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Basing on the assumption that frontotemporal lobar degeneration (FTLD), schizophrenia and bipolar disorder (BPD) might share common aetiological mechanisms, we analyzed genetic variation in the FTLD risk gene progranulin (GRN) in a German population of patients with schizophrenia (n = 271) or BPD (n = 237) as compared with 574 age-, gender- and ethnicity-matched controls. Furthermore, we measured plasma progranulin levels in 26 German BPD patients as well as in 61 Italian BPD patients and 29 matched controls.A significantly decreased allelic frequency of the minor versus the wild-type allele was observed for rs2879096 (23.2 versus 34.2%, P<0.001, OR:0.63, 95%CI:0.49–0.80), rs4792938 (30.7 versus 39.7%, P = 0.005, OR: 0.70, 95%CI: 0.55–0.89) and rs5848 (30.3 versus 36.8, P = 0.007, OR: 0.71, 95%CI: 0.56–0.91). Mean±SEM progranulin plasma levels were significantly decreased in BPD patients, either Germans or Italians, as compared with controls (89.69±3.97 and 116.14±5.80 ng/ml, respectively, versus 180.81±18.39 ng/ml P<0.001) and were not correlated with age.In conclusion, GRN variability decreases the risk to develop BPD and schizophrenia, and progranulin plasma levels are significantly lower in BPD patients than in controls. Nevertheless, a larger replication analysis would be needed to confirm these preliminary results.

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Objective: Despite bioequivalence, the exchangeability of antiepileptic drugs in clinical settings is disputed. Therefore, we investigated the risk for recurrent seizures after switching the manufacturer of the same drug in a large German cohort. Methods: Anonymous patient data from practice neurologists throughout Germany between 2011 and 2016 were collected using the IMS Disease Analyzer database (QuintilesIMS, Frankfurt, Germany). People with epilepsy were included if at least 2 prescriptions within 360 days and 1 within 180 days prior to the index date were available. The cohort was separated into a seizure group and seizure-free controls. Both groups were matched 1:1 according to age, gender, insurance status, and treating physician. The risk for breakthrough seizures after a manufacturer switch of the same antiepileptic drug was analyzed using multivariate regression models. Results: A total of 3,530 people with epilepsy were included (each group, n = 1,765; age = 53.7 ± 19.8 years). Patients with seizures had switched the drug manufacturer more often than controls (26.8% vs 14.2%; odds ratio [OR] = 1.35, 95% confidence interval [CI] = 1.08-1.69, p = 0.009), both from branded to generic (5.5% vs 2.4%; OR = 1.85, 95% CI = 1.30-2.64, p < 0.001) and between generic drugs (14.7% vs 7.1%; OR = 1.45, 95% CI = 1.13-1.87, p = 0.004). Interpretation: In previously seizure-free patients, switching the manufacturer of antiepileptic medications was associated with a higher risk for seizure recurrence. Our retrospective approach does not allow us to determine whether other changes in medical care at the same time could contribute to the recurrence. However, it would be prudent to avoid switching the manufacturer of anticonvulsants in seizure-free patients. ANN NEUROL 2018;84:918-925

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