Morvan syndrome and related disorders associated with CASPR2 antibodies
Jan. 23, 2023
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Sleep-related laryngospasm is a rare sleep condition that refers to episodic, abrupt awakenings from sleep caused by breathing difficulties associated with feelings of suffocation, fear, coughing, and tachycardia. The American Academy of Sleep Medicine’s International Classification of Sleep Disorders third edition (ICSD-3) included sleep-related laryngospasm among the sleep-related medical and neurologic disorders in the Appendix A. Though the literature is still mainly based on case series, there is now evidence that the disorder’s prompt recognition and treatment is vital for the patient’s well-being due to its significant impact on sleep. In this article, the authors elaborate on the broad differential diagnosis that has to be considered. Furthermore, the authors shed light on the pathogenesis, complications, and various treatment options available for this intriguing disorder.
• Sleep-related laryngospasm is a rare condition related to episodic awakenings from sleep, associated with breathing difficulties and a feeling of suffocation.
• Characteristically, patients describe sudden awakenings from sleep due to feelings of acute suffocation, accompanied by coughing, intense fear, airway obstruction, tachycardia, and stridor. This, in turn, resolves within a few minutes, and breathing returns to normal. Such attacks are traumatic experiences, and patients who suffer frequent attacks are afraid to go to sleep.
• Sleep-related laryngospasm can be primary or secondary. To give a correct diagnosis it is necessary to collect a detailed history and perform a neurologic and otolaryngologic examination eventually including fibroscopy. Video-polysomnographic recording represents the ideal diagnostic tool in most cases.
Laryngospasm is defined as a sudden, prolonged, forceful apposition of the vocal cords, and it is believed to be the result of a laryngeal reflex response to noxious stimuli. Sleep-related laryngospasm is a clinical condition characterized by episodic, abrupt awakenings from sleep accompanied by a sense of suffocation and followed by stridor that usually evolves to normal breathing. Little has been published on spontaneous laryngospasm during sleep and its devastating effects on sleep quality and patients’ overall quality of life. In 1977, Chodosh reported the first case of gastroesophageal-pharyngeal reflux-induced laryngospasm (08). The first case series was published in 1995, and the term “sleep-related laryngospasm” was designated to describe this condition (01). In 1999, Morrison and colleagues described a distinct clinical entity under the term “the irritable larynx” characterized by dysphonia, episodic laryngospasm, globus, or cough. The irritable larynx syndrome is hypothesized to arise from repeated exposure to noxious stimuli, such as gastroesophageal reflux, viral illness, or emotional or postural muscle misuse. The authors proposed a hypothesis on neural plastic change to brainstem control networks. According to this theory, the controlling neurons are held in a “spasm-ready” state, and symptoms may be triggered by various stimuli (31).
In the Third International Classification of Sleep Disorders, sleep-related laryngospasm is classified among the sleep-related medical and neurologic disorders in the Appendix A (03).
The clinical presentation of sleep-related laryngospasm is highly characteristic in nature (see Table 1). The attacks begin with short coughs and inspiratory stridor while the patient is asleep (48).
Then the patient suddenly wakes up in a panic, unable to breathe either in or out, with a period of complete blockage lasting seconds. The attack is accompanied by acute fear or suffocation, which yields intense, desperate respiratory maneuvers that produce little or no airflow. After this short phase of total respiratory blockage, the patient’s breathing continues to be labored and is associated with persistent stridor (55). This in turn resolves within a few minutes and breathing returns to normal (46). After an attack, some patients return to sleep though most, fearful of recurrence of the stressful event, try to remain awake (55; 46). Interestingly, patient descriptions of these terrifying episodes share a common pattern. Asked where the blockage occurs, the patients point to the larynx, take the thyroid cartilage between the thumb and index finger, state that it feels like a tightening cord around the neck, or make a throat-cutting gesture (55). The infrequent and almost exclusive nocturnal occurrence of sleep-related laryngospasm and the short duration of the attack make them usually inaccessible to medical observation. By contrast, patients with a history of laryngospasm that is not necessarily sleep-related may experience sudden attacks at any time during the day or night (29).
Patients with sleep-related laryngospasm secondary to a gastroesophageal reflux disease may also awaken from sleep with a sour metallic or bitter taste in the mouth, heartburn, substernal burning, or chest discomfort.
