Herpes Simplex Encephalitis Clinical Presentation

Updated: Jun 03, 2021
  • Author: Shaheen E Lakhan, MD, PhD, MS, MEd, FAAN; Chief Editor: Niranjan N Singh, MBBS, MD, DM, FAHS, FAANEM  more...
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Herpes simplex encephalitis (HSE) is an acute or subacute illness that causes both general and focal signs of cerebral dysfunction. It is sporadic and occurs without a seasonal pattern. Although the presence of fever, headache, behavioral changes, confusion, focal neurologic findings, and abnormal cerebrospinal fluid (CSF) findings are suggestive of HSE, no pathognomonic clinical findings reliably distinguish HSE from other neurologic disorders with similar presentations (see Workup). [4]

Patients may have a prodrome of malaise, fever, headache, and nausea, followed by acute or subacute onset of an encephalopathy whose symptoms include lethargy, confusion, and delirium. The following are typically the most common symptoms of HSE [5] :

  • Fever (90%)

  • Headache (81%)

  • Psychiatric symptoms (71%)

  • Seizures (67%)

  • Vomiting (46%)

  • Focal weakness (33%)

  • Memory loss (24%)

Signs and symptoms of neonatal HSE develop about 6-12 days after delivery, at which time lethargy, poor feeding, irritability, tremors, or seizures may be noted. Those with disseminated disease also have abnormal liver function test results and thrombocytopenia. In contrast to older patients, neonates often have herpetic skin lesions.

The initial presentation may be mild or atypical in immunocompromised patients (eg, those with HIV infection or those receiving steroid therapy).


Physical Examination

The most frequent findings on physical examination are fever and mental status abnormalities. Meningeal signs may be present, but meningismus is uncommon.

Typical findings on presentation include the following [5] :

  • Alteration of consciousness (97%)

  • Fever (92%)

  • Dysphasia (76%)

  • Ataxia (40%)

  • Seizures (38%) - Focal (28%); generalized (10%)

  • Hemiparesis (38%)

  • Cranial nerve defects (32%)

  • Visual field loss (14%)

  • Papilledema (14%)

A causal or temporal relationship between peripheral lesions (eg, herpes labialis) and HSE does not exist. In addition, many febrile diseases may precipitate herpes labialis. Therefore, the presence or absence of such lesions neither confirms nor excludes the diagnosis.

Unusual presentations occur. Both herpes simplex virus type 1 (HSV-1) and herpes simplex virus type 2 (HSV-2) may produce a more subacute encephalitis, apparent psychiatric syndromes, and benign recurrent meningitis. Less commonly, HSV-1 may produce a brain stem encephalitis, and HSV-2 may produce a myelitis.

Ku et al discussed the unique presentation of HSE in a bilingual patient, who developed global aphasia for 1 language (his most recently learned language) but retained most of his birth language ability. [30]

McGrath et al reported on 4 patients with confirmed HSE, each with an anterior opercular syndrome, and observed that the syndrome (ie, paralysis of the masticatory, facial, pharyngeal, and lingual muscles) occurred as the primary manifestation of HSE in 2 patients and as part of the encephalitis picture in the other 2 patients. [31] The authors suggested that unique presentations (eg, anterior opercular syndrome), should alert the clinician to the possibility of HSE.

Mondal et al reported basal ganglia involvement in a child with HSE, demonstrating extrapyramidal symptoms. [32] Li and Sax reported HSE-associated cerebral hemorrhage in an HIV-positive person. [33]



Even in treated cases of HSE, complications and sequelae (both focal and global) are not uncommon. If treatment of HSE is delayed, permanent neurologic deficits may develop in survivors.

Common sequelae among survivors include motor deficits, seizure disorders, and changes in mental status. Cognitive and memory deficits are particularly common. So too are recurrent seizures; some authorities recommend prophylactic treatment with anticonvulsant drugs in patients with severe HSE.

In addition, patients with HSE are subject to the same complications as any other seriously ill and immobilized patients with depressed levels of consciousness (eg, aspiration, deep venous thrombosis, decubitus ulcers).