Chronic Inflammatory Demyelinating Polyradiculoneuropathy

Herpes simplex encephalitis (HSE), overwhelmingly caused by HSV-1 in adults (HSV-2 is a more common cause in neonates, typically from perinatal transmission, see Neonatal Meningitis entry), is the most common cause of sporadic, severe viral encephalitis in immunocompetent individuals.

Itresults from either primary infection with direct neural spread, or, more commonly in adults, reactivation of latent virus within the trigeminal ganglion with retrograde spread, characteristically causing a necrotizing, hemorrhagic inflammation with a strong predilection for the temporal and inferior frontal lobes.

Untreated, mortality approaches 70%, making rapid recognition and empirical treatment before confirmatory testing genuinely essential rather than a stylistic preference.

Fever, headache, and altered mental status are near-universal, but the more specific and diagnostically important features reflect the temporal lobe predilection: behavioral and personality change, olfactory or gustatory hallucinations, anomia and other focal aphasic features, and focal or generalized seizures (occurring in roughly half of cases, sometimes as the presenting feature).

Focal neurological deficits (hemiparesis, cranial nerve palsies) may develop as the disease progresses.

The clinical picture can evolve rapidly over days, and any patient with fever, altered consciousness, and new focal neurological or behavioral features should prompt urgent consideration of this diagnosis.

• CSF HSV PCR is the diagnostic test of choice, with high sensitivity and specificity, though a false negative result is possible very early in the illness course (within the first 24 to 48 hours), and a repeat lumbar puncture and PCR after 3 to 7 days should be performed if clinical suspicion remains high despite an initial negative result
• CSF typically shows a lymphocytic pleocytosis, elevated protein, and normal or mildly reduced glucose; red blood cells or xanthochromia may be present reflecting the hemorrhagic, necrotizing nature of the inflammation, an important supportive clue
• MRI brain is the imaging investigation of choice, showing characteristic asymmetric T2/FLAIR hyperintensity involving the medial temporal lobes, insula, and inferior frontal lobes, often with associated hemorrhage; CT is far less sensitive, particularly early in the disease course, and a normal CT should never be used to defer treatment or lumbar puncture
• EEG may show characteristic periodic lateralized epileptiform discharges (PLEDs) over the temporal region, supporting the diagnosis where imaging or CSF findings are equivocal

• IV aciclovir 10 mg/kg every 8 hours (adjusted for renal function), started empirically on clinical suspicion, without waiting for confirmatory PCR or imaging, given the dramatic mortality difference between early and delayed treatment; this is one of the clearest examples in infectious disease medicine where empirical treatment before diagnostic confirmation is the standard of care rather than an exception to it
• Adequate hydration is essential during aciclovir administration given the risk of crystal nephropathy, and renal function should be monitored
• Treatment duration is typically 14 to 21 days (21 days generally preferred given evidence of reduced relapse with the longer course compared with historically shorter regimens), with some specialists repeating CSF PCR near the end of treatment to confirm viral clearance before stopping, particularly in more severe or complicated cases
• Supportive care includes management of raised intracranial pressure if present, seizure control (levetiracetam or another appropriate anticonvulsant), and, in severe cases, ICU level supportive care and ventilatory support
• If aciclovir is stopped after negative PCR results but the patient fails to improve or worsens, reconsideration of the diagnosis (including a repeat lumbar puncture and PCR, and broadening the differential to other causes of encephalitis) is essential, given the possibility of an early false negative result or an alternative diagnosis
• Neuropsychological and cognitive assessment, along with rehabilitation input, is important during recovery given the significant risk of persistent memory and behavioral sequelae even with prompt treatment, reflecting the vulnerability of the temporal lobe structures affected

Referral: neurology and infectious disease input for all suspected cases; ICU for significant reduction in consciousness, status epilepticus, or evolving raised intracranial pressure; neuropsychology and rehabilitation services during recovery.