REVIEW PAPER

Grisel’s syndrome: a comprehensive review with focuson pathogenesis, natural history, and currenttreatment options

Stephen Osiro & Kevin J. Tiwari & Petru Matusz &

Jerzy Gielecki & R. Shane Tubbs & Marios Loukas

Received: 12 January 2012 /Accepted: 17 January 2012 /Published online: 1 February 2012# Springer-Verlag 2012

AbstractIntroduction Grisel’s syndrome (GS) is a rare otolaryngologiccondition that involves rotatory subluxation of the atlanto-axial joint in the absence of trauma. Sir Charles Bell was thefirst to describe this condition in 1830. However, it was namedafter Pierre Grisel, a French ENT specialist who in 1930described three such cases in children.Methods Using standard search engines, we reviewed themost recent literature regarding GS with special attention toits pathogenesis, natural history, and recent treatment options.Results Although defined over 80 years ago, the exact path-ogenesis leading to GS is still not completely understood.Nevertheless, it occurs mainly as a complication of upperrespiratory tract infections and/or surgical interventions inthe head and neck. Most recent studies postulate that thespread of septic emboli from such infection nidus via thepharyngovertebral veins to the periodontoid vascular plexuscould be the most likely cause. The diagnosis of GS is madeby both clinical assessment as well as radiologic confirmation

with either CT scan or MRI. Our review found out that mostauthors favor immobilization with a soft collar and antibioticsover surgical correction in the initial management of GS.Surgery is reserved for severe and refractory cases.Conclusion GS remains a rare, but potentially lethal chil-dren condition. Early diagnosis and treatment is crucial to itsmanagement and prognosis.

Keywords Grisel’s syndrome . Atlantoaxial subluxation .

Infectious process . Antibiotic therapy

Introduction

Sir Charles Bell is widely regarded as the first to describe acase of atlantoaxial subluxation in a patient who had pharyn-gitis from syphilis and later died from spinal cord compression[2]. Nearly a century later, Pierre Grisel [11] described threepatients with pharyngitis and torticollis who also had disloca-tion of the C1–C2 joint. Ever since, the condition has beencalled Grisel’s syndrome (GS), with numerous casereports showing a strong association between its occur-rence and upper respiratory tract infections or surgicalinterventions in the head and neck region [8, 22, 26].

By definition, GS is a nontraumatic subluxation of C1–C2 joint. This specific joint involvement distinguishes itfrom its variants, where dislocations have been shown tooccur either at the C2–3 or C3–4 joints [16, 17]. It mostoften follows adenoidectomy, tonsillectomy, and rarely,mastoidectomy [8]. Infections of the head and neck are thesecond most common cause [1].

Despite several theories and publications on its etiology,the pathogenesis of GS remains elusive. Most authors pro-pose that the hematogenous spread of infections from theposterior–superior pharynx to the cervical spine is what

S. Osiro :K. J. Tiwari :M. Loukas (*)Department of Anatomical Sciences, School of Medicine,St. George’s University,Grenada, West Indiese-mail: mloukas@sgu.edu

P. MatuszDepartment of Anatomy, Victor Babes University of Medicineand Pharmacy,Timisoara, Romania

J. Gielecki :M. LoukasDepartment of Anatomy, Medical School Varmia and Mazuria,Olsztyn, Poland

R. S. TubbsPediatric Neurosurgery, Children’s Hospital,Birmingham, AL, USA

Childs Nerv Syst (2012) 28:821–825DOI 10.1007/s00381-012-1706-z

initiates the cascade leading to the syndrome [9, 24, 26]. Theanatomical route of possible spread of the septic emboli fromthe pharyngovertebral veins to the periodontoidal vascularplexus, as was first described by Parke, is often used tosupport this postulation [21]. The diagnosis of GS is clinical,with painful torticollis and aversion to head rotation consid-ered pathognomonic [6]. However, since it can mimic severalotolaryngologic conditions, radiographic confirmation of thediagnosis with either CT scan or MRI is often required.

Although rare, GS can be fatal and early recognition andsurgical management is paramount to decrease its morbidityand mortality. In this literature review, we present the mostcomprehensive understanding of GS to date, with emphasisplaced on recent developments on its pathogenesis as wellas treatment options.

Etiology and prevalence

GS primarily affects children with 68% under the age of12 years [10] and close to 90% under the age of 21 years[27]. Since the transverse and alar ligaments that largelyoppose anterior displacement of the atlas on the axis seemto be involved, it is plausible that those with baseline laxityon these ligaments are at higher risk and will be mostlyaffected. It is due to this that children and Down syndromepatients are somewhat more disproportionately affected thanthe general population [14].

