Fever, weakness, and mental confusion in an elderly woman

A second trip to the emergency department within 24 hours revealed a worsening of her symptoms.

Mrs. N, 87 years old, was brought to the emergency department (ED) after demonstrating a lack of responsiveness, weakness, and the inability to get out of bed. This was her second trip to the ED in less than 24 hours. The night before, she presented with a temperature of 101°F, fatigue, weakness, tremor, and an altered mental state. She was evaluated and sent home with her daughter for observation.

Examination

On her return, Mrs. N was pale, with a drawn face and sunken eyes. During the examination, she was responsive but not rousable. Her temperature was elevated at 104°F. Vital signs included a BP of 82/60 mm Hg, heart rate 115 beats per minute, and respiratory rate 28 breaths per minute. Oxygen saturation was 85%-90% on room air.

A review of Mrs. N’s history revealed that she lived alone and did not get out much. Arthritis and bilateral total knee replacements limited her mobility, although she did drive short distances to attend church and visit friends. Her daughter mentioned that Mrs. N recently developed loss of short-term memory. The patient did not smoke or drink alcohol. Her prescription medications included lisinopril, hydrochlorothiazide, alendronate (Fosamax), and lovastatin.

Blood urea nitrogen was elevated at 45 mg/dL (normal 7-30). WBC count was 11,000/µL (normal 3,800-10,800). A head CT revealed an old infarct in the basal ganglia. Evidence of diverticulosis with a possibility of diverticulitis was seen on abdominal CT. No acute pathology was found on ECG or chest x-ray. A lumbar puncture was unsuccessful due to the presence of spinal arthritis. Because the patient had recently complained of multiple mosquito bites, her family requested that we test for West Nile virus (WNV).At this point, Mrs. N was admitted to the hospital.

The following day, a fluoroscopy-guided lumbar puncture was performed. Glucose and protein levels on cerebrospinal fluid (CSF) analysis were 60 mg/dL (borderline high) and 45 mg/dL (low normal), respectively. No xanthochromia was noted.

During the next three days, Mrs. N’s hand tremor worsened; a mouth tremor was also present. As a result, the patient was unable to feed herself. At times, she had difficulty swallowing. A prominent maculopapular rash developed in the intertriginous areas of the axillae and groin. She experienced temperature spikes up to 104°F for three days, with afternoon temperatures of 101°F for another four days. She recognized family members and would introduce her caregivers as “her girls.” Her speech was halting, and she had difficulty finding words. As she became more communicative, she complained of head pain.

Mrs. N was treated with IV hydration and monitored with a Foley catheter. Because diverticulitis was suspected, IV cefoxitin and metronidazole (Flagyl) were added.

Diagnosis and treatment

Five days after the patient was admitted to the hospital, county health officials reported an invasive form of WNV on her serology. Mrs. N was diagnosed with WNV encephalitis. She was hospitalized for three more weeks. Her stay was complicated by prerenal renal insufficiency and a UTI. She was discharged to a rehabilitation facility, where she was to receive intensive physical, occupational, and speech therapy.

Two months after disease onset, Mrs. N was sent to live with her daughter and given at-home therapies. Mrs. N’s physical ability was limited by parkinsonism characterized by tremor and rigidity. She needed the assistance of a walker to ambulate and had to learn how to get up and down safely from a chair or bed. Reflexes and balance were poor. She also required assistance with bathing and fixing meals.

In addition to receiving speech therapy, Mrs. N has had to work on relearning certain life skills, such as counting change, organization, calendar planning, and object and word recognition. Although her mood is upbeat and she does her “homework” willingly, she sometimes expresses frustration. She notes that she “feels stupid sometimes.” However, she expresses great relief that she is out of the “darkness and desperation” of WNV encephalitis.

Analysis

WNV is a single-stranded RNA flavivirus. Mosquitoes serve as the vector for transmission, with the primary reservoir being birds (most commonly crows and jays, although 200 species are known to carry the virus). While the virus can be fatal in birds, most develop an immunity to it. Humans become viremic, and although they cannot transmit the virus through normal contact, there have been reports of organ-transplant, blood-transfusion, and breast-milk transmission.

In 2006, there were 3,752 cases of WNV from January to October in the United States. Most cases occurred in Idaho, Colorado, California, Nebraska, Utah, Arizona, and Nevada. Peak occurrence is during September and October.

Most patients infected with WNV are asymptomatic. One fifth develop flulike symptoms. Table 1 lists the most common symptoms. Additional symptoms include lymphadenopathy, muscle aches, sore throat, nausea, vomiting, diarrhea, and abdominal and eye pain. Most symptoms last about three to six days. A maculopapular rash, which lasts about a week, may also develop. Only 1% of those infected with WNV develop central nervous system diseases (meningitis, encephalitis, or meningoencephalitis). Advanced age is the most important risk factor for the development of neuroinvasive disease with WNV infection.

