Back To Search Results

Glossopharyngeal Neuralgia

Editor: Devang Padalia Updated: 4/27/2023 1:36:58 PM


Glossopharyngeal neuralgia (GN) is a rare pain syndrome in the sensory distribution of the ninth cranial nerve, also known as the glossopharyngeal nerve. As per ICHD-3 (International Classification of Headache Disease- 3) classification, glossopharyngeal neuralgia is a disorder characterized by a brief episodic unilateral pain, with sharp and stabbing in character, with abrupt onset and cessation, in the glossopharyngeal nerve distribution (angle of the jaw, ear, tonsillar fossa and the tongue base). It also involves the pharyngeal and auricular branches of CN X. Pain is commonly triggered by coughing, talking, and swallowing. Pain in glossopharyngeal neuralgia follows a relapsing and remitting pattern. It falls under the International Classification of Diseases (ICD) category as ICD-10-CM-G52.1.[1]

In 1910, T. Weisenburg was the first to describe the symptoms of glossopharyngeal neuralgia in a 35-year-old male with compression of the ninth cranial nerve by a tumor at the cerebellopontine (CP) angle. W. Harris was the first physician to label these symptoms as “glossopharyngeal neuralgia” in 1921, based on his observation of two of his patients. In 1927, there were two significant developments in the understanding and treatment of glossopharyngeal neuralgia. These included a published case series of 18 patients by J. Doyle and the first successful intracranial resection for glossopharyngeal neuralgia performed by W. Dandy.[2]

Riley et al. in 1942 noted that occasionally the painful attacks of glossopharyngeal neuralgia were associated with syncopal episodes, transient or persistent bradycardia, asystole, and even seizures. When these features correlate with glossopharyngeal neuralgia, the term for this condition is vagoglossopharyngeal neuralgia. Glossopharyngeal neuralgia often gets misdiagnosed as trigeminal neuralgia since pain characteristics are very similar in both entities.[3]


Register For Free And Read The Full Article
Get the answers you need instantly with the StatPearls Clinical Decision Support tool. StatPearls spent the last decade developing the largest and most updated Point-of Care resource ever developed. Earn CME/CE by searching and reading articles.
  • Dropdown arrow Search engine and full access to all medical articles
  • Dropdown arrow 10 free questions in your specialty
  • Dropdown arrow Free CME/CE Activities
  • Dropdown arrow Free daily question in your email
  • Dropdown arrow Save favorite articles to your dashboard
  • Dropdown arrow Emails offering discounts

Learn more about a Subscription to StatPearls Point-of-Care


Essential or idiopathic glossopharyngeal neuralgia is where etiology is unknown.[4][5]

Secondary causes of glossopharyngeal neuralgia include:

  • Vascular compression, mainly at the nerve root: the most common cause
  • Demyelinating diseases: e.g., multiple sclerosis
  • Inflammatory and autoimmune diseases: e.g., Sjogren disease
  • Intraoral and peritonsillar infections
  • Intracranial space-occupying lesions, especially medullary tumors or tumors originating from CP angle
  • Posterior fossa and cervical malformations
  • Eagle syndrome or stylalgia: If the styloid process is over 25mm or the stylohyoid ligament is calcified, they can cause compression of the glossopharyngeal nerve
  • Oropharyngeal cancers include carcinoma of the tongue and benign tumors like schwannomas


Glossopharyngeal neuralgia is an extremely rare condition. It accounts for 0.2 to 1.3% of all types of cranial neuralgias. One long-term study of the population in Rochester, Minnesota, from 1945 to 1984 showed a crude incidence rate of 0.7 per 100000 population. The incidence was equal in both sexes. The overall rates increase with age in both males and females.[6]

In 1981 Rushton et al. published a retrospective review of the data on 217 patients with glossopharyngeal neuralgia. These patients were seen at the Mayo Clinic from the years 1922 to 1977. 57% of the cases were in patients over 50 years of age, and 43% were between 18 to 50 years of age. Approximately 74% of patients had spontaneous remissions, whereas 17% experienced no relief. Only 12% of the patients had bilateral pain.[3]


