This study investigates motor (MNCS) and sensory (SNCS) nerve conduction in a sample of non-diabetic obese people without symptoms suggestive of neuropathy and looks for a possible metabolic alteration. Twenty-one patients and 20 age-matched controls underwent (a) MNCS (median, ulnar, peroneal, and tibial) and SNCS (median, ulnar, and sural); (b) quantitative sensory testing to measure sensory threshold for vibration, warm and cold sensation (WS-CS), heat and cold-induced pain; and (c) blood sample analysis to evaluate glucose and insulin levels and calculate the quantitative insulin-sensitivity check index (QUICKI). The obese group showed significantly decreased compound muscle action potential amplitude of tibial and peroneal nerves and decreased sensory action potential amplitude of all nerves. Most of the sensory thresholds were altered in obese patients. Insulin serum levels were significantly increased while QUICKI decreased in obese patients. WS and CS from the index and little fingers and WS from the big toe significantly correlated with QUICKI. Thermal and pain thresholds from the index and thermal thresholds from the little finger correlated with QUICKI values. The non-diabetic obese patients showed a subclinical involvement of different diameter sensory fibers. Such impairment was related to hyperinsulinemia and insulin sensitivity. The increase in sensory threshold of obese patients might be due to a metabolic alteration, potentially leading to a future clinical neuropathy.

The aim of our study was to evaluate the etiopathogenesis and the vascular risk factors in a consecutive series of patients with juvenile ischemic stroke. We enrolled 273 patients (158 males and 115 females), aged between 16 and 49 years, with ischemic cerebrovascular events (ICVE), including transient ischemic attack (TIA) or stroke, referred to our neurology ward between January 1994 and December 2001. Our protocol included medical history, cardiac and neurological examinations, assessment of risk factors and laboratory tests. The instrumental assessment included transthoracic echocardiography (70%), transesophageal echocardiography (60%), conventional angiography (30%), MR angiography (30%), cranial computed tomography (100%) and brain MRI (48%). The ICVE was a stroke in 60% of the cases, a reversible ischemic neurologic deficit in 14% and a TIA in 26%. Thirty-three patients were aged less than 29, 59 were aged between 30 and 39 and 181 between 40 and 49. The percentage of females was higher in patients aged less than 29 while males were prevalent in the 4th and 5th decade. The patients were subtyped according to etiopathogenesis. A large-vessel disease (LVD) was diagnosed in 43 patients (16% of the cases), mostly in patients aged more than 40 years (36 cases). A small-vessel disease (SVD) was found in 48 patients (17% of cases), mostly in patients aged more than 40 years (41 cases). A cardioembolic stroke (CE) was diagnosed in 66 patients (24% of the cases). In the majority of the cases, the cardiopathies were at low-uncertain embolic risk: patent foramen ovale (PFO, 39 cases, in 8 patients associated with an atrial septal aneurism), atrial septal aneurism (12 cases) and myxomatous mitral valve prolapse (3 cases). Stroke due to other causes was found in 51 patients (19% of the cases). Arterial dissection, more frequently involving the carotid region, was diagnosed in 35 patients. Coagulopathies and vasculitis were found in 5 and 6 patients, respectively. Stroke of unknown etiology was found in 65 patients (24% of the cases) with a homogeneous distribution among decades. Our study highlights the role of minor cardiac sources of embolism and arterial dissection in the etiology of juvenile ischemic stroke, whereas coagulopathies and vasculitis are less relevant. LVD and SVD were relevant only in the 5th decade.

SummaryMutations in citron (CIT), leading to loss or inactivation of the citron kinase protein (CITK), cause primary microcephaly in humans and rodents, associated with cytokinesis failure and apoptosis in neural progenitors. We show that CITK loss induces DNA damage accumulation and chromosomal instability in both mammals and Drosophila. CITK-deficient cells display “spontaneous” DNA damage, increased sensitivity to ionizing radiation, and defective recovery from radiation-induced DNA lesions. In CITK-deficient cells, DNA double-strand breaks increase independently of cytokinesis failure. Recruitment of RAD51 to DNA damage foci is compromised by CITK loss, and CITK physically interacts with RAD51, suggesting an involvement of CITK in homologous recombination. Consistent with this scenario, in doubly CitK and Trp53 mutant mice, neural progenitor cell death is dramatically reduced; moreover, clinical and neuroanatomical phenotypes are remarkably improved. Our results underscore a crucial role of CIT in the maintenance of genomic integrity during brain development.