[Persistent hiccups after perforated cholecystitis]. / Vedvarende hikke etter perforert kolecystitt.

BACKGROUND: Persistent hiccups lasting more than 48 hours are rare and have numerous possible causes that require further investigation. CASE PRESENTATION: We present a man in his seventies who was admitted to hospital after 11 days of hiccups. The hiccups were preceded by abdominal pain that spontaneously receded after a few hours. At admission he had no abdominal pain during examination, but a CT scan later suggested that the cause was a perforated cholecystitis with an intra-abdominal abscess. The abscess was drained percutaneously and treated with antibiotics, and the hiccups stopped. INTERPRETATION: Persistent hiccups warrant thorough examination, and it is recommended to consider CT scans of the head and truncus, cerebral MRI scan and an upper GI endoscopy. Treating the underlying cause of hiccups is the ultimate target, while symptomatic treatment simultaneously is preferred.

[Chronic hiccups: diagnosis and treatment]. / Hoquet chronique : diagnostic et traitement.

Chronic hiccups, lasting more than 48 hours, are a medical condition that remains challenging in both diagnosis and treatment. They can be the sole symptom of a serious underlying disorder, and should therefore not be overlooked, although gastroesophageal reflux disease (GERD) constitutes their most prevalent cause. Chronic hiccups mandate a comprehensive etiological assessment. Treatment strategy may include physical, pharmacological and interventional approaches, as described in literature, particularly when direct causal treatment is unattainable.

Le hoquet chronique, de plus de 48 heures, est une entité dont la prise en charge est souvent méconnue. Il ne doit pas être négligé parce qu'il peut être le seul symptôme d'une maladie sous-jacente grave, même si le reflux gastro-œsophagien (RGO) en est la cause la plus fréquente. Face à un hoquet chronique, un bilan étiologique doit donc être effectué. Dans les cas où un traitement causal n'est pas envisageable, plusieurs possibilités de traitements physiques, médicamenteux et interventionnels sont décrites dans la littérature.

Intractable hiccups after VNS implantation: a case report.

BACKGROUND: Hiccups (medically termed, "singultus"), when intractable, can cause significant medical consequences such as aspiration, malnutrition, and depression, leading to poor quality of life. Several case reports have shown that vagus nerve stimulator (VNS) implantation can help treat central idiopathic intractable hiccups. However, we present a contrary case of a patient who developed intractable singultus following VNS placement for medically refractory epilepsy. CASE PRESENTATION: We report a 71-year-old male patient with drug-resistant epilepsy who underwent VNS implantation and developed intractable hiccups shortly thereafter. The hiccups were severe and persistent, such that the patient developed a Mallory-Weiss tear, which required intensive care, invasive intubation and mechanical ventilation, and a prolonged rehabilitation course. Despite multiple therapies including phrenic nerve block and Nissen fundoplication, the patient's hiccups persisted and only stopped once the VNS was permanently deactivated. CONCLUSIONS: Little is known about the incidence of hiccups after VNS implantation. We present one case of hiccups as a direct consequence of VNS implantation. The clinical impact of this report is significant given the relative unfamiliarity of hiccups as an adverse effect of VNS implantation. Neurologists and epileptologists, who present VNS implantation as a surgical option for seizure control to their patients, should be aware of the possibility of singultus development and its significant physical and emotional ramifications.

[Analysis of the clinical characteristics and misdiagnosis of area postrema syndrome manifesting as intractable nausea, vomiting, and hiccups in neuromyelitis optica spectrum disorders].

