Viral Diseases

49 Viral Diseases




Herpes Simplex Encephalitis



Clinical Vignette


An independent 74-year-old man left a family wedding reception early because he did not feel well; he complained of mild nausea and general malaise. His daughter called the next day and when he did not answer the phone she went to his home to check on him, discovering him wandering in his backyard acutely confused. She convinced him to go to the emergency department, where he was found to be febrile with a temperature of 38.5° C (101.3° F). He soon became unresponsive to verbal stimuli, had conjugate right eye deviation, neck stiffness, and bilateral palmar grasps. He withdrew to noxious stimuli; plantar responses were flexor.


A noncontrast head computed tomography (CT) was unremarkable. Cerebrospinal fluid (CSF) examination demonstrated a WBC count of 45/mm3, predominantly lymphocytes, protein of 110 mg/dL, and a normal glucose level. Intravenous acyclovir 10 mg/kg every 8 hours was begun. A magnetic resonance image (MRI) of the brain demonstrated T2-weighted hyperintensity with edematous changes in the left insular cortex region of the inferior temporal lobe, the parahippocampal gyrus, and the hippocampus, extending into the subthalamic nucleus suggestive of herpes simplex virus (HSV) encephalitis. Electroencephalography (EEG) demonstrated periodic lateralized epileptiform discharges (PLEDs). This diagnosis was confirmed by HSV polymerase chain reaction (PCR) 4 days after symptom onset. The patient gradually improved and was treated with a 21-day course of acyclovir. After a short stay in a rehabilitation facility, he was discharged home.


Comment: This is a fine example of the rapidity with which herpes simplex encephalitis (HSE) will declare itself and the urgent need to consider the diagnosis in any acutely confused patient, initiating treatment based on clinical judgment alone without waiting for definitive diagnostic proof to become available. Unless this type of decision making takes place, the HSE will have caused irreversible cerebral damage, particularly involving the temporal lobes with their memory and language function modalities.





Diagnosis


One of the major issues in diagnosis is for the examining clinician to put HSE into his or her diagnostic spectrum very early on in the temporal profile of the patient’s illness. If this is not applied, a major therapeutic window allowing for successful treatment is sometimes lost. One of the saddest neurologic clinical scenarios is to evaluate a patient for confusion that has been present for the past 3–5 days and wrongly attributed to medication, or minor infection such as one involving the urinary or respiratory tracts. This is particularly liable to occur in a previously mentally vital senior citizen who develops a febrile illness with acute confusion and the change in mental status is presumed to be secondary to the fever per se, secondary nonspecific metabolic or toxic effects of empirical antibiotics, a stroke, or even “sundowning.”


For patients with suspected encephalitis, the initial diagnostic studies must include a CT scan (to rule out a mass effect) and then immediate CSF examination. CT scan results are abnormal in 50% of cases early on and usually demonstrate localized edema, low-density lesions, mass effects, contrast enhancements, or hemorrhage. MRI and EEG may be subsequently obtained for further confirmation. These usually demonstrate major temporal lobe damage (Fig. 49-2); however, a normal study does not exclude an HSE diagnosis. If such does occur, it is often wise to repeat the study within a few days, particularly if the patient continues to be confused.



CSF findings are nonspecific, often including a lymphocytic pleocytosis with a slight protein increase. Abnormal CSF findings are found in 96% of biopsy-proven HSE cases. EEG may show repetitive spiked, sharp wave discharges and slow waves localized to the involved area often as PLEDs.


The accuracy of PCR testing for HSV-DNA to detect HSV-1 and -2 in CSF compares favorably with the previous use of brain biopsy. This methodology provides excellent sensitivity and specificity (90–98%). The viral sequence for HSV may be detected months after the acute episode and may be negative in early disease phases. PCR should not be used to monitor therapy success. No standardized commercial assay is available. Brain biopsy was previously the gold standard for specificity, but it is rarely indicated now with the widespread availability of HSV PCR testing. If used, biopsy specimens are examined for both histopathologic changes and HSV antigens by immunofluorescence testing and appropriate culture techniques.





Eastern Equine Encephalitis






Diagnosis


Laboratory diagnosis of EEE virus infection is based on serology, especially IgM testing of serum and CSF, and neutralizing antibody testing of acute- and convalescent-phase serum. MRI is the most sensitive imaging modality for diagnosis of EEE (Fig. 49-3). The most commonly affected areas of the central nervous system (CNS) include the basal ganglia (unilateral or asymmetric, with occasional internal capsule involvement) and thalamic nuclei. Other areas include the brain stem (often the midbrain), periventricular white matter, and cortex (most often temporally). Affected areas appear as increased signal intensity on T2-weighted images.





West Nile Virus







Human Immunodeficiency Virus (HIV)



Clinical Vignette


A 31-year-old mother of a 13-month-old child presented to the emergency department with headache, vertigo, diplopia, and an unsteady gait. She had been treated with antibiotics for acute sinusitis during the preceding 8 days. Her neurologic examination demonstrated a lethargic, restless, febrile woman with meningismus, photophobia, horizontal nystagmus, and slight appendicular ataxia of her right arm and leg.


Brain CT demonstrated diminished absorption bilaterally in both thalami and to a lesser degree her internal capsules, midbrain, pons, and right posterior temporal lobe. There were signs of a primary maxillary and sphenoid sinusitis. Spinal tap demonstrated a CSF with moderate increased pressure of 275 mm/CSF, a cell count of 485 white blood cells (84% neutrophils), a protein concentration of 106 mg/mL, and glucose of 66 mg/dL. Intravenous antibiotics as well as acyclovir were begun. Gram stain and culture were negative initially and on a repeat study within less than 1 day.


During the first day of admission, she developed increased obtundation and intermittently varied automatisms. Bilateral flexor posturing and intermittent left-sided extensor posturing developed during her second day of hospitalization. Dexamethasone was administered every 6 hours. EEG demonstrated bilateral 3–5-Hz activity. Repeat imaging demonstrated extension of the low-density lesions into the basal ganglia and frontal lobe operculum. Temporal lobe biopsy was negative for HSV virus. Three days after admission, all spontaneous movements ceased; her pupils became dilated, fixed, and nonreactive; she was now areflexic and did not respond to any form of sensory stimulation. EEGs were electrically silent on two occasions over the next 24 hours. She died on the fifth hospital day.


A history of marked sexual promiscuity became available during her hospitalization. CSF culture was eventually positive for HIV although no serum or CSF antibodies to HIV were defined; all other cultures for various microbes were negative. Pathologically, there was an encephalopathic demyelinating process affecting cerebral white matter, the thalamus, and brain stem with acute neuronal damage. There was no associated vasculitis.


Comment: This case, seen at Lahey in the mid-1980s, added further support to the proposal that HIV is a primary neurotropic virus. Our experience emphasized the importance of considering HIV in the differential diagnosis of any acute encephalitis even if the patient is HIV antibody negative. Here the initial antibody negativity supported the concept that this patient’s encephalitis represented the primary phase of her HIV. Today when one wishes to consider an acute HIV infection in the setting of a negative HIV antibody one now has available an HIV viral load study. This will be positive, despite a negative HIV antibody study, if the patient has an active HIV infection. Thus, one will not need to depend on a viral culture to make the diagnosis as occurred with this patient. Such was not available at the time we evaluated this person.


Jun 4, 2016 | Posted by in NEUROLOGY | Comments Off on Viral Diseases

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