The glossopharyngeal nerve is a mixed sensorimotor nerve that exits the brainstem from the upper medulla. From that point, it leaves the skull through the jugular foramen, along with the vagus and accessory nerves. It continues its path between the internal jugular vein and the internal carotid artery as it descends and then continues beneath the styloid process. It then curves to make an arch on the side of the neck as it passes under the hyoglossus muscle to its final distribution of the base of the tongue, the palatine tonsil, and the glands of the mouth. A motor efferent supplies the stylopharyngeus muscle, which is essential in swallowing. Sensory afferents provide information from the inner surface of the tympanic membrane, the upper pharynx, as well as the posterior one-third of the tongue. Another important branch is the one to the carotid body and sinus is known as Hering's nerve. It communicates with the vagus nerve and carries information from chemoreceptors in the carotid body and baroreceptors in the carotid sinus; this is important clinically as activation of the visceral sensory branch of the glossopharyngeal neuralgia can activate the vagus nerve (tractus solitarius and dorsal motor nucleus) and produce a reflex arrhythmia. This vagal activation may explain the cardiac-related syncopal episodes sometimes associated with glossopharyngeal neuralgia.  Overall the glossopharyngeal nerve is a very small nerve that runs deep in the neck, and it is sometimes resected accidentally during open-neck dissections. For this same reason, it is often called ‘the neglected cranial nerve.’ Any infectious, inflammatory, or compressive etiologies across the glossopharyngeal nerve’s path from the end organs to the brainstem may result in hyperexcitability of the nerve and produce pain.[5][7][8]

History and Physical

The ICHD-3 provides the following diagnostic criteria for glossopharyngeal neuralgia[1]:

A. Recurrent paroxysmal painful attacks in unilateral glossopharyngeal nerve distribution and should fulfill the criterion.

B. Pain should have all the following characteristics

  • Duration: Pain lasts from a few seconds to about 2 minutes
  • Intensity: Severe
  • Type of pain: Sharp, stabbing, shooting, or electrical shock-like sensations
  • Precipitating factors: The pain is precipitated or exacerbated by coughing, yawning, swallowing, or talking

C. Pain should not be accounted for by any other ICHD-3 diagnosis.

The usual onset for glossopharyngeal neuralgia is anywhere between 21 to 75 years of age.  The incidence is most common in those of middle age. There is no sex predilection. Painful attacks may occur without any prodromal or warning symptoms. The pain occurs anywhere below the ear, in the epiglottis, palatine tonsils, the base of the tongue, and/or the posterior pharynx. Swallowing both solids and liquids can make the pain worse. The pain is aggravated by drinking both hot and cold water. The onset and resolution of pain are abrupt. Some patients experience their initial attacks as excruciating, but the pain can then become relatively mild in the chronic state. Patients usually feel no pain in between the attacks, but some can feel a residual sharp pain in between the paroxysms. In rare cases, the attacks are not transient, sharp, or stabbing painful episodes but present as a deep agonizing pain that can last for days.

The pain pattern in an individual with glossopharyngeal neuralgia is remarkably uniform. Pain episodes can occur within minutes of each other and then stop entirely for days at a time. Paroxysmal pain is felt mostly during the day, but it may wake the patient up at night. Patients with glossopharyngeal neuralgia are predisposed to lose weight from the severe pain associated with chewing and swallowing. Attacks of pain surprisingly subside on their own most of the time, but unpleasant sensations may remain for several weeks to months in the affected areas.

The physical examination of patients with glossopharyngeal neuralgia is generally benign, and the painful areas do not show any signs of sensory abnormalities for both light touch and pinprick. Sometimes glossopharyngeal neuralgia is associated with dysesthesias and/or hyperalgesia in the affected areas. If there is an absent cough or gag reflex, a detailed investigation into the etiology of the pain is necessary. In some rare cases, glossopharyngeal neuralgia and trigeminal neuralgia can occur concurrently.[1]


The diagnosis of glossopharyngeal neuralgia is mainly clinical and should meet all criteria as mentioned in ICHD-3. A detailed history and physical examination of the patient is therefore mandatory. A thorough ENT examination is necessary, including a throat exam and neck palpation. All the patients should have basic laboratory evaluations, including complete blood count, basic metabolic panel and erythrocyte sedimentation rate, and anti-nuclear antibodies to rule out any underlying infection, inflammation, malignancy, or temporal arteritis.

Persistent symptoms are infrequent and warrant further investigation. Complications, including syncope, should have a cardiology evaluation with an echocardiogram and Holter monitoring.

