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Autoimmune Encephalitis After Herpes Simplex Encephalitis: Frequency, Symptoms, Risk Factors and Outcomes

Herpes simplex encephalitis is a neurological disorder caused due to inflammation of the brain. It is a rare condition. Symptoms of herpes simplex encephalitis normally appear after a few days. Some of the early symptoms may include fever, headache, and seizure[1]. After these initial symptoms, the patient may later develop additional symptoms like the lack of ability to speak or write, lack of sense of smell and maybe a memory loss. In some cases, behavioral changes like psychotic episodes or hyperactivity may also occur. More severe symptoms of herpes simplex encephalitis include hallucinations, loss of consciousness, partial paralysis. Some of the patients suffering from Herpes Simplex Encephalitis also develop Autoimmune Encephalitis. Before we understand how Autoimmune Encephalitis happens, let us first know what Autoimmune Encephalitis is.

What is Autoimmune Encephalitis?

Autoimmune encephalitis is a group of a condition which occurs when the body’s immune system starts attacking the brain cells by mistake which leads to the inflammation of the brain. Numerous psychiatric and neurological symptoms are shown by patients who suffer from autoimmune encephalitis. The symptoms may complicate things and may even lead the patient to lose consciousness or be in coma. Autoimmune encephalitis may correspond with antibodies to the proteins present on the surface of the nerve cells or also within nerve cells. These proteins help to pass signals between nerve cells. Researchers are still working to find out the reason as to why certain antibodies attack the healthy cells present in the body. This medical condition isn’t passed onto from the parents to their children. This means that it occurs sporadically. It may affect people with no family history.

What is Autoimmune Encephalitis?

Autoimmune Encephalitis After Herpes Simplex Encephalitis

Herpes simplex encephalitis can provoke autoimmune encephalitis which can lead to neurological worsening. Herpes simplex virus (HSV) causes infectious encephalitis in children which has potentially devastating consequences including severe developmental impairment and neuro-disability. In an observational part of the research, many patients with herpes simplex encephalitis who were diagnosed by pediatricians, neurologist or infection specialists were included (cohort A)[1].

Demography and clinical characteristics of patients who suffered from autoimmune encephalitis and patient who did not suffer from autoimmune encephalitis were compared. Later, comparison of features of patients who suffered from autoimmune encephalitis was done based on their age group.

Multivariable binary logistics regression models were used to assess risk factors associated with autoimmune encephalitis after herpes simplex encephalitis. When herpes simplex started, none of the patients of herpes simplex encephalitis had antibodies to neuronal antigens, 27% of patients started autoimmune encephalitis and all these 27% patients with herpes simplex encephalitis had neuronal antibodies either at onset or during the symptoms[2]. The rest of the patients did not have autoimmune encephalitis although 30% of patients developed antibodies.

Symptoms of Autoimmune Encephalitis After Herpes Simplex Encephalitis

A wide range of neurological and psychiatric symptoms are shown by patients of autoimmune encephalitis. Different types of symptoms may appear at different times and at different levels of intensity. This makes the diagnosis difficult. Initially, some patients only show either psychiatric or neurological symptoms which could, even more, complicate the diagnosis. The signs and symptoms start suddenly and may last up to months. During this period they may progress rapidly. The initial phase of the disease is the prodromal phase which may show symptoms like headaches, nausea, diarrhea, fever, muscle pain, respiratory tract symptoms, and fatigue. The second phase consists of neurological and psychiatric symptoms. In the third phase, the patients show abnormal blood pressure and hypoventilation.

In short all the symptoms linked to autoimmune encephalitis are a loss of balance, some parts of the body feeling weak or numb, change in vision, seizures, cognitive impairment, the problem with memory, loss of inhibitions, visual or auditory hallucinations, severe anxiety, paranoid thoughts, involuntary movements, slowed or loss of ability to speak, sleep disruption which also includes insomnia, decreased level of consciousness which may lead to unresponsiveness, catatonia or coma and behavioral changes like agitation. A patient who shows any one of the above symptoms simply does not indicate autoimmune encephalitis but a mixture of both neurological and psychiatric symptoms may be a hint. One should consult the doctor as soon as possible if they think that they might be suffering from autoimmune encephalitis. From a few pieces of evidence, it was patients take 18 months to recover from autoimmune encephalitis.

Frequency of Autoimmune Encephalitis After Herpes Simplex Encephalitis

The studies conducted till now have shown that the patients suffering from herpes simplex encephalitis are most vulnerable to develop severe autoimmune encephalitis during the coming weeks or months just after they have successfully undergone the treatment for herpes simplex encephalitis. This condition is not a rarity anymore. The presence of antibodies can be an indicator of the presence of this complication.

Risk factors of Autoimmune Encephalitis After Herpes Simplex Encephalitis

No direct cause has been attributed to the development of Autoimmune Encephalitis yet. However, the following conditions are known to trigger an autoimmune response that may lead to Autoimmune Encephalitis such as certain cancers causing the paraneoplastic syndrome, ovarian teratomas, active or previous infection by commonly occurring bacteria, such as Streptococcus and Mycoplasma. Also, not having a risk factor does not mean that an individual will not get the condition.

