Parkinsonism and Rapidly Progressive Dementia Secondary to Neuro‐Behçet

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Behçet's disease (BD) is a chronic inflammatory disorder with higher prevalence along the ancient silk road (from Japan to the Mediterranean region), whereas it is rare in North America. ¹ BD is often associated with HLA‐B51 and has a wide range of clinical manifestations (involving the eyes, oral mucosa, skin, and nervous system). Oral ulcers are the most common and usually the first manifestation of the disease; anogenital ulcers are present in 75% of patients, whereas other skin complications (erythema nodosum, papulopustular, and acneiform lesions) are present in 60% of patients. ² Neurological involvement, often referred to as neuro‐Behçet disease (NBD), is reported in approximately 10% of patients with BD, showing a male predominance (male‐to‐female ratio = 3:1) ³ and can affect both the central and peripheral nervous systems. Involvement of the central nervous system can be classified into parenchymal (hemispheric, brainstem, spinal cord, meningoencephalitis) and nonparenchymal (cerebral venous thrombosis, stroke, aneurysms). ⁴ Proposed diagnostic criteria for NBD include (1) satisfying the International Study Group BD criteria, ⁵ (2) the presence of a compatible neurological syndrome along with characteristic abnormalities in neuroimaging and/or cerebrospinal fluid, and (3) no better explanation for the symptoms. ⁶ Headache, cognitive‐behavioral changes, pseudobulbar speech, brainstem problems, and motor and sensory alterations are commonly seen in NB. ⁷

Case Report

A 66‐year‐old Mexican man without previous relevant medical history presented with sudden bilateral vision loss associated with papilledema on the neurological examination. Contrast‐enhanced magnetic resonance imaging venography was performed showing thrombosis of the superior sagittal and left transverse sinus (Fig. 1A–D). The patient was treated with anticoagulation for 6 months with clinical improvement, followed by antiplatelet aggregation. Three years later, he developed neuropsychiatric symptoms, including personality changes, flat affect, short‐term memory, and calculation impairment along with swallowing difficulties and loss of sphincter control. Neurological examination revealed emotional incontinence, frontal release signs, hypomimia, vertical gaze limitation, global and symmetric bradykinesia, freezing of gait (Video S1), and orthostatic hypotension. His Folstein mini‐mental examination score was 20/30. An oral ulcer affecting the lower lip and a skin lesion on the lower back were also observed. A new brain magnetic resonance imaging showed multiple subcortical hyperintense white matter lesions in T2 and fluid‐attenuated inversion recovery sequences (Fig. 1E–H). Cerebrospinal fluid was normal apart from elevated proteins (80 mg%). The pathergy test was positive. Routine hematology, biochemistry, and immunological tests were unremarkable.

FIG 1.

In the first brain magnetic resonance imaging, axial fluid‐attenuated inversion recovery sequence show hyperintensity in the superior pedunculus and colliculus (A); the magnetic resonance imaging venography shows thrombosis of the superior sagittal and left transverse sinus (B; see arrows). The second brain magnetic resonance imaging, 3 years later, shows multiple subcortical and white matter lesions in the axial fluid‐attenuated inversion recovery sequence (C,D).

Biopsy of the lumbar skin lesion (Fig. 2A) showed polymorphic infiltrate, pseudofolliculitis, pustular necrotic areas, and focal capillary thrombosis (Fig. 2B). The patient was diagnosed with NBD and treated with a bolus of methylprednisolone intravenously followed by oral methotrexate with slight improvement. Levodopa/carbidopa (250/25 mg) therapy was also started, a half tablet every 4 hours, with partial improvement of the bradykinesia. Six months later, he was hospitalized for pneumonia and died as a consequence of respiratory complications.

FIG 2.

(A) Skin lesions in the lower back/gluteal region. (B) Hematoxylin and eosin stained tissue from the skin biopsy showing the polymorphic inflammatory process, with capillary thrombosis and pseudofolliculitis.

Discussion

Here we describe a case of NBD who first presented with cerebral venous sinus thrombosis in his seventh decade. Three years later, he developed multiple clinical manifestations of parenchymal brain disease, including parkinsonism, cognitive impairment, and supranuclear gaze palsy. In 2 previous reports, only 18% to 20.6% of patients showed overlapping parenchymal and nonparenchymal manifestations. ³ , ⁵ , ⁷ The most frequent symptom was headache (85%) in both categories, whereas cerebral venous thrombosis (20%) was the main nonparenchymal finding. ² Cognitive and psychiatric symptoms may be the first clinical presentation of NBD, and therefore clinicians should be aware of this etiology in patients with new‐onset cognitive impairment. ⁸ , ⁹ , ¹⁰ Although the basal ganglia may be affected in NBD, movement disorders are rare. Isolated cases of paroxysmal dystonia, parkinsonism, and chorea have been reported. ¹¹ , ¹²

NBD has a wide range of manifestations that can mimic other disorders, and therefore its diagnosis can be challenging. Furthermore, although the most frequent age of onset is between 20 and 40 years, later onset cases, such as our patient, have been reported. The presence of classic signs of BD, such as oral‐anogenital ulcers and skin lesions, in patients with movement disorders should raise the suspicion of NBD, as this is a potentially treatable disorder and therefore should not be missed.

Author Roles

(1) Research Project: A. Conception, B. Organization, C. Execution; (2) Manuscript Preparation: A. Writing of the First Draft, B. Review and Critique.

M.R.‐H.: 1A, 1C, 2A

I.R.‐L.: 1A, 1B, 2B

A.A.‐G.:1B, 2B

C.G.‐R.: 1B, 2B

C.A.‐M.: 2B

Disclosures

Ethical Compliance Statement

A written consent form was obtained from the patient, who signed the document. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this work is consistent with those guidelines.

Funding Sources and Conflicts of Interest

The authors declare that there are no conflicts of interest relevant to this work.

Financial Disclosures for Previous 12 Months

The authors declare that there are no additional disclosures to report.

Supporting information

Video S1. Clinical evolution, showing prominent parkinsonism that worsens with each evaluation. It is possible to appreciate the presence of oral ulcers in 1 of the videos.