Deep brain stimulation of the nucleus basalis of Meynert in Alzheimer's dementia.

Cholinergic neurons of the medial forebrain are considered important contributors to brain plasticity and neuromodulation. A reduction of cholinergic innervation can lead to pathophysiological changes of neurotransmission and is observed in Alzheimer's disease. Here we report on six patients with mild to moderate Alzheimer's disease (AD) treated with bilateral low-frequency deep brain stimulation (DBS) of the nucleus basalis of Meynert (NBM). During a four-week double-blind sham-controlled phase and a subsequent 11-month follow-up open label period, clinical outcome was assessed by neuropsychological examination using the Alzheimer's Disease Assessment Scale-cognitive subscale as the primary outcome measure. Electroencephalography and [(18)F]-fluoro-desoxyglucose positron emission tomography were, besides others, secondary endpoints. On the basis of stable or improved primary outcome parameters twelve months after surgery, four of the six patients were considered responders. No severe or non-transitional side effects related to the stimulation were observed. Taking into account all limitations of a pilot study, we conclude that DBS of the NBM is both technically feasible and well tolerated.

Magnetic seizure therapy in treatment-resistant depression: clinical, neuropsychological and metabolic effects.

BACKGROUND: Magnetic seizure therapy (MST), despite being in an early phase of clinical research, has been demonstrated to be associated with antidepressant efficacy. However, safety, tolerability and efficacy data in connection with functional brain activity from larger samples are lacking. The aim of this study was to determine clinical and cognitive effects of MST and the influence of MST on regional brain glucose metabolism. METHOD: Twenty-six patients suffering from treatment-resistant depression (TRD) underwent MST. Ten patients underwent a randomized trial and 16 patients an open-label study design. The primary outcome criterion was the severity of depressive symptoms assessed with the Hamilton Depression Rating Scale (HAMD). Depressive symptoms, tolerability and cognitive safety, along with social functioning and quality of life parameters, were assessed using various rating scales. A clinical follow-up visit 6 months following the completion of a course of MST and [18F]-fluorodeoxyglucose positron emission tomography (FDG-PET) scans of 12 patients were analysed. RESULTS: A significant response to MST was demonstrated by 69% of the patient sample, with 46% meeting remission criteria. Anxiety ratings were significantly reduced in responders and their quality of life was improved. Half of the responders relapsed within 6 months. No cognitive side-effects were observed. FDG-PET scans showed a metabolic increase in the frontal cortex bilaterally and a decrease in the left striatum. CONCLUSIONS: Robust antidepressant and anti-anxiety efficacy of MST was demonstrated, and found to be associated with localized metabolic changes in brain areas that are strongly implicated in depression. Thus, MST presents an effective, well-tolerated and safe treatment option for patients unable to respond to other forms of therapy for depression.

Quantitative imaging of zinc, copper and lead in three distinct regions of the human brain by laser ablation inductively coupled plasma mass spectrometry.

Laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) was used to determine the distribution of the trace elements zinc, copper and lead in insular, central and hippocampal areas of thin tissue sections (thickness 20microm) through an entire human brain hemisphere. For the investigation of the tissue samples, a commercial laser ablation system was coupled to a double-focusing sector field ICP-MS. The regions of interest of healthy brain tissue (thickness 20microm) were scanned (raster area approximately 200mm(2)) with a focused laser beam (wavelength 266nm, diameter of laser crater 200microm and laser power density 3x10(9)Wcm(-2)). The ion intensities of (64)Zn(+), (63)Cu(+) and (208)Pb(+) were measured by LA-ICP-MS within the ablated area. For quantification purposes, matrix-matched laboratory standards were prepared by means of dosing of each analyte to the pieces of brain tissue. The mass spectrometric analysis yielded inhomogeneous and largely reciprocal distributions of Zn and Cu in the selected areas of investigated brain samples. The highest concentrations of Zn and Cu with the most distinct distribution pattern were found in the hippocampus (up to 15microg g(-1)). In contrast to zinc and copper, for lead, a more homogeneous distribution throughout all regions examined was found at a low concentration (in the ngg(-1) range) level within the analytical range of LA-ICP-MS.

[Atypical Parkinson syndromes]. / Atypische Parkinson-Syndrome.

