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Fever and Severe Headache in a Young Man


A 28-year-old man presents tothe emergency departmentwith high fever; progressive, severe,generalized, throbbing headache;blurred vision; and increasingconfusion. These symptoms started3 days earlier.

A 28-year-old man presents tothe emergency departmentwith high fever; progressive, severe,generalized, throbbing headache;blurred vision; and increasingconfusion. These symptoms started3 days earlier.

History. The patient had previouslybeen healthy and active; heworks in the oil fields. He is marriedand does not smoke, drink alcohol,or use illicit drugs. He has had noblood transfusions and takes nomedications.

Examination. This well-built manappears ill. Pulse rate is 110 beats perminute; temperature, 38.3C (101F);respiration rate, 22 breaths per minute;blood pressure, 116/72 mm Hg.He is well hydrated. No scleral icterusor oral candidal infection. Pupils areequal and reactive. No palpable adenopathyor rashes. The patient is confused;disoriented to person, time,and place; and agitated. Cranial nervesare intact. Fundi are normal. He can move all his limbs.Deep tendon reflexes are normal; plantar reflexes areequivocal. Neck is supple. Remainder of the examination isnormal.

Laboratory studies. White blood cell (WBC) count,18,000/µL, with 70% polymorphonuclear neutrophils and30% lymphocytes. Hemoglobin level is 13.1 g/dL; plateletcount, 200,000/µL; erythrocyte sedimentation rate,90 mm/h. Serum sodium level is 138 mEq/L; potassium,4 mEq/L; chloride, 102 mEq/L; calcium, 9.2 mg/dL;blood glucose, 101 mg/dL; blood urea nitrogen, 29 mg/dL;serum creatinine, 1 mg/dL; total bilirubin, 1 mg/dL;aspartate aminotransferase, 22 U/L; alanine aminotransferase,26 U/L; alkaline phosphatase, 112 U/L. Results ofcoccidial serologic testing and drug screening are negative.Urinalysis results are normal.

Cerebrospinal fluid (CSF) pressure is increased. CSFprotein level is 180 mg/dL; glucose, 92 mg/dL; WBC count,116/µL (all lymphocytes); red blood cell count, 80/µL.Gram staining of CSF shows WBCs but no organisms.

You order an MRI scan of the brain.

What abnormalities are evident here-and to whatdiagnosis does the clinical picture point?

A. Viral meningitis
B. Acute multiple sclerosis
C. Multifocal leukoencephalopathy
D. CNS lymphoma
E. Herpes encephalitis

WHAT'S WRONG:The MRI scan shows low-density lesions in thebrain, which represent areas of gross demyelination(Figure). In a patient with fever, severe headache, and alteredmental status who has an abnormal level of lymphocytesin the CSF, these MRI findings strongly suggestherpes encephalitis,E.

Hospital course. The patient is promptly admitted,and acyclovir, 500 mg IV q8h, is started. Nasogastricfeeding is initiated; a percutaneous gastric tube is laterinserted.

Polymerase chain reaction (PCR) testing of theCSF reveals herpes simplex virus (HSV). A VDRL testand tests for coccidioidal antibodies and oligobands arenegative. An electroencephalogram (EEG) shows spikeand slow wave activity with a temporal predominance.

Outcome. After 2 weeks, the patient's fever andheadache resolve. Unfortunately, he is still disorientedand has difficulty in remembering and recognizingpeople. He is transferred to a rehabilitation hospital forfurther treatment; a maintenance regimen of acyclovir,400 mg bid, is prescribed.

A CASE IN POINTHSV encephalitis accounts for approximately 10% ofall cases of encephalitis in the United States. About 2000cases of HSV encephalitis occur each year, and up to 70%of patients die. The majority of those who survive have seriousneurologic sequelae.

Herpes encephalitis occurs throughout the year andaffects patients of all ages. It is most commonly caused byHSV-1; HSV-2 can cause neonatal encephalitis, in whichthe virus is acquired from the mother.

Clinical features. The illness evolves over severaldays. Symptoms include fever, headache, acute alterationof mental status (for example, confusion, stupor, or coma),seizures, and focal neurologic findings, such as aphasia orhemiplegia.

CSF tests. The CSF pressure is often increased. Examinationof the fluid almost invariably shows pleocytosis(up to 500/µL, mainly lymphocytes). Red blood cells arefound in some patients; this finding reflects the hemorrhagicnature of the CNS lesions. The protein level is increasedin most patients. The CSF glucose level may benormal or decreased; tuberculosis and fungal meningitisare also associated with a decreased glucose level, whichcan create confusion.

The PCR technique has revolutionized the diagnosisof HSV encephalitis. The sensitivity of this test is 95% atthe time of presentation; the specificity is nearly 100%.Viral cultures may be obtained from the CSF and HSVantibody may be detected 8 to 12 days after the onset ofthe disease.

Other diagnostic studies. CT scanning of the braindemonstrates low-density lesions with nonenhancingareas and surrounding edema in about 70% of patients afew days after the onset of symptoms. MRI can revealfrontobasal and temporal lesions earlier than CT and isthe imaging method of choice for HSV encephalitis.

EEG changes usually consist of periodic high-voltagesharp waves in the temporal regions and slow wave complexesat regular 2 to 3 per second intervals. These findingsare suggestive of, but not specific for, the disease.

Brain biopsy and viral cultures, which are rarelydone today, definitively establish the diagnosis. TypicalCSF findings that are confirmed by the results of PCR andMRI studies are now accepted for the diagnosis of HSVencephalitis.

Treatment. The management of HSV encephalitis includesaggressive supportive measures, such as maintenanceof fluid-electrolyte balance and nutritional and respiratorysupport. Specific therapy consists of IV acyclovir,30 mg/kg/d for 14 days; however, such therapy has notbeen proved in randomized, controlled trials to reducemorbidity and mortality.

Prognosis. The patient's age and state of consciousnessat the time acyclovir is initiated govern both mortalityand morbidity. If patient is unconscious, the outcome isuniformly poor. If treatment is begun within 4 days of theonset of illness in a conscious patient, survival is increasedto 92%-although two thirds of those who survive will beneurologically impaired. Untreated HSV encephalitis israpidly progressive, and mortality approaches 70%.

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