Question:

What should I expect to see in my recovery?

Answer:

Autoimmune Encephalitis often has a single phase. Instances of spontaneous recovery without immunotherapy or tumor removal, when present, have been reported. A patient enters recovery when the disease is no longer present. However, recovery from Autoimmune Encephalitis is not without the patient experiencing abnormality following the disease or permanent deficits resulting in an acquired brain injury (ABI) because of the disease. Deficits the patient experiences in cognitive domains at the beginning of their recovery may slowly improve even years following the end of treatment. Nevertheless, it is not uncommon for a patient to need several months of convalescence with intensive rehabilitation. Rehabilitation plays an important role in re-learning and re-training the brain from an acquired brain injury. (See: Rehabilitation cognitive exercises). Persistent cognitive impairment observed in long-term follow-up suggests irreversible neuronal death.  

A longitudinal study for cognitive outcome has now been produced with 43 anti-NMDAr patients.  All patients had cognitive deficits about 2 years after disease onset, mainly affecting memory and executive function. After 4 years, moderate or severe cognitive deficits persisted in 2/3 of patients despite good functional neurological outcome. Impaired cognitive outcome was predicted by delayed treatment and higher disease severity. However, continued improvement of cognitive function was observed for several years after disease onset in some patients. AE has a 7% mortality rate. AE-related deaths during the acute stage or follow up after discharge from the hospital have also been noted.  Even if patients survive without immunotherapy, they may suffer a slower recovery requiring prolonged hospitalization.

Treatment for AE is a marathon, not a sprint.  In practice, most patients are treated with glucocorticoids, intravenous immune globulin, or plasma exchange, and if there is no clinical response, rituximab and cyclophosphamide are used. Rituximab is usually effective in cases resistant to treatment. Rituxan appears to reduce the risk of a clinical relapse, which accounts for its increasing use as an initial treatment. Those who remain refractory to this treatment have benefited from IL6 blockade (tocilizumab) or plasma cell-specific therapy (proteasome inhibitors). 

The speed of recovery, degree of residual deficit, and frequency of relapse vary according to the type of autoimmune encephalitis. AE is a family of syndromes, (group of diseases). Therefore it is important to understand that the experience of patients with one autoimmune encephalitis syndrome might differ from that of patients with different syndromes. A 2017 study concluded that patients with autoimmune encephalitis frequently suffer from persistent impairment in neurologic disability, neurocognitive symptoms, and adaptive function.  Many of these impairments are not captured adequately by the Modified Rankin Scale.  Clinicians use caution when extrapolating findings from anti-NMDAR encephalitis to other forms of autoimmune encephalitis because each type (syndrome) of AE reacts a bit differently.

Cognitive deficits are frequent and severe long-term sequelae following NMDAR encephalitis. These deficits show a slow and incomplete recovery and persist beyond recovery of other neuropsychiatric symptoms of the disease. Rapid diagnosis and treatment at disease onset as well as for continued and customized cognitive rehabilitation to improve the long-term outcome is of vital importance. Anti-NMDAr recovery is often protracted with long hospital admissions. One remarkable feature of NMDAR encephalitis is the prolonged recovery, with progressive improvements in cognitive domains noted for years following the end of treatment. Another study showed that patients with anti-LGI1 encephalitis, the second most common type of AE, had a more rapid response to treatment but that only 70% had substantial recovery at 24 months. In LGI1 encephalitis, structural damage to the hippocampus often leads to permanent cognitive deficits. These persisting deficits can, however, be prevented by early immunotherapy after the first epileptic seizures.

 The rapid increase in the number of syndromes and autoantibodies identified since the first antibody was identified in 2007 suggests that other autoimmune encephalitides have yet to be discovered.  Antibody titers correlate imperfectly with the course of the disease and may remain detectable (albeit at a low titer) after clinical recovery.