---
title: "Parenchymal Neuro-Behçet Disease Case Report: Heterogeneous Clinical Presentations"
id: "frontiers-in-immunology-16-parenchymal-neuro-beh-et-disease-with-heterogeneous-clinical-presentations-a"
canonical_url: "https://medichelpline.com/clinical-feed/frontiers-in-immunology-16-parenchymal-neuro-beh-et-disease-with-heterogeneous-clinical-presentations-a"
content_type: "clinical_feed_article"
specialty: "Infectious Disease"
source_name: "Frontiers in Immunology"
source_url: "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1965989"
published_at: "2026-10-09T00:00:00.000Z"
evidence_level: "Journal Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Parenchymal Neuro-Behçet Disease Case Report: Heterogeneous Clinical Presentations
## Provenance & Clinical Metadata
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- **Specialty:** [Infectious Disease](https://medichelpline.com/clinical-feed/infectious-disease.md)
- **Primary Source:** Frontiers in Immunology
- **Source URL:** [Original Journal Publication](https://www.frontiersin.org/articles/10.3389/fimmu.2026.1965989)
- **Published At:** 2026-10-09T00:00:00.000Z
- **Evidence Rating:** Journal Feed
## Executive GIST (TL;DR)
- The source is a CASE REPORT titled “Parenchymal Neuro-Behçet disease with heterogeneous clinical presentations” published in Frontiers in Immunology. - The article type is explicitly identified as a Case Report. - The provided source text contains only journal navigation and metadata; substantive clinical content from the case report (patient details, signs and symptoms, diagnostics, imaging, treatments, outcomes) was not present in the supplied source. - Specifics about the number of cases, demographics, clinical timelines, neurologic findings, laboratory or imaging results, pathologic data, therapeutic interventions, and follow-up were not reported in the provided source text. - Because the supplied content lacks the article body, no clinical conclusions, comparative analyses, or data-driven observations from the authors are available to extract or summarize. - Readers should consult the full Frontiers in Immunology article at the original URL for complete case descriptions and authors’ interpretations; those details were not included in the supplied source content.
## Clinical Analysis & Structured Key Points
Frontiers | Parenchymal Neuro-Behçet disease with heterogeneous clinical presentations: a comparative case report CASE REPORT article Front. Immunol. , 09 October 2026 Sec. Autoinflammatory Disorders Volume 17 - 2026 | https://doi.org/10.3389/fimmu.2026.1965989 Published in Frontiers in Immunology Autoinflammatory Disorders 7 impact factor 11.3 citescore Editor & Reviewers Edited by S K Senthil Kumaran Satyanarayanan Reviewed by J A Juan Antonio Antonio Encarnacion M O MUSA OZTURK Outline Figures and Tables Figure 1 View in article Figure 2 View in article Table 1 Cerebrospinal fluid (CSF) analysis, case 1. View in article Table 2 Diagnostic criteria, admissions and clinical timeline for both cases. View in article CASE REPORT article Front. Immunol. , 09 October 2026 Sec. Autoinflammatory Disorders Volume 17 - 2026 | https://doi.org/10.3389/fimmu.2026.1965989 Parenchymal Neuro-Behçet disease with heterogeneous clinical presentations: a comparative case report A N Alaa Naiem Zaro 1 † * Y A Yumna Alatrash 1 † * R N Raya N. Amro 1,2 † M Y Mohammed Y. Nairoukh 3 † N I Nidal Itmaiza 3 I Q Ikram Qaysia 4 1. Faculty of Medicine, Al-Quds University, Jerusalem, Palestine 2. Alia Hospital, Hebron, Palestine 3. Department of Radiology, Alia Hospital, Hebron, Palestine 4. Department of Internal Medicine, Alia Hospital, Hebron, Palestine See more Article metrics View details Abstract Background: Neuro-Behçet disease (NBD) is a rare but potentially disabling manifestation of Behçet disease (BD). Its heterogeneous neurological presentation can mimic central nervous system infection, cerebrovascular disease, inflammatory demyelination or intracranial tumors, making early diagnosis difficult. Importantly, there is still limited published data on NBD from Palestine regarding presentation, diagnosis, imaging and management. Case presentation: We describe two patients with a long history of recurrent oral and genital ulceration who were diagnosed with parenchymal Neuro-Behçet disease (P-NBD). The first patient was a 26-year-old man with a two-week progressive headache, fever, vomiting, and blurred vision, which resembled