# Horner Syndrome: Gateway to Neuro-Behçet Syndrome

Chaïmaâ Zeroual, Mina Moudatir, Khadija Echchilali, Leïla Barakat, Safaâ Mourabit, Hassan El Kabli

► To cite this version:

Chaïmaâ Zeroual, Mina Moudatir, Khadija Echchilali, Leïla Barakat, Safaâ Mourabit, et al. Horner Syndrome: Gateway to Neuro-Behçet Syndrome. International Journal of Medical and Pharmaceutical Case Reports, 2025, 18 (2), pp.14-19. 10.9734/ijmpcr/2025/v18i2416. hal-05035618

HAL Id: hal-05035618

https://hal.science/hal-05035618v1

Submitted on 15 Apr 2025

HAL is a multi-disciplinary open access
archive for the deposit and dissemination of sci-
entific research documents, whether they are pub-
lished or not. The documents may come from
teaching and research institutions in France or
abroad, or from public or private research centers.

L'archive ouverte pluridisciplinaire HAL, est
destinée au dépôt et à la diffusion de documents
scientifiques de niveau recherche, publiés ou non,
émanant des établissements d'enseignement et de
recherche français ou étrangers, des laboratoires
publics ou privés.

<figure><img src="image_1.png" /></figure>

Distributed under a Creative Commons Attribution 4.0 International License
<figure><img src="image_2.png" /></figure>

# Horner Syndrome : Gateway to Neuro-Behçet Syndrome

Chaïmaâ Zeroual a*, Mina Moudatir a, Khadija Echchilali a, Leïla Barakat a, Safaâ Mourabit a and Hassan El Kabli a

**Authors' contributions**

This work was carried out in collaboration among all authors. All authors read and approved the final manuscript.

**Article Information**

DOI: https://doi.org/10.9734/ijmpcr/2025/v18i2416

**Open Peer Review History:**

This journal follows the Advanced Open Peer Review policy. Identity of the Reviewers, Editor(s) and additional Reviewers, peer review comments, different versions of the manuscript, comments of the editors, etc are available here:

https://pr.sdiarticle5.com/review-history/134241

Received: 10/02/2025

Accepted: 12/04/2025

Published: 15/04/2025

**Case Report**

## ABSTRACT

**Background:** Horner syndrome (HS), a rare neurological condition caused by disruption of the oculosympathetic pathway, can occasionally serve as an early indicator of systemic diseases such as Behçet syndrome (BS). Neuro-Behçet syndrome (NBS) represents a severe manifestation of BS affecting the central nervous system (CNS). It is associated with significant morbidity.

**Case Description:** This report describes an unusual case of NBS revealed by HS in 43-year-old male who initially presented with progressive-onset left ptosis. The symptomatology was enriched by left-sided hemicranial headaches and homolateral carotidynia. NBS diagnosis was established after ruling out other potential differential diagnosis. The association of corticosteroids (CSs) and other immunosuppressants (ISs) led to a significant improvement.

**Conclusion:** Considering atypical revelation's mode of NBS remains a noteworthy occurrence for clinicians. Prompt diagnosis and intervention are crucial to prevent further neurological deterioration.

<footnote>a Department of Internal Medicine, Ibn Rochd University Hospital, Faculty of Medicine and Pharmacy of Casablanca, Casablanca, Morocco.</footnote>

<footnote>*Corresponding author: E-mail: chaimaazeroual42@gmail.com;</footnote>

<footnote>**Cite as:** Zeroual, Chaïmaâ, Mina Moudatir, Khadija Echchilali, Leïla Barakat, Safaâ Mourabit, and Hassan El Kabli. 2025. "Horner Syndrome : Gateway to Neuro-Behçet Syndrome". International Journal of Medical and Pharmaceutical Case Reports 18 (2):14-19. https://doi.org/10.9734/ijmpcr/2025/v18i2416.</footnote>
Keywords: Behçet syndrome; neuro-behçet syndrome; horner syndrome; central nervous system; corticosteroids; immunosuppressants; case report.

