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Mitochondrial complex I appears to be dysfunctional in progressive supranuclear palsy (PSP). Coenzyme Q(10) (CoQ(10)) is a physiological cofactor of complex I. Therefore, we evaluated the short-term effects of CoQ(10) in PSP. We performed a double-blind, randomized, placebo-controlled, phase II trial, including 21 clinically probable PSP patients (stage < or = III) to receive a liquid nanodispersion of CoQ(10) (5 mg/kg/day) or matching placebo. Over a 6-week period, we determined the change in CoQ(10) serum concentration, cerebral energy metabolites (by (31)P- and (1)H-magnetic resonance spectroscopy), motor and neuropsychological dysfunction (PSP rating scale, UPDRS III, Hoehn and Yahr stage, Frontal Assessment Battery, Mini Mental Status Examination, Montgomery Asberg Depression Scale). CoQ(10) was safe and well tolerated. In patients receiving CoQ(10) compared to placebo, the concentration of low-energy phosphates (adenosine-diphosphate, unphosphorylated creatine) decreased. Consequently, the ratio of high-energy phosphates to low-energy phosphates (adenosine-triphosphate to adenosine-diphosphate, phospho-creatine to unphosphorylated creatine) increased. These changes were significant in the occipital lobe and showed a consistent trend in the basal ganglia. Clinically, the PSP rating scale and the Frontal Assessment Battery improved slightly, but significantly, upon CoQ(10) treatment compared to placebo. Since CoQ(10) appears to improve cerebral energy metabolism in PSP, long-term treatment might have a disease-modifying, neuroprotective effect. [ABSTRACT FROM AUTHOR]

The article cites a study that aims to evaluate the short-term effects of different fiber sources on the stool characteristics, gastrointestinal transit time and nutrient digestibility in normal dogs. Five healthy adult female beagle dogs used in the study were fed each of five diets in a randomized block design, once daily at a rate that maintained a constant body weight. After the animals were acclimitized to each diet for 11 days, the total amount of feces passed during a 3-day period was collected and determined. One of the findings showed that dry matter digestibility was not different among the high fiber diets but was lower than when fed the starch diet.

Non-invasive methods, such as neurofeedback training, could support cognitive symptom management in Huntington's disease by targeting brain regions whose function is impaired. The aim of our single-blind, sham-controlled study was to collect rigorous evidence regarding the feasibility of neurofeedback training in Huntington's disease by examining two different methods, activity and connectivity real-time functional MRI neurofeedback training. Thirty-two Huntington's disease gene-carriers completed 16 runs of neurofeedback training, using an optimized real-time functional MRI protocol. Participants were randomized into four groups, two treatment groups, one receiving neurofeedback derived from the activity of the supplementary motor area, and another receiving neurofeedback based on the correlation of supplementary motor area and left striatum activity (connectivity neurofeedback training), and two sham control groups, matched to each of the treatment groups. We examined differences between the groups during neurofeedback training sessions and after training at follow-up sessions. Transfer of training was measured by measuring the participants' ability to upregulate neurofeedback training target levels without feedback (near transfer), as well as by examining change in objective, a priori defined, behavioural measures of cognitive and psychomotor function (far transfer) before and at 2 months after training. We found that the treatment group had significantly higher neurofeedback training target levels during the training sessions compared to the control group. However, we did not find robust evidence of better transfer in the treatment group compared to controls, or a difference between the two neurofeedback training methods. We also did not find evidence in support of a relationship between change in cognitive and psychomotor function and learning success. We conclude that although there is evidence that neurofeedback training can be used to guide participants to regulate the activity and connectivity of specific regions in the brain, evidence regarding transfer of learning and clinical benefit was not robust., (© The Author(s) (2020). Published by Oxford University Press on behalf of the Guarantors of Brain.)

