What is neurobehcets and how is it treated?

Neurobehçet's Disease: Diagnosis and Treatment

Neurobehçet's disease (NBD) is a serious manifestation of Behçet's syndrome requiring prompt immunosuppressive therapy to prevent irreversible neurological damage and disability. 1

Definition and Classification

• Neurobehçet's disease refers to the neurological manifestations of Behçet's syndrome, affecting approximately 5-30% of Behçet's patients 2
• NBD is classified into two major forms:
  • Parenchymal NBD: Characterized by focal or multifocal CNS involvement, typically presenting as a subacute brainstem syndrome and hemiparesis (majority of cases) 3
  • Non-parenchymal NBD: Primarily caused by cerebral venous sinus thrombosis leading to intracranial hypertension (10-20% of cases), with generally better prognosis 3

Clinical Presentation

• Parenchymal NBD typically presents with brainstem syndromes, hemiparesis, cognitive changes, and psychiatric symptoms 3
• Non-parenchymal NBD presents with symptoms of increased intracranial pressure such as headache, papilledema, and visual disturbances 3
• Poor prognostic factors include multifocal involvement, spinal presentations, more than two attacks per year, progressive course, and increased CSF cell count and protein 2

Diagnostic Approach

• Diagnosis requires evidence of Behçet's syndrome (recurrent oral ulceration plus two of: recurrent genital ulceration, eye lesions, skin lesions, or positive pathergy test) 4
• MRI is the imaging modality of choice, showing characteristic lesions in the brainstem, basal ganglia, and cerebral white matter in parenchymal NBD 5
• CSF analysis may show moderate pleocytosis and elevated protein in parenchymal NBD 5
• Cerebral venous sinus thrombosis in non-parenchymal NBD is best visualized with MR venography 5

Treatment of Neurobehçet's Disease

Acute Treatment

• For acute attacks of parenchymal NBD, high-dose intravenous methylprednisolone (1g/day for 3-7 days) followed by oral prednisolone (1 mg/kg/day) with gradual tapering over 6-12 months is the first-line treatment 1, 6
• Oral steroids should be tapered by 5-10 mg every 10-15 days, aiming for a maintenance dose of 5-10 mg/day 1

Maintenance/Preventive Treatment

• Azathioprine (2.5 mg/kg/day) is recommended as first-line maintenance therapy for patients without poor prognostic factors 2, 1
• For high-risk patients or those with severe disease, cyclophosphamide should be considered in combination with corticosteroids 2
• Mycophenolate mofetil is an alternative option for maintenance therapy in acute NBD 7
• For chronic progressive NBD, low weekly dose methotrexate may be beneficial 7

Treatment for Refractory Cases

• TNF-alpha inhibitors, particularly infliximab, are recommended for patients who fail conventional therapy 1, 7
• First-line infliximab may be preferred in severe cases with high risk of permanent damage 7
• Other biological agents to consider in refractory cases include:
  • Tocilizumab (IL-6 inhibitor) 6, 7
  • IL-1 inhibitors (anakinra, canakinumab) 6, 7
  • Interferon-alpha 2, 3

Treatment of Non-parenchymal NBD (Cerebral Venous Thrombosis)

• High-dose corticosteroids with the same regimen as parenchymal NBD 1
• Anticoagulation therapy should be considered, though this remains controversial due to the risk of bleeding, especially with coexisting pulmonary arterial aneurysms 1, 2

Important Considerations and Pitfalls

• Cyclosporine A should be avoided in patients with NBD due to potential neurotoxicity 1
• Young men with early disease onset have a higher risk of severe disease and may benefit from early aggressive immunosuppression 1, 8
• Regular monitoring of disease activity through clinical symptoms and inflammatory markers is essential 8
• Long-term treatment should be determined by a multidisciplinary approach due to multiple organ involvement in Behçet's syndrome 7
• Disease manifestations often ameliorate over time, allowing for potential tapering and even discontinuation of treatment during the course of the disease 4

Prognosis

• Parenchymal NBD, especially in its chronic progressive form, is associated with significant morbidity and can lead to permanent disability 7
• Non-parenchymal NBD generally has a better neurologic prognosis 3
• Early recognition and timely treatment are crucial to prevent long-term disability 7
• Ocular, vascular, neurological, and gastrointestinal involvement are associated with poor prognosis and can cause serious damage or death if left untreated 8