The primary role of imaging is to identify potential causes of nerve compression at the base of the skull.

Computed Tomography (CT)

CT scans do not show the nerve directly but can identify an elongated and ossified styloid process in the axial images.[9]


An elongated and heavily calcified styloid process can be present on the cervical spine plain radiograph on the lateral view.[9]

Magnetic Resonance Imaging (MRI)

Neurovascular compression of the glossopharyngeal nerve is most visible on MRI. Thin section T2 weighted images are ideal for seeing pathology. An MRI with contrast should be performed to see any abnormal enhancement of the nerve, vessels, or surrounding structures. The most common vascular source of nerve compression is the posterior inferior cerebellar artery (PICA). The vertebral artery and anterior inferior cerebellar artery are the second and third most common culprit vessels. The MRI can also show demyelinating brain lesions, tumors in the posterior fossa, or any malformations.

Magnetic resonance angiogram (MRA)

MRA should also be done to evaluate for a vascular loop compressing on the nerve root entry zone.[10]

Treatment / Management


Medical management: Glossopharyngeal neuralgia is usually responsive to pharmacotherapy, especially with carbamazepine or oxcarbazepine.

Carbamazepine: Starting dose 200 mg/day in a single dose (extended-release), two divided doses (immediate-release tablet), or in four divided doses (oral solution). Increase the dose gradually with increments of 200 mg/day as needed. If the dose exceeds 200mg per day, it is advisable to administer extended-release capsules in two divided doses. Maintenance dose: 400 to 800 mg daily in two divided doses (immediate-release tablet) forms) or four divided doses (oral solution); maximum dose: no more than 1,200 mg/day.

The other neuropathic pain medicines recommended by the International Association for the Study of Pain (IASP) are as below:

  • Gabapentin (100 to 5000 mg/day in 1 to 4 divided doses),
  • Duloxetine (20 to 90mg/day),
  • Valproic acid (125-2500 mg/day in 1 to 2 divided doses),
  • Clonazepam (0.5-8 mg/day),
  • Lamotrigine (50 to 500 mg/day in 1 to 2 divided doses),
  • Baclofen (10 to 80 mg/day in 1 to 4 divided doses),
  • Phenytoin (200 to 600 mg/day in 1 to 3 divided doses),
  • Pregabalin (75 to 500 mg/day in 1 to 2 divided doses) and
  • Topiramate (50 to 1000 mg/day in 1 to 2 divided doses)

As a general rule, these medications should be started at low doses and titrated up as needed based on their effectiveness, tolerability, and side effects. This pain condition often shows a relapsing-remitting course, so medication can be tapered down to a low maintenance dose. Combining two or more medications with different mechanisms of action can help achieve better pain relief while avoiding side effects. A short course of opioids can be useful for intractable pain.

Adjuvant care: Cold and hot compresses, physical therapy, and psychological counseling are all options in addition to medical therapy. The success rate is variable but can be helpful.[11](B3)

Interventional Pain Management Techniques

Glossopharyngeal nerve blocks merit consideration for both diagnostic and therapeutic purposes. This block can be an option in conjunction with pharmacotherapy. A diagnostic block with a local anesthetic should be tried first to confirm the origin of the pain. If diagnostic blocks are successful, chemical neurolysis or thermal radiofrequency ablation can be performed on the nerve. Chemical neurolytic agents such as alcohol, glycerol, or phenol are typical choices. Radiofrequency ablation is typically performed at the jugular foramen to target the inferior petrous ganglion of Andersch. Accurate needle placement is critical as life-threatening bradycardia and hypotension can occur if the vagus nerve gets stimulated during the procedure. There are two common approaches to block the glossopharyngeal nerve: the intraoral and extra-oral approaches. The extra-oral technique is preferred since it is safe and easy to perform. Complications are not uncommon with glossopharyngeal neuralgia blocks. The glossopharyngeal nerve is in the vicinity of the internal jugular vein, and the carotid artery and intravascular injection can easily occur. The concomitant block of the recurrent laryngeal nerve may cause hoarseness of the voice. Always avoid bilateral glossopharyngeal nerve blocks at the same time to avoid complete vocal cord paralysis. Blockade of the vagus nerve may result in tachycardia and hypertension via blockade of parasympathetic fibers.[12][13][14](B3)

Surgical Management of Glossopharyngeal Neuralgia

Several surgical modalities are used for the treatment of glossopharyngeal neuralgia based on the etiology of the pain. The compression of the glossopharyngeal nerve by a vascular structure is the most common cause of secondary glossopharyngeal neuralgia. Microvascular decompression (MVD) of the glossopharyngeal nerve is the most widely used surgical modality to correct vascular compression of the nerve. Alternatively, a resection of the glossopharyngeal nerve alone or with branches of the vagus nerve can also be performed.