Human behavior is surprisingly variable, even when facing the same problem under identical circumstances. A prominent example is risky decision making. Economic theories struggle to explain why humans are so inconsistent. Resting-state studies suggest that ongoing endogenous fluctuations in brain activity can influence low-level perceptual and motor processes, but it remains unknown whether endogenous fluctuations also influence high-level cognitive processes including decision making. Here, using real-time functional magnetic resonance imaging, we tested whether risky decision making is influenced by endogenous fluctuations in blood oxygenation level-dependent (BOLD) activity in the dopaminergic midbrain, encompassing ventral tegmental area and substantia nigra. We show that low prestimulus brain activity leads to increased risky choice in humans. Using computational modeling, we show that increased risk taking is explained by enhanced phasic responses to offers in a decision network. Our findings demonstrate that endogenous brain activity provides a physiological basis for variability in complex human behavior., Competing Interests: The authors declare no conflict of interest., (Copyright © 2019 the Author(s). Published by PNAS.)

We evaluated whether task-related fMRI (functional magnetic resonance imaging) BOLD (blood oxygenation level dependent) activation could be acquired under conventional anaesthesia at a depth enabling neurosurgery in five patients with supratentorial gliomas. Within a 1.5 T MRI operating room immediately prior to neurosurgery, a passive finger flexion sensorimotor paradigm was performed on each hand with the patients awake, and then immediately after the induction and maintenance of combined sevoflurane and propofol general anaesthesia. The depth of surgical anaesthesia was measured and confirmed with an EEG-derived technique, the Bispectral Index (BIS). The magnitude of the task-related BOLD response and BOLD sensitivity under anaesthesia were determined. The fMRI data were assessed by three fMRI expert observers who rated each activation map for somatotopy and usefulness for radiological neurosurgical guidance. The mean magnitudes of the task-related BOLD response under a BIS measured depth of surgical general anaesthesia were 25% (tumour affected hemisphere) and 22% (tumour free hemisphere) of the respective awake values. BOLD sensitivity under anaesthesia ranged from 7% to 83% compared to the awake state. Despite these reductions, somatotopic BOLD activation was observed in the sensorimotor cortex in all ten data acquisitions surpassing statistical thresholds of at least p < 0.001 uncorr . All ten fMRI activation datasets were scored to be useful for radiological neurosurgical guidance. Passive task-related sensorimotor fMRI acquired in neurosurgical patients under multi-pharmacological general anaesthesia is reproducible and yields clinically useful activation maps. These results demonstrate the feasibility of the technique and its potential value if applied intra-operatively. Additionally these methods may enable fMRI investigations in patients unable to perform or lie still for awake paradigms, such as young children, claustrophobic patients and those with movement disorders., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Quantitative MRI with T2, T2*, and T2' mapping has been shown to non-invasively depict microstructural changes (T2) and oxygenation status (T2* and T2') that are invisible on conventional MRI. Therefore, we aimed to assess whether T2 and T2' quantification detects cerebral (micro-)structural damage and chronic hypoxia in lesions and in normal appearing white matter (WM) and gray matter (GM) of patients with ischemic leukoaraiosis (IL). Measurements were complemented by the assessment of the cerebral blood flow (CBF) and the degree of GM and WM atrophy., Methods: Eighteen patients with IL and 18 age-matched healthy controls were included. High-resolution, motion-corrected T2, T2*, and T2' mapping, CBF mapping (pulsed arterial spin labeling, PASL), and segmentation of GM and WM were used to depict specific changes in both groups. All parameters were compared between patients and healthy controls, using t testing. Values of p < 0.05 were accepted as statistically significant., Results: Patients showed significantly increased T2 in lesions (p < 0.01) and in unaffected WM (p = 0.045) as well as significantly increased T2* in lesions (p = 0.003). A significant decrease of T2' was detected in patients in unaffected WM (p = 0.027), while no T2' changes were observed in GM (p = 0.13). Both unaffected WM and GM were significantly decreased in volume in the patient-group (p < 0.01). No differences of PASL-based CBF could be shown., Conclusion: Non-invasive quantitative MRI with T2, T2*, and T2' mapping might be used to detect subtle structural and metabolic changes in IL. Assessing the grade of microstructural damage and hypoxia might be helpful to monitor disease progression and to perform risk assessment.