Diabetes mellitus and alcohol abuse increase the risk of encephalitis. Additional factors that place the patient at increased risk include pregnancy, recent chemotherapy, HIV infection, and organ transplant, all of which represent immune-system compromise.

Neuroinvasive disease, especially encephalitis, increases the risk of limb weakness, respiratory failure, and dysrhythmia. Mrs. N did have a persistent sinus tachycardia probably related to initial dehydration. Respiratory failure may be preceded by signs of bulbar dysfunction, including dysarthria, dysphagia, and limb weakness, all of which Mrs. N exhibited. Although her oxygen saturations were low, she did not require ventilatory support. She showed no signs of meningeal irritation, such as photophobia or nuchal rigidity, which is frequently seen with meningitis. In addition, there were no seizures or other focal neurologic symptoms, such as hemiparesis or cranial-nerve palsy, that can occur with encephalitis.

In one recent year in New York City, 59 patients were hospitalized with WNV. Half presented with neuroinvasive disease. Flaccid paralysis, myoclonus, parkinsonism with cogwheeling rigidity, hypokinesia, postural instability, and tremor that worsened with movement were also seen. Mortality rate was 12%.

In a study of 16 patients with WNV encephalitis, tremor, myoclonus, and parkinsonism were noted in 9%, 31%, and 69%, respectively. In a recent study of 49 patients evaluated 13 months after infection, 50% experienced long-term sequelae, including fatigue, headache, weakness, depression, imbalance, and tremor. Cognitive and other physical impairment were also noted.

Diagnostic methods

Serology is used to diagnosis WNV infection. Identification is made by viral-specific immunoglobulin (Ig) M antibodies. Viral-specific IgM and IgG assays are done at the state laboratory.

Closely related arboviruses (e.g., St. Louis encephalitis virus and WNV) may exhibit cross-reactivity. Serum IgM antibodies can be detected 8-14 days after infection or in CSF collected within eight days of infection. In WNV encephalitis, the IgM antibody can persist for up to 16 months. DNA testing through polymerase chain reaction is also used to detect WNV genetic material, but it has a 50% incidence of false negatives. The virus usually cannot be isolated in the serum or CSF. Long-term immunity and protection against reinfection is believed to occur with persistent antibodies. Patients with encephalitis may or may not demonstrate abnormalities on CT or MRI.

When visualized on MRI, abnormalities are found in the basal ganglia, thalamus, and temporal, brain-stem, or cerebellar areas. Lumbar puncture will differentiate between infectious and noninfectious causes of an altered mental state. The presence of subarachnoid hemorrhage (SAH) would result in xanthchromia in the CSF. RBCs in the CSF can reflect a traumatic tap; however, two hours post-SAH, the degradation of RBCs would result in xanthochromia, which can be confirmed on spectrophotometry when the RBCs in the CSF break down to bilirubin. Protein in the CSF can be elevated in both infectious and noninfectious conditions. In the absence of xanthochromia, an elevation in protein levels would be more consistent with an infectious process. In encephalitis, CSF glucose may be normal or low.

Treatment/prevention options

Currently, there is no treatment for WNV infection; however, there are ongoing studies involving the use of interferon, immunoglobulins, and antivirals. Ribavirin and interferon-alfa have shown limited efficacy in trials. Hydration, corticosteroids, and mannitol can be administered to support perfusion and control cerebral edema. Medical care is needed to prevent complications of dehydration, thromboembolism, decubiti, and gastric ulceration.

Prevention focuses on elimination of mosquito breeding areas, including removal of stagnant water and treatment of suspected areas with larvacide. Patients in high-risk areas should be advised to use repellents with 10%-30% N,N-diethyl-3-methylbenzamide (DEET). However, infants and pregnant women should not use DEET, and children should not be exposed to more than 10% DEET. Clothing may be treated with permethrin to protect against mosquito bites.

Effective vaccines are available; however, universal vaccination would not be cost-effective unless there is an increase in incidence or virulence. In the general population, it has been determined that there is a low risk of WNV infection. A live, attenuated recombinant WNV vaccine has been developed and has shown promise in early trials. A vaccine constructed from a clone of yellow fever and a neutralizing antibody from WNV has been shown to provide immunity to both infections.

Scattered outbreaks of WNV will continue to occur. Local surveillance, mosquito control, and vaccination programs in endemic areas need to be considered.

Ms. Mulligan is a nurse practitioner at Carl T. Hayden Veterans Affairs Medical Center in Phoenix.

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