Laryngeal Hemiplegia / Recurrent Laryngeal Neuropathy

Laryngeal hemiplegia, also known as recurrent laryngeal neuropathy (RLN), is a progressive, degenerative neuropathy of the recurrent laryngeal nerve, predominantly affecting the left side, leading to paralysis of the cricoarytenoideus dorsalis muscle and subsequent collapse of the arytenoid cartilage and vocal fold into the airway during inspiration. This results in inspiratory dyspnea, exercise intolerance, and the characteristic 'roaring' or whistling sound during high-intensity exercise. The condition is most commonly seen in large breed horses, particularly Thoroughbreds and draft breeds, and is a significant cause of poor performance in racing and other athletic disciplines. The disease is classified into four grades based on endoscopic appearance, with grade 1 being normal and grade 4 indicating complete paralysis with arytenoid collapse. Laryngeal hemiplegia is a major concern in equine sports medicine, as it can severely impair respiratory function and limit athletic potential. Surgical interventions such as prosthetic laryngoplasty (tie-back) and ventriculocordectomy are commonly employed to restore airway patency and improve performance.

The primary etiology of laryngeal hemiplegia is idiopathic, but it is believed to be a distal axonopathy of the recurrent laryngeal nerve, with the left nerve being more susceptible due to its longer course within the thorax. The condition is often referred to as 'idiopathic laryngeal hemiplegia' when no specific cause is identified. However, several factors may contribute to the development of the disease, including: 1) Trauma to the recurrent laryngeal nerve, such as from jugular vein thrombosis, perivascular injection, or cervical trauma; 2) Toxicity from lead or organophosphates; 3) Neoplasia or abscessation in the thoracic inlet or cervical region compressing the nerve; 4) Infectious causes, such as equine herpesvirus myeloencephalopathy (EHV-1) or guttural pouch mycosis, which can damage the vagus or recurrent laryngeal nerves; 5) Nutritional deficiencies, such as vitamin E or selenium deficiency, which may predispose to neuropathy; 6) Inherited predisposition, as certain bloodlines in Thoroughbreds and draft breeds show higher prevalence. The exact pathogenesis remains unclear, but it is characterized by axonal degeneration and demyelination, with the left recurrent laryngeal nerve being more severely affected due to its greater length and metabolic demands.

Laryngeal hemiplegia is most prevalent in large breed horses, particularly Thoroughbreds, Standardbreds, and draft breeds such as Shires and Clydesdales. It is less common in ponies and Arabians. The condition is more frequently diagnosed in males than females, and the risk increases with age, with most cases presenting in horses over 3 years old. Performance horses, especially those used for racing, eventing, and dressage, are at higher risk due to the high respiratory demands of these disciplines. The prevalence in Thoroughbred racehorses has been reported to be as high as 30-40% in some studies, with a significant impact on racing performance. The condition is often bilateral in a small percentage of cases, but left-sided involvement is overwhelmingly predominant. There is no seasonal or geographic predilection, but horses housed in stalls with poor ventilation may have increased respiratory stress, potentially exacerbating clinical signs. The economic impact is substantial, as affected horses may require surgical intervention and prolonged rehabilitation, and some may fail to return to their previous level of athletic performance.

The pathophysiology of laryngeal hemiplegia involves progressive degeneration of the recurrent laryngeal nerve, leading to denervation of the intrinsic laryngeal muscles, particularly the cricoarytenoideus dorsalis (CAD) muscle, which is the primary abductor of the arytenoid cartilage. The left recurrent laryngeal nerve is more vulnerable due to its longer course, as it loops around the aortic arch, making it susceptible to traction and ischemic injury. The degenerative process is characterized by axonal loss, demyelination, and subsequent muscle atrophy. Initially, there is a loss of large myelinated fibers, leading to a reduction in nerve conduction velocity. As the disease progresses, the CAD muscle becomes atrophied and fibrotic, resulting in an inability to abduct the arytenoid cartilage during inspiration. This causes dynamic collapse of the arytenoid and vocal fold into the airway, creating turbulence and obstruction, particularly during high-intensity exercise when negative pressure in the airway is greatest. The obstruction leads to increased inspiratory resistance, hypoxemia, hypercapnia, and exercise intolerance. In severe cases, the airway may become critically compromised, leading to respiratory distress and even collapse. The condition is progressive, and early stages may show only subtle abnormalities, such as asynchronous arytenoid movement, which can progress to complete paralysis over time.

