High-frequency oscillations (>200 Hz) in the human non-parkinsonian subthalamic nucleus.

The human basal ganglia, and in particular the subthalamic nucleus (STN), can oscillate at surprisingly high frequencies, around 300 Hz [G. Foffani, A. Priori, M. Egidi, P. Rampini, F. Tamma, E. Caputo, K.A. Moxon, S. Cerutti, S. Barbieri, 300-Hz subthalamic oscillations in Parkinson's disease, Brain 126 (2003) 2153-2163]. It has been proposed that these oscillations could contribute to the mechanisms of action of deep brain stimulation (DBS) [G. Foffani, A. Priori, Deep brain stimulation in Parkinson's disease can mimic the 300 Hz subthalamic rhythm, Brain 129 (2006) E59]. However, the physiological role of high-frequency STN oscillations is questionable, because they have been observed only in patients with advanced Parkinson's disease and could therefore be secondary to the dopamine-depleted parkinsonian state. Here, we report high-frequency STN oscillations in the range of the 300-Hz rhythm during intraoperative microrecordings for DBS in an awake patient with focal dystonia as well as in a patient with essential tremor (ET). High-frequency STN oscillations are therefore not exclusively related to parkinsonian pathophysiology, but may represent a broader feature of human STN function.

[Influence of Ankle Braces on the Prevalence of Ankle Inversion Injuries in the Swiss Volleyball National League A]. / Einfluss von Sprunggelenksorthesen auf die Prävalenz von Supinationstraumen im Volleyball in der Schweizer Nationalliga A.

BACKGROUND: Ankle inversion is a common injury among volleyball players. The injury rate during a game is 2.1 times higher than during training. As a result, the preventive use of ankle braces is frequently observed in Swiss volleyball leagues. Studies have shown that ankle braces have a preventive effect on the prevalence of ankle inversion. In Switzerland there has been no investigation into the preventive use of braces and their influence on prevalence. For this reason, the goals of this study are 1) to determine when, why and by whom ankle braces are worn and 2) to evaluate the injury rate of users and non-users of ankle braces. SUBJECTS AND METHODS: A modified questionnaire was sent to 18 men's and women's teams of the Swiss National League A. The questionnaire included questions about injury rates and the circumstances of ankle inversion injuries. The data were statistically analysed with Microsoft Excel 2012 and SPSS Version 20. RESULTS: The overall response rate was 61 %, allowing data from 181 players to be analysed. 33 % (59 of 181) of the players used an ankle brace. There was a statistically significant difference in the prevalence of ankle inversion between users (12 injured) and non-users (8 injured) (p = 0.006). Wearing an ankle brace during training or during a game made no difference in the prevention of injuries (p = 0.356). More athletes were injured during training (n = 13) than during a game (n = 7). CONCLUSION: The results of the present study indicate that volleyball players preferably wear ankle braces to prevent injury. More than one third of the players in the study wore an ankle brace, 60 % for primary prevention and 40 % for secondary prevention due to a previous injury. The study shows that significantly more users than non-users of ankle braces were injured. This is contrary to literature. Furthermore it was shown that more injuries occur during training than during a game. This finding results from the fact that ankle braces were rarely worn during training. It is concluded that ankle braces must be worn consistently, especially during training.

Cerebral blood flow in schizophrenia: effects of memory processing on regional activation.

Regional cerebral blood flow (rCBF) was measured with the 133Xenon clearance technique and a high resolution (254 detectors) scanner during the performance of a verbal and a facial memory task in 18 patients with schizophrenia and 18 sociodemographically matched controls. Patients and controls had comparable resting rCBF, but differed in global and hemispheric rCBF changes induced by the memory tasks. Patients had less global increase, which was relatively higher in the left hemisphere, and this was more pronounced for the verbal task. Although controls showed appropriate laterality changes (L > R for verbal and R > L for facial memory) in the midtemporal region, patients failed to show such a focal pattern. They did not show appropriate laterality change in the midtemporal region, but instead showed such changes in other regions. Patients showed greatest impairment in specificity of verbal recognition performance, and this correlated with severity of hallucinations and delusions. This supports a model of left temporal lobe dysfunction in schizophrenia.

Effect of non-steady-state perfusion on xenon-133 cerebral blood flow measurements: an analytical study.

