Rationale:
Singultus, colloquially known as hiccups, is characterized by paroxysmal diaphragmatic contractions that produce a reflexive sound. This is mediated by a reflex arc with afferent fibers (i.e., vagus, phrenic, and T6-T12 sympathetic chain innervation) signaling to a central nervous center followed by efferent fibers (i.e., phrenic, recurrent laryngeal, and partial cervical-brachial plexus innervation) activating involved muscles.
2 Hiccups are often idiopathic and self-limiting, but when they persist, consideration of other potential etiologies (e.g., CNS injuries, drug effect, etc.) is necessary.
1,2 Hiccups become intractable if they do not remit for at least 30 days and refractory if they are resistant to conventional treatments.
1 There are case reports of vagus nerve stimulator (VNS) therapy successfully treating refractory cases.
1,2 Here we report the opposite: a case of iatrogenic and paradoxical singultus caused by VNS treatment.
Methods:
Informed consent was obtained. Chart review was conducted.
Results:
A 24 year-old male with Lennox-Gastaut Syndrome developed intractable singultus after undergoing VNS replacement. The original model (LivaNova Aspire M105) was implanted 8.5 years prior to the current evaluation, was programmed to rapid cycling with high output current (Table 1), and was well-tolerated. Two years prior to the current evaluation, the generator was replaced (SenTiva M1000) with identical programming. Mother subsequently reported new onset hiccups, which became incredibly disruptive, occurring throughout the day and even interrupting sleep. Thorazine was ineffective and was discontinued. In an attempt to suppress the hiccups, he resorted to drinking over 20 water bottles per day, causing urinary incontinence and emesis.
He was admitted to our hospital for evaluation. MRI brain did not reveal acute or contributing abnormalities. VNS was turned off, after which hiccups immediately ceased. Video-EEG monitoring captured stereotypic seizures, but no seizures causing hiccups. Prior to discharge, the VNS was turned back on at lower settings (Table 1), which after a short observation did not cause hiccups. He was seen four months later in clinic with continued hiccup remission, except with self-limited recurrence from VNS magnet use. An attempt to increase on-time resulted in hiccup recurrence and was reverted back the next day (Table 1).
Conclusions:
To our knowledge this is the first reported case of VNS-induced singultus. While the precise cause remains unclear, we suspect it may be due to aberrant signaling within the reflex arc provoked or caused by VNS stimulation, and in this case, could be related to technical differences between generator models. This case raises awareness to a rare, novel, and paradoxical complication of VNS therapy.
References:
1 Cole JA, Plewa MC. Singultus. In: StatPearls. Treasure Island (FL): StatPearls Publishing; August 7, 2022.
2 Tariq K, Das JM, Monaghan S, Miserocchi A, McEvoy A. A case report of Vagus nerve stimulation for intractable hiccups. Int J Surg Case Rep. 2021;78:219-222. doi:10.1016/j.ijscr.2020.12.023
Funding:
No funding disclosures.