# 1. INTRODUCTION

Behçet syndrome (BS) is a chronic inflammatory disorder characterized by mucocutaneous lesions, ocular inflammation and systemic vasculitis. While it commonly presents with oral aphthous ulcers and uveitis, its involvement in the central nervous system (CNS) can lead to diverse symptoms. Neuro-Behçet syndrome (NBS) refers to neurological involvement occurring in approximately 5% to 59% of patients with BS (Kidd, 2023). These manifestations are divided into two main forms that are parenchymal lesions as meningoencephalitis and non-parenchymal lesions as cerebral venous thrombosis (Al-Araji and Kidd, 2009). In rare instances, NBS might reveal itself through symptoms akin to Horner syndrome (HS). In NBS, brainstem or diencephalic lesions often resulting from inflammatory vasculitis, may impair sympathetic fibers and lead to HS. Such rare mode of revelation is diagnostic and prognostic marker necessitating early intervention and prompt immunosuppressive therapy (Matsui et al., 2010). This can prevent irreversible neurological damage and severe complications, emphasizing the importance of vigilance in interpreting isolated neurological symptoms.

We present the case of 43-year-old male who presented with HS, ultimately leading to a

diagnosis of BS. Treatment combining corticosteroids (CSs) and immunosuppressants (ISs) led to notable improvement.

# 2. CASE DESCRIPTION

## 2.1 Patient Presentation and Initial Symptoms

The 43-year-old male agricultural worker from El Jadida first presented with progressive onset of left ptosis. Few days later, clinical presentation was supplemented by hemicranial headaches, left hemifacial pain and homolateral carotidynia. The symptoms occurred in the absence of fever but were associated with noticeable decline in his overall health status. Upon clinical examination, the patient exhibited signs of severe cerebral vascular involvement, including reactive myosis, left ptosis and pseudo-enophthalmos (Fig. 1). Additionally, his lower limbs were large, symmetrical, warm, red and painful, though they did not exhibit pitting edema.

## 2.2 Diagnostic Confirmation and Imaging Findings

The diagnosis of BS was confirmed with a score of 6 points according to the *International Diagnostic Criteria for Behçet Syndrome* (ICBS):

<figure><img src="image_3.png" /><figcaption>Fig. 1. The left HS</figcaption></figure>

<table><caption>Table 1. The criteria used to retain BS in the patient according to ICBS</caption><thead><tr><td>Symptom</td><td>Points</td></tr></thead><tbody><tr><td>Oral Aphthosis</td><td>2 points</td></tr><tr><td>Genital Aphthosis</td><td>2 points</td></tr><tr><td>Pseudofolliculitis</td><td>1 point</td></tr><tr><td>Vascular Lesions</td><td>1 point</td></tr></tbody></table>
Imaging studies were performed to further evaluate the extent of vascular involvement. A cervicoencephalic magnetic resonance angiography (MRA) revealed a sacciform aneurysm of the left internal carotid artery (Figs. 2 and 3), with extensive thrombotic material extending from the carotid bulb to the cervical portion. Calcification of the intracavernous segment was also noted. Additionally, MRA showed extensive cerebral thrombophlebitis affecting the superior longitudinal sinus and lateral sinuses. Doppler ultrasound venous of the lower limbs detected deep vein thrombophlebitis in the iliofemoropopliteal region. Transthoracic echocardiography ruled out intracardiac thrombus, and thoracic angiography excluded pulmonary embolism.

## 2.3 Histopathology and Laboratory Findings

A biopsy of the left aortic aneurysm was performed, which revealed fibrosis of the media and chronic inflammation with acute fibrinous exacerbation in the vascular wall. These findings were consistent with vasculitis and supported the diagnosis of BS. Laboratory tests confirmed a severe inflammatory syndrome, with C-reactive protein (CRP) level of 260 mg/L, hyperthrombocytosis (491,000/mm³), and

hyperfibrinogenemia (6.3 g/L). Infectious workup, including retroviral serologies, tests for syphilis, hepatitis B and C returned negative.