GS is seen equally in bothmales and females [25], and onlyrare cases been described in adults [4, 12, 20]. Most literaturesreport that it predominantly follows surgical procedures of thehead and neck, with upper respiratory tract infections (URTIs)a close second [8]. Gourin et al. [10] reported that 21 of 78(26.9%) GS cases occurred post-op, while 14 of 78 (18%)were secondary to URTIs. This finding was corroborated byDeichmueller and his colleagues who reported that 67% oftheir GS were post-ENTsurgery patients, while 33% followednasopharyngeal infections [6].

Nevertheless, there are isolated reports showing that GSstems mainly from URTIs. Karkos et al., for instance,reported that of their 96 GS cases, 48% were due to infec-tions while 31% occurred after surgery [15]. There are alsoliteratures describing GS in the setting of an unknown pre-disposing factor, but these are rare [4].

Pathogenesis and anatomy

The pathogenesis of GS is not completely understood de-spite numerous hypotheses over the years. Grisel’s initialthought was that the atlantoaxial subluxation was due tomuscle spasm from an infectious process [1, 11]. He postu-lated that the spasm, along with the resultant torticollis and

subluxation, was the body’s attempt to reduce the pressureon the inflamed tissue. However, this theory could not bevalidated because Grisel was not able explain the spread ofthe infection leading to the spasm. In addition, he could notaccount for the increased incidence of Grisel’s syndrome inchildren [1].

Since then, others have since proposed that inflammatoryprocesses leading to hyperemic state in the paravertebraltissues is the possible cause of GS [7]. The argument is thatwith inflammation, C1 and C2 steadily decalcify, causing aweakening of the insertions of the transverse ligament ontothe C1 vertebrae. The resultant transverse ligament laxitythen leads to subluxation reminiscent of GS. Supporters ofthis theory point to a previous finding by Parke and col-leagues who in 1984 described a new system of pharyngo-vertebral veins that drain the pharynx into the periodontalvenous plexus [21]. In their landmark study, they used latexto inject cervical epidural sinuses of a series of humanperinatal cadavers and showed retrograde filling of thesenovel venous systems with numerous lymphovenous anas-tomoses. These veins are thought to pass the septic exudatesto the C1–C2 joint from the upper respiratory tract (Fig. 1).

Despite the existence and description of this direct path-way that possible infections and inflammatory mediatorscan use to reach the cervical ligaments, prior studies hadfound little evidence linking hyperemia or septic infiltratewith either C-1 decalcification or ligamentous laxity [19],with only one study in favor [28]. This paucity of evidenceover the years is what prompted Welinderet al. [26] topostulate that the atlantoaxial subluxation (AAS) was due

Fig. 1 A schematic diagram showing the venous drainage of the upperairway tract and the routes of possible spread of septic emboli to theperiodontoidal venous plexus. 1 anterior and posterior ethmoidal veins;2 tributaries of the sphenopalatine veins; 3 tributaries of the maxillaryveins and posterior pharyngeal plexus; 4 pharyngovertebral veins,which communicates with periodontoidal plexus and epidural veins(reproduced and used with permission from [21])

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to a spasmic distention of the ligaments connecting the atlasand axis rather than their loosening by the spreading edemafrom the inflamed soft neck tissues. These authors suggestedthat GS starts as a typical torticollis from the spasm ofirritated neck muscles. In the presence of preexisting laxC1–C2 ligaments, this spasm can lead to distension andeventually subluxation of the atlas and axis. They arrivedat this conclusion after following a 6-year-old boy withserial CT scans for 2 months. The boy apparently had anepisode of retropharyngeal abscess and later developed GS[26].

The above observation gained considerable tractionbecause it could partly explain the prevalence of GS in chil-dren and Down syndrome patients. Studies show that the latterhave a greater laxity of the atlantoaxial ligaments and wideratlantodental intervals than the general population [14].Battiata and his colleagues used this line of reasoning topropose a two-hit hypothesis of GS development, with thefirst hit being the existence of this baseline laxity [1]. Theynoted that the increased mobility of C1 on C2 places thesesusceptible individuals at a higher risk of GS following thesecond hit, or the induction of spasm caused by the inflam-matory mediators carried to the cervical muscles by pharyng-overtebral venous plexus [1]. The explanation by Battiata isthe most widely accepted theory [21]. Nevertheless, it still

falls short in accounting for the overall relative rarity of GS inthe population given the many URTIs in children and/or ENTprocedures performed each year. A more plausible pathoge-netic mechanism is therefore still needed.

