It seems that every few years, a new virus gets its grip on the U.S. Many of these have neurological complications that arise with the disease or as later sequelae. Neurologists must be alert for the impact of infectious disease, particularly viruses, on the nervous system. They must use their own neurology training and tap into those of the diagnostician, the infectious disease specialist, and in some cases the detective.
At the most recent meeting of the American Academy of Neuromuscular and Electrodiagnostic Medicine, multiple sessions were devoted to the neurological effects of various viruses. Most prominent in many minds has been the Zika virus, the newest virus in the West, but our understanding of neurological complications of other viruses continues to grow. Coverage of three of these AANEM sessions is included below.
West Nile Virus
The West Nile Virus (WNV) made its U.S. debut in New York City in 1999. In that year, neurological complications of the virus—peripheral nerve paralyzing illness and encephalitis—were responsible for seven deaths.
Since 1999, WNV rapidly made its way across the U.S., using birds as its host. The disease is now a normal, if dreaded, aspect of mosquito season in much of the country.
While only a small percentage of those infected with WNV have neurological involvement, the mortality is high—5–15 percent—for those who do.
Arturo Leis, MD, of the Center for Neuroscience and Neurological Recovery, Methodist Rehabilitation Center, Jackson, MS addressed WNV some of these neurological complications in his AANEM presentation. He explained that West Nile meningitis, which is mildly neuroinvasive, has a favorable outcome much like the non-neuroinvasive West Nile fever.
Beyond these less severe cases is a spectrum of neurological disease that is much more devastating for the small population it affects.
West Nile Encephalitis
West Nile encephalitis is the severe form of neuroinvasive disease with which most neurologists are familiar. It includes altered consciousness, confusion, or coma and focal neurological deficits. It carries a 5–15 percent mortality, and mortality is higher in immunocompromised and elderly patients.
Acute Flaccid Paralysis
Acute flaccid paralysis is pathologically and clinically identical to poliomyelitis. WNV targets anterior horn cells in these cases, so it produces primarily motor deficits and few sensory deficits. This is an uncommon condition and affects those who are younger and previously healthy.
Autonomic Nervous System Effects
Autonomic Nervous System effects can include changes in heart rate, blood pressure, breathing, digestion, bowel and bladder function and sweating. In one case Lei explained how surgical exploration for a bloated abdomen revealed no blockage, and respiratory arrest occurred when the patient was removed from mechanical ventilation after surgery. The virus had attacked breathing centers in the spinal cord. Leis emphasized the importance of neurologists recognizing that WNV can and does cause gastroparesis.
WNV Dysautonomia, another WNV complication, is the culprit in one case affecting a 79-year-old man. He was confused and went into respiratory failure requiring eight days on a ventilator. He had triplegia (two legs and an arm), severe orthostatic hypotension such that he became unresponsive on sitting up, and suffered from alternating bradycardia and tachycardia.
Leis points out that diagnosis of WNV is difficult because it is almost impossible to isolate virus after five days in a person with normal immune system. But people with neuroinvasive disease develop problems beyond this five-day window, so IgM is the only way to make the diagnosis.
Acute Flaccid Paralysis
Another unusual neurological complication is attracting attention in the world of enterovirus.
Ann Tilton, MD, Professor of Neurology and Pediatrics and Section Chair of Child Neurology at Louisiana State Health Science Center, New Orleans, LA discussed the recent increase in reported cases of acute flaccid myelitis associated with enterovirus.
- 2012, California: Two reports of a polio were made, rising to 59 cases by 2015
- 2014, Colorado: In the midst of an enterovirus D68 outbreak, 12 children developed acute flaccid myelitis
- 2014, Nationwide: The CDC instituted surveillance in response to Colorado and discovered 120 children with acute flaccid myelitis in 34 states from August to December
This is a rare complication, but one neurologists must be aware of so appropriate intervention can be made. The prodrome to acute flaccid myelitis associated with enterovirus can include fever and respiratory, GI, and neurologic symptoms.
The myelitis then rapidly progresses in hours to days with asymmetric weakness typically involving the C5 and C6 distribution, with proximal weakness worse than distal. Cranial Nerves 6,7,9, and 10 have also been involved. Four percent of patients experience seizures.
CSF is negative except in the case of D68, and evidence of anterior horn cell disease and hypotonic weakness are present.
Neuromuscular Complications of HIV Infection
Jeffrey Cohen, MD, FAAN, Department of Neurology, Dartmouth-Hitchcock Medical Center, Lebanon, NH
While HIV infects 35 million people worldwide, antiretroviral therapy has transformed the neurologist’s experience with the virus. With a longer life, patients experience many of the issues that are more typical as we age such as diabetes and hypertension. In addition, they must deal with more specific neurological effects of HIV infection. Cohen discussed many of the known neurological complications of HIV disease, many are quite unusual.
Distal Symmetric Polyneuropathy (DSP)
Distal Symmetric Polyneuropathy (DSP) is the most common neurological complication of HIV, affecting 30–60 percent of HIV patients. Patients can experience numbness, tightness, burning pain, and allodynia which begins distally and extends upward later in the disease. There are no FDA approved medications for this complication, so therapies must target symptoms.
Autonomic Neuropathy results in orthostatic dizziness, nausea, vomiting, other GI symptoms, dry eyes and mouth, urinary incontinence, sexual dysfunction, and sweating dysfunction.
Inflammatory Demyelinating Polyneuropathy
Inflammatory Demyelinating Polyneuropathy is a symmetric ascending motor weakness and can be acute or chronic in nature.
Mononeuropathy Multiplex is a painful symmetric polyneuropathy affecting multiple nerves in a stepwise fashion.
Polyradiculopathies show up with sub-acute onset of back and radicular pain. They progress to weakness and numbness of the lower extremities and bowel and bladder sphincter dysfunction. They are characterized by inflammation and necrosis of nerve roots at the spinal cord.
HIV Associated Myelopathy
HIV Associated Myelopathy is a slowly progressive weakness of lower extremities, resulting in gait, bowel, and bladder dysfunction.
Myopathies and Neuromuscular Junction Disorders
Myopathies and Neuromuscular Junction Disorders affect up to 25 percent of AIDS patients. These can include AZT myopathy, inclusion body myositis, and pyomyositis, Diffuse Infiltrative Lymphocytosis Syndrome, HIV or AIDS Muscle Wasting Syndrome, and Myasthenic Syndrome.
Complications from Antiretroviral Therapy
Complications from Antiretroviral therapy can be difficult to distinguish from the HIV disease itself because the differences may be subtle. It is important to pay attention to the small details to make an accurate diagnosis.
The world is becoming increasingly interconnected and mosquito-borne disease more widespread. In addition, prolonged life due to better treatments and technology reveal new medical problems previously unseen in younger patients. This neurologists have an increasingly difficult—and important— job. They must be not only neurologists, but also diagnosticians, detectives, and skilled at infectious disease care. It’s a brave new world of neuroviruses, and neurologists are at the center.