Editorial [Hot Topic: New Therapeutic Options in Central Nervous System Involvement of Rheumatologic Diseases (Executive Editor: Ali Gur)]

It is clear that disorders of the nervous system continue to burden the planet's population with not only increasing morbidity and mortality, but also with a significant financial drain through increasing medical care costs coupled to a progressive loss in economic productivity. Causes underlying the pain and inflammation in rheumatologic diseases are interactive effects between tissues, the extracellular environment and the nervous system, complex interactions within the nervous system itself, and changes in the properties of nerve cells. The central nervous system (CNS) modulates immune functions by signaling target cells of the immune system through autonomic and neuroendocrine pathways. These immune cells relay information back to autonomic, limbic and cortical areas of the CNS to affect neural activity and consequently modify behavior, hormone release and autonomic functions. The entire neuraxis may be affected by rheumatologic conditions. CNS manifestations may vary according to the location of the lesion and range from focal findings (eg,stroke-like presentations) to global dysfunction (eg, encephalopathy or psychiatric symptoms). Most rheumatologic and vasculitic syndromes are characterized by pathologic changes in systemic organs and can affect the CNS. However, involvement of the nervous system may be a striking early or presenting feature with a wide variety of manifestations. Some of these diseases in both child and adult, including rheumatoid arthritis, systemic lupus erythematosus (SLE), primary Sjogren's syndrome (PSS), Behcet syndrome, cryoglobulinemia and lymphomatoid granulomatoses can present with CNS findings in the absence of any peripheral evidence of the underlying process. Central nervous system involvement in rheumatic diseases may occur in 4 forms: 1) CNS involvement of a systemic rheumatic disease, 2) primary CNS vasculitis, 3) indirect involvement secondary to hypertension, hypoxia and metabolic changes, and 4) drug associated adverse events. There have been advances in understanding the mechanisms behind the initiation and perpetuation of inflammatory processes in vasculitic neuropathy. Clinically relevant data have been obtained on the predictive criteria for a positive biopsy result in giant cell arteritis, the imaging characteristics of primary angiitis of the central nervous system, and Behçet disease, and the clinical and radiologic features of neuro-Behçet disease. There is more clarity about the central nervous system syndromes attributable to systemic lupus erythematosus and new insights into the central mechanisms involved in the manifestations of Sjögren syndrome and rheumatoid arthritis. A thorough knowledge of the rheumatic diseases and therapy related adverse event is mandatory to evaluate a child or adult with rheumatic disease and CNS manifestations. When vasculitis occurs in the setting of a preexisting connective tissue disorder, it often correlates with disease severity and portends a poorer prognosis. It may involve virtually any organ system and present in a myriad of ways. Prompt recognition and treatment of vasculitis can dramatically improve the outcome for the patient. Specific diagnostic tests are inadequate and early intervention with immunosuppressive therapy is frequently necessary. Therefore knowledge of these CNS complications is essential for early diagnosis and treatment. Current treatments include standard immunosuppressive agents, such as corticosteroids and cyclophosphamide, plasmapheresis, intravenous immunoglobulin, thalidomide, and intratechal treatment; however, more directed therapy, such as tumor necrosis factor-alpha blocking agents may hold promise in rheumatoid vasculitis and Sjogren syndrome. On the other hand, because of the clinical similarities between fibromyalgia syndrome (FM) and chronic fatigue syndrome (CFS) it was suggested that they share a common pathophysiological mechanism, namely, CNS dysfunction. The etiology and pathophysiology of these diseases remain unclear. Current hypotheses center on atypical sensory processing in the CNS and dysfunction of skeletal muscle nociception and the hypothalamic- pituitary- adrenal axis. Researches suggest that the CNS is primarily involved in both disorders in regard to the pain, fatigue and sleep disturbances. Medical treatments are poorly effective and only helpful for a subset of patients. With further understanding of the pathophysiological abnormalities involved in fibromyalgia-chronic fatigue one may expect to find more effective therapeutic modalities........