Posterior circulation stroke presenting as a new continuous cough: not always COVID-19.

A 19-year-old man was admitted with a 2-week history of continuous cough along with a day history of acute onset unsteadiness and hiccups. Given the current pandemic, he was initially suspected to have COVID-19, however he tested negative on two occasions. Subsequent brain magnetic resonance imaging (MRI)confirmed a small left acute and subacute lateral medullary infarction with chest X-ray suggesting aspiration pneumonia with right lower lobe collapse. This is a distinctive case of posterior circulation stroke presenting with a new continuous cough in this era of COVID-19 pandemic. We anticipate based on MRI findings that his persistent cough was likely due to silent aspiration from dysphagia because of the subacute medullary infarction. It is therefore imperative that healthcare workers evaluate people who present with new continuous cough thoroughly to exclude any other sinister pathology. We should also be familiar with the possible presentations of posterior circulation stroke in this pandemic era.

Singultus, paper-bag ventilation, and hypercapnia.

Sir Louis Francis Knuthsen (1869-1957), the physician who painstakingly listed almost all treatments known for obstinate hiccough, ascribes the holding of breath method to Philip Henry Pye-Smith, FRS (1840-1914), consultant at Guy's Hospital in London. In fact, the strategy is much older and was mentioned by greats such as Francis Bacon (1561-1626), Aristoteles (384-322 BC), and Eryximachus (late-fifth century bce). Hypoventilation to reduce central nervous system excitability was used in antiquity as evidenced by Cyriacus' treatment of Artemia, the daughter of Emperor Diocletian (≈ 244-311). She was suffering from (among others) seizures that Cyriacus was apparently controlling by tightening a scarf around her neck, as depicted by Mathias Grünewald (1460-1528) on a wing of the so-called Heller Altar now on display at the Historical Museum, Frankfurt, Germany. In modern times, around 1920, inducing hypercapnia by CO2 inhalation as therapy for hiccups was suggested and tried by a number of anesthetists, such as Americans Russel Firth Sheldon (1885-1960) and Brian Collins Sword (1889-1956) in Boston; Briton Christopher Langton Hewer (1896-1986) at St. Bartholomew's Hospital in London; Austrian Karl Doppler (1887-1947) in Vienna; and the German/Polish Arthur Dzialoszynski (1893-1977) in Berlin. Although various authors assign the scientific primate to any of them, the first mention of carbon dioxide inhalation as treatment of singultus in the scientific literature is of French origin and was made by Paris pharmacist Henri Bocquillon-Limousin (1856-1917) in his 1892 Formulaire des médicaments nouveaux et des médications nouvelles.

A Systematic Review of the Effectiveness of Oral Baclofen in the Management of Hiccups in Adult Palliative Care Patients.

Hiccup is a recognised symptom amongst the palliative care population. It can be debilitating, with significant impact on quality of life. The pathophysiology is poorly understood and the list of aetiological factors is extensive. The current treatment recommendations are based on a small body of evidence and there remains uncertainty regarding optimal management. The aim of this study was to systematically review the evidence for oral baclofen in the management of hiccups in adult palliative care patients. A search was conducted using MEDLINE, Embase, the Cochrane library and CINAHL, as well as a hand search and review of the grey literature. Relevant articles were identified using pre-defined eligibility criteria. Quality assessment was guided by the SIGN grading system, CASP, Hawker et al's checklist and Cochrane's risk of bias tool. A narrative approach was used for data synthesis. Four relevant articles were identified; one randomised controlled trial and three case series. This gave a combined total of 22 patients, all of whom benefited from the use of oral baclofen in the treatment of hiccups, with few reports of side effects. The dose ranged from 10mg once only to 20mg TDS, and the duration from 1-24 days. However, the overall quality of the evidence was low. While baclofen is an option in the management of hiccups, it is difficult to make recommendations based on the body of evidence presented in this systematic review. There is a lack of RCTs in this field and further research is warranted.

Diaphragmatic dysfunction associates with dyspnoea, fatigue, and hiccup in haemodialysis patients: a cross-sectional study.