Several intrinsic and extrinsic factors predispose horses to laryngeal hemiplegia. Intrinsic factors include: 1) Breed: Large breeds, especially Thoroughbreds, Standardbreds, and draft horses, have a higher incidence due to anatomical and genetic factors. 2) Age: The condition is more common in older horses, as the degenerative process is progressive. 3) Sex: Males are more frequently affected, possibly due to a larger laryngeal anatomy and greater respiratory demands. 4) Conformation: Horses with a long neck and large body size may have increased tension on the recurrent laryngeal nerve. 5) Genetic predisposition: Certain familial lines show a higher prevalence, suggesting a heritable component. Extrinsic factors include: 1) High-intensity training: Horses engaged in strenuous exercise are more likely to exhibit clinical signs due to increased respiratory effort. 2) Environmental stress: Poor ventilation, dust, and ammonia in stables can cause respiratory irritation, potentially exacerbating the condition. 3) Nutritional deficiencies: Inadequate intake of antioxidants such as vitamin E and selenium may contribute to neuronal damage. 4) Trauma: Neck injuries or perivascular injections can damage the recurrent laryngeal nerve. 5) Infectious agents: Viral infections like EHV-1 can cause neurological damage, including to the recurrent laryngeal nerve.

The clinical signs of laryngeal hemiplegia vary depending on the severity of the condition. In mild cases, horses may show no obvious signs at rest, but during exercise, they may exhibit a characteristic 'roaring' or 'whistling' sound, especially at high speeds. This is due to the turbulent airflow caused by the collapsed arytenoid and vocal fold. Other signs include: 1) Exercise intolerance: Horses may tire easily, have a poor performance, and show a decrease in speed or stamina. 2) Increased respiratory effort: There may be visible nostril flaring, increased abdominal effort, and a prolonged recovery time after exercise. 3) Coughing: Some horses may cough, especially after exercise, due to airway irritation. 4) In severe cases, respiratory distress may occur, with cyanosis of the mucous membranes and a distressed appearance. On endoscopic examination, the arytenoid cartilage may be seen to collapse into the airway during inspiration, and there may be asymmetry in the movement of the arytenoids. The condition is graded from 1 to 4 based on the degree of arytenoid movement and collapse, with grade 4 indicating complete paralysis. In addition, there may be atrophy of the left side of the larynx, and the vocal fold may be flaccid. The clinical signs are typically exacerbated by exercise, and the diagnosis is often confirmed by dynamic endoscopy during exercise on a high-speed treadmill.