• Abrupt arousal from sleep
The prognosis of sleep-related laryngospasm in published case reports is usually good, especially when the underlying factors can be addressed promptly and appropriately. Patients overcome by anxiety or those fearful of suffering recurrent episodes stay awake, resulting in poor sleep quality with its antecedent problems. Medium-term prognosis for these patients seems good, but not enough data are available to be certain about the long-term prognosis. Nonetheless, a case was reported of a patient with a prolonged attack resulting in syncope, which can cause potential complications (29). Besides, a rare complication of sleep-related laryngospasm may be death, though this has occurred mainly in older patients with concomitant neurologic illnesses, and the demise may have been due to other etiologies. Moreover, ictal laryngospasm might play a role in pathophysiology of sudden unexpected death in epilepsy (SUDEP) (06; 25; 05; 30). Indeed, laryngospasm related to acid reflux has been observed as a possible cause of SUDEP in an acute kainic acid model of seizure (06; 30). Furthermore, ictal laryngospasm might result from the autonomic coactivation caused by seizure generalization to brainstem autonomic and respiratory networks. Thus, ictal laryngospasm can be sufficient for obstructive apnea (defined as periods of no airflow with evidence of inspiratory effort), which is related to an extra autonomic coactivation and is associated with oxygen desaturation that may lead ultimately to cardiac arrest (52).
A 67-year-old Caucasian male with a past medical history of aortic valve replacement, dyslipidemia, depression, and neurogenic bladder presented to the Sleep Disorder Center for excessive snoring and excessive daytime sleepiness. He was referred to the Movement Disorder Center for difficulty in walking, bradykinesia, and limb rigidity. The patient’s wife, who accompanied her husband, slept in a separate room because the patient presented complex motor behaviors and somniloquy associated with vivid dreams during sleep for at least five years. She also said that her husband presented a loud and “strange” snoring. The patient had an excessive daytime sleepiness with a score of 13 on the Epworth Sleepiness Scale. A video-PSG was performed and showed REM sleep behavior disorder, an apnea-hypopnea index of 38.5 events per hour, and stridor. Finally, the diagnosis of multiple system atrophy was made. The patient was treated with continuous positive airway pressure with remission of both stridor and obstructive sleep apnea syndrome.
A 67-year-old Caucasian male with a history of sleep-related laryngospasm, excessive daytime sleepiness, and MSA. The video-polysomnography showed persistent laryngospasm, REM sleep behavior disorder, and severe obstructive sle...
Laryngospasm is the involuntary, rapid, and forceful contraction of the laryngeal sphincter in response to a noxious stimulus (29). It consists of a prolonged glottic closure reflex mediated by the superior laryngeal nerve, which provides motor supply to the inferior constrictor and the cricothyroid muscles. The superior laryngeal nerve also provides sensory innervation to the epiglottis, larynx, and vocal cords. Thus, this reflex arc, as described by Sasaki and Suzuki, consists of an afferent limb carried by the superior laryngeal nerve (SLN) and an efferent limb carried by the recurrent laryngeal nerve (RLN) (47). The authors showed that electrical stimulation of the SLN produces repetitive excitatory “after discharges” of the RLN, which in turn cause prolonged adduction of the vocal folds by stimulation of the thyroarytenoid and lateral cricoarytenoid muscles and inhibition of the posterior cricoarytenoid muscle. Laryngeal closure is an important component of the coughing and swallowing reflexes.
Laryngospasm is an example of exaggeration of upper airway defensive reflexes. Mechanical or chemical irritation of the laryngeal mucosa causes laryngeal adduction even if the stimuli are too weak to cause coughing or respiratory changes. For instance, gastroesophageal reflux disease may trigger laryngospasm in at-risk patients (46). Findings suggest that gastroesophageal reflux disease-induced irritation of the superior laryngeal nerve may cause CNS changes, resulting in the reflex central apnea and nocturnal choking that characterizes sleep-related laryngospasm (46). Sleep itself induces several factors that can contribute to acid reflux: decrease in lower esophageal sphincter tone, prolongation of acid clearance time (46), and impaired swallowing.