Muscle wasting is associated with increased mortality and morbidity in chronic kidney disease (CKD) patients, especially in the haemodialysis (HD) population. Nevertheless, little is known regarding diaphragm dysfunction in HD patients. We conducted a cross-sectional study at the Institute of Nephrology, Southeast University, involving 103 HD patients and 103 healthy volunteers as normal control. Ultrasonography was used to evaluate diaphragmatic function, including diaphragm thickness and excursion during quiet and deep breathing. HD patients showed lower end-inspiration thickness of the diaphragm at total lung capacity (0.386 ± 0.144 cm vs. 0.439 ± 0.134 cm, p < 0.01) and thickening fraction (TF) (0.838 ± 0.618 vs. 1.127 ± 0.757; p < 0.01) compared to controls. The velocity and excursion of the diaphragm were significantly lower in the HD patients during deep breathing (3.686 ± 1.567 cm/s vs. 4.410 ± 1.720 cm/s, p < 0.01; 5.290 ± 2.048 cm vs. 7.232 ± 2.365 cm; p < 0.05). Changes in diaphragm displacement from quiet breathing to deep breathing (△m) were lower in HD patients than in controls (2.608 ± 1.630 vs. 4.628 ± 2.110 cm; p < 0.01). After multivariate adjustment, diaphragmatic excursion during deep breathing was associated with haemoglobin level (regression coefficient = 0.022; p < 0.01). We also found that the incidence of dyspnoea and hiccup and the fatigue scores, all of which were related to diaphragmatic dysfunction, were significantly higher in HD patients than in controls (all p < 0.01). Improving diaphragm function through targeted therapies may positively impact clinical outcomes in HD patients.

Event-related potentials following contraction of respiratory muscles in pre-term and full-term infants.

OBJECTIVE: Involuntary isolated body movements are prominent in pre-term and full-term infants. Proprioceptive and tactile afferent feedback following limb muscle contractions is associated with somatotopic EEG responses. Involuntary contractions of respiratory muscles, primarily the diaphragm - hiccups - are also frequent throughout the human perinatal period during active behavioural states. Here we tested whether diaphragm contraction provides afferent input to the developing brain, as following limb muscle contraction. METHODS: In 13 infants on the neonatal ward (30-42 weeks corrected gestational age), we analysed EEG activity (18-electrode recordings in six subjects; 17-electrode recordings in five subjects; 16-electrode recordings in two subjects), time-locked to diaphragm contractions (n = 1316) recorded with a movement transducer affixed to the trunk. RESULTS: All bouts of hiccups occurred during wakefulness or active sleep. Each diaphragm contraction evoked two initial event-related potentials with negativity predominantly across the central region, and a third event-related potential with positivity maximal across the central region. CONCLUSIONS: Involuntary contraction of the diaphragm can be encoded by the brain from as early as ten weeks prior to the average time of birth. SIGNIFICANCE: Hiccups - frequently observed in neonates - can provide afferent input to developing sensory cortices in pre-term and full-term infants.

Supratentorial infarcts accompanying hiccup.

BACKGROUNDS: The main culprit lesion causing hiccup in patients with ischemic stroke is thought to involve the medulla oblongata, but some cases of hiccups caused by damage to the supratentorial cortex have been reported. The present study aimed to address the clinical and radiological characteristics of acute stroke patients accompanied by hiccups caused by supratentorial lesions. METHOD: We retrospectively studied 5,309 consecutive patients with acute ischemic stroke or transient ischemic attack who were admitted to our institute within 7 days after onset between April 2006 and September 2017. We searched for the term "hiccup" in prospectively collected descriptive datasets and analyzed associations between hiccup and clinical and radiological findings, with particular focus on patients with supratentorial lesions. RESULTS: We finally selected 16 stroke patients accompanied by hiccup. Nine patients had infarcts in the lateral medulla oblongata, and others had supratentorial infarcts (three patients with cortical infarcts, four patients with subcortical infarcts). Moreover, the right hemisphere was frequently damaged in this series (6/7, 86%). CONCLUSIONS: Hiccup could be caused by supratentorial infarcts including the insular cortex, temporal lobe, and subcortex.

Myocardial Ischemia Presenting with Hiccups.

Myocardial infarction/ischemia can be an underlying etiology and a major causative risk factor of cardiovascular hiccups. The objective of this systematic review was to review the literature regarding clinical features and treatments of hiccups of cardiac ischemia origin. PRISMA guidelines were followed. In elderly patients with hiccups of uncertain causes, electrocardiography is necessary to ensure the cardiogenic etiology. Both symptomatic and etiologic treatments can be effective in terminating hiccups. Of the therapeutic regimens, gabapentin is a second-line agent alternative to baclofen in treating hiccups. It is especially helpful in patients undergoing stroke rehabilitation or palliative care when chlorpromazine is prohibited due to its adverse effects. Inferior myocardial infarction is the most common cause of hiccups in this patient setting. In addition to anti-myocardial ischemia agents and percutaneous coronary intervention, coronary artery bypass grafting could be an alternative to hiccups in such patients.

