Summary Purpose:  Epilepsies have a highly heterogeneous background with a strong genetic contribution. The variety of unspecific and overlapping syndromic and nonsyndromic phenotypes often hampers a clear clinical diagnosis and prevents straightforward genetic testing. Knowing the genetic basis of a patient’s epilepsy can be valuable not only for diagnosis but also for guiding treatment and estimating recurrence risks. Methods:  To overcome these diagnostic restrictions, we composed a panel of genes for Next Generation Sequencing containing the most relevant epilepsy genes and covering the most relevant epilepsy phenotypes known so far. With this method, 265 genes were analyzed per patient in a single step. We evaluated this panel on a pilot cohort of 33 index patients with concise epilepsy phenotypes or with a severe but unspecific seizure disorder covering both sporadic and familial cases. Key Findings:  We identified presumed disease‐causing mutations in 16 of 33 patients comprising sequence alterations in frequently as well as in less commonly affected genes. The detected aberrations encompassed known and unknown point mutations (SCN1A p.R222X, p. E289V, p.379R, p.R393H; SCN2A p.V208E; STXBP1 p.R122X; KCNJ10 p.L68P, p.I129V; KCTD7 p.L108M; KCNQ3 p.P574S; ARHGEF9 p.R290H; SMS p.F58L; TPP1 p.Q278R, p.Q422H; MFSD8 p.T294K), a putative splice site mutation (SCN1A c.693A> p.T/P231P) and small deletions (SCN1A p.F1330Lfs3X [1 bp]; MFSD8 p.A138Dfs10X [7 bp]). All mutations have been confirmed by conventional Sanger sequencing and, where possible, validated by parental testing and segregation analysis. In three patients with either Dravet syndrome or myoclonic epilepsy, we detected SCN1A mutations (p.R222X, p.P231P, p.R393H), even though other laboratories had previously excluded aberrations of this gene by Sanger sequencing or high‐resolution melting analysis. Significance:  We have developed a fast and cost‐efficient diagnostic screening method to analyze the genetic basis of epilepsies. We were able to detect mutations in patients with clear and with unspecific epilepsy phenotypes, to uncover the genetic basis of many so far unresolved cases with epilepsy including mutation detection in cases in which previous conventional methods yielded falsely negative results. Our approach thus proved to be a powerful diagnostic tool that may contribute to collecting information on both common and unknown epileptic disorders and in delineating associated phenotypes of less frequently mutated genes.

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A video-assisted thoracoscopic microsurgical approach was developed in the laboratory and subsequently used clinically to resect abnormalities of the thoracic vertebrae, to decompress the thoracic spinal cord, and to reconstruct the thoracic vertebral bodies. This report describes the development of the clinical operative techniques for microsurgical thoracoscopic vertebrectomy, neural decompression, and spinal reconstruction. This minimally incisional approach was clinically used in 17 patients to treat vertebral osteomyelitis, tumors, and compression fractures. Microsurgical thoracoscopic techniques were performed using several narrow, flexible, working portals placed in small incisions in the intercostal spaces. Access to the thoracic spine was achieved through the pleural cavity after temporary deflation of one lung using a double-lumen endotracheal tube. The parietal pleura, segmental vessels, and rib heads were dissected off the surfaces of the involved vertebrae to expose the region of interest. Long narrow spine dissection tools were used to perform the spinal decommpression and reconstruction. This technique achieved the same amount of spinal dissection as that achieved with conventional open spinal procedures and used microsurgical visualization techniques. The small incisions with reduced soft tissue dissection may reduce postoperative pain, shorten the length of hospitalization, and have cosmetic and functional advantages. Thoracoscopic vertebrectomies and reconstruction of the spine were technically feasilble procedures that were performed with excellent clinical results. This minimally incisional technique provides a viable alternative to thoracotomy or to posterolateral approaches for thoracic vertebrectomy and vertebral body reconstruction.

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