Autoimmune encephalitis in patients recovering from herpes simplex encephalitis can be extremely lethal for the patient. The children infected by the disease are more at risk to contract the complication. Early detection of the disease is extremely important for therapies like immunology to work. This neurologic relapse can be extremely morbid for the patients and treatment should be initiated as soon as possible. Patients should always be checked for anti-NDMA receptor antibodies during the early stage of the disease.

Diagnosis and Treatment of Autoimmune Encephalitis After Herpes Simplex Encephalitis

Tests like cerebrospinal fluid analysis, electric encephalography, CT scan, and MRI are crucial to know the extent of the disease and the different parts affected by it. Diagnosis is done on the basis of laboratory tests for antibodies which cause these disorders; it is advised to get the blood (serum) and the cerebrospinal fluid tests to be done at the same time. However, the most reliable tests amongst all is the cerebrospinal fluid testing. Brain MRI with and without contrast to check for abnormalities that suggest autoimmune encephalitis is found very useful in patients with who have limbic encephalitis.

To treat this condition, immunosuppressive therapy is used and the tumor is also removed if necessary. Early immunotherapy is considered the most effective way of treating the disease. Medications like rituximab and cyclophosphamide also help in the treatment. It should be noted that the dosage of these medicines should be prescribed by the doctor and no personal experiments should be undertaken with the medicines. Treatments with steroids are also a way of curing the problem.

Symptomatic treatment or plasma exchange is also considered as viable options for this treatment. Routine monitoring is essential for recognizing patterns of the effects of the treatment.

Intravenous (IV) aciclovir is a well-entrenched effective therapy. The use of adjunctive steroids is quite controversial; however, proof exists in favor of potential benefit, suggesting a role of inflammation in addition to direct viral effects in disease pathogenesis. If discovered at an early stage, this condition can be treated and future complications can be avoided. Patients can also recover quickly and it also reduces the chances of recurrence.

Outcomes of Autoimmune Encephalitis After Herpes Simplex Encephalitis

The prognosis of Autoimmune Encephalitis is dependent upon the severity of the signs and symptoms and associated complications if any. Timely diagnosis and prompt treatment may slow its progression and aid in faster recovery times. Some affected individuals may succumb to the complications arising from the condition. It is reported that Autoimmune Encephalitis may recur within 2 years, in about 12% of the individuals who have recovered from the condition.

The presence of neuronal antibodies is an indicator of impending complications. They start showing their appearance approximately after 2 months of the treatment of herpes simplex encephalitis. This could be very useful in understanding the relapse and working towards a cure. Older patients also showed signs of psychosis which is a direct outcome of the presence of the antibodies. On the onset of herpes, the signs of the antibodies were not there. Regular follow up is essential to catch the growth of these antibodies that can cause so much damage.

Autoimmune encephalitis can gradually lead to neurological deterioration and may even prove to be life-threatening if not treated early. Autoimmune encephalitis is a type of encephalitis which may result in a number of autoimmune diseases like Sydenham chorea, Behcet disease, autoimmune limbic encephalitis, Rasmussen encephalitis, Hashimoto encephalopathy, and systemic lupus erythematosus. Few patients cannot recover even after first-line and second-line therapies they require further treatment to recover. A study shows that few patients relapse after the treatment due to the presence of herpes virus and some show no signs of a virus and their treatment includes increased steroids and anti-neuronal antibodies. Neurological worsening can be caused to the patient suffering from herpes simplex encephalitis who also contract autoimmune encephalitis. This complication can affect the central nervous system of the patient within the first 24 hours.


Autoimmune encephalitis can lead to inflammation of the brain. Patients suffering from this condition almost take 18 months to recover. If discovered at an early stage then the patient can recover easily and quickly. This disease isn’t communicable that is it cannot transmit from one person to another. There are neurological and psychiatric symptoms of this medical condition. People should consult the doctor immediately if they feel that they might be suffering from the disease as it can be life-threatening.

The growing spread of this complication makes it pivotal for more research to take place and also more and more doctors need to be aware of this problem and its treatments.


  1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4965403/
  2. Armangue, T., Spatola, M., Vlagea, A., Mattozzi, S., Cárceles-Cordon, M., & Martinez-Heras, E. et al. Frequency, symptoms, risk factors, and outcomes of autoimmune encephalitis after herpes simplex encephalitis: a prospective observational study and retrospective analysis. The Lancet Neurology, (2018). 760-772. doi: 10.1016/s1474-4422(18)30244-8
  3. Fitzgerald, S. Symptoms of Autoimmune Encephalitis Following Herpes Simplex Encephalitis Appear Different in Adults than in Children. Neurology Today, (2015). 1. doi: 10.1097/01.nt.0000473693.91906.3c

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Pramod Kerkar, M.D., FFARCSI, DA
Pramod Kerkar, M.D., FFARCSI, DA
Written, Edited or Reviewed By: Pramod Kerkar, M.D., FFARCSI, DA Pain Assist Inc. This article does not provide medical advice. See disclaimer
Last Modified On:March 6, 2020

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