Behçet’s Disease (BD) is a rare, chronic inflammatory disorder characterized by systemic vasculitis, affecting multiple organ systems, including the skin, eyes, joints, and major vessels. Neuro Behçet’s Disease (NBD) represents a serious complication where the underlying vasculitis targets the central or peripheral nervous system. This neurological involvement occurs in a minority of BD patients but can lead to severe and potentially disabling outcomes.
The Foundations of Behcet’s Disease
Behçet’s Disease is classified as a multisystem disorder where inflammation affects arteries and veins of all sizes. The underlying cause is presumed to involve an autoimmune response triggered by environmental factors in genetically susceptible individuals. A strong genetic association exists with the HLA-B51 allele, found frequently in people with BD, particularly those whose ancestry traces back to the ancient Silk Road region.
The diagnosis of BD typically relies on non-neurological clinical features that often appear before NBD onset. Recurrent oral aphthous ulcers are the most common sign, affecting nearly all patients and often serving as the initial symptom. Genital ulcers, which often leave scars, are another defining feature, along with characteristic skin lesions.
Skin manifestations can include acne-like lesions or tender, raised nodules known as erythema nodosum, typically appearing on the lower legs. Ocular inflammation, such as uveitis, is a severe feature that can cause redness, pain, and blurred vision, posing a risk of permanent vision loss. When the inflammatory process extends to involve the central or peripheral nervous system, it is categorized as Neuro Behçet’s Disease, which can occur years after the initial systemic symptoms.
Specific Neurological Manifestations
The neurological presentation of NBD is diverse, based on the location of the inflammation within the nervous system. The more common form is parenchymal involvement, which refers to inflammation directly affecting the brain tissue and spinal cord. This type often presents with a sub-acute onset of symptoms related to the brainstem, a frequently affected region.
Damage to the brainstem can lead to difficulties with movement and coordination, manifesting as pyramidal signs or cerebellar dysfunction, such as ataxia. Patients may experience cranial nerve palsies, resulting in symptoms like double vision or facial weakness, along with problems in speech or swallowing. Lesions can also occur in the basal ganglia and diencephalon, which may contribute to cognitive impairment, behavioral changes, and confusion. Spinal cord involvement, though less common, can cause symptoms resembling transverse myelitis, including weakness and sensory changes in the limbs.
The second category is non-parenchymal involvement, which affects the vascular structures and meninges surrounding the brain. This form is often characterized by cerebral venous sinus thrombosis (CVST). CVST can obstruct blood flow and absorption of cerebrospinal fluid, leading to an increase in intracranial pressure.
A primary consequence of increased intracranial pressure is a persistent, chronic headache, often accompanied by papilledema. Aseptic meningitis can also occur, presenting with fever and a stiff neck. Headaches resulting from CVST or meningoencephalitis represent a specific and serious neurological complication of NBD.
Establishing a Diagnosis
Diagnosing Neuro Behçet’s Disease is challenging because no single laboratory test confirms the condition definitively. Diagnosis relies on combining evidence of systemic Behçet’s Disease with objective neurological findings. This requires the patient to first meet established criteria for systemic BD, which focus on recurrent oral ulcers and other characteristic features like genital ulcers or eye inflammation.
Once the systemic diagnosis is established, a medical evaluation must confirm that the neurological symptoms are attributable to BD. Neuroimaging is an essential tool, with Magnetic Resonance Imaging (MRI) used for visualizing the brain and spinal cord. In cases of parenchymal NBD, MRI typically reveals characteristic inflammatory lesions, often found in the brainstem, thalamus, and basal ganglia.
Further confirmation often involves Cerebrospinal Fluid (CSF) analysis, obtained through a lumbar puncture. In parenchymal NBD, the CSF frequently shows signs of inflammation, such as pleocytosis and a mildly increased protein level. Patients with non-parenchymal NBD often have CSF with normal cell counts and protein levels but may exhibit a high opening pressure. Ruling out other conditions that mimic NBD, such as multiple sclerosis or infectious diseases, is a necessary step.
Treatment Strategies and Management
Treatment of Neuro Behçet’s Disease focuses on suppressing inflammation, preventing further neurological damage, and managing specific symptoms. Therapy is stratified based on the type of involvement and the severity of the flare. Acute attacks, particularly those involving parenchymal inflammation, are typically managed with high-dose intravenous corticosteroids administered over several days.
Following the acute phase, long-term maintenance therapy is initiated to sustain remission and minimize relapse risk. Conventional immunosuppressive agents, such as azathioprine, form the foundation of this management by moderating the overactive immune response responsible for the vasculitis.
An increasing number of patients are treated with biologic agents, particularly Tumor Necrosis Factor-alpha (TNF-alpha) inhibitors like infliximab, especially when the disease is resistant to conventional immunosuppressants. For non-parenchymal involvement, such as cerebral venous sinus thrombosis, treatment typically involves short-term corticosteroids, with or without immunosuppressants, and sometimes anticoagulation. Symptomatic management may include specific medications to control headaches, seizures, or psychiatric manifestations.