Familial presenile dementia with bitemporal atrophy

This study describes the clinical, neuropsychological, neuroimaging and genetic characteristics in two generations of a Swedish family affected by presenile dementia. The pedigree includes 5 cases (mother and 4 of 5 children) of progressive dementia with onset between 54 and 62 years. The clinical picture is characterized by insidious onset and progressive decline in episodic memory without spatial impairment or dyspraxia, followed by changes in personality and behaviour, with signs of disinhibition, irritability, impulsivity and loss of social awareness. Three siblings, examined after 10 years of duration, showed moderate language deficits but preserved spatial function and praxis. CT and MRI showed progressive bilateral temporal atrophy and moderate frontal white matter changes. Regional cerebral blood flow measurements showed hypoperfusion in temporal areas bilaterally. Quantitative EEG was normal within 5 years after symptom onset and thereafter showed a moderate increase in relative theta power. Sequencing of the tau gene (chromosome 17) revealed the previously described R406W mutation in exon 13 as a likely cause of the disease. This mutation was identified in all affected cases. The clinical picture of this family shows striking similarities not only to frontotemporal dementia but also to Alzheimer's disease.     

CD34-immunoreactive balloon cells in cortical malformations

Balloon cells are histopathological hallmarks of various cortical malformations, i.e., focal cortical dysplasia (Taylors type, FCD IIb), hemimegalencephaly (HME) or cortical tubers (tuberous sclerosis, TSC). Whether this intriguing cell type results from similar pathogenetic pathways remains to be shown. Here, we analyzed the immunohistochemical distribution pattern of the CD34 epitope in surgical specimens from 34 patients with FCD IIb, compared to that of 6 patients with TSC and 3 patients with HME. In normal brain, CD34 occurs only transiently during neurulation, but cannot be detected in mature neuroectodermal cell progenies. In contrast, 58% of our patients showed CD34 immunoreactivity within a subpopulation of balloon cells. Interestingly, CD34-positive balloon cells were confined to the white matter, but never observed in neocortical layers. Furthermore, balloon cells expressing neurofilament protein were also restricted to white matter, whereas GFAP-positive balloon cells were observed either in white or gray matter location. Clinical characteristics did not significantly differ between patients with CD34-positive versus CD34-negative lesions. No significant correlation was found between CD34 expression and genetic alterations of the TSC1 gene, which is affected in many FCD and TSC patients and which plays a role in the regulation of cell size. Further studies are warranted to clarify the restricted expression of CD34 in balloon cells of the white matter.     

Cerebral glucose metabolism and early EEG/aEEG in term newborn infants with hypoxic-ischemic encephalopathy

The objective was to investigate how early electrocortical background pattern, as recorded with amplitude integrated EEG (aEEG), correlates with global and regional cerebral glucose metabolism (CMRgl) measured by positron emission tomography during the subacute phase after birth asphyxia. Nineteen term infants with hypoxic-ischemic encephalopathy were investigated. The aEEG background was evaluated at 0-6, 6-12, 12-24, 24-48, and 48-72 h postnatal age, and classified into four categories according to increasing degree of abnormality. The aEEG were also evaluated for sleep-wake cycling and epileptic seizure activity. CMRgl was measured by positron emission tomography with 2-(18F) fluoro-2-deoxy-d-glucose at a median (range) postnatal age 10 (4-24) d. Increasing degree of abnormality in aEEG correlated significantly with decreasing CMRgl: at 6-12 h (-0.593; 0.012) (r value; p value), 12-24 h (-0.669; 0.003), and 24-48 h (-0.569; 0.014) postnatal age. Presence of sleep-wake cycling at 0-6 h (0.697; 0.012), 6-12 h (0.668; 0.003), and 12-24 h (0.612; 0.009) of age correlated with increased CMRgl. Delayed seizure activity at 12-24 h correlated with decreased CMRgl (-0.661; 0.004). Infants with abnormal aEEG at 6-12 h had lower CMRgl in all regions of the brain compared with infants with normal aEEG. CMRgl of any specific region of the brain was not significantly more correlated to aEEG than CMRgl of other regions. Early electrocortical background patterns, early presence of sleep-wake cycling, and delayed seizure activity were highly correlated with global CMRgl measured during the subacute phase after asphyxia, but did not correlate with any specific pattern of regional uptake.     

Endoneurial capillary abnormalities presage deterioration of glucose tolerance and accompany peripheral neuropathy in man

To explore whether microangiopathy is associated with disturbed glucose tolerance and peripheral neuropathy, we assessed endoneurial capillary morphology in sural nerve biopsies from men with diabetes, impaired glucose tolerance (IGT), and normal glucose tolerance (NGT). Baseline morphology was related to glucose tolerance and neuropathy at baseline and at follow-up 6 years later. Capillary density (in number per millimeters squared) at baseline was higher in subjects with diabetes (n = 10) compared with those with NGT (n = 5) at follow-up (median [interquartile range]) (86.0 [24.3] vs. 54.9 [17.1]; P = 0.0200) and in those progressing from IGT to diabetes (n = 4) compared with those with persistent IGT (n = 4) (86.7 [25.2] vs. 54.1 [14.6]; P = 0.0433). The capillary luminal area (in micrometers squared) was lower in subjects with NGT progressing to IGT (n = 2) or subjects with IGT progressing to diabetes (n = 3) compared with subjects with constant NGT (n = 6) or constant IGT (n = 4) (11.9 [2.4] vs. 20.8 [7.8]; P = 0.0201). The capillary basement membrane area (in micrometers squared) was increased in patients with peripheral neuropathy (n = 10) compared with those without (n = 7) (114.6 [68.8] vs. 75.3 [28.7]; P = 0.0084). In conclusion, increased capillary density was associated with current or future diabetes, decreased capillary luminal area with future deterioration in glucose tolerance, and increased basement membrane area with peripheral neuropathy.     