Extracranial techniques are percutaneous radiofrequency rhizotomy and direct surgical resection. These techniques are ideal in patients with essential glossopharyngeal neuralgia who failed medical management but cannot tolerate an open intracranial resection. Resection of the ipsilateral styloid process, also known as stylectomy, is a therapeutic option for Eagle syndrome. The physician must rule out other central causes of glossopharyngeal neuralgia before pursuing this surgery.

Intracranial techniques include rhizotomy or an intracranial root resection of the glossopharyngeal nerve and/or vagus nerves from its origin in the brainstem at the cerebellopontine angle. Persistent dysphagia and hoarseness of voice are the most common complications of these surgeries. Stereotactic radiosurgery with gamma knife surgery provides a less-invasive option, but data on safety and efficacy is limited.[14][15][16][17](B2)

Differential Diagnosis

  • Trigeminal neuralgia: Glossopharyngeal neuralgia is most commonly mistaken for trigeminal neuralgia since both have similar pain characteristics. Additionally, both of them are cranial neuralgias with similar pathophysiology and medical management. In certain rare cases, these conditions can coexist. Since the incidence of glossopharyngeal neuralgia is 1/1000 times less than trigeminal neuralgia, underdiagnoses of glossopharyngeal neuralgia are very common; this is why a thorough history and physical examination are essential since they both differ in the location of pain and provoking factors. Pain from glossopharyngeal neuralgia occurs in the throat and tonsillar region and is exacerbated by swallowing and chewing movement, whereas pain from trigeminal neuralgia occurs on the face in the trigeminal nerve distribution and is exacerbated by a light touch on the face, washing the face and brushing the teeth.
  • Jacobson’s neuralgia: When the only symptom of glossopharyngeal neuralgia is the sensory loss at the ear (the otic form of glossopharyngeal neuralgia), it gets confused with intermedius or Jacobson neuralgia.
  • Temporal arteritis and temporomandibular joint dysfunction: Pain in these pathologies occurs in the same distribution, but the pain characteristics in both pathologies are entirely different from glossopharyngeal neuralgia.[5]


Glossopharyngeal neuralgia has a variable prognosis based on the patient’s symptoms. Most of the patients have a single episode of painful paroxysmal attacks. The annual recurrence rate is as low as 3.6%. Only 25% of patients require surgery, and the rest are manageable medically. Less than one in four patients will have bilateral pain.

Bilateral pain, multiple bouts of severe excruciating pain, and constant pain are poor prognostic indicators.[18][1]


Syncope and cardiac dysrhythmias: When the glossopharyngeal nerve gets irritated, it sends feedback via the dorsal motor nucleus of the Xth nerve. These signals also stimulate the nucleus tractus solitarius in the midbrain. Thus, during the acute glossopharyngeal neuralgia attack, abnormal stimulation produces an amplified vagal response, resulting in bradycardia, hypotension, and cardiac dysrhythmias. These autonomic changes cause cerebral hypoperfusion, slow waves on EEG, seizures, and syncope. Convulsive movements, limb clonus, automatic smacking movements of the lips, and upward turning of the eyes are signs of cerebral hypoxia.

Cardiovascular complications occur during painful episodes or immediately after the pain symptoms resolve. Management of glossopharyngeal neuralgia pain attacks with drugs and/or surgical treatment can help manage these complications. Some patients only develop cardiovascular manifestations of glossopharyngeal neuralgia without painful paroxysms, also known as non-neurologic glossopharyngeal neuralgia. These patients can receive therapy with glossopharyngeal nerve avulsion or microvascular decompression.[19][20]

Deterrence and Patient Education

Patients with glossopharyngeal neuralgia need to understand the nature of their condition and have realistic expectations regarding their therapeutic regimen. Patients need to keep their clinicians informed as to the effectiveness or lack thereof of any therapy so that adjustments can be made.

