Villaret Syndrome: A Systematic Review

Abstract

Villaret syndrome (VS) is a rare condition characterized by concurrent involvement of cranial nerves (CNs) IX–XII and the cervical sympathetic chain, suggesting a pathological process in the retrostyloid compartment. We conducted a systematic review to synthesize current knowledge regarding etiologies, clinical presentation, management strategies, and CN outcomes. A systematic search was performed across the PubMed and Scopus databases up to January 2025, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We included all case reports and case series describing patients with clinically and/or radiologically confirmed VS. Twelve studies met inclusion criteria. Data were extracted regarding demographics, etiology, onset modality, imaging findings, treatment strategies, and clinical outcomes. Among the 13 identified patients (mean age 48.7 years), neoplastic causes were most common (58.3%), followed by vascular (25%) and infectious/inflammatory etiologies (16.7%). The most frequent mode of onset was subacute (58.3%), and MRI was the preferred imaging modality in all cases. Conservative management (including steroids or antithrombotic therapy) was used in 41.6% of cases, while 33.3% underwent surgery. Complete or near-complete recovery was observed in 50% of patients, predominantly those with vascular or inflammatory etiologies. Neoplastic VS was associated with poorer outcomes. VS, although rare, should be recognized early and should prompt the clinician to use modern imaging modalities to search for a pathological process in the retrostyloid compartment. Given its rarity and complexity in most cases, the treatment strategy should be tailored to each specific patient and involve a multidisciplinary team of physicians.

Introduction

Due to their close anatomical proximity, the glossopharyngeal (IX), vagus (X), spinal accessory (XI), and hypoglossal (XII) nerves, together with the cervical sympathetic trunk, are particularly vulnerable to combined dysfunction in the event of a space-occupying lesion or an injury along their course. ¹ In this confined anatomical corridor, even small pathological processes can affect cause combined nerve deficit, leading to distinct and well-described clinical syndromes. ²

Among these syndromes, Villaret syndrome (VS) is a rare but striking entity. ³ It was first described in 1916 by the French neurologist Maurice Villaret, based on his observation of two soldiers with gunshot wounds to the mastoid region. ⁴ VS is defined by unilateral palsy of the four lower cranial nerves (CN), i.e., IX–XII, accompanied by ipsilateral Horner syndrome, due to involvement of the cervical sympathetic fibers. ⁴

Overlapping syndromes include Vernet syndrome characterized by deficits of CN IX–XI, ⁵ reflecting a lesion at the jugular foramen, and Collet–Sicard syndrome, involving deficits of CN IX–XII, ^{1 2} indicating an injury in the mastoid region. VS involves the same four lower CNs but is distinguished by the additional involvement of the ipsilateral sympathetic fibers, causing Horner syndrome, i.e., ptosis, miosis, and anhidrosis. This constellation of deficits localizes the lesion to the posterior retroparotid – or retropharyngeal space. Recognizing these overlapping syndromes is essential for accurate anatomical localization and etiological differentiation, especially in the context of complex skull base or vascular lesions.

Despite the clear anatomical basis of VS, it remains a rarely reported and underrecognized condition, with most data scattered across isolated case reports. No comprehensive synthesis currently outlines the full clinical spectrum, etiologies, management strategies, and outcomes associated with this condition. This systematic review aims to address this gap by analyzing all reported cases of VS. We seek to identify its most common causes, describe diagnostic and therapeutic approaches, evaluate cranial nerve recovery, and assess patient outcomes using the Glasgow Outcome Scale (GOS). This knowledge would contribute in decision making and to inform patients on prognosis when facing with VS.

Materials and Methods

Study Design

We conducted a systematic review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline, using the MEDLINE/PubMed database from inception to January 2025. Our aim was to systematically compile reported cases of VS. Hence, we included articles providing individual extractable data on cases of Villaret's syndrome. We excluded articles that were not directly relevant to the subject, letters or reviews without an institutional case displayed, and articles with a significant lack of data ( Fig. 1 , Flowchart). Non-English articles were not excluded (cf search strategy).