Laryngospasm most commonly occurs under three circumstances:
Idiopathic laryngeal spasm. Primary or spontaneous laryngospasm arises in the absence of any apparent underlying abnormality, occurs at night, and wakes the patient from sleep but can also arise at any time with no obvious precipitant event. Primary or spontaneous laryngospasm have been implicated in sudden infant death syndrome. The pathogenesis of isolated sleep-related laryngospasm is still incompletely elucidated, and it may be associated with dysfunction of tracheal muscles or gastroesophageal reflux (03).
Secondary laryngeal spasm. Secondary laryngospasm most commonly occurs in the setting of gastrointestinal disturbances, with gastroesophageal reflux disease being the most common underlying cause (46; 22). Paroxysmal laryngospasm associated with laryngopharyngeal reflux is the result of both hypersensitization of laryngeal tissue and protective reflexes (22; 39). In addition, otolaryngologic diseases (vocal cord tumors), neurologic disorders (multiple system atrophy, Kennedy disease, neuropathy involving the superior or recurrent laryngeal nerve, brainstem lesions, spinocerebellar ataxia type 17, and brainstem encephalitis), and metabolic abnormalities (hypoparathyroidism) may contribute to laryngospasm (14). In these cases, laryngospasm usually occurs during day and night without nocturnal preponderance (19; 46). Sleep-related laryngospasm has been found in a patient with spinocerebellar ataxia type 17 (23). In rare cases, the laryngospasm could be an isolated respiratory symptom of epilepsy. In particular, stridor has been observed as the initial presentation of Rolandic epilepsy in a 5-year-old girl (42). Sleep-related laryngospasm associated with neurodegenerative diseases, especially multiple system atrophy, is thought to be related to a sleep-related adductor muscle dystonia and abductor muscle weakness associated with hyperactivation of vocal cord adductors and sympathetic surges, such as tachypnea or tachycardia during sleep (58). According to this pathogenetic hypothesis, patients with multiple system atrophy have shown stridor-related gray matter changes in cerebral areas implicated in laryngeal dystonia, namely striatal and cerebellar regions (24; 54). Moreover, laryngeal stridor in multiple system atrophy may be related to impairment of serotoninergic neurotransmission, which leads to abductor muscle weakness (41). Sleep-related laryngospasm has been documented in a patient with subacute paraneoplastic autoimmune rhomboencephalitis associated with antineuronal nuclear antibody type-2 (ANNA-2, or anti-Ri) and Kelch-like protein 11 (KLCHL11)-IgG, along with inguinal lymph node metastasis of germ cell tumor (37).
Iatrogenic or surgical manipulation. Laryngospasm is a recognized complication of general anesthesia, typically occurring during extubation and resulting from acute irritation of the vocal folds (48). It often occurs with insufficient depth of anesthesia on endotracheal intubation, light anesthesia on tracheal extubation, or a combination of either of the preceding with an airway irritant such as blood, mucus, laryngoscope blade, suction catheter, surgical debris, or other foreign body. Conversely, no significant difference was found between the incidence of laryngospasm with intubated versus no-intubated general anesthesia during dental treatment in children (09).
The pathogenesis of perioperative laryngospasm remains unclear. It has been suggested, however, that anesthesia precipitates the closure of the true vocal cords alone resulting in either incomplete or complete airway obstruction. Moreover, iatrogenic laryngospasm is thought to be related to the presence of airway irritants such as blood, mucus, laryngoscope blade, suction catheter, surgical debris, or other foreign body. The contribution, if any, of the false vocal cords in the development of laryngospasm is also unclear. Incidentally, laryngospasm is the most commonly reported respiratory complication associated with upper respiratory infection. Use of hypnotics and other central nervous depressants commonly have been reported as precipitating factors.
The incidence of sleep-related laryngospasm is unknown, and only three case series have been published in the medical literature. The disorder most commonly affects middle-aged males. Laryngospasm is common during general anesthesia, with an incidence of 0.78% to 5%, depending on surgical type, patient age, pre-existing conditions, and anesthetic technique (35). The incidence in children 0 to 9 years of age is higher at 17.4/1000 patients; within this age group, infants one to three months of age have the greater incidence (more than three times the rate in any other age group). The risk factors for postoperative laryngospasm are recent respiratory tract infections, younger age, atopy, familiarity for asthma, preexisting airway abnormalities, and smoking (65; 60). Moreover, children aged 6 ± 3.6 years-old that underwent ear-nose-throat surgery have shown higher relative risk of postoperative laryngospasm compared with other surgical procedures (60).