Activation studies employing the noninvasive xenon-133 technique are widely used to investigate the cerebral circulation. Typical examples are the investigation of hemispheral specialization of higher cortical function with cognitive activation or the assessment of the hemodynamic reserve in occlusive cerebrovascular disease by CO2 inhalation. Traditionally, in studies using this technique, there is the requirement of a circulatory steady state during the measurement. Due to limitations in the duration of the stimulus or habituation to the stimulus, the basic assumption is often violated. In this study we investigated with the aid of a computer model to what extent blood flow measurement results are affected by non-steady-state blood flow. The findings indicate that cortical activation need not extend throughout the whole measurement to be detectable. Maintenance of activation for at least 5 min is sufficient for a successful measurement. In addition, the results show that the activation should be fully established when the measurement starts to achieve maximal sensitivity. Delay in activating the circulation will result in attenuated responses, especially if the stimulus is delayed beyond 2 min.

The effect of hematocrit and systolic blood pressure on cerebral blood flow in newborn infants.

The effects of hematocrit and systolic blood pressure on cerebral blood flow were measured in 15 stable, low birth weight babies. CBF was measured with a modification of the xenon-133 (133Xe) clearance technique, which uses an intravenous bolus of 133Xe, an external chest detector to estimate arterial 133Xe concentration, eight external cranial detectors to measure cephalic 133Xe clearance curves, and a two-compartmental analysis of the cephalic 133Xe clearance curves to estimate CBF. There was a significant inverse correlation between hematocrit and CBF, presumably due to alterations in arterial oxygen content and blood viscosity. Newborn CBF varied independently of systolic blood pressure between 60 and 84 mm Hg, suggesting an intact cerebrovascular autoregulatory mechanism. These results indicate that at least two of the factors that affect newborn animal CBF are operational in human newborns and may have important clinical implications.

Noninvasive method of estimating human newborn regional cerebral blood flow.

A noninvasive method of estimating regional cerebral blood flow (rCBF) in premature and full-term babies has been developed. Based on a modification of the xenon-133 inhalation rCBF technique, this method uses eight extracranial NaI scintillation detectors and an i.v. bolus injection of xenon-133 (approximately 0.5 mCi/kg). Arterial xenon concentration was estimated with an external chest detector. Cerebral blood flow was measured in 15 healthy, neurologically normal premature infants. Using Obrist's method of two-compartment analysis, normal values were calculated for flow in both compartments, relative weight and fractional flow in the first compartment (gray matter), initial slope of gray matter blood flow, mean cerebral blood flow, and initial slope index of mean cerebral blood flow. The application of this technique to newborns, its relative advantages, and its potential uses are discussed.

Estimation of component and parameter distributions in spectral analysis.

A method is presented for estimating the distributions of the components and parameters determined with spectral analysis when it is applied to a single data set. The method uses bootstrap resampling to simulate the effect of noise on the computed spectrum and to correct for possible bias in the estimates. A number of bootstrap procedures are reviewed, and one is selected for application to the kinetic analysis of positron emission tomography dynamic studies. The technique is shown to require minimal assumptions about noise in the measurements, and its small sample properties are established through Monte-Carlo simulations. The advantages and limitations of spectral analysis with bootstrap resampling for deriving inferences for tracer kinetic modeling are illustrated through sample analyses of time-activity curves for [18F]fluorodeoxyglucose and [15O]-labeled water.

Cerebral blood flow in systemic lupus erythematosus with or without cerebral complications.

We measured mean cerebral blood flow (CBF) in 25 lupus patients using the xenon-133 method. The CBF was normal in lupus patients without cerebral disease and also in CNS lupus patients in remission. The CBF was lower than normal during bouts of cerebral lupus (p less than 0.001). Repeat studies showed a stereotyped pattern consisting of depressed CBF during exacerbation of CNS disease and normalization of CBF during remission (p less than 0.01). These results show that CBF is a sensitive indicator of activity of CNS disease and that the direction of change in CBF reflects the clinical course of CNS lupus.

Predictors of outcome after anterior temporal lobectomy: positron emission tomography.

We assessed the relationship between temporal lobe metabolism measured quantitatively and qualitatively with PET using [18F]-fluorodeoxyglucose (FDG) and postoperative seizure frequency after anterior temporal lobectomy. Forty-three patients with refractory partial epilepsy had anterior temporal lobectomy and preoperative assessment with PET-FDG. Qualitative PET analysis was performed visually by two blinded observers, and quantitative PET analysis was performed using an anatomic template for six control and six temporal lobe subregions, deriving an asymmetry index for each region. Seizure outcome was assessed 1 year after surgery; patients were classified as being seizure-free or as having persistent seizures. Qualitative data were analyzed using Fisher's exact test and the t test, and quantitative data were analyzed using a repeated-measures ANOVA. Thirty-two patients (74%) were seizure-free at follow-up, and 11 had persistent seizures, although most improved. Twenty-nine of 35 patients (83%) with restricted temporal lobe hypometabolism by visual analysis were seizure-free, compared with three of eight patients (37.5%) with normal scans or multilobar hypometabolism. Quantitative analysis revealed that an asymmetry of mesial temporal lobe glucose consumption (uncal region) correlated with improved surgical outcome (p < 0.02). We developed a logistic regression model to predict individual outcome based on the asymmetry in uncal metabolism. Lateral temporal metabolism did not correlate with outcome. We conclude that both visual PET analysis and quantitative PET analysis predict outcome after temporal lobectomy, although quantitative measures offer more precise information.

