Background Central nervous system involvement is one of the most serious complications in Behçet's disease (BD). This condition is referred to as neuro-Behçet's disease (NB) and can be classified into acute type (ANB) and chronic progressive type (CPNB) based upon differences in the clinical course and responses to corticosteroid treatment. Cerebellar ataxia, such as gait disturbances and dysarthria, is one of the representative manifestations in CPNB. Accordingly, brainstem atrophy is frequently observed in CPNB, but not in ANB. Notably, progressive neurobehavioral changes mimicking those in Alzheimer's disease (AD) are also frequently observed in CPNB, but these changes cannot be accounted for by brainstem atrophy.
Objectives In the present study, volumes of the hippocampus were examined to identify the responsible lesions for neurobehavioral changes in CPNB, and patterns of atrophy in the hippocampus and brainstem were compared between patients with CPNB and AD.
Methods The subjects were 32 patients, including 13 with CPNB (11 males and 2 females, age 51.2±12.1 years old [mean ± SD]), 13 with Behçet's disease without NB (non-NB) (10 males and 3 females, age 54.4±11.4 years old), and 6 with AD (5 males and 1 female, age 78.8±7.5 years old). All patients with BD satisfied the international classification criteria for BD. CPNB was defined as intractable, slowly progressive neurobehavioral changes and/or cerebellar ataxia accompanied by persistent elevation of interleukin-6 of >20 pg/mL in cerebrospinal fluid on two different occasions at an interval of at least 2 weeks. All patients with AD satisfied Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV criteria. Brain magnetic resonance imaging (MRI) was obtained from each subject. The areas of the midbrain tegmentum and pons were measured on mid-sagittal sections of T1-weighted images using image analysis software (Image J ver.1.45: NIH, USA). Severity of gray matter loss in the hippocampal region and whole brain were investigated using Voxel-Based Specific Regional Analysis System for Alzheimer's Disease (VSRAD) software (Eisai Co., Ltd) to determine the degrees of hippocampal region atrophy (Z score) and whole-brain atrophy (WBAI). Thus, the 1/Z score is positively correlated with the hippocampus volume. The ratio of the degree of brainstem atrophy to that of hippocampal atrophy was evaluated by the brainstem area value divided by the 1/Z score (BA/H score) in each patient.
Results The brainstem area was significantly decreased in CPNB (461.8±87.3 [mean ± SD]) compared with that in AD (661.9±56.1) and non-NB (666.1±50.6) (Figure A). VSRAD analysis showed that Z score was significantly increased in CPNB (1.46±0.70) and AD (3.13±1.21) compared with that in non-NB (0.77±0.40) (Figure B). Of note, the BA/H score, reflecting the brainstem/hippocampus volume ratio, was much lower in CPNB than in AD [663.5±311.8 vs 2018±667.6, p=0.001] (Figure C).
Conclusions These results indicate that the hippocampus, in addition to the brainstem, is a common target lesion in CPNB, and this accounts for the progressive neurobehavioral dysfunction in this disease. Moreover, the data emphasize that brainstem atrophy is disproportionately greater than hippocampal atrophy in CPNB, in contrast to AD.
Disclosure of Interest None declared