If left untreated, laryngospasm can result in serious psychological and physical sequelae. In the surgical patient, topical lidocaine administration at the time of intubation may help prevent postoperative laryngospasm. The mechanism of action of lidocaine may be interruption of the superior laryngeal nerve reflex pathway, or the drug may directly affect the nerve’s sensory or motor terminals. Moreover, topical lidocaine premedication has been shown to reduce the incidence of laryngospasm in children during upper gastrointestinal endoscopies under ketamine sedation without oxygen supplementation (16).
Also, albuterol premedication prior to tonsillectomy under general anesthesia in young children has led to significant reduction in perioperative laryngospasm (62).
There are controversial results in the literature concerning the use of neuromuscular blocking agents to facilitate tracheal intubation and to prevent postoperative laryngospasm (60). Moreover, there is conflicting evidence about the preventive effect of removing the tracheal tube in awake children to prevent laryngospasm (60).
The characteristic spells of sleep-related laryngospasm can be produced or mimicked by a wide variety of sleep and non-sleep disorders (49). Thus, a thorough and reflective differential diagnosis is critical to establish the correct diagnosis. Table 2 lists the disorders whose clinical presentation resembles that seen in sleep-related laryngospasm or the diseases that can cause laryngospasm during sleep.
• Epileptic seizures
Epileptic seizures. Laryngospasm as a solitary manifestation of epilepsy is rare with only few cases reported in the literature (10; 64; 42). However, it should be recalled that frontal opercular seizures include throat constriction, facial jerks, salivation, and dysesthetic burning (33).
Oro-pharyngo-laryngeal symptoms (associated with strange sounds such as death rattle, gargling, grunting, and guttural sounds) and hypersalivation are also two cardinal clinical manifestations of the seizures in childhood rolandic epilepsy. Patients referred with a history of high frequency dyspneic attacks occurring only during sleep could be suspected for an epileptic origin. The attacks are usually identical, beginning with a short cough followed by an intensive inspiratory effort with severe air hunger. In these cases, laryngoscopic examination is normal, and the workup includes polysomnography and sleep-deprived EEG, which could show interictal or ictal abnormalities (64). Treatment with antiepileptic drugs (in particular, carbamazepine) can result in a partial or complete resolution of the symptoms.
Nocturnal panic attacks. It is possible that during panic attacks, respiratory symptoms characterized by a false suffocation alarm, shortness of breath, choking, chest pain, palpitations, and fear of dying may be prominent. Nocturnal panic attacks begin with an abrupt arousal from sleep but are strikingly similar in severity and duration to panic attacks experienced during waking, although in some patients panic attacks may be experienced predominantly or exclusively during sleep. More than half of patients with panic disorder suffer from nocturnal panic attacks (51). In severe cases, nocturnal panic attacks may lead to a phobic fear of the sleep environment, and patients may exhibit chronic avoidance of sleep and, thus, severe sleep deprivation. Indeed, the “fear of loss of vigilance” theory is an accepted model for nocturnal panic, characterized by a fear of the incapacity to protect oneself and to react to dangerous situations during nonawake states (51).
Sleep-related abnormal swallowing syndrome. Sleep-related abnormal swallowing is a condition of unknown etiology in which excess saliva in the upper airway results in persistent coughing, choking, and ultimately arousal from sleep. Sleep-related abnormal swallowing results from the dysfunction of muscles associated with deglutition, which leads to pooling of saliva in the upper airway. Predisposing factors for sleep-related abnormal swallowing include old age, neuromuscular conditions, and central nervous system dysfunction involving the laryngeal or pharyngeal muscles. Complications may include aspiration and transient hoarseness after coughing or laryngospasm. In patients with sleep-related abnormal swallowing, polysomnogram recordings do not demonstrate obstructive sleep apnea syndrome but show repetitive short-lived episodes of coughing or gagging. Furthermore, a visual survey of the oropharynx and a cricothyroid muscle electromyogram will often reveal abnormal swallowing with accumulation of saliva in the hypopharynx and aspiration into the trachea. Incidentally, although these coughing and choking bouts can be frequent, they typically cease quickly after arousal.
