Herpes Simplex Encephalitis
Author: Wayne E Anderson, DO; Chief Editor: Nicholas Y Lorenzo, MD
HSE (Herpes Simplex Encephalitis)
HSE (Herpes Simplex Encephalitis) is the most common nonepidemic encephalitis. Incidence is 2 cases per million of population per year. HSE (Herpes Simplex Encephalitis) may occur year-round. HSV-1 is ubiquitous and HSV-2 is also common.
International incidence is similar to that in the United States.
HSV-1 and HSV-2 infections often recur. HSE rarely occurs. Untreated HSE is progressive and often fatal in 7-14 days. However, significant morbidity exists among those treated. A landmark study by Whitley et al in 1977 revealed a 70% mortality rate in untreated patients and severe neurologic deficits in most of the survivors. The following demonstrate the variety of complications.
- Elbers and colleagues followed properly treated children for 12 years after the HSE.
- They found seizures in 44% of the children and developmental delay in 25% of the children.
- They concluded that HSE (Herpes Simplex Encephalitis) continues to be associated with poor long-term neurologic outcomes despite appropriate therapy.
- Shelley and colleagues reported a case of intracerebral hematoma occurring in a patient successfully treated with a full course of acyclovir after apparent eradication of the virus. The hematoma occurred in the region of the encephalitis
- In HSE, patients may have a prodrome of malaise, fever, headache, and nausea.
- This is followed by acute or subacute onset of an encephalopathy whose symptoms include lethargy, confusion, and delirium.
Headaches, seizures, aphasia, and other focal deficits also may occur.
- On neurologic examination, global and focal neurologic findings include encephalopathy, delirium, aphasia, cranial nerve deficits, and hemiparesis.
- Meningeal signs may be present.
- Unusual presentations occur. Both HSV-1 and 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, a myelitis.
- HSE (Herpes Simplex Encephalitis) is a neurologic emergency. Consultation with a neurologist is required.
- Neurosurgical consultation is helpful only if a brain biopsy is being considered.
- An infectious disease consultation may be appropriate.
- An evaluation for rehabilitation is often appropriate to deal with the long-term neurological sequelae of HSE.
- Common sequelae among survivors include motor deficits, seizure disorders, and changes in mental status.
- If treatment of HSE (Herpes Simplex Encephalitis) is delayed, permanent neurological deficits may occur in survivors.
- Even in treated cases of HSE, complications and sequelae are not uncommon.
- Both focal and global sequelae may occur, and survivors may require permanent assistance.
- Cognitive and memory deficits are particularly common, as are recurrent seizures.
- Anterograde memory often is impaired even with successful treatment of HSE.
- Retrograde memory, executive function, and language ability also may be impaired. A study by Utley et al showed that patients who had a shorter delay (< 5 d) between presentation and treatment had better cognitive outcomes.
- Encephalitis is inflammation of the brain
- Inflammation is usually caused by infection or an inappropriate auto-immune response to infection
- The incidence is reported as 7.4/100,000 (based on US statistics)
- Anyone can become ill with encephalitis, at any age
- The inflammation can damage nerve cells resulting in “acquired brain injury”
Compared to other infectious diseases, encephalitis has a high mortality rate
Herpes Simplex Encephalitis
This paper was prepared by Dr Graham Cleator, Head, Division of Virology, Clinical Sciences Building, Manchester Royal Infirmary Revised by Dr Nick Davies, St Mary’s Hospital, London
HSE (Herpes Simplex Encephalitis)is rare. How HSV gains access to the brain is not known, but here are various hypotheses, Firstly, viruses may enter the brain from the blood stream. To do this the virus must be small, present in large numbers and able to cross the blood/brain barrier (BBB). Taking into account the properties of the virus this is a possible but probably infrequent route of entry to the central nervous system (CNS). Secondly, there is a direct route, via nerves, from the nose to the olfactory lobes of the brain.
The virus may “move “from its site of latency via nerves to the base of the skull, cross the meninges and infect the brain. There is however little evidence to support this suggestion. A further possibility is that the virus moves from its site of latency in the trigeminal ganglia ”backwards” to the spinal cord and then upwards into the brain. The appropriate nerve pathways exists to support this suggestion but to date there is no definite evidence to support this or indeed any of the other suggested routes.
Whichever way HSV- I gains access to the brain, in the acute illness, the damage that results from the viral infection and associated inflammation is often severe. Early in infection, the virus shows a distinct predilection for certain parts of the brain. Typically it is initially present in the limbic cortices. It may then spread to the adjacent frontal and temporal lobes. It is the destruction of tissue in these areas together with brain swelling from the inflammation, which causes many of the symptoms associated with HSE.
HSE usually develops over a period of days but, like any other viral infection, depending, for example, upon the immunity of the patient, the disease may take a variable course. Typically it begins with “flu-like” symptoms followed by neurological deterioration, which may include personality and behavioral changes, and perhaps fits and dysphasia. If untreated it may lead to progressive impairment of consciousness, coma and death.
The rapid onset and development of HSE (Herpes Simplex Encephalitis) presents a dilemma to the clinician. During the early stages, when treatment would be most effective, the symptoms can be very general, so there may be several possible diagnoses.
Most hospitals do an EEG (an electro-encephalogram to monitor the brains electrical activity), plus brain imaging by a CT scan (computerized tomography), or, for a clearer picture, an MRI (magnetic resonance imaging). These procedures, together with careful and continuous clinical assessment provide data, which may be suggestive of HSE and, importantly, may exclude other conditions. However the diagnostic procedure now accepted as providing an etiological diagnosis of HSE is the polymerase chain reaction (PCR). This is a test that has been developed using the methods of modern molecular biology. The PCR is not used exclusively for the diagnosis of HSE but is also used in many other areas of research and diagnosis. In principle of the test is simple (they always are when they have been developed!) but because the test is so sensitive great care must be exercised at all stages of the procedure. The risk of producing false results is always present especially if suitable care and precautions are not taken during taking specimens and in the PCR laboratory.
The role of Acyclovir is central to the treatment of HSE. If therapy can be started during the first few days of the illness there is a dramatic reduction in the mortality rate – c.80% down to 25%.. The provision of high levels of nursing care and the management of complications such as brain edema (i.e. swelling) are also key factors, which may influence the outcome of HSE. As experience with the use of Acyclovir has grown it has become apparent that the currently accepted 10 day course of treatment may not always be sufficient to provide effective treatment. Rare cases of “relapse” of encephalitic illnesses have and are being noted.
The reduction in mortality has led to a paradoxical situation. There are without doubt more survivors, but many may suffer from permanent neurological and/or psychological deficits, for example amnesia (memory loss). For a child with a potentially long life ahead this is a particularly distressing situation. Improvements are still needed in both diagnosis and treatment.
Recent recognition of mild cases of HSE (Herpes Simplex Encephalitis) and the suggestion that latent infection of the brain can occur add a further dimension to this disease. If a patient suffers repeated episodes of mild (undiagnosed and not debilitating) HSE (Herpes Simplex Encephalitis), there could be progressive damage to the brain. The relationship of such episodes to the development of various psychological disorders must now be given serious consideration and form the basis of future research programs.
The message is that our understanding of conditions such as viral encephalitis is continually developing. However, these are complex conditions and whilst it is unlikely that encephalitis will be preventable (in the foreseeable future) the prospect for the rapid and efficient diagnosis for many of these conditions will improve during coming years. The consequence of improved and rapid diagnosis is that early treatment (which is so important) can and will increasingly be introduced.