ABSTRACT
BACKGROUND AND OBJECTIVES: To assess seizure characteristics in antibody (ab)-associated autoimmune encephalitis (ab + AE) with the 3 most prevalent abs against N-methyl-d-aspartate receptor (NMDAR), leucine-rich glioma-inactivated protein 1 (LGI1), and glutamic acid decarboxylase (GAD). METHODS: Multicenter nationwide prospective cohort study of the German Network for Research in Autoimmune Encephalitis. RESULTS: Three hundred twenty patients with ab + AE were eligible for analysis: 190 NMDAR+, 89 LGI1+, and 41 GAD+. Seizures were present in 113 (60%) NMDAR+, 69 (78%) LGI1+, and 26 (65%) GAD+ patients and as leading symptoms for diagnosis in 53 (28%) NMDAR+, 47 (53%) LGI+, and 20 (49%) GAD+ patients. Bilateral tonic-clonic seizures occurred with almost equal frequency in NMDAR+ (38/51, 75%) and GAD+ (14/20, 70%) patients, while being less common in LGI1+ patients (27/59, 46%). Focal seizures occurred less frequently in NMDAR+ (67/113; 59%) than in LGI1+ (54/69, 78%) or in GAD+ patients (23/26; 88%). An aura with déjà-vu phenomenon was nearly specific in GAD+ patients (16/20, 80%). Faciobrachial dystonic seizures (FBDS) were uniquely observed in LGI1+ patients (17/59, 29%). Status epilepticus was reported in one-third of NMDAR+ patients, but only rarely in the 2 other groups. The occurrence of seizures was associated with higher disease severity only in NMDAR+ patients. DISCUSSION: Seizures are a frequent and diagnostically relevant symptom of ab + AE. Whereas NMDAR+ patients had few localizing semiological features, semiology in LGI1+ and GAD+ patients pointed toward a predominant temporal seizure onset. FBDS are pathognomonic for LGI1 + AE. Status epilepticus seems to be more frequent in NMDAR + AE.
Subject(s)
Encephalitis , Status Epilepticus , Humans , Glutamate Decarboxylase , Receptors, N-Methyl-D-Aspartate , Prospective Studies , Leucine , Intracellular Signaling Peptides and Proteins , Seizures/etiology , AutoantibodiesABSTRACT
OBJECTIVE: The increasing incidence of new-onset seizures with age is well known. Often, the etiology cannot be clarified. In the present study, patients with unprovoked late-onset seizures and without known neoplasm, who might have had paraneoplastic encephalitis, were investigated for a potentially underlying autoimmunity. METHODS: Sixty-six consecutive patients (36 women; aged ≥55 years) after having at least one seizure or seizures for ≤6 months were prospectively identified over a period of 4.75 years. All patients were tested for serum and cerebrospinal fluid (CSF) antibodies (Abs) to both neural cell-surface and intracellular antigens. Forty-five (68%) underwent brain magnetic resonance imaging (MRI). Follow-up in Ab-positive cases was ≥6 months. RESULTS: Two patients had high titers of anti-CASPR2 (contactin-associated protein-like 2) Abs in serum and CSF and fulfilled the diagnostic criteria of definite limbic encephalitis. Another two patients had bilateral encephalitic temporal MRI abnormalities. They also satisfied the criteria of definite limbic encephalitis, even though they had no Abs in serum or CSF. All four were in the age range of 55-70 years. They received immunotherapy and/or antiepileptic drug treatment and became seizure-free. SIGNIFICANCE: Our findings suggest that autoimmunity should be considered an important etiology in patients with late-onset seizures. Testing for neural antibodies and brain MRI may be worthwhile in this patient group.