Fig. 1.

Flow chart.

IRB was not required for this study. A preliminary search based on PubMed, Cochrane Library, and Google Scholar revealed no previous systematic review on this specific subject. This study did not receive any funding or financial support. The authors have no personal, financial, or institutional interest related to this article.

Search Strategy

A search strategy was developed based on the Cochrane Handbook for Systematic Review [X]. First, we defined the following medical subject headings (MeSH): “Villaret's syndrome,” “Villaret,” “case report,” “case series,” “retroparotid space.” We then conducted a comprehensive literature search of the MEDLINE/PubMed database ( https://pubmed.ncbi.nlm.nih.gov/ ) using the advanced search mode, from inception to January 01, 2025.

The initial research yielded 34 results. A first screening of those articles found 16 in English, four in French, three in Spanish, five in Japanese, four in Polish languages, and two in German. To include most of the described cases, we included coauthors who are fluent in French (M.S., A.C., N.B.), Spanish (M.S.), Japanese (Y.M.), and Polish (P.Ł.).

Data Collection

The data item list included general information related to the article (first author, year of publication, country of the first author), the patients (gender, age), mechanism and precise causative disease, deficit of cranial nerve IX, X, XI, XII, presence of sympathetic involvement and eventual presence of other cranial nerve deficit, diagnostic imaging, treatment modalities, cranial nerve function improvement; and functional outcome according to the GOS score.

Primary and Secondary Endpoints

The primary endpoint of the study was to determine the improvement of CN function of patients presenting with VS according to a three-grade scale: complete recovery (CR), partial recovery (PR), and no recovery. An overall improvement (OI) of CN function was defined as follows: PR of all the impacted CN, plus CR of at least two impacted CN.

The secondary endpoints were to define the most common causes of VS, to provide an overview of the treatment strategies employed, and to assess the functional outcome according to the GOS score.

Statistical Analysis

Categorical variables were summarized as counts and percentages. For the primary endpoint, the proportion of patients with significant improvement was estimated with Fisher's exact test. and compared with reference proportions using the exact binomial test. Associations between age groups (≤40 vs >40 years) and outcome, as well as between etiology (vascular, oncological, traumatic) and outcome (good vs. poor prognosis according to dichotomized GOS), were assessed using Fisher's exact test. Relative risks with 95% confidence intervals were calculated when appropriate. Statistical significance was set at p  < 0.05, and results should be interpreted with caution due to the small sample size.

Results

Database Research

The initial research yielded 34 articles. Seven articles were excluded after the first screening because they were not related to the topic ( n  = 6) or involved animal studies ( n  = 1). Five articles were not retrieved, and 10 articles were excluded after full content review, due to a lack of data ( n  = 8) or lack of direct relevance to the topic ( n  = 2; one article on shoulder luxation and another on fatty tongue in patients with VS). Ultimately, 12 studies were included ^{6 7 8 9 10 11 12 13 14 15 16 17} in the final review, comprising a total of 13 cases ( Table 1 ). The mean age was 48.7 years, and the male-to-female ratio was 1/1.2 ( Table 2 ).

Table 1. Medline-based systematic literature review of patients presenting with Villaret syndrome.