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.

The effect of gender differences in protracted hiccups.

BACKGROUND: Although little importance is attached to hiccups, they may be associated with several diseases. The purpose of this study was to investigate the effects of gender differences on types of hiccups and the relation with diseases involved in the etiology. MATERIALS AND METHODS: Patients presenting to the Kirikkale University Medical Faculty Hospital with hiccups were investigated retrospectively. Patients' age, sex, duration of hiccups, additional diseases, advanced imaging results, laboratory tests, and clinical follow-up were recorded. Patients were divided into two groups; Group transient hiccup (TH) consisted of subjects with a duration of hiccups less than 48 h, and Group protracted hiccup (PH) of patients with a duration exceeding 48 h. The Chi-square test was used for comparisons, and P < 0.05 were regarded as significant. RESULTS: Eighty-four patients were enrolled, 44.1% (n = 37) in Group TH, and 55.9% (n = 47) in Group PH. Male patients comprised 67.5% (n =25) of Group TH and 89.4% (n = 42) of Group PH (P = 0.027). The conditions most associated with hiccups were gastrointestinal system (GIS) diseases. Correlation was determined between GIS diseases and male gender (P = 0.034), no relation between other system diseases and gender. Correlation was determined between GIS diseases and protracted hiccups (P = 0.037), but no relation between other system diseases and type of hiccups. CONCLUSION: Protracted hiccups are more common in males. This gender variation applies particularly to hiccups of GIS origin.

Intractable Hiccups.

PURPOSE OF REVIEW: Hiccups are a common problem that crosses multiple disciplines including neurology, gastroenterology and pulmonology, and primary care. There are no formal guidelines to the treatment of intractable hiccups and treatment is based on experience and anecdotal evidence often relying on older medications. We have reviewed the relevant literature with an emphasis on the last five years or so in management of intractable hiccups. RECENT FINDINGS: The production of hiccups is a complex mechanism which involves multiple neurotransmitters and anatomical structure within the central and peripheral nervous system. A number of medications and other therapy have been reported successful for intractable hiccups. Intractable hiccups can occur more often than we realize and present to multiple medical disciplines. A number of pharmacologic option have been found to be useful including dopamine-blocking medication, baclofen, and gabapentin along with anticonvulsants.

CO2 retention: The key to stopping hiccups.

BACKGROUND: While investigating the mechanisms behind hiccups, our team discovered what could be the sufficient physiological conditions for terminating even persistent cases. METHODS: To investigate the role of CO2 retention, a healthy male volunteer was asked to perform three kinds of rebreathing experiments using different materials: (I) a 20 L air-filled plastic bag, (II) a 20 L air-filled plastic bag with a 1.5 × 1.5 cm hole and (III) a 20 L oxygen-filled plastic bag. During each experiment, CO2 level upon expiration (EtCO2 ) and inspiration (InspCO2 ) were measured until the volunteer gave up. Once the safety of this manoeuvre was demonstrated with the volunteer, we performed the technique using the materials from experiment (I) on two actual patients with persistent hiccups. RESULTS: In experiments (I) and (III), InspCO2 increased from the beginning and reached almost the same level as EtCO2 after 90 seconds. Both levels continued simultaneously increasing, finally reaching 56 mm Hg in (I) and 79 mm Hg in (III), respectively. In (II), both increased; however, after 120 seconds, EtCO2 plateaued at 47 mm Hg and InspCO2 at 37 mm Hg. In the actual patients, both CO2 levels reached the same value of 35.9 mm Hg at 60 seconds and 37.0 mm Hg at 90 seconds, and hiccups stopped at 195 seconds and at 359 seconds when EtCO2 reached 50 mm Hg and 53 mm Hg, respectively. CONCLUSION: The study determined that to successfully obstruct the mechanisms causing hiccups, it is necessary that the level of InspCO2 not only increases at the same level as EtCO2 , but also reaches approximately 50 mm Hg.

Treatment by ultrasound-guided local infiltration in adhesion-related abdominal pain and intractable hiccups: A case report.