meningitis, in whom examination showed central facial weakness, gait imbalance and pathological laughter. The second patient was a 41-year-old woman with a two-year history of gait imbalance and dysarthria who presented with three days of dizziness, horizontal nystagmus, central facial weakness, right lower-limb weakness, and a positive bilateral extensor plantar response. Laboratory testing and brain magnetic resonance imaging (MRI) were performed to exclude other differential diagnoses. Both received intravenous methylprednisolone followed by an immunosuppressive agent. Results: The first patient had clinical and radiological improvement after corticosteroids and initiation of induction cyclophosphamide, with clinical improvement on follow-up. The second patient improved significantly on imaging after infliximab maintenance therapy. She also improved clinically, but chronic symptoms of gait imbalance and dysarthria were still present. Conclusion: These two cases illustrate the variable presentation of P-NBD, including a meningitis-like febrile syndrome with pathological laughter and an acute-on-chronic brainstem syndrome. In patients with recurrent oro-genital ulceration and unexplained brainstem or diencephalic neurological findings, NBD should be considered after careful exclusion of other disorders. Early diagnosis and immunosuppressive treatment can lead to substantial clinical and radiological improvement. 1 Introduction Behçet disease (BD) is a chronic, multisystemic, variable-vessel vasculitis of unknown etiology characterized by a relapsing course. Its reported prevalence varies markedly with geography: the pooled global estimate is 10.3 per 100,000 population (95% CI 6.1–17.7) ( 1 ), and the disease is concentrated along the historical Silk Road ( 1 , 2 ). A recent systematic review and meta-analysis of the Middle East and North Africa reported a pooled regional prevalence of approximately 300 per 100,000 population, among the highest worldwide ( 3 ). The classical manifestations include recurrent oral and genital ulcers, skin hypersensitivity and lesions, and ocular inflammation, with variable involvement of other systems, including the joints, vasculature, the gastrointestinal system, and even the nervous system. Diagnosis of BD is primarily clinical, as there is no pathognomonic laboratory test or definitive diagnostic test. Nowadays, much evidence suggests that environmental and infectious factors in genetically susceptible individuals trigger BD ( 1 ). Due to its diverse manifestations and wide geographical distribution, it has a global health impact ( 1 , 2 ). Neurological involvement (i.e., Neuro-Behçet disease [NBD]) is one of the most serious manifestations of BD and a major cause of long-term disability. It has been reported in approximately 5–10% of patients in large series ( 4 ), with higher pooled estimates in high-prevalence regions, for example, 18.54% (95% CI 13.93–24.25%) across 4,262 North African patients with BD ( 5 ), and 10.3% in a Lebanese tertiary-centre cohort ( 6 ). Central nervous system involvement in NBD is divided into a parenchymal form (P-NBD), which affects parenchymal structures (e.g., the brainstem, diencephalon, and cerebral hemispheres), and a non-parenchymal form (NP-NBD), which encompasses cerebral venous sinus thrombosis, aseptic meningitis, and intracranial hypertension. Peripheral nervous system involvement is rare ( 7 ). Early recognition of NBD is required to limit long-term complications and death ( 8 ). The meningeal irritation in NBD is a particular diagnostic challenge. Its manifestations and cerebrospinal fluid (CSF) features overlap with infectious meningitis and occasionally with neoplastic and demyelinating disease. So, a diagnosis of exclusion in these situations is often required and is established by repeated sterile CSF analysis, a negative infectious workup, evidence of NBD on imaging, and the systemic features of BD ( 9 ). Although several case reports have been published in multiple countries, there is a shortage of published NBD cases in the Palestinian territories in particular; no dedicated NBD series has been identified. To address this gap, the article presents a comparative case report of two cases of NBD diagnosed at Alia Hospital in Hebron, Palestine. This report highlights two contrasting presentations of parenchymal Neuro-Behçet disease: a meningitis-like febrile syndrome with pathological laughter in Case 1 and an acute neurological deterioration superimposed on a chronic progressive brainstem syndrome in Case 2. Both cases demonstrated characteristic brainstem–diencephalic MRI involvement, including mesodiencephalic extension, illustrating how markedly different clinical presentations may converge on a similar radiological phenotype. 