Extrapyramidal signs in neurosarcoidosis versus multiple sclerosis: Is TNF alpha the link?

Specific inflammatory pathways and specifically Tumor Necrosis Factor alpha (TNF-alpha) have been associated with the neurodegeneration in Parkinson's disease (PD). TNF alpha is also known to play an important role in the pathogenesis of sarcoidosis and TNF blockers can ameliorate the disease. In contrast, multiple sclerosis (MS) is clearly exacerbated by anti- TNF-alpha medications. We have therefore hypothesized that Parkinson-like disease would be more common in neurosarcoidosis (NS) compared to MS. The aim of this case-control study was therefore to assess the frequency of extrapyramidal signs in patients with NS compared to MS patients. In order to do so the medical records of NS patients and of age and gender matched MS patients were reviewed and data regarding the clinical features, ancillary tests performed, treatment, and outcome were documented. Patients were then examined in a uniform manner for the presence of extrapyramidal signs. We found that in the NS group 8 patients had minor signs, one had mild functional disability and 3 subjects had significant extra pyramidal signs compatible with the diagnosis of Parkinson's disease. All extrapyramidal signs found in 5 of the MS group were minor. The proportional severity of extrapyramidal signs was significantly higher (p = 0.045, chi square test) in the NS group compared to the MS group. We conclude that the specificity of extrapyramidal to NS raises the intriguing question of whether specific inflammatory pathways involving TNF-alpha play a role in the pathogenesis of PD and therefore may be a therapeutic target.