Inexpensive signal averager for evoked potentials based on a small personal computer: a technical note.

The authors report their development of a relatively inexpensive signal averager for evoked potentials based on an Apple home computer.

Effects of hydrocephalus and increased intracranial pressure on auditory and somatosensory evoked responses.

Recent studies in human and animal subjects have suggested a relationship between intracranial pressure (ICP) and ventricular dilatation and multimodality evoked responses which, if substantiated, would be of value to clinical practice as a noninvasive way of assessing the need for shunting in selected patients in whom computed tomography (CT) is not definitive. In an attempt to better define these changes, auditory evoked response (BAER) and somatosensory evoked response (SER) were performed on 16 cats as a base line, after which they were made hydrocephalic by the cisternal injection of kaolin. Nine cats survived, and CT or magnetic resonance scans were performed on them 4 to 6 weeks later. In those animals in which ventricular dilatation was noted, repeat evoked responses were recorded. In the 6 hydrocephalic cats, the ventricle was punctured to measure ICP, which in all cases was less then 5 mm Hg. The lumbar spinal dural sac was then ligated, which resulted in periodic plateau waves up to 75 to 100 mm Hg after 4 to 6 hours, lasting up to 10 minutes. In neither group of cats was any change in either BAER or SER observed until preterminally, when ICP was in the range of 75 to 100 mm HG and cerebral perfusion pressure was compromised. This suggests that the BAER and SER are not sensitive to either ventricular dilatation or intracranial hypertension.

Cerebral blood flow and metabolism in comatose patients with acute head injury. Relationship to intracranial hypertension.

Cerebral blood flow (CBF) measurements were made in 75 adult patients with closed head injuries (mean Glasgow Coma Scale score 6.2) using the xenon-133 intravenous injection method with eight detectors over each hemisphere. All patients were studied acutely within 96 hours of trauma, and repeatedly observed until death or recovery (total of 361 examinations). Arteriojugular venous oxygen differences (AVDO2) were obtained in 55 of the patients, which permitted assessment of the balance between metabolism and blood flow, and provided estimates of cerebral metabolic rate for oxygen (CMRO2). Based on mean regional CBF, the patients were classified into two groups: those who exhibited hyperemia on one or more examinations, and those who had a consistently reduced flow during their acute illness. "Hyperemia" was defined as a normal or supernormal CBF in the presence of coma, a definition that was independently confirmed by narrow AVDO2's indicative of "luxury perfusion". During coma, all patients showed a significant depression in CMRO2. Forty-one patients (55%) developed an acute hyperemia with an average duration of 3 days, while 34 patients (45%) consistently had subnormal flows. Although more prevalent in younger patients, hyperemia was found at all age levels (15 to 85 years). There was a highly significant association between hyperemia and the occurrence of intracranial hypertension, defined as an intracranial pressure above 20 mm Hg. Patients with reduced flow showed little or no evidence of global cerebral ischemia, but instead revealed the expected coupling of CBF and metabolism. The CBF responses to hyperventilation were generally preserved, with the hyperemic patients being slightly more reactive. In 10 patients with reduced flow, hyperventilation resulted in wide AVDO2's suggestive of ischemia.

The effects of deep barbiturate coma on multimodality evoked potentials.

The authors report their investigation of the effects of high-dose barbiturates on the multimodality evoked response in 9 cats. After baseline evoked responses were obtained, boluses of pentobarbital were infused intravenously at regular intervals, amounting to cumulative total doses of 9, 18, 27, 45, 63, 123, and 183 mg/kg at respective infusions. This resulted in gradually increasing serum pentobarbital levels, reaching therapeutic coma levels (4 to 5 mg/dl) after the fifth infusion. At this point, the electroencephalogram was flat, and pressor agents were required to maintain cardiovascular stability. Evoked responses were obtained 15 minutes after each infusion. Brain-stem auditory evoked response (BAER) showed little change in wave latencies at therapeutic coma levels of pentobarbital. Further barbiturates resulted in delay of the late components of this response. In the somatosensory evoked responses (SER), early brain-stem components were relatively unaffected by therapeutic coma levels. Late brain-stem components and the initial cortical response showed progressive latency increase. Late cortical (association cortex) waves were abolished at relatively low doses. The central conduction time was relatively unaffected. The late waves of the visual evoked responses (VER) were abolished with low-dose barbiturates (9 mg/kg). A single positive-negative complex persisted despite massive infusions. It is concluded that evoked responses may prove useful in monitoring patients in deep barbiturate coma, but barbiturate effects must be kept in mind.