Objective: To investigate the misdiagnosis of area postrema syndrome (APS) manifesting as intractable nausea, vomiting and hiccups in neuromyelitis optic spectrum disease (NMOSD) and reduce the risk of misdiagnosis. Methods: We retrospectively analyzed data from NMOSD patients attending the Department of Neurology at the First Medical Center of PLA General Hospital between January 2019 and July 2021. SPSS25.0 was then used to analyze the manifestations, misdiagnosis, and mistreatment of APS. Results: A total of 207 patients with NMOSD were included, including 21 males and 186 females. The mean age of onset was 39±15 years (range: 5-72 years). The proportion of patients who were positive for serum aquaporin 4 antibody was 82.6% (171/207). In total, 35.7% (74/207) of the NMOSD patients experienced APS during the disease course; of these patients, 70.3% (52/74) had APS as the first symptom and 29.7% (22/74) had APS as a secondary symptom. The misdiagnosis rates for these conditions were 90.4% (47/52) and 50.0% (11/22), respectively. As the first symptom, 19.2% (10/52) of patients during APS presented only with intractable nausea, vomiting and hiccups; 80.8% (42/52) of patients experienced other neurological symptoms. The Departments of Gastroenterology and General Medicine were the departments that most frequently made the first diagnosis of APS, accounting for 54.1% and 17.6% of patients, respectively. The most common misdiagnoses related to diseases of the digestive system and the median duration of misdiagnosis was 37 days. Conclusions: APS is a common symptom of NMOSD and is associated with a high rate of misdiagnosis. Other concomitant symptoms often occur with APS. Gaining an increased awareness of this disease/syndrome, obtaining a detailed patient history, and performing physical examinations are essential if we are to reduce and avoid misdiagnosis.

Hiccups in patients with cancer: a multi-site, single-institution study of etiology, severity, complications, interventions, and outcomes.

BACKGROUND: To our knowledge, previous studies have not investigated hiccups in patients with cancer with detailed patient-level data with the goal of capturing a broad spectrum of hiccup symptomatology. METHODS: This multi-site, single institution study examined consecutive medical records to better understand hiccups in patients with cancer. RESULTS: A total of 320 patients are the focus of this report. The median age of patients when hiccups were first reported in the medical record was 63 years (range: 21, 97 years) with 284 (89%) men and 36 (11%) women. The most common diagnose was gastrointestinal cancer. Hiccups most frequently occurred daily, as seen in 194 patients (62%), and the most common duration was less than 1 week, as seen in 146 patients (47%). However, nine patients had had daily hiccups for greater than 6 weeks, and 5 had symptoms for years. Cited etiology was non-chemotherapy medications in 36 (11%) and cancer chemotherapy in 19 (6%). Complications occurred in approximately a third and included insomnia in 51 patients (16%); hospitalization or emergency department visit in 34 (11%); and musculoskeletal pain in 23 (7%). Baclofen was the single most prescribed agent for hiccup palliation, but 100 patients received more than one medication. Medical procedures, which included acupuncture, paracentesis, or phrenic nerve block, were performed in 5 patients. In 234 patients (73%), the medical record documented hiccup cessation. CONCLUSIONS: Hiccups appear to be highly problematic in a small subset of patients with cancer with no well-defined palliative approaches.

Autoimmune Glial Fibrillary Acidic Protein Astrocytopathy Presenting with Area Postrema Syndrome-Like Symptoms without Medulla Oblongata Lesions.

