those lasting more than 1 month are called ‘intractable hiccups’.³ Intractable hiccups are more common in middle-aged men.⁶ However, psychogenic hiccups occur more commonly in women.⁵

Acute hiccups are benign and usually self-limited. They are usually caused by gastrointestinal pathologies like gastro-oesophageal reflux disease and hiatal hernia.⁷ The presence of persistent or intractable hiccups should prompt a detailed evaluation as they usually signify a serious medical pathology.⁸ They can also have an adverse impact on the quality of life as they may interfere with sleeping, eating, speaking and other social activities.

Any process stimulating any component of the reflex arc can result in hiccups. They may result from cardiovascular disorders, central nervous system disorders, ENT (ear, nose and throat) disorders, infectious disorders, gastrointestinal disorders, metabolic abnormalities, psychogenic disorders, surgery and drugs.⁹ Among the central nervous system itself, a myriad of conditions may result in intractable hiccups, such as cerebrovascular disease, brain tumours and Parkinson’s disease. A lesion in the medulla is the most common cause with the usual involvement of nucleus tractus solitarius and/or nucleus ambiguous.^{10 11} However, it is extremely rare for hiccups to be the sole presenting symptom of a serious neurological disease.²

The treatment of hiccups should be directed towards the treatment of the underlying cause wherever possible. Multiple physical and pharmacological therapies have been described for the treatment of hiccups, although there is insufficient good-quality evidence to formulate a treatment recommendation. Physical therapy includes nasopharyngeal stimulation, vagal stimulation and respiratory manoeuvres. Pharmacological therapy comprises baclofen, gabapentin, pregabalin, metoclopramide, domperidone, chlorpromazine, carbamazepine, valproate, phenytoin, nifedipine and amitriptyline. Certain alternate therapies like hypnosis and acupuncture have also been reported to be effective.³

Our patient only complained of hiccups for over 3 months and was ultimately diagnosed with diffuse pontine glioma. Although multiple case reports exist in the literature of mass lesions in the brain resulting in intractable hiccups, it is rare for a pontine tumour to solely present with hiccups. The pathophysiology of hiccups in this case is outlined in figure 4. Patients with persistent and intractable hiccups may occasionally present to the emergency owing to the resultant discomfort. It is crucial that these patients undergo a detailed evaluation as a timely diagnosis of underlying medical pathologies can help prevent further complications. Unfortunately, diagnosing the aetiology can be quite challenging considering the multiple aetiologies involved.

Figure 4.

The pathophysiology of hiccups in our patient (figure created by Dr Nagasubramanyam Vempalli).

Learning points.

• Hiccups are usually benign and self-limited. However, they may signal a serious medical condition when they persist beyond 48 hours.

• A detailed diagnostic work-up is warranted in every patient presenting with an intractable hiccup.

• Intracranial pathologies, especially tumours, must be considered when dealing with a patient with intractable hiccups.

Ethics statements

Patient consent for publication

Consent obtained from next of kin.