Study	Sex, age	Mechanism/ disease	Causative lesion	CN deficits						Diagnostic imaging	Treatment	Alimentation	CN outcome					GOS
				IX	X	XI	XII	Sympathetic involvement	Others				IX	X	XI	XII	Sympathethic involvement
Boon et al 1990, Belgium	Female 58	Infection Mastoiditis MR: breast ADK	Thrombophlebitis of right jugular vein	Y	Y	Y	Y	Horner's sign	VIIc	CT, Tc99, MRI, Xa	_	_	_	_	_	_	_	−
Garrett et al (1993), United States	Female 16	Vascular	Pseudo aneurysm of the LICA	Y	Y	Y	Y	Horner's sign	Hemiparesis L Hemi-hypalgesia R	CT, Xa	Surgery (clipping)	_	CR 6m	CR 3y	CR 6m	CR 6m	_	5
Garrett et al, (1993), United States	Male 19	Traumatic	Ballistic injury (?)	Y	Y	Y	Y	Overactivity: Mydriasis	VII R	CT, Xa	Surgery (partial severance of VII)	_	NR	NR	NR	NR	PR of VII and mydriasis	3
Tiliket et al (1996), France	Male 68	Tumor Lung large cell carcinoma	Metastasis	Y	Y	Y	Y	Horner's sign	_	CT, Doppler US, MRI	Chemotherapy Radiotherapy	NGT	NR	NR	NR	NR	NR	1
Sicenica et al (2000), United States	Male 64	Tumor Prostate carcinoma	Metastasis closed to jugular foramen	Y	Y	Y	Y	Horner's sign	_	CT, MRI	Palliative radiation therapy	_	NR	NR	NR	NR	NR	1
Flis et al (2015), United States	♀Female 62	Tumor MR: breast ADK	Metastasis	Y	Y	Y	Y	Horner's sign	_	CT, MRI	Surgery (biopsy) Radiotherapy	_	_	_	_	_	_	_
Pavan et al (2017), India	Female 26	Tumor Malignant hepatic epithelioid hemangioendothelioma	Metastasis Jugular foramen	Y	Y	Y	Y	Horner's sign	_	MR	Supportive treatment	_	_	_	_	_	_	1
Guerra-Mora et al (2016), Mexico	Female 37	Tumor MR: NF1	MPNST at left jugular foramen	Y	Y	Y	Y	Horner's sign	_	MRI, TEP-CT	Surgery	_	NR	NR	NR	PR 6m	PR 6m VII post surgery (HB 4 to 3)	3
Magistrelli et al (2017), Italy	Female 67	Tumor Breast cancer	Metastasis	Y	Y	Y	Y	Horner's sign	_	MR, CT, PET-CT	Chemotherapy	_	PR	_	_	PR	PR	4
Mizutani et al (2011), Japan	Male 50	Vascular	Left ICA dissection	Y	Y	Y	Y	Horner's sign	_	CT, Doppler US, MRI, DSA	Antithrombotic therapy	_	PR	PR	PR	PR	PR	4
Oba et al (1983), Japan	Male 69	Vascular	Aneurysm of the R ICA (cervical)	Y	Y	Y	Y	Horner's sign	L hemiparesis due to surgery for aneurysm	CT, angiogram	Surgery (ICA ligation with bypass)	_	CR 2y	CR 2y	CR2 y	CR 2y	CR 2y	4
Szulc-Kuberska et al (1978) Poland	Male 73	Tumor Renal cancer (renal clear cell carcinoma)	Metastasis (damaged skull. Base in jugular foramen and foramen magnum areas, damaged anterior part of atlas)	Y	Y	Y	Y	Not mentioned	Villaret–Sicard–Collet, VII left	Urography, X-ray of skull base	–	–	–(No further follow-up)	–	–	−	−	1 Patient died after 9 months (acute circulatory failure)
Kozik and Pioch (1958), Poland	Female 24	Tumor subcarinal psammomatous	Tumor lesion in pharyngeal area (between foramen lacerum and jugular foramen)	Y	Y	Y	Y	Horner's sign	Palatine tonsillitis (tonsillitis chronic hypertrophic), VII left	X-ray of skull base	Tonsillectomy, therapeutic irradiation (roentgenotherapy), surgery (removal of neoplasm lesion)	–	(No information about improvement)	–-	–-	−	VII slight hemiparesis	=

Abbreviations: CR, complete recovery; DSA, digital subtraction angiography; ICA, internal carotid artery; LICA, left internal carotid artery; MPNST, malignant peripheral nerve sheath tumor; NR, no recovery; PR, partial recovery.

Table 2. Causes of Villaret syndrome.