INTRODUCTION: Autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy is a recently described steroid-responsive meningoencephalomyelitis positive for cerebrospinal fluid (CSF) anti-GFAP antibody. Area postrema syndrome (APS) involves intractable hiccups, nausea, and vomiting, which is caused by medulla oblongata (MO) impairment. APS is a characteristic symptom of aquaporin-4 (AQP4) autoimmunity, and it helps to differentiate between AQP4 and GFAP autoimmunity. Conversely, although 6 cases of autoimmune GFAP astrocytopathy with APS and MO lesions have been reported, the association between GFAP autoimmunity and APS is unclear. We report the case of a patient with autoimmune GFAP astrocytopathy presenting with APS-like symptoms without MO lesions and discuss the mechanisms underlying the symptoms. METHODS: CSF anti-GFAP antibody was detected using cell-based assays and immunohistochemical assays. RESULTS: A 54-year-old Japanese man developed persistent hiccups, intermittent vomiting, fever, anorexia, and inattention. Brain magnetic resonance imaging (MRI) showed periventricular lesions with radial linear periventricular enhancement, suggesting autoimmune GFAP astrocytopathy. However, no obvious MO lesions were identified on thin-slice images. Spinal cord MRI revealed hazy lesions with patchy enhancement along the cervical and thoracic cord. CSF analysis demonstrated inflammation, with positive results for anti-GFAP antibodies. Anti-AQP4 antibodies in the serum and CSF were negative. Esophagogastroduodenoscopy revealed gastroparesis and gastroesophageal reflux disease, and vonoprazan, mosapride, and rikkunshito were effective only against persistent hiccups. Steroid therapy was initiated, allowing clinical and radiological improvements. Repeated MRIs demonstrated no obvious MO lesions. CONCLUSION: This report suggests that autoimmune GFAP astrocytopathy presents with APS-like symptoms without obvious MO lesions. The possible causes of hiccups were gastroparesis and cervical cord lesions. Gastroesophageal reflux disease was not considered a major cause of the hiccups. Intermittent vomiting appeared to be associated with gastroparesis, cervical cord lesions, and viral-like symptoms. Testing for anti-GFAP antibodies should be considered in patients with APS-like symptoms in the context of typical clinical-MRI features of autoimmune GFAP astrocytopathy.

Autoimmune glial fibrillary acidic protein astrocytopathy presented as isolated area postrema symdrome: a case report.

BACKGROUND: Area postrema syndrome (APS) as the isolated manifestation in autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy has been rarely reported. CASE PRESENTATION: A 61-year-old male patient presented with intractable hiccup. He was first admitted to the department of Gastroenterology because he had no symptoms other than hiccup. Then he was diagnosed with possible digestive system disease and started on treatment. 2 weeks later, his symptom didn't improve at all. After consultation, the patient was referred to our department. Cerebrospinal fluid (CSF) analysis revealed lymphocytes pleocytosis, elevated protein level. Cell-based assays demonstrated GFAP antibodies in blood and CSF. His symptom improved with steroid pulse therapy (methylprednisolone, 1 g for 5 days), followed by a gradual tapering of oral prednisolone. Three months after the initial presentation, he showed no relapses. CONCLUSIONS: We report atypical manifestation of autoimmune GFAP astrocytopathy which presented as APS, suggesting that autoimmune GFAP astrocytopathy should be added to the list of possible cause of APS.

Persistent hiccup as one of the initial symptoms of leucine-rich glioma-inactivated-1 encephalitis: a case report.

BACKGROUND: Anti-leucine-rich glioma-inactivated 1 (LGI1) encephalitis, an autoimmune disorder, is characterized by faciobrachial dystonic seizures, epilepsy, memory deficits and altered mental status while hiccup is not commonly found in patients. CASE PRESENTATION: A 62-year-old male was presented with slurred speech, abnormal gait, faciobrachial dystonic seizures and impaired cognition. Besides, the hiccup was one of the initial symptoms. His brain magnetic resonance images (MRI) revealed multiple lesions with left caudate nucleus, putamen, insula and left hippocampus involvement. Because a diagnosis of antibody-related limbic encephalitis was suspected, studies including an autoimmune profile were done by cell-based assays. After anti-LGI1 antibodies were detected in both cerebrospinal fluid and serology, pulse methylprednisolone and intravenous immunoglobulin were started and hence hiccups disappeared along with other symptoms. CONCLUSIONS: Clinicians should be aware that persistent hiccups might be one of the initial manifestations of LGI1 subtype of voltage-gated potassium channel complex antibody associated autoimmune encephalitis.

A randomized, double-blinded feasibility trial of educational materials for hiccups in chemotherapy-treated patients with cancer.

