Emerging and Controversial Issues in Neurology: Infectious Diseases

In this issue of Seminars in Neurology, the articles cover a range of topics in neurologic infectious diseases. Rather than following an organization of neurologic syndrome localization or category of infectious agent, this issue focuses on some areas of controversy and on topics that may not be emphasized as much in the general neurologic literature. Certainly, this publication and others have previously discussed some of the included topics, but the goal is to put together in one issue some of the ongoing challenges in neurologic infectious disease and suggest areas for needed research, including discussion of other topics not addressed in this issue.

In recent years, the scope of neurology seen in developed countries has evolved substantially. As the world has become smaller through travel and immigration (and the spread of digital media), neurologists must be familiar with many diseases that have been previously geographically limited. Kiran Thakur and Joe Zunt review a subset of these, focusing on neurologic parasitic infections in travelers and immigrants, including cerebral malaria, neuroschistosomiasis, and neurocysticercosis.

Michael Wilson and Ken Tyler review some of the most cutting-edge tools for diagnosing viruses in the setting of encephalitis, discuss immune-mediated encephalitides that can mimic viral processes, and examine some specific examples of recent viral infections impacting the United States.

Due to advances in combination antiretroviral therapy, the burden of opportunistic infections in human immunodeficiency virus (HIV) has decreased dramatically in developed countries over the past two decades. However, new challenges have arisen in the form of immune dysregulation, both early in the course of infection and with the initiation of effective antiretroviral therapy. In addition, even in developed countries some patients may still present with neurologic complications of HIV due to lack of access or compliance. Jennifer Lyons, Nagagopal Venna, and I review some of the atypical and emerging neurologic complications of HIV.

In addition to emerging infectious diseases, classic syndromes, such as general paresis of the insane and tuberculous vasculopathy have reemerged in new settings and with newly recognized manifestations. Furthermore, with advances in neuroimaging and microbial diagnostic techniques, the range of potential infectious etiologies of dementia and stroke is widening. Scott McGinnis reviews the infectious causes of rapidly progressive dementia. Familiarity with the clinical and laboratory features of these diseases may help identify treatable entities and avoid potentially unnecessary studies and treatments in others. Before advanced neuroimaging, including sensitive diffusion-weighted magnetic resonance imaging (MRI) and noninvasive cerebral angiography techniques, cerebrospinal fluid examination was a standard part of the evaluation in otherwise unexplained stroke syndromes. Recently, there has been increasing recognition of the role of infection and inflammation in the pathophysiology of certain forms of cerebrovascular disease. Felicia Chow, Christina Marra, and I review the infectious causes of stroke with a focus on central nervous system infections with this predilection.

As immunologic basic science, translational research, and new immunomodulatory therapies have advanced, some syndromes and diseases have continued to elude definitive etiologic explanation. Particularly in cases in which attribution to any etiologic agent rests on indirect lines of evidence, the potential for controversy is high. Multiple sclerosis (MS) has long been attributed to inappropriate immune attack of the central nervous system myelinated fibers, but the underlying trigger(s) of this attack has remained elusive. Alex Tselis reviews the history behind the infectious hypothesis of MS and distills the scientific literature addressing the role of viral infections in the etiology of MS, pointing to future directions for research.

More than 30 years after the original description of migrating polyarthritis in a group of children in a heavily wooded town in Connecticut, Lyme disease continues to generate controversy due to its attribution by some in numerous symptom complexes. Like another spirochetal disease, syphilis, the diagnosis of Lyme disease is based on indirect evidence of exposure in the setting of typical clinical findings. Both in Europe and the Unites States, the classic triad of lymphocytic meningitis, facial nerve palsy, and painful radiculitis have long been recognized in association with early disseminated Lyme disease. John Halperin reviews the spectrum of neurologic involvement in Lyme disease, addressing some of the challenges in attributing certain syndromes to ongoing Borrelia burgdorferi infection.

Another syndrome with neurologic symptoms, chronic fatigue syndrome, has eluded a unifying pathophysiological explanation. Many processes can directly and indirectly lead to fatigue, concentration and memory problems, and malaise. Although it is well established that certain infections can be followed by a chronic fatiguing illness, the underlying cause of the initial infection or of the ongoing symptoms has been challenging to elucidate. Anthony Komaroff and I review the evidence for neurologic involvement in chronic fatigue syndrome and make an argument for an infectious trigger of chronic or recurrent inflammation as a cause of chronic fatigue syndrome.

Finally, one of the greatest advancements in modern medicine has been the development of effective vaccines for several widespread infections. As the burden of previously epidemic and endemic infections has decreased, the focus for some has turned to potential adverse effects of vaccination through its activation of the immune system. James Sejvar reviews the underlying basis for vaccination, some of the neurologic diseases prevented through vaccines, and some of the purported adverse neurologic effects of vaccine use.

Neurologic infectious disease is a growing subspecialty that focuses on the overlap of systemic infectious diseases with every part of the nervous system. Neurologists bring special skills to patients with infectious or inflammatory involvement of the nervous system, as often the localization and constellation of deficits points to a specific etiologic agent. In addition to the more commonly reviewed syndromes of meningitis, encephalitis, and parenchymal abscess, less frequent but characteristic syndromes are important to recognize. Even in clinical syndromes not typically associated with infection, it is important to consider the possibility of infection in certain cases. The authors of this issue have provided thorough and illustrative reviews of these emerging and controversial topics, and we are indebted to them for their hard work and expertise. The coming decades are sure to provide an ever-evolving landscape influenced by infection, inflammation, and immunomodulation.