Parameter	Number of patients	Percentage
Total	13	100
Mean age	48.7
Male-to-female ratio	6/7 (1/1.2)
Cause
Tumor	8	61.5
Metastasis	6	46.1
MPNST	1	7.7
Meningioma	1	7.7
Traumatic	1	7.7
Ballistic	1	7.7
Vascular	3	23.1
Infection	1	7.7
Thrombophlebitis	1	7.7

Mechanisms and Etiologies

Tumors were the main etiology among patients with VS (61.5%, n 8/13). These included skull base metastases (46.1%, 6/13) comprising two cases of breast cancer ( n  = 2/6), one lung cancer ( n  = 1/6), one prostate cancer ( n  = 1/6), and one kidney cancer ( n  = 1/6). Other tumor cases were meningiomas (7.7%, n  = 1/13) and malignant peripheral nerve sheath tumor (7.7%, n  = 1/13). Trauma accounted for 23.1% of the cases (23.1%, n  = 3/13), including traffic accident ( n  = 2/3) and a ballistic injury ( n  = 1/3). Vascular causes accounted for 23.1% of the cases ( n  = 3/13) with one internal carotid artery (ICA) aneurysm (23.1%, n  = 3/13), one ICA pseudoaneurysm ( n  = 1/3), and one dissection of the ICA ( n  = 1/3). Infection was identified in one case (7.7%) involving a patient with a thrombophlebitis secondary to mastoiditis, with no organism identified.

Treatment

Treatment strategy was based on the etiology. Among patients with skull base tumors, 37.5% ( n  = 3/8) underwent surgery: one meningioma, one breast metastasis, and one malignant peripheral nerve sheath tumor. These tumors were located near the jugular foramen. Additionally, 18.2% ( n  = 2/11) benefited from palliative radiotherapy or supportive care (metastasis). The mean age of these patients was 41 years (range: 24–62).

Among patients with vascular etiologies, 66.7% ( n  = 2/3) benefited from surgery. Clipping was performed for the ICA pseudoaneurysm, and ligation with vascular bypass was performed for the ICA aneurysm. ICA dissection was treated medically with antithrombotic therapy.

Progressive Recovery of Cranial Nerve Deficits

Among the available data, only seven cases provided exhaustive information regarding cranial nerve functional outcomes. Of these, two fulfilled the predefined criteria for an overall improvement, corresponding to 28.6% of cases (CI 95%: 3.7–70.9%; p  = 0.42). Given the small sample size, no statistically significant conclusion could be drawn. More precisely, CN improved partially or completely for 50% of CN IX ( n  = 4/8), 42.9% of both CN X–XI cases ( n  = 3/7), 62.5% of CN XII cases ( n  = 5/8), and 71.4% of cases with sympathetic involvement ( n  = 5/7) ( Table 3 ). CR was observed in 15.4% of cases for all CN IX–XII, and in 7.7% of cases with sympathetic involvement.

Table 3. Nerve function upon admission and after treatment.

Admission cranial nerve status		Number	Percentage
IX		13	100
X		13	100
XI		13	100
XII		13	100
Sympathetic involvement		13	100
Other		4	30.8
VII		4	30.8
Long-term cranial nerve status
IX	CR	2	15.4	50% ( n 4/8)
	PR	2	15.4
	NR	4	30.8
	Not reported	5	38.5
X	CR	2	15.4	42.9% ( n 3/7)
	PR	1	7.7
	NR	4	30.8
	Not reported	6	46.1
XI	CR	2	15.4	42.9% ( n 3/7)
	PR	1	7.7
	NR	4	30.8
	Not reported	6	46.1
XII	CR	2	15.4	62,5% ( n 5/8)
	PR	3	23.1
	NR	3	23.1
	Not reported	5	38.5
Sympathetic involvement	CR	1	7.7	71,4% ( n 5/7)
	PR	4	30.8
	NR	2	15.4
	Not reported	6	46.1

Abbreviations: CR, complete recovery; NR, no recovery; PR, partial recovery.