Functional MRI (fMRI) used for neurosurgical planning delineates functionally eloquent brain areas by time-series analysis of task-induced BOLD signal changes. Commonly used frequentist statistics protect against false positive results based on a p-value threshold. In surgical planning, false negative results are equally if not more harmful, potentially masking true brain activity leading to erroneous resection of eloquent regions. Bayesian statistics provides an alternative framework, categorizing areas as activated, deactivated, non-activated or with low statistical confidence. This approach has not yet found wide clinical application partly due to the lack of a method to objectively define an effect size threshold. We implemented a Bayesian analysis framework for neurosurgical planning fMRI. It entails an automated effect-size threshold selection method for posterior probability maps accounting for inter-individual BOLD response differences, which was calibrated based on the frequentist results maps thresholded by two clinical experts. We compared Bayesian and frequentist analysis of passive-motor fMRI data from 10 healthy volunteers measured on a pre-operative 3T and an intra-operative 1.5T MRI scanner. As a clinical case study, we tested passive motor task activation in a brain tumor patient at 3T under clinical conditions. With our novel effect size threshold method, the Bayesian analysis revealed regions of all four categories in the 3T data. Activated region foci and extent were consistent with the frequentist analysis results. In the lower signal-to-noise ratio 1.5T intra-operative scanner data, Bayesian analysis provided improved brain-activation detection sensitivity compared with the frequentist analysis, albeit the spatial extents of the activations were smaller than at 3T. Bayesian analysis of fMRI data using operator-independent effect size threshold selection may improve the sensitivity and certainty of information available to guide neurosurgery.

Background and Purpose: Cerebral perfusion and O(2) metabolism are affected by physiologic age-related changes. High-resolution motion-corrected quantitative T2'-imaging and PASL were used to evaluate differences in deoxygenated hemoglobin and CBF of the gray matter between young and elderly healthy subjects. Further combined T2'-imaging and PASL were investigated breathing room air and 100% O(2) to evaluate age-related changes in cerebral autoregulation., Materials and Methods: Twenty-two healthy volunteers 60-88 years of age were studied. Two scans of high-resolution motion-corrected T2'-imaging and PASL-MR imaging were obtained while subjects were either breathing room air or breathing 100% O(2). Manual and automated regions of interest were placed in the cerebral GM to extract values from the corresponding maps. Results were compared with those of a group of young healthy subjects previously scanned with the identical protocol as that used in the present study., Results: There was a significant decrease of cortical CBF (P < .001) and cortical T2' values (P < .001) between young and elderly healthy subjects. In both groups, T2' remained unchanged under hyperoxia compared with normoxia. Only in the younger but not in the elderly group could a significant (P = .02) hyperoxic-induced decrease of the CBF be shown., Conclusions: T2'-mapping and PASL in the cerebral cortex of healthy subjects revealed a significant decrease of deoxygenated hemoglobin and of CBF with age. The constant deoxyHb level breathing 100% O(2) compared with normoxia in young and elderly GM suggests an age-appropriate cerebral autoregulation. At the younger age, hyperoxic-induced CBF decrease may protect the brain from hyperoxemia.

