Growing evidence from animal studies indicates brain-damaging properties of nicotine exposure. Investigations in humans found a wide range of functional cerebral effects of nicotine and cigarette smoking, but studies focusing on brain damage are sparse. In 22 smokers and 23 never-smokers possible differences of the cerebral structures were investigated using magnetic resonance imaging and voxel-based morphometry. Significantly smaller grey matter volume and lower grey matter density (P = 0.05, corrected) were observed in the frontal regions (anterior cingulate, prefrontal and orbitofrontal cortex), the occipital lobe and the temporal lobe including parahippocampal gyrus, in smokers than in never-smokers. Group differences of either grey matter volume or grey matter density were also found in the thalamus, cerebellum and substantia nigra, among other regions. Smokers did not show greater volumes than never-smokers in any cerebral region. Magnitude of lifetime exposure to tobacco smoke (pack-years) was inversely correlated with volume of frontal and temporal lobes and cerebellum (P = 0.001, uncorrected). The data indicate structural deficits of several cortical and subcortical regions in smokers relative to never-smokers. The topographic profile of the group differences show some similarities to brain networks known to mediate drug reinforcement, attention and working memory processing. The present findings may explain in part the frequently reported cognitive dysfunctions in chronic cigarette consumers.

Sepsis presents a major health care problem and remains one of the leading causes of death within the intensive care unit (ICU). Therapeutic approaches against severe sepsis and septic shock focus on early identification. Adequate source control, administration of antibiotics, preload optimization by fluid resuscitation and further hemodynamic stabilisation using vasopressors whenever appropriate are considered pivotal within the early—golden—hours of sepsis. However, organ dysfunction develops frequently in and represents a significant comorbidity of sepsis. A considerable amount of patients with sepsis will show signs of severe muscle wasting and/or ICU-acquired weakness (ICUAW), which describes a frequently observed complication in critically ill patients and refers to clinically weak ICU patients in whom there is no plausible aetiology other than critical illness. Some authors consider ICUAW as neuromuscular organ failure, caused by dysfunction of the motor unit, which consists of peripheral nerve, neuromuscular junction and skeletal muscle fibre. Electrophysiologic and/or biopsy studies facilitate further subclassification of ICUAW as critical illness myopathy, critical illness polyneuropathy or critical illness myoneuropathy, their combination. ICUAW may protract weaning from mechanical ventilation and impede rehabilitation measures, resulting in increased morbidity and mortality. This review provides an insight on the available literature on sepsis-mediated muscle wasting, ICUAW and their potential pathomechanisms.

Words: main text 3490, abstract 250 2 ABSTRACT Objectives: Neuromuscular dysfunction in critically ill patients is attributed to either critical illness myopathy (CIM) or critical illness polyneuropathy (CIP) or a combination of both. But it is unknown whether differential diagnosis has an impact on prognosis. This study investigates whether there is an association between the early differentiation of CIM versus CIP and clinical prognosis. Methods: We included mechanically ventilated patients who featured a Simplified AcutePhysiology Score II (SAPS-II) ≥ 20 on three consecutive days within the first week after ICU admission. 53 critically ill patients were enrolled and examined by conventional nerve conduction studies and direct muscle stimulation (184 examinations in total). The first examination was conducted within the first week after admission to the intensive care unit (ICU). Results: In this cohort of critically ill patients, CIM was more frequent (68%) than CIP (38%).Electrophysiological signs of CIM preceded electrophysiological signs of CIP (median at day 7 in CIM patients vs. day 10 in CIP patients, p<0.001). Most patients with CIP featured concomitant CIM. At discharge from ICU, 25% of patients with isolated CIM showed electrophysiological signs of recovery and significantly lower degrees of weakness. Recovery could not be observed in patients with combined CIM/CIP even though ICU length of stay was significantly longer (mean 35 days in CIM/CIP vs. mean 19 days in CIM, p<0.001). Conclusion:Prognoses of patients differ depending on electrophysiological findings during early critical illness: Early electrophysiological differentiation of ICU acquired neuromuscular disorder enhances the evaluation of clinical prognosis during critical illness.

We suggest that electrophysiological nonexcitable muscle membrane predicts preferential type II fiber atrophy in intensive care unit patients during early critical illness.