2 Case presentation 2.1 Case 1 presentation A 26-year-old male, a 10-pack-year smoker from the West Bank with an otherwise unremarkable medical history and no history of alcohol consumption, was admitted to the internal medicine department with a headache of two weeks’ duration. He had been in his usual state of health until two weeks before presentation, when he developed a progressively worsening headache. It increased in intensity over time, was not relieved by simple analgesics, and reached approximately 6/10 in severity. It was associated with nausea, two episodes of vomiting, blurred vision, and documented fever up to 39 °C. There was no photophobia or neck stiffness, seizure activity, rash, diarrhea, weight loss, night sweats, recent travel, or known tuberculosis contact. Six months before the presentation, he had experienced recurrent episodes of headache associated with blurred vision and ocular dryness. He also reported a two-year history of recurrent oral (more than 3 times per year) and genital ulcers, together with polyarthralgia. A pathergy test was positive in an external clinic. Against this background, BD was clinically suspected. On admission, the temperature was 38.5 °C. He was conscious, alert, and oriented but exhibited episodes of inappropriate, involuntary laughter (pathological laughter). The Glasgow Coma Scale score was 15/15 (E4V5M6). Cardiovascular, respiratory, and abdominal examinations were unremarkable: the abdomen was soft and non-tender, and breath sounds were normal bilaterally with good air entry. No skin rash and no active oral or genital ulcers were seen at the time of examination. Neurological examination showed normal muscle power (5/5) in all four limbs with intact sensation. A left central (upper motor neuron [UMN]) facial palsy was documented on the neurology assessment. There was no neck stiffness and no signs of meningeal irritation. Due to brainstem localization, gait imbalance was also noted during the illness. The patient had a modified Rankin Scale (mRS) score of 3, reflecting moderate neurological disability due to UMN facial palsy, brainstem dysfunction, and gait imbalance. 2.1.1 Laboratory findings on admission High-sensitivity C-reactive protein was normal (2.2 mg/L, falling to <1.0 mg/L; reference <5 mg/L) and the erythrocyte sedimentation rate was elevated (20 mm/h; reference 0–15 mm/h). Hepatitis B surface antigen, hepatitis C antibody, and HIV serology were all non-reactive. The admission complete blood count showed leukocytosis (white cell count 12.2 ×10 9 /L, rising to 24.3 ×10 9 /L during steroid pulse therapy) with neutrophil predominance; hemoglobin, platelets, renal function, and electrolytes were within or close to normal limits. Liver transaminases were mildly elevated (peak ALT 45 U/L). Coagulation studies (INR 1.05, APTT 32.6 s) and D-dimer (270 ng/mL) were normal. Complement C3 (127) and C4 (33.3) were normal, and rheumatoid factor was negative; Brucella (Rose Bengal) was negative. Glycated hemoglobin was 5.2%, thyroid-stimulating hormone (2.84) and vitamin B12 (354 pg/mL) were normal, and 25-hydroxyvitamin D was low (18.4 ng/mL). Per the hospital’s infectious workup protocol, two sets of blood cultures were obtained from separate venipuncture sites; both showed no growth. Two lumbar punctures were performed during the course. Both yielded clear cerebrospinal fluid with normal glucose and protein, no organisms on Gram stain, and no growth on culture ( Table 1 ), arguing against pyogenic bacterial meningitis. The first sample showed a mild pleocytosis (10 cells/µL, 70% neutrophils), consistent with the aseptic inflammatory picture of NBD; a second lumbar puncture, performed during the third admission on 10 June 2026 before cyclophosphamide initiation, showed no white blood cells and 20 RBC/µL, which can be traumatic. Opening pressure was not measured at either tap. Table 1 CSF parameter LP1 (17/05/2026) LP2 (10/06/2026) Reference Appearance Clear, colourless Clear — White cell count (/µL) 10 0 0–5 Red cell count (/µL) — 20 — Neutrophils 70% 0 — Lymphocytes 30% 0 — Protein (mg/dL) 27.4 28.4 15–45 Glucose (mg/dL) 55 58 40–70 Gram stain Negative Negative — Culture No growth No growth — Cerebrospinal fluid (CSF) analysis, case 1. LP1, first lumbar puncture (LP), performed during the first admission; LP2, second lumbar puncture, performed during the third admission before cyclophosphamide initiation. 