Purpose: To use T2'-mapping together with Pulsed Arterial Spin Labeling (PASL) providing quantitative information of deoxygenation level and cerebral blood flow (CBF) in the cerebral gray matter to obtain simultaneous information about the cerebral oxygen metabolism and the resulting cerebral vasoreactivity under normoxic and hyperoxic conditions., Materials and Methods: Twelve young, healthy volunteers underwent MRI under normoxic and hyperoxic conditions performing PASL and high-resolution, motion-corrected T2* and T2-mapping to calculate T2'values. Regions of interest (ROI) were placed in the frontoparietal cortex and thalamus by manual and automatic segmentation. For each ROI, mean normoxic T2'- and CBF values were extracted and compared with the same parameters assessed under hyperoxic ventilation., Results: A hyperoxic-induced decrease of the CBF could be shown in the frontoparietal cortex (P = 0.009). The T2 values of frontoparietal cortex decreased under hyperoxic inhalation compared with normoxia (P = 0.01), whereas T2' remained unchanged., Conclusion: Motion-corrected high-resolution T2'-maps can be used together with PASL to evaluate the DeoxyHb content in relation to CBF in the cerebral gray matter. We could show that cortical CBF decreases under hyperoxic inhalation in healthy young subjects, whereas the T2' values remained constant. These data suggest that hyperoxic-induced vasoconstriction may protect the brain against hyperoxemia., (Copyright © 2012 Wiley Periodicals, Inc.)

In this study, we investigate whether aberrant integrity of white matter (WM) fiber tracts represents a genetically determined biological marker of schizophrenia (SZ), and its relation with clinical symptoms. We collected brain DTI data from 28 SZ patients, 18 first-degree relatives and 22 matched controls and used voxel-based analysis with tract-based spatial statistics (TBSS) in order to compare fractional anisotropy (FA) between groups. Mean voxel-based FA values from the entire skeleton of each group were compared. We did a multiple regression analysis, followed by single post-hoc contrasts between groups. FA values were extracted from the statistically significant areas. The results showed significantly smaller FA values for SZ patients in comparison with controls in cortico-spinal tracts, in commissural fibers, in thalamic projections, in association fibers and in cingulum bundles. A significant increase of FA in SZ patients in comparison with healthy controls was only found in the arcuate fasciculus. Relatives had intermediate values between patients and controls which were deemed significant in the comparison to patients and controls in association fibers, arcuate fasciculus and cingulum bundles. Lower FA values in association fibers were significantly associated with predisposition toward hallucinations (in SZ patients and relatives), with higher PANSS scores of positive symptoms and with duration of illness (SZ patients). Our results suggest that clinical and subclinical presentations of psychotic symptoms are associated with aberrant integrity of multiple WM tracts. This association may represent an endophenotype of schizophrenia, since it is present in unaffected relatives as well. Such endophenotypes may serve as quantitative traits for future genetic studies and as candidate markers for early and preclinical identification of subjects at risk., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Major depression disorder (MDD) is one of the most common causes of disability in people over 60years of age. Previous studies have linked affective and cognitive symptoms of MDD to white matter (WM) disruption in limbic-cortical circuits. However, the relationship between clinical cognitive deficits and loss of integrity in particular WM tracts is poorly understood. Fractional anisotropy (FA) as a measure of WM integrity was investigated in 17 elderly MDD subjects in comparison with 18 age-matched controls using tract-based spatial statistics (TBSS) and correlated with clinical and cognitive parameters. MDD patients revealed significantly reduced FA in the right posterior cingulate cluster (PCC) compared with controls. FA in the right PCC (but not in the left PCC) showed a significant positive correlation with performance in a verbal naming task, and showed a non-significant trend toward a correlation with verbal fluency and episodic memory performance. In control subjects, no correlations were found between cognitive tasks and FA values either in the right or left PCC. Results provide additional evidence supporting the neuronal disconnection hypothesis in MDD and suggest that cognitive deficits are related to the loss of integrity in WM tracts associated with the disorder., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Introduction: There are hints for changes in phospholipid membrane metabolism and structure in the brain of adolescents with anorexia nervosa (AN) using either proton ((1)H) or phosphorus ((31)P) magnetic resonance spectroscopic imaging (MRSI). We aimed to specify these pathological metabolite changes by combining both methods with additional focus on the neuronal metabolites glutamate (Glu) and N-acetyl-l-aspartate (NAA)., Methods: Twenty-one female patients (mean 14.4  ±  1.9 years) and 29 female controls (mean 16  ±  1.6 years) underwent (1)H and (31)P MRSI at 3 T applied to the centrum semiovale including the anterior cingulate cortex. We assessed gray matter (GM) and white matter (WM) metabolite concentration changes of the frontal and parietal brain measuring choline(Cho)- and ethanolamine(Eth)-containing compounds, Glutamate (Glu) and glutamine (Gln) and their sum (Glx), myoinositol, NAA, and high-energy phosphates., Results: For (1)H MRSI, a clear discrimination between GM and WM concentrations was possible, showing an increase of Glx (p < 0.001), NAA (frontal p < 0.05), pooled creatine (tCr) (p < 0.001), and choline (tCho) (p < 0.05) in the GM of AN patients. The lipid catabolites glycerophosphocholine (p < 0.07) and glycerophosphoethanolamine (p < 0.03) were increased in the parietal region., Conclusions: Significant changes in GM metabolite concentrations were observed in AN possibly triggered by elevated excitotoxin Glu. Increased tCho may indicate modifications of membrane phospholipids due to increased catabolism in the parietal region. Since no significant changes in phosphorylated choline compounds were found for the frontal region, the tCho increase in this region may hint to fluidity changes.