Sleep-related choking syndrome. Patients with sleep-related choking usually report multiple awakenings during the night with choking sensation and inability to breathe. Fear and anxiety predominate in sleep-related choking syndrome, which may cause insomnia and may induce brief arousals or awakenings (15). Unlike the clinical picture that characterizes laryngospasm, there is no evidence of stridor or breathing abnormalities witnessed by the bed partner or documented by video-PSG in patients with sleep-related choking.
Sleep-related gastroesophageal reflux. Sleep-related gastroesophageal reflux may be associated with poor sleep quality, early morning awakening, decreased daytime performances, excessive daytime sleepiness, and decreased quality of life (27). Laryngospasm may be an associated feature of this disorder. Controversy exists on whether obstructive sleep apnea and nocturnal reflux are causally linked or merely associated because of shared risk factors (27). Usually, patients complain of heartburn, burning sensation in the substernal area, chest discomfort, sour or bitter taste in the mouth, regurgitation, or choking sensations.
Nocturnal asthma. Asthma is a chronic inflammatory disease of the airways characterized by widespread but variable airflow obstruction and bronchial hyperresponsiveness. Asthma has a tendency to destabilize and worsen at night, probably due to multifactorial and interactive circadian and noncircadian factors such as an increase in bronchial responsiveness, increases in nocturnal airway resistance, airway inflammation, gastroesophageal reflux disease, supine posture, and sleep-disordered breathing like snoring or obstructive sleep apnea (50). Nocturnal asthma phenotype is associated with heavier burden of disease by means of poorer control of symptoms, increased use of medications, and greater morbidity and mortality (21). Thus, the recognition of this clinical pattern is important because nocturnal worsening is associated with increased asthma fatality. Indeed, a greater proportion of patients with asthma tends to die at night. Adolescents with asthma are at heightened risk for sleep quality and deficits in daytime dysfunction, so sleep hygiene may serve as an important domain for clinical intervention (Lawless al 2020). The pathophysiology of nocturnal asthma seems to be related to changes in circadian rhythm control by means of neuropeptide S receptor 1 and retinoid acid receptor-related orphan receptor alpha genes interactions (17).
Stridor in multiple system atrophy. Multiple system atrophy (MSA) is a neurodegenerative disorder involving the cerebellar, extrapyramidal, and autonomic nervous systems in many combinations. Complaints of sleep disorder are common among patients with multiple system atrophy with two major findings: sleep-related respiratory disorder and sleep-related motor phenomena. Nocturnal stridor is considered one red flag of the disease and may occur in all clinical stages of multiple system atrophy: it may be the first symptom of the disease (20). Up to 42% of patients with multiple system atrophy present stridor and it may be a possible cause of sudden death during sleep (20; 11). Stridor is a harsh or strained, high-pitched respiratory noise whose sound is usually distinguishable from snoring (07; 11). Nocturnal stridor is hypothesized to be due to sleep-related laryngeal dystonia, causing hyperactivation of vocal cord adductors and is often associated with neurogenic tachypnea or tachycardia during sleep (58; 56). Indeed, stridor-related gray matter changes in striatal and cerebellar regions have been shown in patients with multiple system atrophy (54). In fact, abnormalities in these regions have been observed in laryngeal dystonia, supporting the dystonia-related mechanism of stridor (24; 11). Moreover, laryngeal stridor in MSA may be related to depletion of medullary serotoninergic neurons leading to abductor weakness. (41). Moreover, laryngeal dysfunction may be observed prior to a full-blown diagnosis of multiple system atrophy that may help in differentiating from idiopathic Parkinson disease (63). Thus, stridor may represent a potential biomarker for multiple system atrophy (63).
Psychogenic nocturnal stridor. Psychological factors may also cause stridor in the absence of obvious anatomic or physiologic disorders, that is, psychogenic stridor (57). Stridor caused by psychogenic causes is uncommon and probably underrecognized. Structural and organic causes must be considered and excluded before stridor can be attributed to psychogenic causes (19).