Differential diagnoses for laryngeal hemiplegia include: 1) Epiglottic entrapment: This condition involves the epiglottis being trapped by the aryepiglottic folds, causing respiratory noise and exercise intolerance. Endoscopy reveals the epiglottis is covered by the aryepiglottic fold, which can be corrected surgically. 2) Dorsal displacement of the soft palate (DDSP): This occurs when the soft palate displaces dorsally, obstructing the airway during exercise. It is characterized by a 'gurgling' sound and can be diagnosed by dynamic endoscopy. 3) Arytenoid chondritis: Inflammation of the arytenoid cartilage can cause swelling and airway obstruction. Endoscopy shows a thickened, irregular arytenoid, and treatment may involve surgical debridement. 4) Laryngeal paralysis due to other neuropathies: Conditions such as guttural pouch mycosis or trauma can cause laryngeal paralysis, but these are often associated with other neurological signs. 5) Tracheal collapse: This is rare in horses but can cause respiratory distress and noise. Radiography or endoscopy can confirm the diagnosis. 6) Exercise-induced pulmonary hemorrhage (EIPH): This condition causes bleeding in the lungs during exercise, leading to poor performance and coughing. It is diagnosed by endoscopy after exercise, showing blood in the trachea. 7) Lower airway disease, such as recurrent airway obstruction (RAO) or inflammatory airway disease (IAD), can cause exercise intolerance and respiratory noise. These are diagnosed by bronchoalveolar lavage and response to bronchodilators. 8) Cardiac disease, such as atrial fibrillation, can cause exercise intolerance and poor performance. Auscultation and electrocardiography are used to diagnose cardiac arrhythmias.

The diagnostic algorithm for laryngeal hemiplegia begins with a thorough history and physical examination, including auscultation of the respiratory tract at rest and during exercise. The next step is resting endoscopic examination of the upper airway, which is performed with the horse sedated and the endoscope passed through the nasal passage to visualize the larynx. The arytenoid cartilages are observed for symmetry and movement, and the larynx is graded according to the Havemeyer grading system (grades 1-4). If resting endoscopy is inconclusive, dynamic endoscopy during exercise on a high-speed treadmill is recommended. This allows for the assessment of arytenoid function under the high negative pressures of exercise, which may reveal dynamic collapse that is not apparent at rest. Additional diagnostic tests may include: 1) Radiography of the larynx to assess for chondritis or other abnormalities. 2) Ultrasonography to evaluate the laryngeal muscles for atrophy. 3) Electromyography (EMG) to assess the function of the recurrent laryngeal nerve. 4) Blood tests to rule out other causes of neuropathy, such as lead toxicity or EHV-1 infection. 5) In some cases, a nerve biopsy may be performed to confirm the diagnosis. The diagnostic algorithm should also include a thorough evaluation of the lower airway, as concurrent conditions such as EIPH or RAO may be present. Once a diagnosis is confirmed, the severity of the condition is graded, and a treatment plan is formulated.

Laboratory findings in laryngeal hemiplegia are generally non-specific, as the condition is primarily a neurological and muscular disorder. However, certain tests may be performed to rule out other causes of neuropathy or to assess the overall health of the horse. A complete blood count (CBC) may reveal mild elevations in white blood cell count if there is concurrent infection or inflammation. Serum biochemistry may show elevated muscle enzymes (creatine kinase, CK, and aspartate aminotransferase, AST) if there is muscle damage, but this is not typical. In cases where a toxic cause is suspected, blood lead levels or organophosphate levels may be measured. If an infectious cause such as EHV-1 is suspected, serology or PCR testing may be performed. Additionally, vitamin E and selenium levels may be assessed to rule out nutritional deficiencies. In some cases, cerebrospinal fluid analysis may be performed if there is suspicion of a central nervous system disorder. However, in most cases of idiopathic laryngeal hemiplegia, laboratory findings are within normal limits, and the diagnosis is based on endoscopic and clinical findings.

Imaging modalities used in the diagnosis of laryngeal hemiplegia include: 1) Endoscopy: This is the primary imaging modality, allowing direct visualization of the larynx. Resting endoscopy is performed to assess arytenoid movement and symmetry, and dynamic endoscopy during exercise is used to evaluate the airway under stress. The Havemeyer grading system is used to classify the severity of the condition. 2) Radiography: Plain radiographs of the larynx may be useful to evaluate for chondritis, fractures, or other bony abnormalities. However, radiography is not typically diagnostic for laryngeal hemiplegia. 3) Ultrasonography: This can be used to assess the thickness and echogenicity of the laryngeal muscles, particularly the cricoarytenoideus dorsalis muscle. Atrophy of this muscle may be seen in chronic cases. 4) Computed tomography (CT) and magnetic resonance imaging (MRI): These advanced imaging modalities provide detailed anatomical information and may be used to evaluate for compressive lesions or other structural abnormalities. They are particularly useful in cases where a secondary cause of laryngeal paralysis is suspected. 5) Scintigraphy: This is rarely used but may be helpful in assessing inflammation or muscle activity. Overall, endoscopy remains the gold standard for diagnosis, and other imaging modalities are used as adjuncts.