## 2.4 Treatment and Management

The patient underwent surgical repair of the left carotid aneurysm using an inverted saphenous graft between the common carotid artery and external carotid artery. Postoperatively, he was started on venous compression therapy combined with anticoagulation using acenocoumarol (4 mg/day). Immunosuppressive therapy was initiated to manage the underlying vasculitis. This included intravenous (IV) methylprednisolone pulses (1g/day for 3 days), followed by a tapering course of oral CSs. The patient also received six cyclophosphamide IV boluses (1g every 3 weeks), transitioning to azathioprine maintenance therapy (150 mg/day).

## 2.5 Outcome and Follow-Up

The patient's clinical and biological evolution improved significantly under the treatment regimen. Notably, the left HS disappeared (Fig. 4). The combination of surgical intervention, anticoagulation and ISs effectively addressed the severe presentation.

<figure><img src="image_4.png" /><figcaption>Fig. 2. Cervical MRI (sagittal view) with the red arrows showing left internal carotid aneurysm</figcaption></figure>
<figure><img src="image_5.png" /><figcaption>Fig. 3. MRA 3D of the Willis's circle revealing the sacciform aneurysm of the left internal carotid artery</figcaption></figure>

<figure><img src="image_6.png" /><figcaption>Fig. 4. Regression of the left HS in the patient after treatment</figcaption></figure>

### 3. DISCUSSION

Johann Friedrich Horner, a Swiss ophthalmologist, is widely recognized for providing the first comprehensive description of HS in 1869 and accurately attributing it to oculosympathetic paresis (Kanagalingam and Miller, 2015). This syndrome is resulting from disruption in the sympathetic pathways connecting the brain to the eye. The classic triad of symptoms includes ptosis, miosis, and pseudo-enophthalmos. Anhidrosis on the affected side may also occur but is not universally present (Khan and Bollu, 2023). The sympathetic pathway responsible for maintaining

normal ocular function involves complex neural circuits originating from hypothalamic centers that descend through cervical spinal cord segments before synapsing in superior cervical ganglia. From there, postganglionic fibers travel along blood vessels to reach their target organs in the head. Disruption at any point along this pathway can lead to HS (Lykstad et al., 2023). Causes are diverse and include central lesions affecting brainstem or spinal cord areas involved in sympathetic transmission, peripheral causes such as carotid artery dissection or tumors compressing nerves near superior cervical ganglia, and even iatrogenic causes like surgical damage during neck procedures (Sabbagh et al.,
2020; Martin, 2018). BS, characterized by recurrent oral aphthous ulcers, genital ulcers, and uveitis, was first comprehensively described by Turkish dermatologist *Hulusi Behçet* in 1937. This landmark description marked the recognition of these symptoms as a distinct medical condition (Kocak et al., 2024). BS is known for its inflammatory-driven damage to blood vessels throughout the body. Neurological involvement can manifest either parenchymally with meningoencephalitis or non-parenchymally through cerebral venous thrombosis or arterial complications like aneurysms. In BS, inflammation primarily targets medium-sized arteries but can affect any size vessel leading to both arterial and venous complications. Neurological manifestations arise when these inflammatory processes disrupt normal vascular function within critical regions such as those supplying sympathetic nerves responsible for ocular control.

While direct evidence linking HS specifically as a revelation for BS might be limited compared to more common manifestations like oral ulcers or uveitis, understanding these complex interactions can enhance diagnostic acumen. The vasculitic nature of BS could theoretically disrupt sympathetic pathways leading to HS.

Few case reports highlight the occurrence of HS in patients with BS, often associated with CNS involvement such as medullary ischemia, acute NBS's attacks or bulbar lesions (Matsui et al., 2010; Kaido et al., 2012; Certal et al., 2014).

Treatment typically involves CSs as a first-line approach. High-dose CSs such as methylprednisolone pulses are commonly used to reduce inflammation quickly (Certal et al., 2014). Following initial pulse therapy, maintenance treatment often includes oral CSs like prednisone at doses adjusted based on clinical response. In cases where CS therapy alone is insufficient or for long-term management, ISs such as azathioprine or methotrexate may be added (Borhani, 2009). These drugs help control chronic inflammation and prevent further neurological damage. For high-risk patients or those with severe manifestations, IV cyclophosphamide may be considered alongside CSs. If these regimens fail to achieve desired outcomes, tumor necrosis factor-α (TNF-α) inhibitors like infliximab can be introduced as an additional therapeutic option (Matsui et al., 2010; Borhani, 2009; Hirohata et al., 2020).