Data limitations prevent firm conclusions regarding the role of etiology in CN outcome. However, some trends could be observed. In vascular cases ( n  = 3/13), functional outcomes seemed superior, with CR of cranial nerve deficits in two patients operated on for aneurysm or pseudoaneurysm, and PR in the patient who received antithrombotic therapy for ICA dissection. In contrast, oncological etiologies, particularly brain metastases, appeared to be associated with poorer prognosis, accounting for three of the four cases (75%) without recovery. Traumatic causes also seemed unfavorable, as illustrated by the patient with ballistic injury who showed no improvement despite surgical management. These patterns suggest that prognosis may vary according to etiology, although the small sample size precludes definitive conclusions.

Similarly, when assessing the potential influence of age on outcome, no difference was observed between patients younger or older than 40 years, and the result was not statistically significant ( p  = 1.0).

Glasgow Outcome Scale

By dichotomizing GOS into good outcome ^{1 2 3} and poor outcome, ^{4 5} three comparisons were performed (cf Table 4 .).

Table 4. Distribution of patients by Glasgow Outcome Scale.

GOS	Number of patients	Percentage
1–2	4	40 ( n 4/10)
3	2	15.4 ( n 3/10)
4–5	4	40 ( n 4/10)
Not assessable	3	23.1 ( n 3/13)
Total	13

For vascular versus non-vascular etiologies, all three vascular cases were in the poor-outcome group compared with one of seven in the non-vascular group ( p  = 0.033), with a relative risk of 7.0 (95% CI: 1.14–42.97), indicating a significant association with a worse prognosis. The relevance of this result and the possibility of bias are further addressed in the Discussion section.

For oncological versus non-oncological causes, one of six patients had a poor outcome compared with three of four ( p  = 0.19), with a relative risk of 0.22 (95% CI: 0.03–1.45), which was not significant.

For traumatic versus non-traumatic causes, none of the traumatic cases had a poor outcome compared with four of nine in the non-traumatic group ( p  = 1.00), with a relative risk of 0.56 (95% CI: 0.05–6.74), also not significant (cf Table 4 .).

These results suggest only a significant association between vascular etiologies and poor outcome. The outcome according to the GOS score was not reported in 23.1% of the patients ( n  = 3/13) (cf Table 4 ).

Discussion

The lower CNs maintain close anatomical relationships from their origin at the surface of the brainstem to their extracranial course, passing through a succession of narrow anatomical corridors. ¹⁸ Along this pathway, they lie in intimate proximity to each other and to adjacent neurovascular structures, including the cervical sympathetic trunk. This configuration explains why isolated involvement of a single lower cranial nerve is uncommon, and why combined deficits are more frequently encountered in clinical practice. ¹⁸

Historical Context

Wartime has historically advanced neuroanatomical understanding. During World War I, the high incidence of penetrating craniofacial injuries offered unique opportunities to associate specific clinical deficits with defined anatomical lesions. In 1915, Collet reported combined palsy of CNs IX, X, XI, and XII in a soldier with a mastoid injury. ² Two years later, Sicard described similar findings. In 1916, Villaret added ipsilateral Horner's syndrome to this picture, implicating the cervical sympathetic chain. In 1918, Vernet identified CNs IX, X, and XI as being affected by lesions of the jugular foramen. These early clinical observations led to the definition of several overlapping eponymous syndromes, each associated with a distinct anatomical location.

Relevant Anatomy

Villaret's “posterior retroparotid space,” now referred to as the retrostyloid compartment, is a deep neck region whose anatomical boundaries can be defined as follows ( Figs. 2 and 3 ): ^{19 20 21 22} anteriorly, it is bounded by the styloid process and its muscular and ligamentous attachments, including the styloglossus, stylohyoid, stylopharyngeus muscles, and the stylohyoid and stylomandibular ligaments, which separate it from the prestyloid parapharyngeal space. Posteriorly, the prevertebral fascia limits the retrostyloid compartment, overlying the cervical vertebrae and prevertebral muscles, notably the longus capitis and longus colli muscles. Medially, it is delimited by the pharyngeal wall, including the superior constrictor muscle and the buccopharyngeal fascia; these structures also form the lateral boundary of the retropharyngeal space. Laterally, it is bordered by the deep lobe of the parotid gland, the mandibular ramus, and the surrounding parotid fascia. Superiorly, the space extends up to the base of the skull, particularly the region of the jugular foramen and hypoglossal canal, where CNs IX through XII exit the cranium. Inferiorly, it continues caudally into the posterior cervical space, following the trajectory of the carotid sheath and its neurovascular contents.