Hypertension and cognition

Hypertension is a risk factor for stroke, ischemic white-matter lesions, cardiovascular disorders, and vascular dementia. This risk increases with increasing blood pressure. Several studies report that high blood pressure precedes Alzheimer's disease (AD) by decades, but blood pressure decreases the years before dementia onset and is lower in individuals with AD than in controls. High blood pressure has also been related to the neuropathological manifestations of AD. The exact mechanism behind these associations is not clear. Hypertension may cause cerebrovascular disease that may increase the likelihood that individuals with AD encephalopathy will express a dementia syndrome, this may accelerate the AD process, subclinical AD may lead to increased blood pressure, and similar biological mechanisms may be involved in the pathogenesis of both disorders. Hypertension is a common disorder and often untreated. Even if hypertension results only in a moderately increased risk of AD, or overall dementia, better treatment of hypertension may have an immense effect on the total number of individuals with dementia.     

Drug craving and addiction: integrating psychological and neuropsychopharmacological approaches

In the present review, an integrated approach to craving and addiction is discussed, which is based on recent insights from psychology and neuropsychopharmacology. An integrated model explains craving and relapse in humans by the psychological mechanism of "attentional bias" and provides neuropsychopharmacological mechanisms for this bias. According to this model, cognitive processes mediate between drug stimulus and the subject's response to this stimulus and subsequent behavioral response (e.g., drug use, relapse). According to the model, a conditioned drug stimulus produces an increase in dopamine levels in the corticostriatal circuit, in particular the anterior cingulate gyrus, amygdala, and nucleus accumbens, which in turn serves to draw the subject's attention towards a perceived drug stimulus. This process results in motor preparation and a hyperattentive state towards drug-related stimuli that, ultimately, promotes further craving and relapse. Evidence for this attentional bias hypothesis is reviewed from both the psychopharmacological and the neuroanatomical viewpoints. The attentional bias hypothesis raises several suggestions for clinical approaches and further research.     

Detection and evaluation of initial cartilage pathology in man: A comparison between MRT,arthroscopy and near-infrared spectroscopy (NIR) in their relation to initial knee pain

Background and aims: MRI and arthroscopy are important methods in the evaluation of cartilage pathology. But frequently initial changes of cartilage in combination with chronic knee pain cannot be detected by employing these two methods. Better diagnostic tools for the detection of the early stages of osteoarthritis (OA) are required. The objective of this study was to show that near-infrared spectroscopy (NIRS) can be incorporated into routine arthroscopy to improve detection and assessment of the initial cartilage pathology. Furthermore correlations between findings in MRI, arthroscopy and NIRS in patients with initial symptoms of OA have studied. Methods: Patients (n = 21, 12 women, 9 men, age: 15–59 years, mean 34.19 years) with knee pain lasting for at least half a year without any trauma of the knee in their history were interviewed (body weight, smoking behaviour) and clinically evaluated using the Knee Injury and Osteoarthritis Outcome Score (KOOS). Also serum parameters (cholesterol, lipids) were analysed, conventional X-rays in three directions (evaluated according to Kellgren and Lawrence) and MRI (evaluation of cartilage damage according to the ICRS-score) were performed preoperatively in all patients. During subsequent arthroscopy cartilage damage was evaluated according to the ICRS-score. In addition the spectral reflection of cartilage was investigated in all knees using a special micro-glass-fiber probe in the near-infrared light region (spectral range between 1150 and 1475 nm). To characterize relations between the investigated parameters the Spearman's rank correlation coefficient was used. Inter-observer variance was calculated employing the Cohens–Kappa-test. Results: MRI demonstrated a strong inter-observer variance with no significant correlations to other parameters. The same was observed for arthroscopic findings. Only NIRS showed significant correlations with three out of five KOOS subscores. Within the general parameters only smoking behaviour showed a significant correlation with two of the KOOS-scores. NIRS therefore seemed to be a sensitive diagnostic tool in detection of initial pathology in human cartilage. The additional necessary time for the spectroscopic investigation as part of the routine arthroscopy ranged between 3 and 7 min (mean: 4 min 18 s). Conclusion: Particularly for early-stage cartilage lesions (ICRS 0/I) MRI and arthroscopy have rather low predictive value. The inter-observer variance is very high (Cohens–Kappa < 0.4). Correlations found between NIRS and KOOS suggest that NIRS potentially can be used for detection of initial cartilage pathology and may be helpful in the evaluation of the benefit of different medical or surgical interventions at early-stage of articular cartilage damage.     

Impact of age on risk of complications after gastric bypass: A cohort study from the Scandinavian Obesity Surgery Registry (SOReg)

Background

An increasing number of older patients undergo bariatric surgery.