PURPOSE: Chemotherapy can cause hiccups but few randomized controlled trials have focused on hiccups. This trial examined the feasibility of such research. METHODS: This single-institution, multi-site trial used phone recruitment for patients: (1) 18 years or older, (2) able to speak/read English, (3) with a working e-mail address, (4) with hiccups 4 weeks prior to contact, and (5) with ongoing oxaliplatin or cisplatin chemotherapy. The primary outcome was feasibility. Patients were randomly assigned to one of two sets of educational materials, each of which discussed hiccups and palliative options. The experimental materials were almost identical to the standard materials but provided updated content based on the published medical literature. At 2 weeks, patients responded by phone to a 5-item verbally administered questionnaire. RESULTS: This trial achieved its primary endpoint of recruiting 20 eligible patients within 5 months; 50 patients were recruited in 3 months. Among the 40 patients who completed the follow-up questionnaire, no statistically significant differences between arms were observed in hiccup incidence since initial contact, time spent reviewing the educational materials, and the troubling nature of hiccups. Twenty-five patients tried palliative interventions (13 in the experimental arm and 12 in the standard arm), most commonly drinking water or holding one's breath. Eleven and 10 patients, respectively, described hiccup relief after such an intervention. CONCLUSIONS: Clinical trials for chemotherapy-induced hiccups are feasible and could address an unmet need.

[Hiccups, not always unremarkable]. / Les hoquets : pas toujours banals.

Hiccups are most often benign and of short duration. However, they may also be persistent (superior to 48h) or even refractory (superior to 1 month). In such cases, they markedly alter the quality of life and can lead to severe impairment of health. We here review hiccups pathophysiology, etiologies, work up and treatment. We suggest that hiccups should be considered as a non-epileptic myoclonic movement disorder.

Le hoquet est le plus souvent bénin et de courte durée, mais il peut aussi être persistant (sup�rieur a 48h), voire réfractaire (sup�rieur a 1 mois). Dans ces cas, il altère la qualité de vie et peut avoir des conséquences graves sur la santé. Nous en revoyons ici la physiopathologie, les étiologies, la mise au point diagnostique et les traitements. Nous concluons par une réflexion sur la nature du hoquet que nous considérons comme un mouvement anormal appartenant au groupe des myoclonies non épileptiques.

The action of aripiprazole and brexpiprazole at the receptor level in singultus.

The hiccup (Latin singultus) is an involuntary periodic contraction of the diaphragm followed by glottic closure, which can be a rare side effect of aripiprazole. In contrast to the structurally closely related aripiprazole, brexpiprazole was not associated with this particular adverse drug reaction. Having two very similar drugs that differ in their ability to induce hiccups represents a unique opportunity to gain insight into the receptors involved in the pathophysiology of the symptom and differences in clinical effects between aripiprazole and brexpiprazole. The overlap between maneuvers used to terminate paroxysmal supraventricular tachycardia and those employed to terminate bouts of hiccups suggests that activation of efferent vagal fibers can be therapeutic in both instances. Recent work seems to support a pivotal role for serotonin receptors in such vagal activation. It is unlikely that a unique receptor-drug interaction could explain the different effects of the examined drugs on hiccup. The different effect is most likely the consequence of several smaller effects at more than one receptor. Brexpiprazole is a highly affine (potent) α2C antagonist and, therefore, also an indirect 5-HT1A agonist. In contrast, aripiprazole is a partial 5-HT1A agonist (weak antagonist) and an HT3 antagonist. Activation of 5-HT1A receptors enhances vagal activity while HT3 blockade reduces it. Vagus nerve activation is therapeutic for hiccups. A definitive answer continues to be elusive.

A young woman with persistent nausea, vomiting and hiccups. / En ung kvinne med langvarig kvalme, oppkast og hikke.