Fig. 2.

Schematic illustration of the lateral skull base and jugular foramen anatomy. A space-occupying lesion is depicted at the level of the jugular bulb, showing its close relationships with the sigmoid sinus, inferior petrosal sinus, and adjacent neurovascular structures. Cranial nerves VII–XII, the internal carotid artery (ICA), and the internal jugular vein (IJV) are illustrated, along with potential associated complications such as ICA dissection and IJV thrombosis.

Fig. 3.

Lateral view of the neck and parotid region with magnified depiction of the stylomandibular space. The parotid gland, styloid process, stylohyoid ligament, and surrounding neurovascular structures are shown, including cranial nerves IX, X, XI, and XII, the internal carotid artery, the internal jugular vein, and the cervical sympathetic chain, in relation to the pharynx.

Within this space, the lower four CNs travel together down to approximately the level of the mastoid tip, running in close association with the internal jugular vein and the carotid artery, alongside which the cervical sympathetic chain also descends. ²³

Instead of Collet Sicard which appears as an intracranial or foraminal compressive syndrome, Villaret appears as a foraminal or extracranial compressive syndrome

Clinical Features and Imaging

VS presents with a characteristic constellation of clinical signs resulting from the combined involvement of CNs IX, X, XI, and XII, along with the cervical sympathetic trunk ( Figs. 2 and 3 ). (1) CN IX palsy leads to impaired sensation of the soft palate and posterior pharynx, resulting in loss of the gag reflex. (2) CN X palsy causes vocal cord paralysis, typically with the cord fixed in a paramedian position, leading to dysphonia. (3) CN XI palsy manifests as shoulder droop due to trapezius weakness, and reduced head rotation toward the contralateral side, reflecting sternocleidomastoid involvement. (4) CN XII palsy is characterized by ipsilateral tongue atrophy with deviation toward the affected side upon protrusion. (5) Horner's syndrome, due to disruption of the cervical sympathetic chain, presents as the triad of ipsilateral ptosis, miosis, and facial anhidrosis. When observed together, this combination of signs offers strong topographic value and should prompt the clinician to consider a lesion within the posterior retroparotid or retrostyloid space. The goal here is not to provide an exhaustive list of symptoms, but rather to outline consistent and identifiable clinical features that can guide timely recognition of this rare entity in clinical settings. De Beer and Post, provide a non-exhaustive, open access, illustrative case with clinical pictures of VS. ²⁴

In cases of suspected VS, prompt imaging is required, prioritizing the most accessible and reliable modalities. Depending on the suspected etiology, evaluation typically relies on CT and/or MRI, with or without angiography. When these modalities remain inconclusive, digital subtraction angiography is mandatory to establish the diagnosis.

Etiology, Treatment, and Prognosis

Skull Base Tumor

Skull base tumors represented the most common cause of VS in this review, accounting for 61.5% of cases (8/13). ¹⁶ Most were metastases to the skull base, while primary lesions included meningioma and malignant peripheral nerve sheath tumor.

Treatment options included surgery, radiotherapy, chemotherapy, or combined strategies, which could be either curative or palliative. The therapeutic approach was determined by tumor pathology, anatomical features such as size and infiltration, and patient-related factors including performance status and prognostic scores. Surgical removal through a functional sparing strategy requires high technical expertise given the significant risk of postoperative clinical worsening. ^{25 26 27} When surgery was performed, posterior median routes were most often reported, though far lateral approaches and their variants remain important alternatives. ^{28 29 30} In the study by Sawada et al, a tumor of the accessory nerve mimicking VS was removed via a suboccipital craniectomy, resulting in near-CR of cranial nerve deficits. The authors attributed this favorable outcome primarily to the selection of the surgical approach. ³¹ For peripheral nerve tumors, a preplanned subtotal removal followed by second-line treatment could be a potential strategy for selected cases. ³²

