Seizure and movement disorder in CACNA1E developmental and epileptic encephalopathy: Two sides of the same coin or same side of two different coins?

Pathogenic variants in CACNA1E are associated with early-onset epileptic and developmental encephalopathy (DEE). Severe to profound global developmental delay, early-onset refractory seizures, severe hypotonia, and macrocephaly are the main clinical features. Patients harboring the recurrent CACNA1E variant p.(Gly352Arg) typically present with the combination of early-onset DEE, dystonia/dyskinesia, and contractures. We describe a 2-year-and-11-month-old girl carrying the p.(Gly352Arg) CACNA1E variant. She has a severe DEE with very frequent drug-resistant seizures, profound hypotonia, and episodes of dystonia and dyskinesia. Long-term video-EEG-monitoring documented subsequent tonic asymmetric seizures during wakefulness and mild paroxysmal dyskinesias of the trunk out of sleep which were thought to be a movement disorder and instead turned out to be focal hyperkinetic seizures. This is the first documented description of the EEG findings in this disorder. Our report highlights a possible overlap between cortical and subcortical phenomena in CACNA1E-DEE. We also underline how a careful electro-clinical evaluation might be necessary for a correct discernment between the two disorders, playing a fundamental role in the clinical assessment and proper management of children with CACNA1E-DEE.

Food allergy to apple and specific immunotherapy with birch pollen.

Conflicting results concerning the effect of specific pollen immunotherapy (SIT) on allergy to plant foods have been reported. The aim of this study was to investigate the effect of SIT using a birch pollen extract on food allergy with focus on allergy to apple. Seventy-four birch pollen-allergic patients were included in a double-blind, double-dummy, and placebo-controlled comparison of sublingual-swallow (SLIT) and subcutaneous (SCIT) administration of a birch pollen extract. Sixty-nine percent of these patients reported allergy to apple. The clinical reactivity to apple was evaluated by open oral challenges with fresh apple and a questionnaire. The immunoglobulin E (IgE)-reactivity was assessed by skin prick test (SPT), specific IgE, and leukocyte histamine release (HR). Forty patients were included in the final evaluation of the effect of SIT. The challenges were positive in 9 (SCIT), 6 (SLIT), and 8 (placebo) patients after treatment compared to 10, 4, and 10 patients, respectively, before SIT. The symptom scores to apple during challenges decreased in all groups, but only significantly in the placebo group (p = 0.03). As evaluated by the questionnaire, the severity of food allergy in general did not change and there were no differences between the groups. In spite of a significant effect on seasonal hay fever symptoms and use of medication and decrease in IgE-reactivity, SIT was not accompanied by a significant decrease in the severity of allergy to apple compared to placebo. Therefore, oral allergy syndrome (OAS) to apple should not be considered as a main criterion for selecting patients for birch pollen immunotherapy at present.