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Neurosurgery is considered a technically demanding specialty; nonetheless, it also requires non-technical skills (NTSs) to reach mastery.

In migraine, an interictal reduction of mitochondrial energy metabolism and a preventive effect of high-dose riboflavin were reported. To explore the relation between the two, we tested if the therapeutic response to riboflavin is associated with specific mitochondrial DNA (mtDNA) haplogroups. We focused our attention on haplogroup H, which is known to differ from others in terms of energy metabolism.

Ataxia with oculomotor apraxia type 2 (AOA2) is characterized by onset between age 10 and 22 years, cerebellar atrophy, peripheral neuropathy, oculomotor apraxia (OMA), and elevated serum alpha-fetoprotein (AFP) levels. Recessive mutations in SETXhave been described in AOA2 patients.

Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is an early-onset familial disease with prominent myelinated fibers in the optic fundus. ARSACS is frequent in the Charlevoix-Saguenay region of Quebec but rare elsewhere. Mutations in SACS, encoding sacsin, a protein of unknown function, are associated with ARSACS. The authors identified three new SACSmutations in two Italian patients whose phenotype closely matches that of Quebec cases, but without retinal striation.

A complicated form of recessive hereditary spastic paraplegias (HSPs) with thin corpus callosum (TCC) was first described in Japan, and most of the Japanese families showed linkage to chromosome 15q13–15. A recessive HSP locus (SPG11) has also been mapped to chromosome 15q13–15 in Italian and North American families with and without TCC, and it overlaps the region identified in the Japanese families.

SummaryBackground:The dissociation of mechanical from non-mechanical energy utilisation can be studied using BDM (2,3-butanedione monoxime), which inhibits the actin-myosin interaction without inhibiting Ca2+transport. The objective of the present study was to establish if increasing the non-mechanical energy demand of perfused isolated pig hearts by dobutamine stimulation requires glycolysis with increased exogenous glucose uptake.Methods:Five isolated pig hearts (CTRL) were perfused for 90 min at constant flow (1 ml g−1 min−1) with non-recirculating blood containing 30 mM BDM and 26 MBq/l of fluorine-18 2-fluoro-2-deoxyglucose (18FDG). This was compared with five hearts (DOBU) subjected to the same protocol for the first 30 min and then to dobutamine (1.5 μM) for the following 30 min and dobutamine (4 μM) for the last 30 min. Five other isolated hearts were perfused as for the DOBU group but without BDM (CTRLDOBU). Using a clinical PET scanner, glucose uptake was assessed by estimating 18FDG uptake using linear regression. The slope variations were compared using a global test of coincidence.Results:Heart rate was at 100 ± 2 b.p.m. in the CTRL group and at 180 ± 7 b.p.m. in the DOBU group. 18FDG uptake was homogeneous within the whole myocardium and we observed a linear and regular increase in both the CTRL and DOBU groups (p, NS). In the CTRLDOBU group, 18FDG uptake was also homogeneous within the whole myocardium, but slopes of 18FDG uptake during dobutamine perfusion were higher than without dobutamine.Conclusion:In blood-perfused isolated pig hearts, exogenous glucose is not necessarily required when non-mechanical energy is increased by dobutamine stimulation. These findings suggest that ATP derived from glycolysis is not necessary to preserve myocardial Ca2+transport during β-adrenergic stimulation.

The authors report on a novel frameshift mutation (c.1688insA) in the SPG3Agene resulting in premature translation termination of the gene product atlastin. These data add a new variant to the second disease gene in autosomal dominant hereditary spastic paraplegia (ADHSP) and lend definitive support to its causative role. By combining direct testing of SPASTand SPG3A,at least 50 of ADHSP families can now receive appropriate genetic diagnosis.

The authors describe a family of Sephardic Jews with progressive external ophthalmoparesis, skeletal muscle weakness, and parkinsonism. Autosomal recessive inheritance was suggested by many consanguineous marriages, although a dominant disorder could not be excluded. No linkage to known progressive external ophthalmoparesis locus was found. The presence of cytochrome coxidase-negative ragged-red fibers, biochemically reduced respiratory chain complexes, and multiple mitochondrial DNA deletions in muscle biopsies from four patients suggested a new mitochondrial disorder of intergenomic communication.

Abstract: Muscle biopsy tissue from a patient affected by the juvenile form of neuronal ceroid lipofuscinosis (NCL) was studied immunohistochemically using antibodies to β-amyloid peptide and amyloid precursor protein. Positive reaction in muscle was specifically localized to autophagic vacuoles and blood vessel walls. Increased acid phosphatase reaction suggested enhanced lysosomal activity. We hypothesize that β-amyloid is deposited in NCL muscle by a lysosomal mechanism similar to that proposed in other disorders involving β-amyloid.