## 4. CONCLUSION

Early recognition and treatment of NBS can significantly improve patient outcomes by reducing neurological complications and improving life's quality. Therefore, clinicians should remain vigilant for signs like HS that may signal more severe systemic involvement in patients with suspected or confirmed BS. Future efforts should focus on early diagnosis using advanced tools and multidisciplinary teams for comprehensive care. Personalized treatment strategies as biological therapies are crucial and combination therapy trials should be explored. Further research is needed to better understand the mechanisms linking HS to NBS and to refine therapeutic approaches for affected patients.

## DISCLAIMER (ARTIFICIAL INTELLIGENCE)

Authors hereby declare that no generative AI technologies such as Large Language Models (ChatGPT, COPILOT, etc.) and text-to-image generators have been used during the writing or editing of this manuscript.

## CONSENT

Written informed consent was obtained from the patient for publication of this case report.

## ETHICAL APPROVAL

All procedures performed in this study are in accordance with the ethical standards of the institutional and/or national research committee.

## COMPETING INTERESTS

Authors have declared that no competing interests exist.

## REFERENCES

Al-Araji, A., & Kidd, D. P. (2009). Neuro-Behçet's disease: Epidemiology, clinical characteristics, and management. *Lancet Neurol*, *8*(2), 192-204.

Borhani Haghighi, A. (2009). Treatment of neuro-Behçet's disease: An update. *Expert Rev Neurother*, *9*(4), 565-574.

Certal, M., Alves, A., Santos, M. B., et al. (2014). Neuro-Behçet disease presenting as a bulbar lesion: A case report. *Cureus*, *16*(8), e68236.

Hirohata, S., Kikuchi, H., Sawada, T., Okada, M., et al. (2020). Recommendations for the
management of neuro-Behçet's disease by
the Japanese National Research
Committee for Behçet's Disease. *Intern
Med*, **59**(19), 2359–2367.

Kaido, T., Otsuki, T., Ogawa, M., Takahashi, A., et al. (2012). Medullary ischemia due to vertebral arteritis associated with Behçet syndrome: A case report. *Asian Pac J Allergy Immunol*, **30**, 239-242.

Kanagalingam, S., & Miller, N. R. (2015). Horner syndrome: Clinical perspectives. *Eye Brain*, **7**, 35–46.

Khan, Z., & Bollu, P. C. (2023, April 10). Horner Syndrome. In *StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan–*. PMID: 29763176.

Kidd, D. P. (2023). Neurological involvement by Behçet's syndrome: Clinical features, diagnosis, treatment and outcome. *Pract Neurol*, **23**(5), 386–400.

Kocak Nuhoglu, G. E., Nuhoglu, C., Osoydan, M., & Arslan, B. (2024). Dr. Hulusi Behçet:

A pioneer in dermatology and the legacy of
Behçet's disease. *Cureus*, **16**(9), e69600.

Lykstad, J., Reddy, V., & Hanna, A. (2023, August 8). Neuroanatomy, Pupillary Dilation Pathway. In *StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan–*. PMID: 30571042.

Martin, T. J. (2018). Horner Syndrome: A clinical review. *ACS Chem Neurosci*, **9**(2), 177–186.

Matsui, T., Ishida, T., Tono, T., Yoshida, T., Sato, S., & Hirohata, S. (2010). An attack of acute neuro-Behçet's disease during the course of chronic progressive neuro-Behçet's disease: Report of two cases. *Mod Rheumatol*, **20**(6), 621–626.

Sabbagh, M. A., De Lott, L. B., & Trobe, J. D. (2020). Causes of Horner Syndrome: A study of 318 patients. *J Neuroophthalmol*, **40**(3), 362–369.

**Disclaimer/Publisher's Note:** The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of the publisher and/or the editor(s). This publisher and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content.

© Copyright (2025): Author(s). The licensee is the journal publisher. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Peer-review history:

The peer review history for this paper can be accessed here:

https://pr.sdiarticle5.com/review-history/134241