Relationship of early cerebral blood flow and metabolism to outcome in acute head injury.

Cerebral blood flow (CBF) measurements were obtained acutely in 96 comatose patients with closed head injury, using the intravenous 133Xe technique. Arteriojugular venous oxygen differences and cerebral metabolic rate for oxygen (CMRO2) were determined in a subgroup of 66 patients. The relationship between each of these variables and outcome at 6 months was analyzed, using the Glasgow Outcome Scale. The CMRO2 was significantly depressed in patients who subsequently died or remained in a vegetative state, whereas higher values were obtained in patients who later regained consciousness. Although CBF was not predictive of outcome in the total sample, omission of patients with acute hyperemia resulted in a significant relationship that paralleled the metabolic findings. Follow-up studies in the survivors revealed a correlation between CBF and degree of functional recovery, the lowest blood flows being obtained among patients with severe disability. Age, initial Glasgow Coma Scale score, and occurrence of intracranial hypertension were each found to be predictive of outcome, thus confirming previous reports. When these variables were combined with CMRO2 in a logistic regression analysis, the probability of recovery was correctly predicted in 82% of the cases. The CMRO2 was relatively independent of the other prognostic indicators and, next to age, contributed most to the prediction.

Efficacy of unilateral deep brain stimulation of the thalamic ventralis intermedius nucleus in a patient with bipolar disorder associated with Klinefelter syndrome and essential tremor. Case report.

Deep brain stimulation (DBS) of the ventralis intermedius nucleus (Vim) is a safe and effective treatment for essential tremor. Bipolar disorder and essential tremor had each been reported to occur in association with Klinefelter syndrome but the three diseases have been reported to occur together in only one patient. The genetic basis and natural history of these disorders are not completely understood and may be related rather than coincidental. The authors report on a 23-year-old man with Klinefelter syndrome (47,XXY) and bipolar disorder who was treated successfully with unilateral DBS of the thalamic Vim for essential tremor.

Revision of deep brain stimulator for tremor. Technical note.

The treatment of essential tremor with thalamic deep brain stimulation (DBS) is considered to be more effective and to cause less morbidity than treatment with thalamotomy. Nonetheless, implantation of an indwelling electrode, connectors, and a generator is associated with specific types of morbidity. The authors describe three patients who required revision of their DBS systems due to lead breakage. The connector between the DBS electrode and the extension wire, which connects to the subclavicular pulse generator, was originally placed subcutaneously in the cervical region to decrease the risk of erosion through the scalp and to improve cosmesis. Three patients presented with fractured DBS electrodes that were located in the cervical region near the connector, necessitating reoperation with stereotactic retargeting and placement of a new intracranial electrode. At reoperation, the connectors were placed subgaleally over the parietal region. Management of these cases has led to modifications in the operative procedure designed to improve the durability of DBS systems. The authors recommend that surgeons avoid placing the connection between the DBS electrode and the extension wire in the cervical region because patient movement can cause microfractures in the electrode. Such microfractures require intracranial revision, which may be associated with a higher risk of morbidity than the initial operation. The authors also recommend considering prophylactic relocation of the connectors from the cervical area to the subgaleal parietal region to decrease the risk of future DBS electrode fracture, which would necessitate a more lengthy procedure to revise the intracranial electrode.

Computerized tomography, magnetic resonance imaging, and positron emission tomography in the study of brain trauma. Preliminary observations.

Results of computerized tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET), xenon-133 measurement of cerebral blood flow (CBF), and neuropsychological assessments are described in three head-injured patients. The patients were selected because they presented with intracranial hemorrhage diagnosed by CT. Two of the patients were studied acutely and again approximately 6 months later. In the acute stage, MRI was superior to CT in identifying the precise location and extent of intracranial hemorrhage and associated edema. Small subdural hematomas diagnosed on MRI were missed with CT scanning. The extent of apparent encephalomalacia in the chronic stages of injury was also better defined with MRI. Positron emission tomography showed disturbances of glucose metabolism that extended beyond the structural abnormalities demonstrated by MRI and CT; anterior temporal lobe dysfunction was particularly evident in all three patients. Regional CBF studies failed to detect a number of the abnormalities seen on MRI and CT, and even ignored the metabolic dysfunction evident on PET that should have been accompanied by changes in regional CBF. The neuropsychological studies localized frontal lesions, but did not reveal abnormalities attributable to the structural lesions and the reduced metabolism in the anterior temporal lobes.

