Evaluation of seizure treatment in anti-LGI1, anti-NMDAR, and anti-GABA _B R encephalitis

Abstract

ObjectiveThis nationwide cohort study evaluates seizure responses to immunotherapy and antiepileptic drugs (AEDs) in patients with anti-leucine-rich glioma-inactivated 1 (LGI1), anti-NMDA receptor (NMDAR), and anti-gamma-aminobutyric-acid B receptor (GABABR) encephalitis.MethodsAnti-LGI1, anti-NMDAR, and anti-GABABR encephalitis patients with new-onset seizures were included. Medical information about disease course, AEDs and immunotherapies used, effects, and side effects were collected. Outcome measures were (1) seizure freedom while using AEDs or immunotherapy, (2) days to seizure freedom from start of AEDs or immunotherapy, and (3) side effects.ResultsOf 153 patients with autoimmune encephalitis (AIE) (53 LGI1, 75 NMDAR, 25 GABABR), 72% (n = 110) had epileptic seizures, and 89% reached seizure freedom. At least 53% achieved seizure freedom shortly after immunotherapy, and 14% achieved seizure freedom while using only AEDs (p < 0.0001). This effect was similar in all types (p = 0.0001; p = 0.0005; p = 0.013, respectively). Median time to seizure freedom from AEDs start was 59 days (interquartile range [IQR] 27–160), and 28 days from start of immunotherapy (IQR 9–71, p < 0.0001). Side effects were psychotic behavior and suicidal thoughts by the use of levetiracetam, and rash by the use of carbamazepine. Carbamazepine was more effective than levetiracetam in reducing seizures in anti-LGI1 encephalitis (p = 0.031). Only 1 patient, of 86 surviving patients, developed epilepsy after resolved encephalitis.ConclusionEpilepsy after resolved encephalitis was rare in our cohort of patients with AIE treated with immunotherapy. In addition, seizure freedom is achieved faster and more frequently after immunotherapy. Therefore, AEDs should be considered as add-on treatment, and similar to treatment of other encephalitis symptoms, immunotherapy is crucial.

Seizure specificities in patients with antibody‐mediated autoimmune encephalitis

“…The rationale for this choice is that: (a) a minority of patients, especially seronegative ones, could become seizure‐free using AEDs alone, and (b) patients can benefit from AEDs, even if immunotherapy fails . Of note, sodium‐channel blockers seem to be the most effective in achieving seizure freedom . On the other hand, it has been reported that levetiracetam might be less effective than carbamazepine in LGI1‐Ab encephalitis and its use limited by the risk of inducing and/or aggravating serious behavioral disorders …”

“…Of note, sodium‐channel blockers seem to be the most effective in achieving seizure freedom . On the other hand, it has been reported that levetiracetam might be less effective than carbamazepine in LGI1‐Ab encephalitis and its use limited by the risk of inducing and/or aggravating serious behavioral disorders …”

“…Our practical recommendation would be to use immunotherapy as the cornerstone of etiologic treatment for seizures in AE. AEDs should be utilized as symptomatic treatment, starting with a single drug, possibly a sodium‐channel blocker (eg, carbamazepine, oxcarbazepine, eslicarbazepine acetate, lamotrigine, or lacosamide) . However, special caution is needed in rapid dosage increase of aromatic AEDs in LGI1‐Ab encephalitis, given the high incidence of cutaneous adverse effects in this population .…”

“…Treatment of status epilepticus requires intravenous administration and rapid drug titration, as recommend by international guidelines . Long‐term treatment with AEDs is probably unnecessary in the majority of patients with NMDAR‐Ab, GABA B R‐Ab, and LGI1‐Ab after resolution of the encephalitis stage . Therefore, we advise that AED discontinuation be considered in seizure‐free patients who lack epileptiform discharges on EEG and do not demonstrate signs of active inflammation on brain MRI.…”

“…102 Of note, sodiumchannel blockers seem to be the most effective in achieving seizure freedom. [102][103][104] On the other hand, it has been reported that levetiracetam might be less effective than carbamazepine in LGI1-Ab encephalitis and its use limited by the risk of inducing and/or aggravating serious behavioral disorders. 104 Our practical recommendation would be to use immunotherapy as the cornerstone of etiologic treatment for seizures in AE.…”