BACKGROUND: Neuromyelitis optica is an inflammatory syndrome of the central nervous system, associated with anti-aquaporin-4 IgG antibodies. It is associated with severe neurological symptoms and risk of permanent neurological disability. The diagnosis can be established on the basis of clinical core characteristics of neuromyelitis optica, together with serological testing for anti-aquaporin-4 IgG antibodies and magnetic resonance imaging of the central nervous system. CASE PRESENTATION: We describe the case of a young woman presenting with obstipation, persistent nausea, vomiting and hiccups. The initial diagnostic workup confirmed obstipation, but did not find any underlying gastrointestinal pathology that could explain her persistent symptoms. Her condition deteriorated, she was unable to eat or drink without inducing vomiting, and eventually she received parenteral nutrition. Further diagnostic workup included magnetic resonance imaging of the brain, which revealed a T2-hyperintense lesion in the medulla oblongata, more specifically in the area postrema. Neurological and neuroradiological assessment led to a tentative clinical diagnosis of neuromyelitis optica spectrum disorder with a well-described, but rare, presentation: the area postrema syndrome. The diagnosis was confirmed by serological testing for anti-aquaporin-4 IgG antibodies. She was successfully treated with methylprednisolone with complete remission of symptoms. Patients with neuromyelitis optica spectrum disorders frequently experience relapses of the disease if untreated, and she was therefore treated with rituximab to prevent future relapses. INTERPRETATION: This case is a reminder that common gastrointestinal symptoms may be caused by diseases of the central nervous system.

Intradermal injection for hiccup therapy in the Emergency Department.

Hiccup is a condition caused by involuntary contraction of inspiratory muscles, especially the diaphragm. Although it is generally considered as a physiological. response, if hiccup persists for a long time, it can lead to many undesirable conditions such as depression, weight loss, insomnia, and fatigue. A 35-year-old male patient was admitted to our emergency department with hiccup lasting for 15 h. He had a history of several hiccup attacks. Classical non-pharmacological and pharmacological therapies were used to treat the condition without any response. As an alternative method, an intradermal injection was applied. A mixture of thiocolchicoside and lidocaine was administered intradermally to a depth of 1-3 mm at the epigastric region and adjacent to the sternocleidomastoid muscle. The patient's hiccup ended after the intradermal injection procedure. During 48 h of follow-up the hiccup attack did not develop again. No complications related to the process were detected. This is the first case in the literature demonstrating the use of intradermal injection to terminate hiccups. The intradermal injection approach can be administered in cases of hiccups that do not respond to medical treatment.

Persistent hiccups as an atypical presenting complaint of COVID-19.

Hiccups (singultus) are reflex inspiratory movements that involve the swallowing reflex arc and can be classified as acute (<48 h) or persistent (>48 h). A 62-year-old man with no history of malignancy or pulmonary disease presented to the Emergency Department with a four-day history of persistent hiccups. Other than episodic hiccupping, his physical examination was otherwise unremarkable. An abnormal chest X-ray led to a CT scan of the chest with IV contrast, which demonstrated regional, peripheral groundglass opacities of the upper lobes with small focal groundglass opacities scattered throughout the lungs. He was tested for COVID-19 per admission protocol, started on hydroxychloroquine, his hiccups improved, and he was discharged to home after 3 days. An emergency medicine physician should keep COVID-19 on the differential and be vigilant of exposure in atypical presentations.

Hiccups as the Presenting Manifestation of Cardiac Tamponade: A Case Report.

BACKGROUND: Cardiac tamponade is a life-threatening disease with a high mortality rate. Its clinical manifestations depend on the length of time over which pericardial effusion accumulates. Among those, hiccups are rarely reported. CASE REPORT: We present a 48-year-old man who came in with a chief complaint of persistent hiccups and later had hypotension and dyspnea at the emergency department. Electrocardiogram revealed diffuse ST elevation with mildly elevated cardiac enzymes. Echocardiography showed massive pericardial effusion, implying cardiac tamponade. Catheter pericardiocentesis was performed and massive pericardial effusion was drained. Hiccups subsided after the procedure and the patient recovered uneventfully. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: To the best of our knowledge, this is the first case of cardiac tamponade with the presenting manifestation of persistent hiccups. Emergency physicians should stay vigilant when approaching those patients with unexplainable prolonged hiccups.

Area postrema syndrome: A short history of a pearl in demyelinating diseases.