In spite of several cases reported in the literature, the exact pathogenetic mechanism of neuropathic changes in porphyric neuropathy remains uncertain. Various authors have ascribed the neuropathologic findings to either a dying-back axonal degeneration or segmental demyelination. In recent years, the hypothesis of an axonal and myelinic disorder has received support by the demonstration of a combined and simultaneous involvement of both these structures. Such different opinions are also a consequence of the reduced number of detailed bioptic observations in the different forms of acute porphyria not only during acute phases but also between attacks. In this paper we report the results of light- and electronmicroscopic examination of two sural nerve biopsies from subjects with hereditary coproporphyria. The first was performed 6 months after an acute attack, the second specimen was obtained from a patient without acute attacks, who had clinical and electrophysiologic signs of a chronic progressive neuropathy. In both cases a dying-back axonal degeneration is considered the primary change. The pathogenetic mechanism of peripheral nerve lesions in porphyric neuropathy will be discussed finally.

Multiple mitochondrial DNA (mtDNA) deletions have been described in patients with autosomal dominant progressive external ophthalmoplegia(AD-PEO) and in autosomal recessive disorders including mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) and autosomal recessive cardiomyopathy ophthalmoplegia (ARCO). The pathogenic bases of these disorders are unknown. We studied three patients with AD-PEO and three patients with autosomal recessive (AR)-PEO (two patients with MNGIE and one patient with ARCO). Histochemistry and Southern blot analyses of DNA were performed in skeletal muscle from the patients. Muscle mtDNA was used to characterize the pattern and amounts of the multiple mtDNA rearrangements; PCR analysis was performed to obtain finer maps of the deleted regions in both conditions. The patients with AD-PEO had myopathic features; the patients with AR-PEO had multisystem disorders. The percentage of ragged-red and cytochromecoxidase-negative fibers tended to be higher in muscle from the patients with AD-PEO (19% ± 13.9, 29.7 ± 26.3) than in muscle from the patients with AR-PEO (1.4% ± 1.4, 3.3% ± 3.2;p< 0.10). The sizes of the multiple mtDNA deletions ranged from approximately 4.0 to 10.0 kilobases in muscle from both groups of patients, and in both groups, we identified only deleted and no duplicated mtDNA molecules. Patients with AD-PEO harbored a greater proportion of deleted mtDNA species in muscle (31% ± 5.3) than did patients with AR-PEO (9.7%± 9.1; p< 0.05). In the patients with AD-PEO, we identified a deletion that included the mtDNA heavy strand promoter (HSP) region, which had been previously described as the HSP deletion was not present in the patients with AR-PEO. Our findings show the clinical, histologic, and molecular genetic heterogeneity of these complex disorders. In particular, the proportions of multiple mtDNA deletions were higher in muscle samples from patients with AD-PEO than in those from patients with AR-PEO.

A novel mtDNA mutation at position nt. 4300 in the tRNAIlegene is associated with hypertrophic cardiomyopathy inherited as a maternal trait. Interestingly, this mutation seems to cause a pure heart disease as opposed to most other mtDNA mutations, which are associated with multisystemic disorders. Hypertrophic cardiomyopathies are genetically heterogeneous, and mtDNA defects should be considered in the differential diagnosis, especially when there is evidence of maternal inheritance.

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a multisystemic autosomal recessive disease due to primary thymidine phosphorylase (TP) deficiency. To restore TP activity, we performed reduced intensity allogeneic stem cell transplantations (alloSCTs) in two patients. In the first, alloSCT failed to engraft, but the second achieved mixed donor chimerism, which partially restored buffy coat TP activity and lowered plasma nucleosides. Thus, alloSCT can correct biochemical abnormalities in the blood of patients with MNGIE, but clinical efficacy remains unproven.

Background: The management of a solitary pulmonary nodule is the subject of debate and minimally invasive diagnostic approaches have low sensitivity for small peripheral nodules. We discuss the role of video-assisted thoracoscopic surgery (VATS) in the management of solitary pulmonary nodules (SPNs) ?1 cm performed with a preoperatory computed tomography-guided wire localization. Methods: Thirty-five selected patients underwent VATS resection for SPN, with localization by guide wire before surgery. Results: Seven patients, after VATS exploration, underwent thoracotomy because of pleuropulmonary adhesions, depth or dimensions. Histological diagnosis was obtained in all procedures; there was no postoperative morbility or morbidity. Conclusion: Preoperative computed tomography hook-wire localization is a suitable strategy for peripheral nodules ?1 cm in diameter.

Two cases of hereditary coproporphyria showed unusual nervous system involvement, one epilepsy with onset in childhood, and the other chronic central and peripheral nervous system damage. The literature is briefly discussed.

The authors searched for mitochondrial DNA (mtDNA) A3243G mutation in peripheral blood leukocytes from female migraine patients with pure matrilinear history of migraine along two or three generations. The current study was designed to exclude any male transmission of the disease. The mutation was absent in all patients. We conclude that mtDNA A3243G mutation does not contribute to the pathogenesis of pure matrilinear multigenerational migraine with or without aura.

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