Encephalitis: Diagnosis and Treatment PDF

Preface

"It all depends on your frame of reference." These words, still echoing in my brain four decades after my freshman physics course, are as applicable in infectious diseases as they are in relativity. A clinician in Siberia probably perceives tick-borne encephalitis as very common. One practicing in Central or South America presumably thinks parasitic brain disease is an everyday occurrence. In India, thousands of cases of human rabies occur annually. In pre-1999 New York City, herpes simplex was the most common cause of an extraordinarily rare group of disorders: the encephalitides.

For clinicians at each of these reference points, the other disorders are so vanishingly rare as to be outside consciousness. While it is indeed fortunate that most of us do not have to see patients devastated by these diseases, it is unfortunate that we miss the opportunity to learn from each other. While each disorder is etiologically distinct, clinical issues share many common threads. How does one best identify and treat seizures in comatose patients with severely damaged brains? What is the best way to correct elevated intracranial pressure? Can I use corticosteroids in a patient with a cerebral infection? How do I safely reverse the hyponatremia so often seen in these individuals? How do I manage the myriad medical complications arising in these critically ill patients? These are issues of concern from Stockholm to Singapore, from Melbourne to Moscow. Although the specifics of the anti-infective agents may differ, many aspects of care will be the same. This book is written in the hope of providing a broad perspective to clinicians around the world, hopefully allowing lessons learned in each of these disorders to help with management of others.

From a North American perspective, as recently as a decade ago encephalitis was widely considered an obscure disorder—rarely seen, even less frequently thought about, a vague memory from medical school, where it might have occupied five minutes in one lecture (maybe). The differential diagnosis was considered esoteric and best left to those rare sub-specialists who understood both brain disease and nervous system infections.

That perspective changed abruptly in 1999 when West Nile virus was introduced into the United States. Since then, cases of West Nile virus infection have occurred throughout much of the United States. In 2006, 4,261 cases were confirmed, 1,491 of which were neuro-invasive.^a This epidemic has focused considerable attention on encephalitis in general, and arthropod-borne infections in particular. Interestingly, although this is now perceived as an almost common disease, annual U.S. incidence is only minimally greater than the 1,200 or so cases a year of herpes simplex encephalitis, a disorder most clinicians still consider extremely rare (a not unreasonable perspective on a disease with annual incidence of about 4 to 5 per million population).

In light of this divergence in perceptions, and the fact that brain infections are of significance world wide, it seemed timely to collect, in one volume, information on the most common forms of encephalitis—both infectious and non-infectious. The goal was to provide both a broad perspective on the range of inflammatory disorders that affect the central nervous system, and to provide enough detail on each one to help clinicians understand individual patients—no matter where in the world they might be—helping to arrive at a correct diagnosis. Then, unlike the time-honored neurologic tradition of "diagnose and adios," guidance is provided in patient treatment and management.

Obviously, patients do not walk in with the chief complaint, "I have encephalitis." One of the most difficult things for non-neurologists is deciding if a given patient with a headache and altered cognitive function does or does not have a neurologic disorder of any sort, let alone encephalitis. The chapters by Dr. Cunha and Dr. Politsky provide overviews of the approach to patients with this presentation, including how to decipher if the nervous system is the primary site of disease, or whether its normal physiologic function has been altered by a systemic disorder that does not actually injure the nervous system directly.

Individual chapters address the principal infectious and non-infectious causes of brain inflammation. In recent years we have learned a great deal about brain inflammation occurring as an apparent autoimmune process in patients with malignancies—paraneoplastic encephalitides. Also immune in origin and often discussed but infrequently seen is the uncommon disorder known as acute disseminated encephalomyelitis—a post-infectious disorder that can be devastating but may be reversible.

In differentiating among the various infectious etiologies, the key often lies in the old real-estate adage, "location, location, location." Most forms of infectious encephalitis (other than herpes, which is ubiquitous) occur in geographically limited areas, since their dissemination requires specific host–vector–human interactions. Tick-borne encephalitis is relatively common in Europe and Asia, but rarely, if ever, seen in the Americas. West Nile encephalitis now occurs annually in North America, but only sporadically in the rest of the world. Spirochetal infections occur in specific and identifiable epidemiologic circumstances. Parasitic infections require specific ecosystems. Rabies, which only affects one person every few years in the United States, is actually still a relatively common disorder in parts of Asia. Each of these disorders is addressed in detail in specific chapters.

Location is also key in another classical neurologic sense. Some infections have a particular predilection for specific locations in the nervous system. Herpes preferentially affects the temporal lobes, affecting behavior and memory. West Nile affects the brainstem and spinal cord, causing a flaccid paralysis and ventilatory difficulty. Rabies affects the brainstem, causing dysphagia. Listeria affects the brainstem, affecting cranial nerve function. Different paraneoplastic disorders affect specific areas of the nervous system. These localizing propensities validate the neurologic approach drummed into every medical student—always start by asking, "Where's the lesion?" Such an approach can be tremendously helpful in focusing the differential diagnosis.

Finally, a group of chapters addresses specific issues in diagnosis, pathology, and treatment. The chapter by Dr. Spitzer, Dr. Spitzer, and Dr. Golightly discusses the various laboratory methodologies that are available, elaborating on their strengths and limitations. Dr. Freeman and Dr. Hedley-Whyte provide an overview of the pathologic changes seen in the different disorders, providing insights into both pathophysiology and definitive diagnosis. Dr. Politsky discusses diagnosis and management of the seizures that occur quite frequently in these disorders. Finally, Dr. Wijdicks provides a most helpful summary of the clinical management of these critically ill patients.

By drawing on a group of international experts, I have tried to provide both a broad perspective on, and an in depth discussion of, these disorders. I am grateful to all the authors for their invaluable contributions, and to the publishers for their patience and support. I hope the reader will find this volume helpful in the approach to these complex patients. If the information provided helps improve the diagnosis and treatment of a few such patients, I will have achieved my goal.

^a Lindsey N, Lehman J, Hayes E, et al. West Nile virus activity—United States, 2006. MMWR 2007; 56(22):556–559.