Background and Purpose: Quantitative T2' imaging presumably detects regional changes in the relation of oxygenated and deoxygenated hemoglobin. Regional differences in hemoglobin oxygenation might reflect areas with increased oxygen extraction for compensation of reduced perfusion pressure. We investigated quantitative T2' imaging in patients with high-grade stenoses of brain-supplying arteries and hypothesized that T2' values are lower in perfusion-restricted areas as compared with normally perfused tissue., Methods: Eighteen patients (15 men; mean age±SD, 54±12.8 years) with unilateral symptomatic or asymptomatic high-grade extracranial or intracranial internal carotid artery or proximal middle cerebral artery stenosis/occlusion were included. MR examination included perfusion-weighted imaging and quantitative, motion-corrected mapping of T2' time. Time-to-peak and mean transit time maps were thresholded for different degrees of perfusion delays (eg, >0 seconds, ≥2 seconds) compared with the contralateral hemisphere. Mean T2' values in areas of impaired perfusion were compared with T2' values in corresponding contralateral or ipsilateral, normoperfused areas., Results: Mean size of perfusion-impaired areas in time-to-peak maps (time-to-peak delay>0 seconds) was 10.8 mL (±6.3) and 11.5 mL (±6.4) in mean transit time maps (mean transit time delay>0 seconds). T2' values were significantly (P<0.01) lower in all perfusion-restricted compared with corresponding contralateral brain areas (ipsilateral versus contralateral). For time-to-peak delay >0 seconds, T2' values were 115 ms (±9) versus 125 ms (±12). For mean transit time delay>0 seconds, T2' values were 115 ms (±9) versus 128 ms (±10). Differences in T2' values increased with the severity of the perfusion delay. Ipsilateral T2' values outside the perfusion-disturbed areas did not differ from contralateral T2' values., Conclusions: Motion-corrected T2' imaging presumably detects areas with increased oxygen extraction within perfusion-restricted tissue in patients with high-grade occlusive vessel disease.