Enhancing Healthcare Team Outcomes

Glossopharyngeal neuralgia is a rare but complex pain syndrome requiring multidimensional management. Management of glossopharyngeal neuralgia requires expertise from the fields of neurology, otorhinolaryngology, interventional pain, and neurosurgery. It is best to manage the condition with an interprofessional team of specialists, specialty-trained nursing staff, and pharmacists for optimal patient outcomes. [Level 5]

No clinical trials demonstrate the efficacy of the different groups of medications used in the medical management of glossopharyngeal neuralgia. Since glossopharyngeal neuralgia is a type of neuropathic pain, it would be beneficial to present levels of evidence of medicines used in the management of glossopharyngeal neuralgia. Gabapentin and pregabalin, selective serotonin receptor inhibitors, carbamazepine, and tricyclic antidepressants are first-line treatments. The primary care provider and nurse practitioner should educate the patient on the potential side effects of these drugs. Second-line treatment includes opioids, certain anti-seizure medicines (like lamotrigine), topical capsaicin, and N-methyl-D-aspartate receptor antagonists. These classes of drugs have shown the best evidence with clinically relevant effects without any superiority from one over another. One meta-analysis study reported that despite an increase of published trials by 66%, there is only a limited improvement in the medical management of neuropathic pain.[21][22]



Blumenfeld A, Nikolskaya G. Glossopharyngeal neuralgia. Current pain and headache reports. 2013 Jul:17(7):343. doi: 10.1007/s11916-013-0343-x. Epub     [PubMed PMID: 23709235]


Peet MM. GLOSSOPHARYNGEAL NEURALGIA. Annals of surgery. 1935 Jan:101(1):256-68     [PubMed PMID: 17856446]


Rushton JG, Stevens JC, Miller RH. Glossopharyngeal (vagoglossopharyngeal) neuralgia: a study of 217 cases. Archives of neurology. 1981 Apr:38(4):201-5     [PubMed PMID: 7213143]

Level 3 (low-level) evidence


Singh PM, Kaur M, Trikha A. An uncommonly common: Glossopharyngeal neuralgia. Annals of Indian Academy of Neurology. 2013 Jan:16(1):1-8. doi: 10.4103/0972-2327.107662. Epub     [PubMed PMID: 23661955]


Teixeira MJ, de Siqueira SR, Bor-Seng-Shu E. Glossopharyngeal neuralgia: neurosurgical treatment and differential diagnosis. Acta neurochirurgica. 2008 May:150(5):471-5; discussion 475. doi: 10.1007/s00701-007-1493-6. Epub 2008 Feb 4     [PubMed PMID: 18231706]


Katusic S, Williams DB, Beard CM, Bergstralh EJ, Kurland LT. Epidemiology and clinical features of idiopathic trigeminal neuralgia and glossopharyngeal neuralgia: similarities and differences, Rochester, Minnesota, 1945-1984. Neuroepidemiology. 1991:10(5-6):276-81     [PubMed PMID: 1798430]


Walker HK, Hall WD, Hurst JW, Walker HK. Cranial Nerves IX and X: The Glossopharyngeal and Vagus Nerves. Clinical Methods: The History, Physical, and Laboratory Examinations. 1990:():     [PubMed PMID: 21250227]


Pearce JM. Glossopharyngeal neuralgia. European neurology. 2006:55(1):49-52     [PubMed PMID: 16479122]


Murtagh RD, Caracciolo JT, Fernandez G. CT findings associated with Eagle syndrome. AJNR. American journal of neuroradiology. 2001 Aug:22(7):1401-2     [PubMed PMID: 11498437]

Level 3 (low-level) evidence


Resnick DK, Jannetta PJ, Bissonnette D, Jho HD, Lanzino G. Microvascular decompression for glossopharyngeal neuralgia. Neurosurgery. 1995 Jan:36(1):64-8; discussion 68-9     [PubMed PMID: 7708170]


Dworkin RH, Backonja M, Rowbotham MC, Allen RR, Argoff CR, Bennett GJ, Bushnell MC, Farrar JT, Galer BS, Haythornthwaite JA, Hewitt DJ, Loeser JD, Max MB, Saltarelli M, Schmader KE, Stein C, Thompson D, Turk DC, Wallace MS, Watkins LR, Weinstein SM. Advances in neuropathic pain: diagnosis, mechanisms, and treatment recommendations. Archives of neurology. 2003 Nov:60(11):1524-34     [PubMed PMID: 14623723]

