Pure adult-onset Spastic Paraplegia caused by a novel mutation in the KIAA0196 (SPG8) gene

SPG8 is a rare autosomal dominant hereditary spastic paraplegia (AD-HSP), with only six SPG8 families described so far. Our purpose was to screen for KIAA0196 (SPG8) mutations in AD-HSP patients and to investigate their phenotype. Extensive family investigation was performed after positive KIAA0196 mutation analysis, which was part of an on-going mutation screening effort in AD-HSP patients. A novel pathogenic KIAA0196 mutation p.(Gly696Ala) was identified in two AD-HSP patients, who subsequently were shown to belong to a single large Dutch pedigree with more than 10 affected family members. The phenotype consisted of a pure HSP with ages at onset between 20 and 60 years, distally reduced vibration sense in the legs in all, and urinary urgency in seven out of 10 patients. Frequent features were exercise- or emotion-induced increase of spasticity and gait problems and chronic nonspecific lower back and joint pains. We have identified a fourth pathogenic KIAA0196 mutation in a Dutch HSP-family, the seventh family worldwide, with a less severe clinical course than described before.     

Evidence for Electrical Coupling in the SubCoeruleus (SubC) Nucleus

SubCoeruleus (SubC) neurons, which are thought to modulate rapid-eye-movement (REM) sleep, were recorded in brain stem slices from 7- to 20-day rats and found to manifest spikelets, indicative of electrical coupling. Spikelets occurred spontaneously or could be induced by superfusion of the cholinergic agonist carbachol. Whole cell recordings revealed that carbachol induced membrane oscillations and spikelets in the theta frequency range in SubC neurons in the presence of fast synaptic blockers. Electrical coupling in neurons is mediated by the gap junction protein connexin 36 (Cx 36). We found that Cx 36 gene expression and protein in the mesopontine tegmentum decreased during development. Cx 36 protein levels specifically in the SubC decreased in concert with the developmental decrease in REM sleep. The presence of electrical coupling in the SubC introduces a novel potential mechanism of action for the regulation of sleep-wake states.     

S-R compatibility effect or cerebral laterality effect? Comments on a controversy

This article investigates the role played by misleading terminology in the origins of a recent controversy about the nature of stimulus-response compatibility effects.     

CR1 genotype is associated with entorhinal cortex volume in young healthy adults

Gene-brain structure associations of 3 recently discovered risk genes for Alzheimer's disease, CLU (rs11136000C>T), CR1 (rs6656401G>A), and PICALM (rs3851179G>A), were investigated in 2 independent cohorts of young healthy adults (n = 430 and n = 492, respectively). We assessed structural differences in 2 core structures of Alzheimer pathology, entorhinal cortex and hippocampus, by voxel-based morphometry using high-resolution magnetic resonance imaging (MRI) data. For CLU and PICALM no significant genotype-related differences in local gray matter volume were found. CR1 risk allele (A) carriers showed smaller local gray matter volume in the entorhinal cortex, as confirmed in both cohorts. This association, apparent in young healthy adults, might mediate susceptibility for Alzheimer's disease later in life.     

Fixierungsfehler in der Notfallmedizin

Anamnesis

A 53-year-old patient with known schizophrenia apparently suffered an acute aggravation of the underlying disease. The emergency physician found the patient in his apartment sitting naked on a chair and subsequently committed him to supervision psychiatry where he rapidly developed cardiopulmonary insufficiency. During the subsequent emergency transfer to the university clinic the patient started to show signs of an acute abdomen. On arrival at hospital the patient additionally developed anisocoria and troponin positive acute coronary syndrome (ACS).

Diagnosis and therapy

Emergency laparotomy revealed peritonitis due to gastric perforation making sepsis the probable main cause of the observed clinical symptoms. After abdominal surgery, cardiac catheterization and treatment of severe sepsis with multiorgan dysfunction syndrome, the man was discharged after 20 days in hospital.     

Shift of functional cerebral asymmetry during the menstrual cycle

This study investigated whether for females, who are said to be less strongly lateralized for cognitive functions than men, hemispheric superiority might depend on the phase of the menstrual cycle. The results show that while asymmetry in lexical decisions did not change throughout the menstrual cycle, asymmetry in face perception decreased linearly from a large right hemisphere superiority during menstruation to a small left hemisphere superiority during the premenstrual phase. This is seen as being relevant not only for the discussion of sex differences in cerebral asymmetry but also for the concept of cerebral organization in general.     

Sex differences and cognitive/motor interference with visual half-field stimulation

This study examines the possible influence of the response on the asymmetry of lexical decision in a visual half-field study and whether sex differences in asymmetry might be determined by response factors. The results support the importance of these factors: when response demands were increased (pressing the button three times instead of once) the reaction time asymmetry was reversed for male subjects.     

Mutant mitochondrial elongation factor G1 and combined oxidative phosphorylation deficiency

Although most components of the mitochondrial translation apparatus are encoded by nuclear genes, all known molecular defects associated with impaired mitochondrial translation are due to mutations in mitochondrial DNA. We investigated two siblings with a severe defect in mitochondrial translation, reduced levels of oxidative phosphorylation complexes containing mitochondrial DNA (mtDNA)-encoded subunits, and progressive hepatoencephalopathy. We mapped the defective gene to a region on chromosome 3q containing elongation factor G1 (EFG1), which encodes a mitochondrial translation factor. Sequencing of EFG1 revealed a mutation affecting a conserved residue of the guanosine triphosphate (GTP)-binding domain. These results define a new class of gene defects underlying disorders of oxidative phosphorylation.