Episodic memory dysfunction, commonly assessed with word list recall, is the main characteristic of amnestic Mild Cognitive Impairment (aMCI). While brain pathology underlying this kind of memory impairment is well established in aMCI, little is known about the effect of neurodegeneration on autobiographical memory. The present study investigated neuronal correlates of autobiographical memory in aMCI patients (n=12) and healthy elderly controls (n=13) using functional magnetic resonance imaging (fMRI). Additionally, voxel-based morphometry (VBM) was employed to reveal brain pathology in aMCI patients. Neuropsychological assessment showed significant impairment in episodic memory tasks (immediate and delayed word list recall) in aMCI patients. Moreover, VBM revealed significantly reduced gray matter concentration, which was most pronounced in the temporal lobes of aMCI patients. Despite episodic memory impairment and atrophy in areas that are associated with encoding and recall of episodic memories, aMCI patients showed no alterations in brain activation associated with autobiographical memory retrieval. These findings could suggest that autobiographical memory is subserved by a different neuronal network than episodic memory and that the two memory systems are differently affected by aMCI., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Objective: Our goal was to detect possible unrecognized injury in cerebral white matter (WM) in adult survivors of traumatic brain injury (TBI) during childhood, who showed no detectable axonal injury or chronic contusion on late conventional MRI., Material and Methods: We used voxel-based morphometry (VBM) to detect subtle structural changes in brain morphology and diffusion-tensor imaging (DTI) to non-invasively probe WM integrity. By means of VBM and DTI we examined a group of 12 adult patients who suffered from childhood closed head injury without axonal injury on late conventional MRI., Results: Patients sustained complicated mild or moderate-to-severe TBI with a mean of 7 points based on the Glasgow Coma Scale. The mean time after trauma was 19 years (range 7-31 years). For VBM, group comparisons of segmented T1-weighted grey matter and WM images were performed, while for DTI we compared the fractional anisotropy and mean diffusivity (MD) between the groups. Patients presented with higher MD in the right cerebral white matter, bilaterally in the forceps major and in the body and splenium of the corpus callosum. These findings were supported by VBM, which showed reduced WM volume bilaterally, mainly along the callosal splenium., Conclusion: Our results indicate that persistent focal long-term volume reduction and underlying WM structural changes may occur after TBI during childhood and that their effects extend into adulthood. Normal late conventional MR findings after childhood TBI do not rule out non-apparent axonal injury., (Copyright © 2011 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.)

Numerous clinical and research applications for quantitative mapping of the effective transverse relaxation time T*(2) have been described. Subject motion can severely deteriorate the quality and accuracy of results. A correction method for T*(2) maps acquired with multi-slice multiple gradient echo FLASH imaging is presented, based on acquisition repetition with reduced spatial resolution (and consequently reduced acquisition time) and weighted averaging of both data sets, choosing weighting factors individually for each k-space line to reduce the influence of motion. In detail, the procedure is based on the fact that motion artifacts reduce the correlation between acquired and exponentially fitted data. A target data set is constructed in image space, choosing the data yielding best correlation from the two acquired data sets. The k-space representation of the target is subsequently approximated as linear combination of original raw data, yielding the required weighting factors. As this method only requires a single acquisition repetition with reduced spatial resolution, it can be employed on any clinical system offering a suitable sequence with export of modulus and phase images. Experimental results show that the method works well for sparse motion, but fails for strong motion affecting the same k-space lines in both acquisitions., (Copyright © 2011 Wiley-Liss, Inc.)

(1)H MRSI has evolved as an important tool to study the onset and progression of brain damage in multiple sclerosis. Abnormal increases in total creatine, total choline and myoinositol have been noted in multiple sclerosis. However, the pathobiochemical mechanisms related to these changes are still largely unclear. The combination of (1)H MRSI and (1)H-decoupled (31)P MRSI can specify to what extent phosphorylated components of total creatine and total choline contribute to this increase. Combined (1)H and (31)P MRSI data were obtained at 3 T in 22 patients with multiple sclerosis and in 23 healthy controls, and aligned with structural MRI to allow for correction for partial volume effects caused by cerebrospinal fluid and lesion load. A significant increase in total creatine was found in multiple sclerosis, and this was attributed to equal changes in the phosphorylated and unphosphorylated components. The concentrations of the putative glial markers total creatine and myoinositol in lesion-free (1)H MRSI voxels correlated with the global lesion load. We conclude that changes in total creatine are not related to altered energy metabolism, but rather indicate gliosis. Together with the increase in myoinositol, total creatine can be considered as a biomarker for disease severity. A significant total choline increase was mainly a result of choline components not visible by (31)P MRS. The origin of this residual choline fraction remains to be investigated., (Copyright © 2010 John Wiley & Sons, Ltd.)