In this topical review, we discuss the history of the area postrema syndrome, with special attention given to early studies aimed at identifying the area postrema and its function, possible early cases of the syndrome and its current relevance in neuroimmunology and demyelinating diseases. In 1896, Retzius named a structure in the posterior medulla oblongata as the area postrema. The work of Borison in the middle of the 20th century led to the elucidation of its function as a "vomiting center." The historical medical literature is filled with excellent examples that could be described as "area postrema syndrome." While severe and bilateral optic neuritis and transverse myelitis still constitute the classic components of neuromyelitis optica spectrum disorder (NMOSD), intractable vomiting and hiccups due to area postrema involvement is now recognized as essentially pathognomonic, indeed a shiny pearl in neuroimmunology and demyelinating diseases.

Perspectives on the Medical, Quality of Life, and Economic Consequences of Hiccups.

PURPOSE OF REVIEW: Singultus or hiccups (HU) is a common, usually temporary, event. Its potentially serious consequences are often overlooked. This review explores published evidence describing HU burden (clinical, economic, and quality of life [QoL] consequences) across patient populations. RECENT FINDINGS: Literature review identified 81 articles (including 57 individual case reports). We extracted relevant information to better understand the burden of HU and to identify knowledge gaps for future study. HU are physiologic events that can complicate existing medical conditions and treatments regardless of duration. Relatively short episodes can have devastating consequences in patients who have pre-existing conditions. HU appear to impact physical and psychological health, diminish QoL, increase healthcare resource use, and increase costs. A better understanding of HU burden is needed.

Hiccups as the only symptom of acute myocardial infarction.

Hiccups are usually benign, while myocardial infarction (MI) has the potential for morbidity and mortality. Here, we report 3 cases of MI, with hiccups being the only symptom on presentation to the emergency department. Attention should be given to patients who present with hiccups and multiple risk factors for acute coronary syndrome, especially those with factors predisposing them to atypical presentations, such as diabetes mellitus, and old age.

Medication treatment of singultus in palliative care.

Singultus (hiccup) is caused by periodic involuntary spastic contractions of the respiratory muscles followed by a sharp inspiration and early glottis closure. This results in typical "hic" sound. Brief episodes of hiccups are quite common experience in general population, and they do not indicate serious disease nor require medical treatment. If chronic, they pose a significant problem with plethora of negative consequences on patient condition, particularly in palliative care. Treatment options involve many approaches - both nonmedication and medication options. However, there are no large controlled trials resulting in unambiguous recommendations. Current pharmacologic treatment strategies are therefore only based on small studies and case reports and they report more or less successful outcomes using medications with different mechanisms of action.

[Investigation into the Effect of Shitei Extract, a Traditional Chinese Medicine Formulation, on Hiccups].

Hiccups are occasionally experienced by most individuals, and although not life-threatening, they may leadto a decline in quality of life. Shitei extract(shitei, persimmon calyx)may be usedfor the treatment of hiccups. The effects of shitei extract were investigatedin patients admittedto the Japanese RedCross Musashino Hospital between October 2011 andM ay 2016. Numerous prescriptions for shitei extract were reportedin the Department of Respiratory Organs andNeurosurgery. The primary causes of hiccups were chemotherapy andbrain disease. Of 149 patients, 107(71.8%)sufferedfrom hiccups. None of the patients reported adverse events related to the administration of shitei extract. The incidence of hiccups was significantly higher in patients with brain disease(p=0.0075), treatedwith chemotherapy for cancer(p=0.0402), or requiring the insertion of a gastric tube(p=0.0065). Among those treatedwith chemotherapy for cancer, shitei extract was effective against hiccups in 82.0% patients(45 of 55). Furthermore, four patients receivedprophylaxis with shitei extract for the prevention of hiccups after chemotherapy. In conclusion, these results indicate that shitei extract is an effective and safe therapeutic drug for the treatment of hiccups. In particular, shitei extract was effective in the prevention of hiccups after chemotherapy.