This was a hospital-based study which was aimed at studying the clinical, radiological profile, treatment response and outcome in patients diagnosed with NBD from India. We studied 12 patients who were diagnosed as NBD as per the ICR criteria for NBD diagnosis. The reported frequency of NBD from India is relatively low probably due to low prevalence, lower rate of suspicion by the treating physician and neurologist. BD is commonly characterised by recurrent oral aphthae which is the main and recurrent symptom, genital ulcers, skin lesions, arthritis, uveitis, and thrombophlebitis . The first report of neurological involvement in BD was described in 1941. NBD is seen in 10–20% of BD patients . NBD is relatively uncommon but potentially treatable, and should be considered in the differential diagnosis of inflammatory, infective, or demyelinating central nervous system (CNS) disorders and one of the causes of long-term morbidity in BD. Genetic susceptibility has been reported in BD which has ethnic group susceptibility. The HLA B5 genotype is seen in 40–65% of patients diagnosed with BD in studies from Turkey and Eastern Asia and the prevalence of HLA-B51/B5 among subjects with NBD is not dissimilar to that found in patients with BD without neurological involvement .
There are several studies which have studied large cohort of NBD patients worldwide including Mediterranean, European, Middle East and South East Asian countries. Akman-Demir et al. from Turkey reported one of the largest series on the neurological involvement in BD and assessed the pattern of involvement and prognosis in NBD. They analyzed 200 cases of NBD and found male predominance. The mean interval between onset of BD and NBD was 5.6 years after onset of BD. The skin pathergy test was positive in 83% of patients. The parenchymal involvement was the most common manifestation of NBD. The brainstem involvement was the most common area of parenchymal NBD. Hemiparesis, pyramidal involvement and behavioural change was the most common clinical manifestation in pNBD. Dural sinus thrombosis was the most common presentation of npNBD. CSF pleocytosis was seen in 60% of cases with pNBD. The indicators for favorable prognosis were normal CSF, npNBD, number of attacks less than 2 and functional independence at admission whereas abnormal CSF, pNBD, more than 2 attacks, progressive course, dependent at admission and relapse during steroid tapering were poor prognosis indicators . Al-Araji et al. from Iraq studied the prevalence of neurological involvement and described the clinical patterns of neurological presentation in NBD. Twenty patients of NBD were studied and pNBD was most common presentation with pyramidal signs as the most common clinical sign. CSF pleocytosis with raised protein was seen in 50% of pNBD patients. However, MRI lesions were more frequent in cerebral white matter (92%) than brainstem and thalamus . Hirohata et al. from Japan studied the clinical characteristics of NBD. They reviewed 76 patients with acute NBD, 35 with chronic progressive (CP) NBD, and 33 with non-NBD. They found high-intensity lesions frequently in the pons, midbrain, and basal ganglia in acute NBD as well as CP NBD. Brainstem atrophy was more frequently occurred in CP NBD . Talarico et al. from Italy assessed the prevalence of neurological involvement in BD and the clinical patterns of presentation in NBD. They studied 44 patients with NBD (35 pNBD) and brain MRI showed pons-mesencephalon lesions in 19 patients and meningoencephalitis with brainstem involvement in 16 patients . Sorgun et al. from Turkey studied treatment response and prognosis in patients with NBD. They studied 60 NBD patients and parenchymal NBD was the most common presentation. The time to NBD was 8 years. HLA B51 positivity was very low (5%) whereas positive pathergy test was 50%. Brainstem (60%) was most common site of parenchymal lesion followed by cerebral hemisphere (30%). Patients with severe NBD had older age at onset and longer time to NBD . Kim et al. from South Korea studied 110 patients with NBD. HLA B51 positivity was 50% but positive pathergy test was 16%. pNBD was the most common presentation with brainstem syndrome as the predominant clinical manifestation. Acute pNBD (72%) was more common presentation than cpNBD. Abnormal CSF findings were noted in 70% of patients. Pons, midbrain followed by deep white matter was most common sites of lesions on MRI . Bolek et al. retrospectively reviewed the charts of 77 patients (definite NBD = 61, probable NBD = 16) of NBD. The most common presentation in their cohort was parenchymal NBD (61%). The most frequently affected parenchymal area was brainstem (72.9%) followed by cerebellum and diencephalon. The median time for NBD onset after BD onset was 6 years. Acute onset pNBD was more frequent than CP NBD. All patients with npNBD had favourable outcome whereas 57% of patients with pNBD had favourable outcome .
Based on the findings from large cohort of NBD patients, we can infer that NBD shows male predominance, mean time of onset of 6–8 years after BD onset, parenchymal involvement predominance, brainstem and cerebral white mater as the most common affected areas, acute attacks and relapsing–remitting as the predominant pattern with favourable prognosis in npNBD as compared to cp NBD. The literature of NBD is very limited from India with few anecdotal case reports. We reviewed our patients who were diagnosed as NBD and studied the clinical, radiological, treatment profile and outcome. As compared to above studies, we found similar age at onset, equal gender distribution, parenchymal NBD and pyramidal symptoms predominance, CSF abnormalities, HLA B51 and pathergy test positivity. However, thalamus involvement was seen in all patients followed by pons, subcortical white matter unlike in above studies wherein the brainstem and cerebral white mater involvement is predominant. Poor prognosis was seen in cp NBD in our cohort as demonstrated in other studies.
The management of neuro-Behçet's disease includes treatment of acute attacks and prevention of relapses. The treatment of acute attacks is achieved by high-dose intravenous corticosteroids followed by maintenance treatment with oral steroids for 6–12 months depending on the type and severity of the neurological involvement. Immunosuppressants are used to prevent relapses. Oral immunosuppressants such as azathioprine and mycophenolate are the most commonly used. Patients who are refractory or who cannot tolerate these medications can be managed by cyclophosphamide, interferon alpha, or anti-TNF-α monoclonal antibodies such as infliximab, etanercept, and adalimumab [19,20,21]. All our patients received high-dose intravenous corticosteroids and 3 patients cyclophosphamide for acute attack. Patients requiring cyclophosphamide had poor outcome. The proinflammatory cytokines IL-6 and IL-8 are reported to be elevated in the acute and chronic progressive NBD with significant decrease following initiation of treatment and levels of IL-17, IL-21 has also been found to be increased in NBD [22, 23].
The strength of the study is the detailed description of patients with NBD from India wherein the prevalence and index of clinical suspicion is low. The limitation of this study was very small sample size of 12 patients, non-representation of npNBD, lack of detailed medical evaluation for systemic BD and short follow-up. NBD as etiology of dural sinus thrombosis in Indian sub-continent is very rare and NBD is not considered as a cause for dural sinus thrombosis in routine clinical practice. Hence, there was non-representation of npNBD in our cohort.