Vagal stimulation in a patient with intractable hiccups

The hiccup refl ex arc can be categorised as having afferent and efferent limbs and a central connection. The afferent limb is composed of the vagus and phrenic nerves, and the lower sympathetic (T6-12) segments. The efferent pathway is constituted by the phrenic nerve(C3-5) innervating the diaphragm, plexal branches to the scalene muscles(C5-7), recurrent laryngeal nerve to the glottis and the intercostal nerves(T1-11) innervating the intercostal muscles [2,3]. The hiccup central connection is believed to be spinal cord segments rostral to medulla oblongata(C3-5) in the reticular formation in the middle and dorsolateral segment, connecting to the hiccup rhythm centre in the Pre-Botzinger complex, nucleus ambiguous, lateral reticular nucleus, hypothalamus and mesial temporal lobes [2-5]. Gama-Aminobutyric Acid (GABA) and dopamine act as neurotransmitters for this refl ex. Abstract


Introduction
Hiccup is a widely experienced and less understood phenomenon. Although much is known about the afferent and efferent limbs of the hiccup refl ex pathway, no defi nitive consensus exists on the hiccup centre generating this refl ex.
Even the word ''hiccup'' is an onomatopoeic for the sound the refl ex arc produces [1].
The hiccup refl ex arc can be categorised as having afferent and efferent limbs and a central connection. The afferent limb is composed of the vagus and phrenic nerves, and the lower sympathetic (T6-12) segments. The efferent pathway is constituted by the phrenic nerve(C3-5) innervating the diaphragm, plexal branches to the scalene muscles(C5-7), recurrent laryngeal nerve to the glottis and the intercostal nerves(T1-11) innervating the intercostal muscles [2,3].
The hiccup central connection is believed to be spinal cord segments rostral to medulla oblongata(C3-5) in the reticular formation in the middle and dorsolateral segment, connecting It is speculated that the hiccup centre and the respiratory centre although separate may interact with one another through the various neuronal connections [2,5].
When the hiccup refl ex is triggered there is synchronous contraction of the inspiratory thoracic muscles and the diaphragm. This is followed, in 35 milliseconds, by an abrupt glottal closure producing the typical ''hicc'' [6].
There is no conclusive knowledge on how this refl ex is triggered but a safe idea would be that any mechanism which irritates or damages the components of the refl ex arc, the central nuclei, the vagus, phrenic or other nerves of the autonomic system can trigger a hiccup. Of these the vagus is particularly important. The ''wanderer'' has such immense distribution throughout the body that the refl ex can be triggered by any number of odd reasons such as irritation of the ear drum, rapid change in body temperature, over distension of stomach, irritation of the respiratory tractor stroking of hair [7,8]. As such most initial remedies seem to centre on over stimulating the vagus nerve [9,10]. In cases of known underlying pathology treatment of the causative factor may help relieve the symptoms [11]. Table 1  a cause of as well as a consequence of hiccups [1]. Although GERD can induce hiccups via the irritation of the vagus nerve, long standing hiccups in themselves can cause reduction in the oesophageal motility as well as lowering of oesophagealgastric sphincter pressure thus favouring GERD [1,6].
Hiccups are classifi ed as temporary(<48 hours), persistent(48 hours-1 month) or intractable(>1 month), depending on their duration [3]. Intractable hiccups may cause debilitating problems such as insomnia, anorexia, fatigue, exhaustion, weight loss, depression, opening of surgical wounds, development of hernia and haemorrhoids, inability to undergo imaging such as MRI and even death. In such cases active management is required. Numerous medical and alternative therapies are available for the treatment of hiccups.

Case report
An 85 year old gentleman with a 9 year history of intractable hiccups came to us after numerous unsuccessful traditional medical and alternative treatments.   We therefore document partial success with the surgical placement of vagus nerve stimulator for the treatment of intractable hiccups at our centre with short term results. As seen with epilepsy, VNS tends to continue to improve prognosis up to 1 to 1.5 years. We will continue to monitor the patient and present a follow up report with long term results.

Discussion
Although temporary hiccups are a benign occurrence having no signifi cant impact on the life of a person but intractable hiccups are a serious and debilitating pathology and often lead to dire consequences [1][2][3]7]. The world record of longest hiccups is 69 years with notable people such as Pope Pius XII dying from the ailment [13]. Therefore symptomatic intractable hiccups warrant medical and surgical treatment [1].
The vagus nerve forms a signifi cant component of the hiccup refl ex arc and can explain several odd triggers as well as the basis for most initial remedies [4,9,10]. In fact hiccups most frequently occur during inspiration when lung infl ation impedes vagal afferents known to suppress hiccups [6]. The vagus nerve, also referred to as the ''wandering'' nerve or the ''vagabond'' nerve, greatly innervates multiple organs of the body and forms a part of several bodily refl exes [4,7,10]. Its stimulation has demonstrated varied functional outcomes the exact mechanism of most of which are not clearly understood [7]. VNS is an acknowledged treatment for epilepsy and depression [2].
Medical therapy for intractable hiccups comprises of GABA-derivatives, baclofen, dopaminergic antagonists and anticonvulsants. Non-traditional treatments such as acupuncture, massages and hypnosis are also widely used. Non-pharmacological options such as phrenic nerve blocking, crushing and pacing, percutaneous phrenic nerve stimulation and cervical epidural block have shown limited success due to the occasional presence of an accessory phrenic nerve as well as the bilateral diaphragmatic contraction aetiology of centrally originated hiccups [2,3,7,13].
Recently surgical placement of vagus nerve stimulators have been undertaken for chronic hiccups with varying degrees of success [2,5,7,10]. We report a case of intractable hiccups secondary to pneumonia, treated with VNS placement at our centre with short term results demonstrating partial success. Since the thorax is of immense anatomical importance in the hiccup refl ex, it is reasonable to consider that infections of the chest can lead to hiccups [1]. Seeing as no validated questionnaires have been formulated to document the intensity of hiccups [1], a 10-point patient subjective scale was employed.
Very little research is available on the cure of hiccups and even the pathogenesis of hiccups is less understood. Due to the lack of a physiological relevance in adults and the observation of hiccups in foetuses along with the effi cacy of baclofen in arresting gill-ventilation in tadpoles, it is speculated that hiccup is a phylogenetical refl ex [2,4,6,13]. Future research will help us better understand this phenomenon and its treatment.