A prenatal case of partial trisomy 21 (q22.2q22.3), resulting from a paternal insertion translocation ins(16;21) and uncovered by QF-PCR, and characterized by array CGH and FISH

In addition to detecting trisomies of whole chromosomes, QF-PCR can also detect partial trisomies of the chromosomes 13, 18, and 21, which can suggest an unbalanced translocation. Additional testing with other techniques, such as microarray or FISH, is recommended when an unbalanced translocation is suspected

Low penetrance and effect on protein secretionof LGI1 mutations causing autosomal dominantlateral temporal epilepsy

Purpose: To describe the clinical and genetic findings of four families with autosomal dominant lateral temporal epilepsy. Methods: A personal and family history was obtained from each affected and unaffected subject along with a physical and neurologic examination. Routine electroencephalography and magnetic resonance imaging (MRI) studies were performed in almost all patients. DNAs from family members were screened for LGI1 mutations. The effects of mutations on Lgi1 protein secretion were determined in transfected culture cells. Key Findings: The four families included a total of 11 patients (two deceased), six of whom had lateral temporal epilepsy with auditory aura. Age at onset was in the second decade of life; seizures were well controlled by antiepileptic treatment and MRI studies were normal. We found two pathogenic LGI1 mutations with uncommonly low penetrance: the R136W mutation, previously detected in a sporadic case with telephone-induced partial seizures, gave rise to the epileptic phenotype in three of nine mutation carriers in one family; the novel C179R mutation caused epilepsy in an isolated patient from a family where the mutation segregated. Another novel pathogenic mutation, I122T, and a nonsynonymous variant, I359V, were found in the two other families. Protein secretion tests showed that the R136W and I122T mutations inhibited secretion of the mutant proteins, whereas I359V had no effect on protein secretion; C179R was not tested, because of its predictable effect on protein folding. Significance: These findings suggest that some LGI1 mutations may have a weak penetrance in families with complex inheritance pattern, or isolated patients, and that the protein secretion test, together with other predictive criteria, may help recognize pathogenic LGI1 mutations. KEY WORDS: Autosomal dominant lateral temporal epilepsy, LGI1, Mutation, Low penetrance, Protein secretion

Applications of Ketogenic Diets in Patients with Headache: Clinical Recommendations

Headaches are among the most prevalent and disabling neurologic disorders and there are several unmet needs as current pharmacological options are inadequate in treating patients with chronic headache, and a growing interest focuses on nutritional approaches as non-pharmacological treatments. Among these, the largest body of evidence supports the use of the ketogenic diet (KD). Exactly 100 years ago, KD was first used to treat drug-resistant epilepsy, but subsequent applications of this diet also involved other neurological disorders. Evidence of KD effectiveness in migraine emerged in 1928, but in the last several year's different groups of researchers and clinicians began utilizing this therapeutic option to treat patients with drug-resistant migraine, cluster headache, and/or headache comorbid with metabolic syndrome. Here we describe the existing evidence supporting the potential benefits of KDs in the management of headaches, explore the potential mechanisms of action involved in the efficacy in-depth, and synthesize results of working meetings of an Italian panel of experts on this topic. The aim of the working group was to create a clinical recommendation on indications and optimal clinical practice to treat patients with headaches using KDs. The results we present here are designed to advance the knowledge and application of KDs in the treatment of headaches

Practical and clinical utility of non-invasive vagus nerve stimulation (nVNS) for the acute treatment of migraine. A post hoc analysis of the randomized, sham-controlled, double-blind PRESTO trial

Background: The PRESTO study of non-invasive vagus nerve stimulation (nVNS; gammaCore®) featured key primary and secondary end points recommended by the International Headache Society to provide Class I evidence that for patients with an episodic migraine, nVNS significantly increases the probability of having mild pain or being pain-free 2 h post stimulation. Here, we examined additional data from PRESTO to provide further insights into the practical utility of nVNS by evaluating its ability to consistently deliver clinically meaningful improvements in pain intensity while reducing the need for rescue medication. Methods: Patients recorded pain intensity for treated migraine attacks on a 4-point scale. Data were examined to compare nVNS and sham with regard to the percentage of patients who benefited by at least 1 point in pain intensity. We also assessed the percentage of attacks that required rescue medication and pain-free rates stratified by pain intensity at treatment initiation. Results: A significantly higher percentage of patients who used acute nVNS treatment (n = 120) vs sham (n = 123) reported a ≥ 1-point decrease in pain intensity at 30 min (nVNS, 32.2%; sham, 18.5%; P = 0.020), 60 min (nVNS, 38.8%; sham, 24.0%; P = 0.017), and 120 min (nVNS, 46.8%; sham, 26.2%; P = 0.002) after the first attack. Similar significant results were seen when assessing the benefit in all attacks. The proportion of patients who did not require rescue medication was significantly higher with nVNS than with sham for the first attack (nVNS, 59.3%; sham, 41.9%; P = 0.013) and all attacks (nVNS, 52.3%; sham, 37.3%; P = 0.008). When initial pain intensity was mild, the percentage of patients with no pain after treatment was significantly higher with nVNS than with sham at 60 min (all attacks: nVNS, 37.0%; sham, 21.2%; P = 0.025) and 120 min (first attack: nVNS, 50.0%; sham, 25.0%; P = 0.018; all attacks: nVNS, 46.7%; sham, 30.1%; P = 0.037). Conclusions: This post hoc analysis demonstrated that acute nVNS treatment quickly and consistently reduced pain intensity while decreasing rescue medication use. These clinical benefits provide guidance in the optimal use of nVNS in everyday practice, which can potentially reduce use of acute pharmacologic medications and their associated adverse events. Trial registration: ClinicalTrials.gov identifier: NCT02686034

Association of intronic variants of the KCNAB1 gene with lateral temporal epilepsy.

The KCNAB1 gene is a candidate susceptibility factor for lateral temporal epilepsy (LTE) because of its functional interaction with LGI1, the gene responsible for the autosomal dominant form of LTE. We investigated association between polymorphic variants across the KCNAB1 gene and LTE. The allele and genotype frequencies of 14 KCNAB1 intronic SNPs were determined in 142 Italian LTE patients and 104 healthy controls and statistically evaluated. Single SNP analysis revealed one SNP (rs992353) located near the 3'end of KCNAB1 slightly associated with LTE after multiple testing correction (odds ratio=2.25; 95% confidence interval 1.26-4.04; P=0.0058). Haplotype analysis revealed two haplotypes with frequencies higher in cases than in controls, and these differences were statistically significant after permutation tests (Psim=0.047 and 0.034). One of these haplotypes was shown to confer a high risk for the syndrome (odds ratio=12.24; 95% confidence interval 1.32-113.05) by logistic regression analysis. These results support KCNAB1 as a susceptibility gene for LTE, in agreement with previous studies showing that this gene may alter susceptibility to focal epilepsy