Neurorheumatology

 

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The intersection of neurology and rheumatology, sometimes called the “borderlands” of neurology, is a rich clinical and scientific area. The autoimmune and autoinflammatory processes involved, herein referred to as neurorheumatologic diseases, can affect any part of the nervous system. Not infrequently, the neurologic syndrome is the first or only manifestation of disease. An understanding of the classical neurologic presentations of neurorheumatologic diseases, as well as exposure to the emerging concepts in diagnosis and treatment, is essential for both the practicing neurologist and neurologic investigators. The goal of this issue is to provide in one resource key updates on the diagnosis and management of neurorheumatologic disease, as well as to provide practical guidance for this “borderland” of neurology.

To frame the overall approach, Eli Miloslavsky and I outline the clinical perspective of both rheumatologist and neurologist when faced with potential neurorheumatologic diseases. Using a systematic method including consideration of the host, systemic symptoms, and select laboratory testing, we propose a framework for more specific evaluation and management. Given the complexity of available laboratory testing, familiarity with the serologic and other laboratory testing frequently used by rheumatologists is essential. Meghan Hickey and Mandakolathur Murali provide an indispensable overview of the most commonly used laboratory tests in neurorheumatology. From antinuclear antibody to serum protein electrophoresis, the authors explain the underlying principles and methods used for testing, as well as the appropriate utilization and interpretation of such tests.

One of the classic neurorheumatologic diseases, neurosarcoidosis still proves to be an elusive concept often raised as a diagnostic possibility, but rarely proven definitively. I team up with Shruti Agnigotri, Tarun Singhal, and Barney Stern to characterize the most common neurologic syndromes encountered in sarcoidosis, replete with examples of findings from magnetic resonance imaging. A diagnostic and therapeutic approach is outlined to provide neurologists with the knowledge to recognize and effectively treat the varied manifestations of neurosarcoidosis. One of the more distinctive neurologic syndromes, pachymeningitis, has often been attributed to sarcoidosis or remained idiopathic. More recently, a significant subset of these patients have been diagnosed with a still emerging disease process, IgG4-related disease. Robert Carruthers, Mollie Carruthers, and Emanuel Della-Torre take a closer look at the most cutting-edge research into this process, framed in the setting of meningeal inflammatory disease more broadly.

Long considered one of the most devastating and refractory neurorheumatologic diseases, primary angiitis of the central nervous system (PACNS) has been more clearly defined in recent years. Seby John and Rula Hajj-Ali provide a high-level overview of central nervous system vasculitides, with a focus on PACNS and its mimics including reversible cerebral vasoconstriction syndrome. The authors provide a clear guide for distinguishing these disease processes and directing therapy accordingly. Complementing this review of CNS vasculitis, Haatem Reda and Russell Chin orchestrate a beautiful overview of peripheral neuropathies of rheumatologic disease, many of which are due to vasculitis involving the peripheral as opposed to the central nervous system. In addition, they explore emerging concepts in gluten sensitivity-associated neuropathies and address the optimal treatment of the immune-mediated neuropathies.

The connective tissue diseases have long been known to affect the nervous system in myriad and often unusual ways. Without any clear biomarker to define these diseases, diagnosis is based on a combination of clinical and laboratory findings. Further complicating this challenge is the fact that neurologic syndromes such as cranial neuropathy or myelitis may be the initial manifestation of systemic disease. In a comprehensive review, Shamik Bhattacharyya and Simon Helfgott focus on systemic lupus erythematosus, Sjögren syndrome, systemic scleroderma, and rheumatoid arthritis. Cataloging the possible neurologic manifestations of the connective tissue diseases is a daunting task, but the authors masterfully organize this massive topic into a thorough and practical approach.

Another disease that has proven difficult to classify, Behçet disease has a nonetheless distinctive clinical and pathological footprint suggesting a disturbance of the innate immune system impacting on blood vessels. Julie Miller, Nagagopal Venna, and Aksel Siva outline the most common neurologic manifestations of Behçet disease and an approach to effective diagnosis and treatment. Extrapolating from more well-defined genetic diseases, the authors also suggest a common pathological pathway underlying so-called autoinflammatory diseases of which Behçet disease may be a sporadic example. A devastating syndrome in Behçet is ocular inflammation, which is a common manifestation of several immune-mediated and inflammatory diseases. Ivana Vodopivec, Ann-Marie Lobo, and Sashank Prasad review ocular inflammatory disease as a window into both systemic and more isolated ocular rheumatologic disease. The authors distill the complex anatomical and immunological aspects of ocular disease in a highly practical and readable format, alerting the neurologist to ocular manifestations that help lead to more rapid diagnosis and treatment.

One of the most exciting and promising areas of neurologic advancement is antibody-mediated encephalitis. In their thorough summary, Jenny Linnoila, Myrna Rosenfeld, and Josep Dalmau clarify concepts surrounding neuronal surface antibody-mediated autoimmune encephalitis. As NMDA receptor antibody encephalitis becomes more widely recognized, understanding the boundaries of the disease mediated by this antibody will be essential. The authors review the latest understanding of N-methyl-D-aspartate receptor (NMDAR) encephalitis as well as several other emerging unique antibody-mediated encephalitides.

Once diagnosed, many neurorheumatologic and autoimmune diseases remain a challenge to treat. Although many new immunologic therapeutics have been developed in recent years, the safe and appropriate use of these and older immunomodulatory therapies requires a thorough knowledge of the safety and monitoring parameters of these agents. Ivana Vodopivec, Eli Miloslavsky, Camille Kotton, and I combine the perspectives of neurologic, rheumatologic, and infectious diseases expertise to provide a framework for using the many immunomodulatory therapies available to combat neurorheumatologic disease. In this practical guide, we summarize and distill a large body of work on the key safety issues and monitoring to maximize the safe and effective use of these potent therapies.

Neurorheumatologic disease is a growing area of neurology that focuses on the overlap of often systemic rheumatologic and autoimmune diseases with every part of the nervous system. Neurologists bring special perspective to bear on patients with inflammatory involvement of the nervous system, as often the localization and constellation of neurologic deficits give clues to the specific disease process. The authors of this issue have provided thorough and illustrative reviews of these emerging and challenging topics, and we are indebted to them for their hard work and expertise. The concepts they so deftly review here are sure to develop further in the coming years, shaping the way neurologists approach and manage these diseases.