Signs and symptoms

GS often manifests as a very painful torticollis, with feverand nonspecific signs of infection [26]. Deichmueller andWelkoborsky [6] described 12 cases of GS in which all thepatients had torticollis as the first symptom and three

Fig. 2 AP radiograph showing Grisel’s syndrome in a 3-year-old blackfemale who presented with a 3-day history of torticollis without trau-ma. The girl had developed streptococcal infection with otitis mediaand pharyngitis a week before the presentation. Antibiotic therapyresulted in resolution of the torticollis

Fig. 3 A sagittal CT of the head and neck showing thickened posteriorpharyngeal wall with thickening of tissues around dens and atlas

Table 1 Diagnostic algorithm for Grisel’s syndrome (used with per-mission from [6])

•History of ENT surgery or ENT infection

•Torticollis some days after onset of infection/operation

•Rotation and slight flexion of the head with chin rotatedcontralaterally

•Painful active and passive rotation of the head

•In the first days of torticollis, elevated CRP and leucocytes, and later,normalization of these parameters and usually no fever

•Radiograph of the cervical spine: space between atlas and densaxis >5 mm

•CT scan: atlantoaxial subluxation and rotation

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children had inflamed cervical lymph nodes. Some patientsmay also complain of throat pain and symptoms indicativeof spinal cord or nerve injury. However, such presentationsare mainly typical of previously misdiagnosed cases [18].

Diagnosis

The diagnosis of GS is clinical and should be suspected inany child or a Down syndrome patient who presents withtorticollis after an episode of nasopharyngitis or post-otolaryngologic surgery. Since the condition can mimicseveral other causes of torticollis, such as meningitis, pain-ful lymphadenopathy, or traumatic postsurgical subluxation,a radiographic confirmation is often necessary.

Transoral films can be used, especially in the initialstages, to visualize the rotational deformity (Fig. 2). Theanteroposterior radiographs, on the other hand, can helpdisplay the asymmetry between the facet joints [13]. Anatlantodental interval of greater than 4.5 mm is generallysuggestive of disease [23]. CT scans (Fig. 3) and/or MRI ofthe head and neck are largely considered the gold standardfor GS diagnosis [1, 23]. They can also rule out any associateddeep tissue infections and/or abscess formation. A checklistfor the diagnosis of GS developed by Deichmueller and hiscolleagues is shown in Table 1.

Management and prognosis of GS

Early index of suspicion and diagnosis of GS is crucial to itsmanagement and prognosis [1, 3, 5]. The treatment modalityconsists of reduction of the C1–C2 subluxation and resolutionof the infectious process. So far, no universal treatment algo-rithm exists, but the majority of authors favor conservativetreatments and individualized therapy over algorithms.

Antibiotics and cervical collars are usually regarded asthe first line treatment option, with traction being the nextstep. We found several cases where full recovery wasachieved solely on such treatment [3, 5, 6]. For instance,in the study by Deichmueller et al., 8 of their 12 patients hadfull remission after intravenous antibiotics and oral anti-inflammatory therapies alone. Only four patients requiredfurther intervention.

Patients who present with intractable cases typically haveexperienced torticollis for more than 2 weeks without anytreatment [6, 22]. Such patients are often managed withmanual repositioning under general anesthesia followedtemporary immobilization with a Minerva orthesis or halofixation [6, 8, 22]. We found several surgical approaches toreduce the AAS in the literature with favorable results, butthere is no universal agreement on the best method. Up to15% of untreated GS patients develop severe neurological

complications in the form of nerve damage, paralysis, andeven death [24, 29].

Conclusions

GS remains a rare but potentially lethal condition whose earlydiagnosis and treatment is crucial. Although the mechanismleading to its occurrence is not clearly defined, GS is thoughtto be the result of an infectious process which abnormallydistends the C1 and C2 ligaments and destabilizes the joint.

We emphasize the need for clinicians to suspect thissyndrome in children who present with acute torticollisfollowing either an infection or surgical procedure in theupper aerodigestive tract. While most GS cases respond toantibiotics and anti-inflammatory therapies alone, surgicalintervention should be an option especially in patients whohave prolonged torticollis and/or are refractory to conserva-tive modalities.

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