2.1.2 Imaging A CT scan showed a hypodense lesion in the parietal region and midbrain, so a brain MRI (17/05/2026, with and without contrast) was done and demonstrated T2/fluid-attenuated inversion recovery (FLAIR) hyperintense signal involving the right basal ganglia with patchy contrast enhancement in the right basal ganglia and right thalamus ( Figures 1A, B ). Also, in the internal capsules (more pronounced on the right), the midbrain ( Figure 1C ), and the right side of the pons. An abnormal T1-weighted image revealed mild patchy enhancement on the coronal section ( Figure 1D ). No diffusion restriction was identified on diffusion-weighted imaging (DWI), which argues against acute infarction as the cause of the deficit. The reporting radiologist considered the appearances highly suggestive of NBD. Figure 1 Brain MRI demonstrating parenchymal Neuro-Behçet disease. (A, B) Axial T2-weighted/FLAIR images show a hyperintense lesion involving the right thalamus and basal ganglia. (C) Sagittal T2-weighted image demonstrates longitudinal extension of the lesion from the basal ganglia through the mesodiencephalic junction into the midbrain (red arrows). (D) Coronal contrast-enhanced T1-weighted image reveals mild patchy enhancement (green arrow). To exclude an occult malignant or infective focus before cytotoxic therapy, contrast-enhanced CT of the neck, chest, abdomen, and pelvis was performed (03/06/2026); it was unremarkable, with no mass lesion, lymphadenopathy, effusion, or metastatic disease. A repeat non-contrast brain CT before the second lumbar puncture showed no acute change, intracranial hemorrhage, mass lesion, or significant mass effect. 2.1.3 Management and course The patient received pulsed intravenous methylprednisolone (Solu-Medrol) 1 g daily for five days. Because escalation to cytotoxic therapy (cyclophosphamide) was planned but the patient still had fever, cyclophosphamide was deliberately withheld until repeat lumbar puncture and imaging showed no active bacterial infection or another systemic infectious focus. This staged approach spanned three admissions: the first for diagnosis and steroid pulse therapy (17–21 May); a second (25 May–5 June) during which the rheumatology service advised confirming a sterile CSF and a clear whole-body CT before immunosuppression, during which the leukocytosis was attributed to steroid therapy rather than active pyogenic infection; and a third (8–13 June) at which, following a sterile repeat lumbar puncture and reassuring imaging, cyclophosphamide was initiated (counted as day 1). Cyclophosphamide was then initiated as an intravenous infusion of 1000 mg every four weeks, planned for six months as induction therapy, along with tapering oral corticosteroids. Each infusion was given with adequate intravenous hydration before and after administration, antiemetic prophylaxis, and mesna to prevent hemorrhagic cystitis. The patient improved clinically, and a follow-up imaging study performed before the subsequent cyclophosphamide dose demonstrated improvement of the previously described lesions, with no evidence of active inflammatory disease. He was discharged with a planned follow-up in the rheumatology, neurology, and ophthalmology clinics. On follow-up in outpatient clinics, his functional disability scores significantly improved to an mRS of 1. The patient still had leukocytosis (white cell count 13.7 × 10 9 /L) with neutrophilic predominance. But there was no fever or other signs of infection, and the patient improved clinically. Ophthalmologically, no ophthalmic signs of BD were found. The patient denied experiencing any side effects from the medication. 