Cranial nerve prognosis in this group appeared less favorable: three of the four cases without recovery were associated with brain metastases. This likely reflects the infiltrative nature of malignant disease and the frequent use of adjuvant or palliative treatments. The extent of resection and the surgical approach may also impact postoperative cranial nerve outcome. Nevertheless, partial or CR was observed in some patients, particularly when tumors were localized and surgically accessible. Although this review was not designed to compare surgical approaches, the findings suggest that prognosis in tumor-related VS depends on both lesion aggressiveness and the therapeutic strategy adopted.

Vascular

In our series, vascular etiologies accounted for 23.1% of VS cases (3/13) and primarily involved the ICA, including aneurysm, pseudoaneurysm, and dissection.

A representative case was reported by Mizutani et al, describing a 50-year-old male with classic features of VS of vascular origin. MRI revealed an intramural hematoma consistent with ICA dissection, and the patient achieved partial recovery with antithrombotic therapy. In contrast, surgical treatment was employed for the aneurysm and pseudoaneurysm, with clipping in one case and ligation with bypass in another, both resulting in CR of cranial nerve function. These cases highlight the wide range of therapeutic approaches, ranging from conservative antithrombotic management to vascular surgery, depending on the precise etiology.

Despite the positive impact on cranial nerve recovery, vascular causes in our series were associated with poor GOS. Indeed, all three patients fell into the poor GOS category at 1 year, and this association was statistically significant. However, owing to the small data sample, a bias remain possible.

Trauma

In our review, traumatic causes of VS were rare and associated with poor cranial nerve outcomes at follow-up. An example was a penetrating ballistic injury, while no blunt trauma was reported.

In a review approximately 73 cases of Collet–Sicard syndrome, cases secondary to trauma showed a 41% rate of lower CN recovery. The facial nerve (VII) can also be used as a model, as its higher incidence has led to more extensive study. ³³ In the context of CN VII injury, delayed or incomplete deficits are often managed with corticosteroids, while immediate complete paralysis may prompt surgical decompression or even surgical repair after patient's stabilization. Such strategies, however, have not been validated for lower CNs. Furthermore, in such a narrow surgical corridor, surgical repair has not been proven feasible to date.

Limitations

This study has several limitations inherent to its retrospective design. As it relied exclusively on case reports, a reporting bias in favor of patients with better outcomes is likely. Measurement bias may also have occurred during data extraction, and functional outcomes were reported heterogeneously across studies, leading to potential misinterpretation from authors. A selection bias must also be acknowledged: not all patients with lesions in this anatomical region and presenting with the full clinical picture of VS were explicitly labeled as such in the title or content of the reports. Without mention of this anatomical space or the syndrome itself, relevant cases may have been missed during our search. In addition, the small number of cases limits statistical power, increasing the risk of type II error, and a bias related to sampling fluctuation cannot be excluded.

Nevertheless, to our knowledge, this is the largest review to date focusing on VS. It highlights the most frequent etiologies and treatment strategies, and provides estimates of cranial nerve recovery depending on the underlying cause, thus offering valuable insights for clinicians confronted with this rare condition.

Conclusion

VS is characterized by the combined involvement of CNs IX–XII and the cervical sympathetic chain, providing strong localizing value to the retrostyloid compartment. In this systematic review, skull base tumors were the most frequent cause, followed by vascular lesions and penetrating trauma. Management strategies must be tailored to the underlying etiology, balancing oncological control with functional preservation in tumors and weighing surgical versus conservative approaches in vascular disease. Cranial nerve prognosis was poorest in tumor-related cases, particularly with metastatic disease, whereas vascular and, to a lesser extent, traumatic etiologies offered better chances of functional recovery. The complexity of this anatomical region, the rarity of the diseases involved, and the generally poor functional outcome of the patients warrant multidisciplinary management involving radiologists, otolaryngologists, skull base neurosurgeons, and radiation oncologists.