Catathrenia (nocturnal groaning). Catathrenia is characterized by monotonous expiratory groaning during sleep, particularly evident during the second half of the night, predominantly or exclusively during REM sleep (12; 43; 59; 34; 03; 02; 13). Catathrenia is considered as an isolated symptom included in the sleep-related breathing disorders section in the International Classification of Sleep Disorder, third edition (03). Catathrenia is characterized by monotonous, irregular groans occurring during sleep. It is usually not noticed by the patient but reported by a bed partner. The first symptoms usually appear during adolescence or early adulthood, although catathrenia has also been described in a 4-year-old boy (04). Catathrenia has also been described in a 4-year-old girl with Pitt-Hopkins syndrome, a rare autosomal dominant disorder (32). The typical noise made by patients with nocturnal groaning is loud and occurs on a nightly basis, persisting for several years, with no associated movement disorder (59). In all the polysomnographic studies performed, the features of nocturnal groaning were similar: a deep inspiration without any sound production was followed by a prolonged expiration with groaning, usually lasting seconds; bradypnea was present during catathrenia with no evidence of respiratory muscular effort and no oxygen desaturation (13). The exact mechanisms remain unclear, but changes in upper airway pressure flow characteristic during sleep, like REM sleep-related narrowing of upper airways during expiration or an abnormality of the internal respiratory drive system, seem to be crucial. Ott and colleagues identified active adduction and vibration of the vocal cords during expiration via laryngoscopy in a sedated patient with catathrenia, providing similarities between groaning and phonation (40).
The groaning can be easily confused with stridor of laryngospasm and the snoring of obstructive sleep apnea. Thus, careful evaluation is needed to rule out these possibilities.
Snoring and obstructive sleep apnea. The difference between snoring (with or without sleep apnea) and laryngeal stridor resulting from laryngeal dysfunction may not be readily apparent and requires careful evaluation by the sleep specialist. Obstructive sleep apnea most commonly afflicts obese patients and arises in the setting of airway blockage. Patients with obstructive sleep apnea often exhibit loud snoring sounds that, depending on severity, may sound similar to the guttural noises heard in patients with laryngeal stridor. Polysomnogram studies are helpful in distinguishing the two conditions as well as in accurately diagnosing obstructive sleep apnea.
The diagnosis of sleep-related laryngospasm is based almost entirely on the typical history, with physical and neurologic examination between episodes usually being unremarkable, unless in case of stridor associated with multiple system atrophy. The diagnosis requires a high index of suspicion with attention to exclude other conditions, especially cardiac and pulmonary symptoms or vocal cord dysfunction. Some patients may require further testing, including a video-PSG evaluation.
Gastroesophageal reflux should be considered in patients who are referred for evaluation of obstructive sleep apnea syndrome, especially when they report symptoms of coughing, including hoarseness, recurrent pharyngitis, substernal burning, a sour or bitter taste in the mouth, which are usually more consistent with gastroesophageal reflux than with obstructive sleep apnea syndrome. Conversely, gastroesophageal reflux is often clinically “silent” during sleep and only polysomnography with continuous pH monitoring can demonstrate episodes of reflux during sleep, often associated with arousal (38).
Video-polysomnography can also document minor episodes consisting of NREM-related periodic coughs occurring with arousal fluctuations, as expressed by the A phase of cycling alternating pattern (CAP) (44).
Routine video-polysomnography should be sufficient to exclude many of the above-mentioned sleep disorders. EEG may also be helpful to rule out an underlying seizure disorder.
According to an International consensus, stridor may be recognized clinically by the physician if present at the time of examination, with the help of a witness, or by listening to an audio recording (11). Laryngoscopy is suggested to exclude mechanical lesions or functional vocal cord abnormalities related to different neurologic conditions. If the suspicion of stridor needs confirmation, drug-induced sleep endoscopy or video polysomnography may be useful.
Treatment of sleep-related laryngospasm aims at relieving the underlying causes when they can be identified. In otherwise healthy patients with infrequent symptoms, an explanation of the mechanism and natural history of the condition may provide sufficient reassurance, and the patient may not want any further treatment. Patients with sleep-related laryngospasm should avoid precipitating factors such as hypnotic or other central nervous system depressant drugs (03).
Gastroesophageal reflux disease is the most common triggering factor found in the case series (46). The therapy starts with standard lifestyle modifications (including appropriate spacing of meals, avoidance of late-night meals, and foods that are known to promote elevated acid concentrations in the stomach) and avoidance of triggering factors including medications (calcium channel blockers, theophylline, anticholinergics, beta-blockers, and some calcium supplements will increase gastric acid). The patient can be instructed to raise the head of the bed to produce a 15- to 20-degree elevation. Medical management should be started promptly. Usually, proton pump inhibitors or H2 blockers for acid reflux disease provide excellent results. The addition of the prokinetic agent cisapride can be considered if acid reduction therapy alone fails to stop the laryngospasm. Some patients reluctant to take long-term medication may prefer to have antireflux surgery (18). In some cases, a cough suppressant is indicated to decrease the refluxate.