Level 3 (low-level) evidence


Bean-Lijewski JD. Glossopharyngeal nerve block for pain relief after pediatric tonsillectomy: retrospective analysis and two cases of life-threatening upper airway obstruction from an interrupted trial. Anesthesia and analgesia. 1997 Jun:84(6):1232-8     [PubMed PMID: 9174298]

Level 3 (low-level) evidence


Rao S, Rao S. Glossopharyngeal Nerve Block: The Premolar Approach. Craniomaxillofacial trauma & reconstruction. 2018 Dec:11(4):331-332. doi: 10.1055/s-0037-1606249. Epub 2017 Aug 25     [PubMed PMID: 30574279]


Isamat F, Ferrán E, Acebes JJ. Selective percutaneous thermocoagulation rhizotomy in essential glossopharyngeal neuralgia. Journal of neurosurgery. 1981 Oct:55(4):575-80     [PubMed PMID: 7277005]

Level 3 (low-level) evidence


Rey-Dios R, Cohen-Gadol AA. Current neurosurgical management of glossopharyngeal neuralgia and technical nuances for microvascular decompression surgery. Neurosurgical focus. 2013 Mar:34(3):E8. doi: 10.3171/2012.12.FOCUS12391. Epub     [PubMed PMID: 23451790]


Xiong NX, Zhao HY, Zhang FC, Liu RE. Vagoglossopharyngeal neuralgia treated by microvascular decompression and glossopharyngeal rhizotomy: clinical results of 21 cases. Stereotactic and functional neurosurgery. 2012:90(1):45-50. doi: 10.1159/000333828. Epub 2012 Jan 14     [PubMed PMID: 22249175]

Level 2 (mid-level) evidence


Giorgi C, Broggi G. Surgical treatment of glossopharyngeal neuralgia and pain from cancer of the nasopharynx. A 20-year experience. Journal of neurosurgery. 1984 Nov:61(5):952-5     [PubMed PMID: 6491739]

Level 2 (mid-level) evidence


Katusic S, Williams DB, Beard CM, Bergstralh E, Kurland LT. Incidence and clinical features of glossopharyngeal neuralgia, Rochester, Minnesota, 1945-1984. Neuroepidemiology. 1991:10(5-6):266-75     [PubMed PMID: 1798429]


Ferrante L, Artico M, Nardacci B, Fraioli B, Cosentino F, Fortuna A. Glossopharyngeal neuralgia with cardiac syncope. Neurosurgery. 1995 Jan:36(1):58-63; discussion 63     [PubMed PMID: 7708169]

Level 3 (low-level) evidence


Elias J, Kuniyoshi R, Carloni WV, Borges MR, Peixoto CA, Pimentel D. Glossopharyngeal neuralgia associated with cardiac syncope. Arquivos brasileiros de cardiologia. 2002 May:78(5):510-9     [PubMed PMID: 12045849]

Level 3 (low-level) evidence


Dworkin RH, O'Connor AB, Backonja M, Farrar JT, Finnerup NB, Jensen TS, Kalso EA, Loeser JD, Miaskowski C, Nurmikko TJ, Portenoy RK, Rice ASC, Stacey BR, Treede RD, Turk DC, Wallace MS. Pharmacologic management of neuropathic pain: evidence-based recommendations. Pain. 2007 Dec 5:132(3):237-251. doi: 10.1016/j.pain.2007.08.033. Epub 2007 Oct 24     [PubMed PMID: 17920770]

Level 3 (low-level) evidence


Finnerup NB, Attal N, Haroutounian S, McNicol E, Baron R, Dworkin RH, Gilron I, Haanpää M, Hansson P, Jensen TS, Kamerman PR, Lund K, Moore A, Raja SN, Rice AS, Rowbotham M, Sena E, Siddall P, Smith BH, Wallace M. Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis. The Lancet. Neurology. 2015 Feb:14(2):162-73. doi: 10.1016/S1474-4422(14)70251-0. Epub 2015 Jan 7     [PubMed PMID: 25575710]

Level 1 (high-level) evidence