# Relapse in Tolosa-Hunt syndrome: pooled recurrence rates and associated factors from a meta-analysis of 456 cases

**Authors:** Bernardo Leite Pondé da Luz, Guilherme Diogo Silva

PMC · DOI: 10.1007/s10072-026-08985-7 · Neurological Sciences · 2026-03-26

## TL;DR

This study finds that about 25% of Tolosa-Hunt Syndrome patients experience relapse, with specific cranial nerve involvement linked to higher recurrence risk.

## Contribution

The study provides the first pooled recurrence rate and identifies cranial nerve involvement as a novel factor associated with relapse in THS.

## Key findings

- The pooled recurrence rate of Tolosa-Hunt Syndrome is 23% with significant heterogeneity.
- Involvement of cranial nerves II, IV, and VI is associated with higher recurrence risk.
- Age, sex, follow-up duration, and MRI abnormalities do not significantly affect recurrence.

## Abstract

Tolosa-Hunt Syndrome (THS) is a rare, painful ophthalmoplegia caused by granulomatous inflammation within the cavernous sinus. Despite the effective response to corticosteroid therapy, recurrence rates reported in the literature vary significantly, and clear associated factors of recurrence remain elusive. This systematic review and meta-analysis aim to establish the frequency of relapse and identify f actors associated with recurrence.

Following PRISMA guidelines, we performed a comprehensive database search of MEDLINE/PubMed, EMBASE, and Scopus from inception to June 2024, focusing on observational studies or case series reporting THS recurrence. Meta-analysis employed a random-effects model to estimate pooled recurrence rates. Meta-regression analyses evaluated clinical and demographic associated factors of recurrence, with publication bias assessed via funnel plots and Egger’s test.

Seventeen studies encompassing 456 patients met the inclusion criteria. The pooled recurrence rate was 23% (95% CI, 17–32%), with substantial heterogeneity (I2 = 59.9%). The frequency of cranial nerve involvement specifically nerves II, IV, and VI, correlated with higher recurrence risk (P < 0.05). Age, sex, duration of follow-up, and MRI abnormalities did not show significant associations. Limited data were available concerning the use of steroid-sparing immunosuppressants, inflammatory biomarkers, and characteristics of MRI.

Approximately one-quarter of patients with THS experience recurrence. Involvement of cranial nerves II, IV, and VI was associated with relapses. Further prospective investigations with standardized recurrence definitions and structured therapeutic comparisons are needed to clarify prognostic factors and optimize long-term management.

The online version contains supplementary material available at 10.1007/s10072-026-08985-7.

## Linked entities

- **Diseases:** Tolosa-Hunt Syndrome (MONDO:0018983)

## Full-text entities

- **Genes:** CRP (C-reactive protein) [NCBI Gene 1401] {aka PTX1}
- **Diseases:** ophthalmoplegia (MESH:D009886), diplopia (MESH:D004172), neurological disability (MESH:D009069), THS (MESH:D020333), neurological disorder (MESH:D009461), orbital pain (MESH:D010146), nerves (MESH:C537568), nerve involvement (MESH:C564676), HS (MESH:C567159), Headache (MESH:D006261), granulomas (MESH:D006099), cranial nerve dysfunction (MESH:D003389), paresis (MESH:D010291), nerve dysfunction (MESH:D005155), cavernous sinus abnormalities (MESH:D020226), granulomatous inflammation (MESH:D007249)
- **Chemicals:** steroid (MESH:D013256)
- **Species:** Meleagris gallopavo (common turkey, species) [taxon 9103], Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

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## References

2 references — full list in the complete paper: https://tomesphere.com/paper/PMC13021801/full.md

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Source: https://tomesphere.com/paper/PMC13021801