Mitochondrial dysfunction hypothetically contributes to neuronal degeneration in patients with Parkinson's disease. While several in vitro data exist, the measurement of cerebral mitochondrial dysfunction in living patients with Parkinson's disease is challenging. Anatomical magnetic resonance imaging combined with phosphorus and proton magnetic resonance spectroscopic imaging provides information about the functional integrity of mitochondria in specific brain areas. We measured partial volume corrected concentrations of low-energy metabolites and high-energy phosphates with sufficient resolution to focus on pathology related target areas in Parkinson's disease. Combined phosphorus and proton magnetic resonance spectroscopic imaging in the mesostriatal region was performed in 16 early and 13 advanced patients with Parkinson's disease and compared to 19 age-matched controls at 3 Tesla. In the putamen and midbrain of both Parkinson's disease groups, we found a bilateral reduction of high-energy phosphates such as adenosine triphophosphate and phosphocreatine as final acceptors of energy from mitochondrial oxidative phosphorylation. In contrast, low-energy metabolites such as adenosine diphophosphate and inorganic phosphate were within normal ranges. These results provide strong in vivo evidence that mitochondrial dysfunction of mesostriatal neurons is a central and persistent phenomenon in the pathogenesis cascade of Parkinson's disease which occurs early in the course of the disease.

Indirect evidence from laboratory studies suggests that mitochondrial energy metabolism is impaired in progressive supranuclear palsy (PSP), but brain energy metabolism has not yet been studied directly in vivo in a comprehensive manner in patients. We have used combined phosphorus and proton magnetic resonance spectroscopy to measure adenosine-triphosphate (ATP), adenosine-diphosphate (ADP), phosphorylated creatine, unphosphorylated creatine, inorganic phosphate and lactate in the basal ganglia and the frontal and occipital lobes of clinically probable patients (N=21; PSP stages II to III) and healthy controls (N=9). In the basal ganglia, which are severely affected creatine in PSP patients, the concentrations of high-energy phosphates (=ATP+phosphorylated creatine) and inorganic phosphate, but not low-energy phosphates (=ADP+unphosphorylated creatine), were decreased. The decrease probably does not reflect neuronal death, as the neuronal marker N-acetylaspartate was not yet significantly reduced in the early-stage patients examined. The frontal lobe, also prone to neurodegeneration in PSP, showed similar alterations, whereas the occipital lobe, typically unaffected, showed less pronounced alterations. The levels of lactate, a product of anaerobic glycolysis, were elevated in 35% of the patients. The observed changes in the levels of cerebral energy metabolites in PSP are consistent with a functionally relevant impairment of oxidative phosphorylation.

Captopril, furosemide, and a sodium-restricted diet were administered to 6 normal dogs and 10 dogs with congestive heart failure. Serum electrolyte concentrations and renal function were monitored in both groups. In the normal dogs, no clinically meaningful changes in serum electrolyte, urea nitrogen, or creatinine concentrations developed during therapy with a sodium-restricted diet and 4 weeks each of furosemide alone, captopril alone, or furosemide plus captopril. Three of 6 normal dogs on furosemide and a sodium-restricted diet had at least one serum potassium concentration above the reference range during the 4 weeks of observation. One normal dog on captopril, furosemide, and a sodium-restricted diet developed azotemia, and 2 dogs had serum potassium concentrations above the reference range during the 4 weeks of observation. Ten dogs with congestive heart failure were treated with captopril, furosemide, a sodium-restricted diet, and digoxin. Etiopathogenesis of the heart failure included valvular insufficiency (n = 6), dilated cardiomyopathy (n = 3), and dilated cardiomyopathy and dirofilariasis (n = 1). Serum electrolyte concentrations and renal function were monitored for 5 consecutive weeks in 7 of the 10 dogs and for 17 weeks or longer in 6. Two dogs were euthanized after 4 weeks because of acute decompensation of heart failure, and one dog developed severe azotemia and uremia. Six of 10 dogs with congestive heart failure had at least one serum potassium concentration above the reference range sometime during the 5 weeks of observation, although the changes in the mean serum potassium concentrations were not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)