Acupuncture treatment aimed at improving gastrointestinal motility, should be considered in cases of sleep-related laryngospasm refractory to current medical treatment (48). Acupuncture has also been used to treat post-extubation laryngospasm (48). Laryngeal botulinum toxin injections and superior laryngeal nerve blockade are some of the options in the few patients who fail to respond to maximal medical therapy.
Symptomatic management of patients with cough and laryngospasm due to a suspected sensory neuropathy may include the use of medications such as gabapentin (up to 900 mg/day).
Continuous positive airway pressure and tracheostomy are both suggested as symptomatic treatment of stridor, but whether they improve survival is uncertain (20; 45; 11).
If catathrenia leads to sleep disruption and negative daytime symptoms, treatment with Continuous positive airway pressure should be considered.
The laryngospasm notch maneuver may attenuate or stop the laryngospasm and may be used in case of epilepsy-related laryngospasm together with the emergency airway protocol (28).
The prognosis of sleep-related laryngospasm in published case reports is usually good, especially when the underlying factors can be addressed promptly and appropriately. In a review of a cohort of 19 patients with laryngospasm over 15 years, none were worse and 13 described an improvement or complete resolution of symptoms. Patients overcome by anxiety or those fearful of suffering recurrent episodes stay awake, resulting in poor sleep quality with its antecedent problems. Medium-term prognosis for these patients seems good, but not enough data are available to be certain about the long-term prognosis. A rare complication of sleep-related laryngospasm may be death, though this has occurred mainly in older patients with concomitant neurologic illnesses, and the demise may have been due to other etiologies.
In patients with multiple system atrophy, early stridor onset is an independent predictor for worse prognosis. The impact of stridor on survival and quality of life remains uncertain (11). Tracheostomy could control stridor, influencing disease duration (20).
Although a rare phenomenon, laryngospasm might be implicated in SUDEP (06; 25; 05), and it might be related to acid reflux (06; 30) and to the autonomic coactivation associated by seizure generalization to brainstem autonomic and respiratory networks.
Laryngospasm is considered one of the complications of general anesthesia. To minimize the risk of perioperative laryngospasm, it is necessary to be aware of the factors that increase the risk of laryngospasm, such as preexisting respiratory problems, recent upper respiratory tract infections, and a history of anesthetic complications. Thus, patients with sleep-related laryngospasm disorder can be at high risk for developing this complication after anesthesia, and appropriate care should be taken. Moreover, children presenting for surgery with symptoms consistent with sleep-disordered breathing may be at risk for perioperative respiratory adverse events, including laryngospasm (53). The STBUR (Snoring, Trouble Breathing, Un-Refreshed), a questionnaire, appears to be a simple and clinically useful tool for identifying these individuals.
The management of laryngospasm in the setting of anesthesia consists of noninvasive positive pressure ventilation, intravenous succinylcholine or lidocaine, and tracheal reintubation with extubation only after the patient is thoroughly suctioned and awake (61). Other treatment techniques include doxapram, which increases respiratory drive and rapidly abolishes post-extubation laryngospasm, and nitroglycerin. One case of reported refractory postoperative laryngospasm was successfully treated with nebulized lidocaine (36). Also, premedication with albuterol during tonsillectomy under general anesthesia in young children has shown reduced occurrence of perioperative laryngospasm (62).
All contributors' financial relationships have been reviewed and mitigated to ensure that this and every other article is free from commercial bias.
Michela Figorilli MD
Dr. Figorilli of the University of Cagliari has no relevant financial relationships to disclose.See Profile
Federica Provini MD
Dr. Provini of the University of Bologna and IRCCS Institute of Neurological Sciences of Bologna received speakers' fees from Idorsia, Italfarmaco, and Pfizer.See Profile
Antonio Culebras MD FAAN FAHA FAASM
Dr. Culebras of SUNY Upstate Medical University at Syracuse received an honorarium from Jazz Pharmaceuticals for a speaking engagement.See Profile
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