Cytological and histopathological findings in laryngeal hemiplegia are primarily related to the denervation of the laryngeal muscles. On histopathology, the recurrent laryngeal nerve shows axonal degeneration, demyelination, and loss of large myelinated fibers. The cricoarytenoideus dorsalis muscle exhibits neurogenic atrophy, characterized by angulated atrophic fibers, fiber type grouping, and eventually fibrosis. In chronic cases, there may be fatty infiltration of the muscle. These changes are more pronounced on the left side. Cytological examination of tracheal wash or bronchoalveolar lavage fluid is not typically diagnostic for laryngeal hemiplegia, but may be performed to rule out concurrent lower airway disease. If a nerve biopsy is performed, it may show similar degenerative changes. Histopathology is not commonly performed in clinical cases, as the diagnosis is usually made based on endoscopic findings, but it may be useful in research or in cases where the etiology is unclear.

The treatment of laryngeal hemiplegia depends on the severity of the condition and the intended use of the horse. For horses with mild clinical signs that are not intended for high-intensity athletic performance, conservative management may be sufficient. This includes rest, reducing exercise intensity, and managing any concurrent respiratory conditions. However, for performance horses, surgical intervention is often recommended. The most common surgical procedure is prosthetic laryngoplasty, also known as 'tie-back', which involves placing a suture to pull the arytenoid cartilage into an abducted position. This is often combined with ventriculocordectomy, which removes the vocal fold and laryngeal ventricle to reduce airway turbulence. The surgery is performed under general anesthesia, and the horse is typically rested for several weeks before returning to training. Post-operative complications include suture failure, aspiration pneumonia, and excessive coughing. In some cases, a permanent tracheostomy may be considered for horses with severe bilateral paralysis, but this is rare. Medical management may include the use of corticosteroids to reduce inflammation, but this is not a definitive treatment. The prognosis for return to athletic function after surgery is generally good, with success rates of 70-90% reported in the literature. However, the surgery does not restore normal laryngeal function, and some horses may still have exercise intolerance.

The prognosis for laryngeal hemiplegia depends on the severity of the condition, the intended use of the horse, and the treatment chosen. For horses with mild to moderate disease that undergo surgical correction, the prognosis for return to athletic function is generally good, with success rates of 70-90% reported. However, the surgery does not restore normal laryngeal function, and some horses may still have exercise intolerance. The prognosis is less favorable for horses with severe disease, those that do not undergo surgery, or those with concurrent respiratory conditions. In racing Thoroughbreds, studies have shown that horses that undergo laryngoplasty have a similar racing performance to their pre-operative performance, but may not reach the same level as unaffected horses. The long-term prognosis is also influenced by the development of complications such as aspiration pneumonia or suture failure. For horses that are not intended for athletic performance, the prognosis is good, as the condition does not typically affect quality of life. Overall, the prognosis is guarded to good, depending on the individual case.

Follow-up care for horses with laryngeal hemiplegia is crucial to monitor recovery and detect any complications. After surgical treatment, the horse should be rested for at least 4-6 weeks, with a gradual return to exercise over the following months. Recheck endoscopic examinations are typically performed at 2-4 weeks post-surgery to assess the position of the arytenoid and the healing of the surgical site. Further rechecks may be recommended at 3-6 months to evaluate the long-term outcome. During the rehabilitation period, the horse should be monitored for signs of aspiration pneumonia, such as coughing, nasal discharge, or fever. If these occur, prompt veterinary attention is required. For horses managed conservatively, regular monitoring of clinical signs and periodic endoscopic examinations are recommended to assess disease progression. In all cases, it is important to maintain good respiratory health by providing a clean, dust-free environment and avoiding exposure to respiratory irritants. The horse's exercise program should be tailored to its capabilities, and any signs of exercise intolerance should be investigated promptly.