2.2 Case 2 presentation A 41-year-old woman, a known case of type 2 diabetes mellitus (T2DM) controlled by metformin without any microvascular complications contributing to her diabetes, had been in her usual state of health, though already limited by an unsteady gait and dysarthria for 2 years, until three days before admission. She was admitted to the emergency department with a three-day history of dizziness and fatigue. It was associated with deviation of the mouth to the left, numbness over the entire left side of the body, gait imbalance, and right-sided weakness. There was no loss of consciousness, blurred vision, nausea, vomiting, involuntary movements, sphincter dysfunction, fever, or palpitations. Neurological examination showed the patient was conscious and alert with a Glasgow Coma Scale score of 15/15. Both pupils were reactive to light, horizontal nystagmus was noted, and speech was dysarthric. Head and neck examination showed a normal range of motion without deformity. Facial examination revealed deviation of the mouth to the left with preserved forehead wrinkling, indicating an upper-motor-neuron (central) facial pattern. On motor examination, bulk, tone, and deep-tendon reflexes were normal in all four limbs; power was full (5/5) in both upper limbs and in the left lower limb, with mild weakness (4/5) in the right lower limb. Sensation was preserved in all limbs. Plantar responses were extensor (positive Babinski) bilaterally. The gait was unsteady with incoordination, while the Romberg test was negative. Lower-limb examination showed no oedema and no clinical signs of deep vein thrombosis. The patient’s functional impairment corresponded to a mRS score of 3, reflecting moderate multi-system neurological disability secondary to pyramidal, brainstem, and cerebellar involvement. 2.2.1 Laboratory findings on admission Laboratory investigations showed a markedly elevated erythrocyte sedimentation rate (66 mm/h) and a raised C-reactive protein level (10.1 mg/L). HIV and hepatitis C serology were negative, and the thyroid-stimulating hormone was normal. Transthoracic echocardiography (24/05/2026) showed normal left- and right-ventricular size and function (ejection fraction ~65%), minimal mitral-valve prolapse with trace regurgitation, and a mild pericardial effusion of no hemodynamic significance; a non-contrast chest CT confirmed no lung mass, mediastinal lymphadenopathy, or pleural effusion, with the same mild pericardial effusion. 2.2.2 Imaging A non-contrast CT of the brain showed no intracranial hemorrhage or midline shift, but findings suggestive of right mastoiditis (ENT referral was advised), with minimal fluid in the right mastoid air cells. The subsequent MRI (24/05/2026) showed T2/FLAIR hyperintensity in the left basal ganglia, left thalamus, and left midbrain, with patchy enhancement ( Figures 2A, B ). On the sagittal view, there was longitudinal extension of the lesion from the basal ganglia through the midbrain into the upper pons ( Figure 2C ). Additionally, the coronal view demonstrated abnormal signal extending through the mesodiencephalic junction, consistent with the radiological cascade (waterfall) sign ( Figures 2D, E ). A T1-weighted MRI image was also obtained and revealed moderate patchy enhancement on the coronal view ( Figure 2F ). Although ischemic stroke was initially considered in the differential diagnosis because of the acute focal signs and the inflammatory changes on imaging, no diffusion-restricted infarct was demonstrated on DWI. The appearances were considered highly suggestive of NBD, with infiltrative tumor thought less likely, and follow-up MRI in two months was advised. Figure 2 Brain MRI demonstrating characteristic parenchymal Neuro-Behçet disease. (A, B) Axial T2-weighted/FLAIR images show a hyperintense lesion involving the left basal ganglia. (C) Sagittal T2-weighted image demonstrates longitudinal extension of the lesion from the basal ganglia through the midbrain into the upper pons (red arrows). (D, E) Coronal FLAIR/T2-weighted images demonstrate abnormal signal extending through the mesodiencephalic junction, consistent with cascade or “waterfall” sign (yellow arrow). (F) Coronal contrast-enhanced T1-weighted image reveals moderate patchy enhancement (green arrow). (G) Follow-up coronal post-contrast T1-weighted image obtained 2 months after treatment demonstrates minimal residual enhancement, consistent with significant radiological improvement and reduced parenchymal inflammatory activity. 2.2.3 Further clinical history The history of BD was obtained only after the MRI findings raised the possibility of NBD, and a focused history was obtained. The patient reported a five-year history of recurrent oral and genital ulcers and skin hypersensitivity, with papulopustular lesions according to previous dermatological reports, two years of gait imbalance, and a 10-day history of right-
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