At the moment atypical Parkinson syndromes have unfavorable prognoses and show little response to dopaminergic medication. Early differential diagnosis of these disorders from idiopathic Parkinson syndrome is of pivotal clinical relevance. In case of future causal, neuroprotective therapeutic strategies, early diagnosis will allow a timely start of therapy. In the early stage of disease, it might be difficult clinically to distinguish multiple system atrophy, progressive supranuclear palsy, and corticobasal ganglionic degeneration from idiopathic Parkinson syndrome. Additional electrophysiological, imaging, and nuclear medical investigations may support the clinical diagnosis. During disease progression clinical signs indicative of an atypical Parkinson syndrome should always warrant reevaluation of the diagnosis.

Quantitative imaging of selenium, copper, and zinc in thin sections of biological tissues (slugs-genus arion) measured by laser ablation inductively coupled plasma mass spectrometry.

Quantitative imaging analysis of endogenous an exogenous elements throughout entire organisms is required for studies of bioavailability, transport processes, distribution, contamination and to monitor environmental risks using indicator organisms. An imaging mass spectrometric technique using laser ablation inductively coupled plasma mass spectrometry (LA-ICPMS) was developed to analyze selenium and metal distributions in longitudinal sections (thickness, 100 microm) of entire slugs (genus arion). Slugs were fed with either a placebo or solutions containing 1000 microg mL(-1) Se. Samples (raster area, 25 mmx45 mm) were scanned together with synthetic matrix-matched standards with a focused beam of a Nd:YAG laser (wavelength, 266 nm; diameter of laser crater, 50 microm; laser power density, 3x10(9) W cm(-2)) in a large laser ablation chamber. The ablated material was transported with argon as carrier gas to the ICP ion source at a double focusing sector field ICPMS. Ion intensities of selenium (78Se+, 82Se+) were measured together with 13C+, 63Cu+, and 64Zn+ within the entire tissue section. The regression coefficient of the calibration curve was 0.998. Inhomogeneous distributions for Se but also for C, Cu, and Zn were found. Selenium was enriched in the kidney (150 microg g(-1) in Se-treated animals versus 15 microg g(-1) in the placebo-treated animal, respectively) and in the digestive gland (200 microg g(-1) versus 25 microg g(-1)). Highest Se concentrations were detected in the gut of Se-treated slugs (250 microg g(-1)), and additional Se occurred in the skin of these animals. Cu was enriched in the heart and the mucous ventral skin. Interestingly, in addition to the localization in the digestive gland, Zn was detected only in the dorsal skin but not the ventral skin. The developed analytical technique allows the quantitative imaging of selenium together with selected metals in thin sections of biological tissue with limits of detection at the submicrogram per gram range.

Acute S-ketamine application does not alter cerebral [18F]altanserin binding: a pilot PET study in humans.

Modeling short-term psychotic states with subanaesthetic doses of ketamine provides substantial experimental evidence in support of the glutamate hypothesis of schizophrenia. Ketamine exerts its pharmacological effects both directly via interactions with glutamate receptors and indirectly by stimulating presynaptic release of endogenous serotonin (5-HT). The aim of this feasibility study was to examine whether acute ketamine-induced 5-HT release interferes with the binding of the 5-HT(2A) receptor (5-HT(2A)R) radioligand [(18)F]altanserin and positron emission tomography (PET). Two subjects treated with ketamine and one subject treated with placebo underwent [(18)F]altanserin PET at distribution equilibrium conditions. Robust physiological, psychopathological and cognitive effects were present at ketamine plasma concentrations exceeding 100 microg/l during >70 min. Notwithstanding, we observed stable radioligand binding (changes +/-95% CI of -1.0 +/- 1.6% and +4.1 +/- 1.8% versus -1.2 +/- 2.6%) in large cortical regions presenting high basal uptake of both, [(18)F]altanserin and ketamine. Marginal decreases of 4% of radioligand binding were observed in the frontal lobe, and 8% in a posteriorily specified frontomesial subregion. This finding is not compatible with a specific radioligand displacement from 5-HT(2A)R which should occur proportionally throughout the whole brain. Instead, the spatial pattern of these minor reductions was congruent with ketamine-induced increases in cerebral blood flow observed in a previous study using [(15)O]butanol PET. This may caused by accelerated clearance of unspecifically bound [(18)F]altanserin from cerebral tissue with increased perfusion. In conclusion, this study suggests that [(18)F]altanserin PET is not sensitive to acute neurotransmitter fluctuations under ketamine. Advantageously, the stability of [(18)F]altanserin PET towards acute influences is a prerequisite for its future use to detect sub-acute and chronic effects of ketamine.