Clinical pearls: 1) Always perform a thorough endoscopic examination of the upper airway in any horse presenting with exercise intolerance or abnormal respiratory noise. 2) Dynamic endoscopy during exercise is essential for diagnosing subtle cases of laryngeal hemiplegia that may not be apparent at rest. 3) In racing Thoroughbreds, laryngeal hemiplegia is a common cause of poor performance, and early diagnosis and treatment can improve outcomes. 4) When performing laryngoplasty, careful attention to suture placement and tension is critical to avoid complications such as aspiration. 5) Post-operative management should include anti-inflammatory therapy and careful monitoring for respiratory distress. Pitfalls: 1) Failing to consider other causes of respiratory noise, such as epiglottic entrapment or dorsal displacement of the soft palate, can lead to misdiagnosis. 2) Overlooking concurrent lower airway disease, such as EIPH or RAO, can result in incomplete treatment and poor outcomes. 3) Inadequate rest after surgery can lead to suture failure or other complications. 4) Assuming that a grade 1 larynx is normal without considering dynamic collapse during exercise can miss the diagnosis. 5) Neglecting to monitor for aspiration pneumonia after surgery can lead to serious complications.

Current drug protocols for laryngeal hemiplegia primarily focus on perioperative management and treatment of complications. Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used to reduce inflammation and pain. Flunixin meglumine (1.1 mg/kg IV) is often administered pre-operatively and for 1-3 days post-operatively. Phenylbutazone (4.4 mg/kg IV or PO) may also be used. Corticosteroids, such as dexamethasone (0.05-0.1 mg/kg IV), may be used to reduce swelling, but are used cautiously due to potential side effects. Antibiotics are administered perioperatively to prevent infection, typically penicillin G (22,000 IU/kg IV q6h) and gentamicin (6.6 mg/kg IV q24h) for 24-48 hours. If aspiration pneumonia develops, a broader-spectrum antibiotic protocol may be initiated based on culture and sensitivity. For horses with concurrent respiratory disease, bronchodilators such as clenbuterol (0.8-3.2 mcg/kg PO q12h) may be used. In cases of neurogenic muscle atrophy, anabolic steroids may be considered, but their use is controversial. Supportive care includes adequate hydration and nutrition. It is important to note that these protocols should be tailored to the individual horse and the clinical situation, and dosages should be adjusted based on the horse's weight and condition.

The literature on laryngeal hemiplegia is extensive, with numerous studies evaluating the pathophysiology, diagnosis, and treatment of the condition. Key findings include: 1) The prevalence of laryngeal hemiplegia in Thoroughbred racehorses is high, with studies reporting rates of 30-40% in some populations. 2) Dynamic endoscopy during exercise is superior to resting endoscopy for diagnosing the condition, as many horses show normal arytenoid function at rest but collapse during exercise. 3) Prosthetic laryngoplasty has been shown to improve airway function and exercise tolerance, with success rates of 70-90% reported in various studies. 4) The long-term outcome after surgery is generally good, but complications such as aspiration pneumonia and suture failure can occur. 5) The condition is progressive, and early intervention may improve outcomes. 6) Genetic studies have identified potential heritable factors, suggesting that selective breeding may help reduce the incidence. 7) Conservative management is not effective for performance horses, and surgery is the treatment of choice. 8) Post-operative rehabilitation is critical for a successful outcome, with a gradual return to exercise over several months. Overall, the evidence supports the use of surgical intervention for performance horses, with careful patient selection and post-operative management.