RATIONALE: Abdominal pain and hiccups secondary to intra-abdominal adhesion are surgical complications that are often treated by painkillers and secondary surgeries with an unsatisfactory therapeutic effect. This study presents a new treatment method that uses ultrasound-guided local infiltration in peritoneal and abdominal wall adhesions in patients with hiccups and abdominal pain. PATIENT CONCERNS: A 62-year-old patient presented to our hospital with a history of intractable hiccups and abdominal pain for 30 years. DIAGNOSES: Her abdominal examination revealed a scar with an approximate length of 10 cm on the abdominal umbilical plane; pressing the right scar area could simultaneously induce abdominal pain and hiccups. Intraperitoneal computed tomography examination clearly demonstrated that the bowel had no obvious expansion. Ultrasonographic examination found that peritoneal motility below the normal peritoneal adhesion regions was significantly slower than in the normal regions. The diagnosis of chronic postoperative pain syndrome was clear. INTERVENTIONS: The symptoms were significantly alleviated by a successful treatment with ultrasound-guided local infiltration in the peritoneal and abdominal wall scar adhesions. OUTCOMES: After 3 stages of hospitalization and 1 year of follow-up, the patient's abdominal wall pain was relieved by approximately 80% and hiccups were relieved by approximately 70%. LESSONS: The above treatment is a useful option for managing abdominal adhesion and accompanying pain or hiccups resulting from abdominal surgery. This method could ease the psychological and economic burden of patients and improve their quality of life.

Continuous cervical epidural block: Treatment for intractable hiccups.

Intractable hiccups, although rare, may result in severe morbidity, including sleep deprivation, poor food intake, respiratory muscle fatigue, aspiration pneumonia, and death. Despite these potentially fatal complications, the etiology of intractable hiccups and definitive treatment are unknown. This study aimed to evaluate the effectiveness of continuous cervical epidural block in the treatment of intractable hiccups.Records from 28 patients with a history of unsuccessful medical and invasive treatments for hiccups were evaluated. Continuous cervical epidural block was performed with a midline approach at the C7-T1 or T1-T2 intervertebral space with the patient in the prone position. The epidural catheter was advanced through the needle in a cephalad direction to the C3-C5 level. Catheter placement was confirmed using contrast radiography. A 6-mL bolus of 0.25% ropivacaine was injected, and a continuous infusion of 4 mL/h of ropivacaine was administered through the epidural catheter using an infuser containing 0.75% ropivacaine (45 mL ropivacaine and 230 mL normal saline). When the hiccups stopped and did not recur for 48 hours, the catheter was removed.Cumulative complete remission rates were 60.71% after the first cervical epidural block, 92.86% after the second, and 100% after the third. One patient complained of dizziness that subsided. No other adverse effects were reported.Continuous C3-C5 level cervical epidural block has a successful remission rate. We suggest that continuous cervical epidural block is an effective treatment for intractable hiccups.

[Singultus - Diagnostic Workup and Therapy]. / Singultus ­ Diagnostik und Therapie.

A hiccup is a reflex movement with diffusely distributed afferents and efferents in the thorax; its functional relevance is controversial. In its physiological form, it is mostly a minor complaint that stops spontaneously and rarely leads to medical consultation. However, prolonged agonizing hiccups represent serious deterioration of quality of life. Chronic hiccups by definition last for more than 48 h, with gastroesophageal reflux being the frequent underlying disease. Various other causes affect multiple organ systems, some with serious underlying diseases. A hiccup may be the only symptom at the first manifestation of some neurological disorders. In neuroimaging a lesion of the medulla oblongata is often seen. A NMO and an ischemic stroke with Wallenberg syndrome are 2 frequently underlying neurological diseases, but other inflammatory and vascular diseases and tumors of the central nervous system may be present. No optimal evidencebased recommendations for diagnosis and management of chronic hiccups are available. The search for the underlying disease often requires an interdisciplinary approach by internists, neurologists, and otolaryngologists. Symptomatic treatment may be necessary even before diagnosis. Persistent hiccups, a common problem in oncological palliative care, are often challenging. Proton pump inhibitor or prokinetics are used for treating underlying gastroesophageal reflux and baclofen with or without gabapentin in other cases. Anticonvulsants, antipsychotics, antidepressants, and calcium channel blockers represent other alternative treatment possibilities. In therapy-refractory cases, invasive procedures such as the selective phrenic nerve block are available. More studies are needed to help deal with the diagnostic and therapeutic challenge that hiccups present for neurologists.