Neuronal antibodies in adult patients with new‐onset seizures: A prospective study

Abstract

ObjectivesImmunotherapy in addition to antiepileptic drugs can improve seizure freedom rates in autoimmune epilepsy, highlighting the importance of early diagnosis. A diagnosis of autoimmune epilepsy can be supported by presence of serum antibodies to neuronal antigens. We asked how often neuronal antibodies are found in the serum of unselected adult patients with new‐onset seizures and whether such testing could improve detection of autoimmune epilepsy.Material and MethodsWe included 44 patients over the age of 25 presenting after at least one unprovoked seizure to the Neurology Clinic at Sahlgrenska University Hospital, Gothenburg, Sweden. The median time between the first‐ever seizure in life and the serum sampling was 50 days (range 22–11,000). Antibody testing in serum was performed according to the manufacturer's instructions. The patients were followed for at least 1 year.ResultsEpilepsy could be diagnosed already at the first visit in 21/44 patients (47.7%). Two patients (4.5%) were positive for neuronal antibodies: one against contactin‐associated protein 2 (CASPR‐2) and one against glutamate acid decarboxylase (GAD). Three patients (6.7%) displayed very weak immunoreactivity that was deemed clinically insignificant. One of the antibody‐positive patients had only a single seizure. The other had a focal cortical dysplasia and was seizure‐free on levetiracetam. None of the five patients with antibodies or immunoreactivity displayed any feature of autoimmune epilepsy.ConclusionsWe conclude that indiscriminate testing in patients presenting to a first seizure clinic with new‐onset seizures or epilepsy is unlikely to improve detection of autoimmune epilepsy.

Antibody Prevalence in Epilepsy before Surgery (APES) in drug‐resistant focal epilepsy

“…Although the sub-cohort of patients receiving immunosuppression is small and no further detailed analysis was performed, previous studies have shown similar trends that early immunotherapy is the mainstay for treatment of autoimmune epilepsy. 19,20,24,[28][29][30] Consistent with our study, a previous study of 32 patients with focal immune epilepsy with predominant or exclusive seizure presentations showed that 81% reported improvement after immunotherapy, and the median time from seizure onset to immunotherapy was 4 months for responders and 22 months for nonresponders. 31 In addition, most patients have established epilepsy, and the long delay of an average of 14.2 years in our cohort between seizure onset and a comprehensive pre-surgical evaluation including workup for immune etiologies underscores the known barrier of delayed diagnosis and referral of focal DRE patients to a comprehensive pre-surgical evaluation.…”

“…Early diagnosis and treatment are important for focal DRE with potential immune cause because early initiation of immunotherapy is associated with favorable outcome. 20,23,24,28,29 In our study, five of nine (55.5%) showed favorable or possibly favorable responses, which is similar to what has been reported in patients with suspected autoimmune epilepsy with a 62% response rate. 11 In addition, all of the patients in our study who had improved seizure control received immunotherapy ≤7 months after seizure onset, whereas all the nonresponders received immunotherapy trials 1-10 years after seizure onset (Table 4).…”

“…Early diagnosis and treatment are important for focal DRE with potential immune cause because early initiation of immunotherapy is associated with favorable outcome 20,23,24,28,29 . In our study, five of nine (55.5%) showed favorable or possibly favorable responses, which is similar to what has been reported in patients with suspected autoimmune epilepsy with a 62% response rate 11 .…”

“…Early widespread screening of patients with new-onset seizures is unlikely to increase detection of the rare entity of immune-associated epilepsy, but a careful history and application of the APE 2 or APES score in cases of focal DRE of unknown etiology could be used to improve early diagnosis and treatment of autoimmune-associated epilepsy as it is well known that early immunotherapy improves outcomes. 23,24 In addition, the clinician must be aware of the high false-positive rate of Ab panels and discount positive results that are not compatible with the patient's clinical history and results that do not indicate CNS disease. 25 A combination of different testing methods may be needed, such as the one performed by Mayo clinic panel, for final confirmation because some commercial diagnostic kits using only immunoblots can cause false-positive results.…”

Autoimmune Encephalitis in Late-Onset Seizures: When to Suspect and How to Treat

“…Epilepsy and new onset seizures in elderly patients are an important health issue of the aging population ( 1 , 2 ). Epileptic seizures are a core symptom of autoimmune encephalitis (AE) ( 3 , 4 ), and autoimmune epilepsy has been reported to account for up to 20% of epilepsy of unknown etiology ( 5 ). The prevalence ranges from 6% up to 37% ( 3 , 6 ), with non-paraneoplastic AE being more common than paraneoplastic AE.…”