From the Guidelines
Autoimmune encephalitis associated with HSV-1 encephalitis primarily includes anti-NMDA receptor encephalitis, which is the most common post-HSV autoimmune complication, as supported by a recent study in 2021 1. This condition occurs when the immune system produces antibodies against NMDA receptors in the brain following HSV-1 infection, leading to a secondary autoimmune response. Other autoimmune conditions that may develop after HSV-1 encephalitis include:
- anti-GABA-A receptor encephalitis
- anti-GABA-B receptor encephalitis
- anti-AMPA receptor encephalitis
- anti-D2 receptor encephalitis These post-infectious autoimmune encephalitides typically manifest as a biphasic illness, with initial improvement from the viral encephalitis followed by neurological deterioration weeks later, as described in a study from 2017 1. Treatment generally involves immunotherapy with first-line agents such as:
- high-dose corticosteroids (methylprednisolone 1g daily for 3-5 days)
- intravenous immunoglobulin (IVIG at 2g/kg divided over 2-5 days)
- plasma exchange, as recommended in a study from 2021 1 Second-line therapies for refractory cases include:
- rituximab (375 mg/m² weekly for 4 weeks)
- cyclophosphamide The pathophysiology involves molecular mimicry or exposure of neural antigens during viral-induced neuronal damage, triggering autoantibody production, as discussed in a study from 2021 1. Early recognition and prompt immunotherapy are crucial for improving outcomes in these autoimmune complications following HSV-1 encephalitis.
From the Research
Autoimmune Diseases Associated with Herpes Simplex Virus Type 1 (HSV-1) Encephalitis
- Autoimmune encephalitis can be triggered by HSV-1 encephalitis, and should be considered in patients who are not responding to treatment 2
- The association of HSV-1 encephalitis and autoimmune conditions was strong, with an adjusted odds ratio of 2.6 3
- Autoimmune diseases such as N-methyl D-aspartate receptor (NMDAR) antibody encephalitis are increasingly recognized as causes of encephalitis 4
- Limbic encephalitis can be caused by both herpetic and autoimmune etiologies, with some clinical and radiological features overlapping between the two 5
- Post-HSV-1 encephalitis autoimmune encephalitis is a recognized complication, with a combined cohort of 110 patients reported in the literature 6
Clinical and Radiological Features
- Acute onset of symptoms, fever, and aphasia are more frequent in herpetic encephalitis, while psychiatric symptoms and tumors are more common in autoimmune encephalitis 5
- Neuroimaging is abnormal in all cases of herpetic encephalitis, but only in 60% of autoimmune encephalitis 5
- Insular and diffuse temporal lobe involvement and absence of basal ganglia involvement are more frequent in herpetic encephalitis, while mesial temporal involvement is more common in autoimmune encephalitis 5
Immunobiology and Treatment
- The immunobiology of HSV-1 encephalitis and post-viral autoimmunity is complex, involving cytokines, chemokines, and T- and B-cell immunity 6
- Treatment of HSV-1 encephalitis with aciclovir dramatically improves outcome, but the optimal management of autoimmune encephalitis is still uncertain 4
- Initial corticosteroid therapy may be evaluated to prevent complications in autoimmune encephalitis triggered by HSV-1 encephalitis 2