A proposal for minimum detectable compartment in MIRD dosimetry modelling.

The accuracy of radiation dose estimates from radiopharmaceutical administrations has recently become more important for three main reasons: (i) clinical providers are demanding more information on diagnostic procedures; (ii) regulatory groups are scrutinizing dosimetry for research subjects; and (iii) accurate organ doses are crucial in therapeutic administrations. These dose estimates are a sensitive function of the residence times. Because most clinical data acquisition protocols are limited to the first 24 h after dose administration, the area under the remainder of the time-activity curve (TAC) must be estimated. Estimation methods range from assuming physical decay only (overly conservative) to extrapolating end point physiological kinetics (overly liberal). This study demonstrates how much the results from these two methods vary and develops an alternative method which more accurately estimates this remainder term. A method, called the minimum detectable compartment (MDC), is constructed so that an accurate dose estimate can be made with a realistic measure of the remainder term. The method for determining MDC uses standard hypothesis testing. Using an analogue of the traditional minimal detectable activity calculation, a model with and without constant compartments is fitted to the TAC. The size of the constant compartment is varied until the relative likelihood of the two models meets the desired measure of power and sensitivity. Computer simulations of a simple mono-exponential are used to demonstrate the MDC as a function of the model, the number of data points, the range of the data and the noise in the data. The MDC is a very sensitive function of the data range. It falls by more than 50% when the data range is increased from two to three half-lives. In addition, the MDC is moderately sensitive to the noise in the data and relatively insensitive to the number of data points. These findings suggest that the MDC method can also be uses a priori to indicate what type of data collection regimen is necessary to achieve a certain accuracy.

Differential effects of mood on cortical cerebral blood flow: a 133xenon clearance study.

Studies of healthy and clinical populations have suggested valence-specific cortical and subcortical neural systems regulating emotions. In a study of 12 normal volunteers, the 133xenon clearance method for measuring regional cerebral blood flow (CBF) was used to study the effects of experimentally controlled mood states on regional brain activity within superficial cortex. CBF was measured with 254 detectors and bolus infusion during a happy mood induction task, a sad mood induction task, a sex differentiation task, and a resting baseline condition. CBF increased during sad and decreased during happy mood induction, relative to the activated (sex differentiation) and the nonactivated (resting) nonemotional control conditions. Increased CBF during sad mood induction was correlated with greater negative mood changes. Conversely, increased CBF was associated with a stronger subjective experience of positive affect during happy mood induction. This suggests that cortical arousal may serve to intensify the conscious experience of emotion. Heart rate accelerated during happy and sad mood induction and during sex differentiation relative to a pretask baseline condition. Some regional specificity of effects was also observed. The occipital temporal region showed higher overall CBF during sad mood induction than during happy mood induction. The only region that showed specific lateralized changes in CBF which differentiated sad from happy states was the frontal pole, with left CBF being higher during sad and lower during happy mood induction relative to right CBF. For sad mood induction, there were significant regional differences among correlations between CBF and self-ratings. These were attributable to higher negative correlations (i.e., higher CBF correlates with negative self-rating) in midtemporal, occipital temporal, and postcentral regions. These correlations did not vary across the 15 regions for happy mood induction. For sad mood induction, heart rate correlated positively with CBF increase and with negative affect. Correlations were opposite for happy mood induction. The results suggest high cortical and autonomic arousal during negative/sad mood and low cortical and high autonomic arousal during positive/happy mood. They underscore the value of integrating emotional experience with physiologic measures in neuroimaging activation studies.

Cerebral blood flow in preterm infants affected by sex, mechanical ventilation, and intrauterine growth.

Sex differences in cerebral blood flow (CBF) values have been demonstrated in adults but not in newborns. This study evaluated the influence of sex, intrauterine growth, and need of mechanical ventilation on resting cerebral blood flow in preterm neonates. Sixty-eight preterm infants with gestational ages of less than 34 weeks and birth weights of less than 1,500 gm were enrolled into the study. Cerebral blood flow was measured by the noninvasive intravenous xenon 133 method 3 times. Measurements were classified into 3 groups: group 1: measurement at 2-36 hours (n = 46); group 2: measurement at 36-108 hours (n = 39); and group 3: measurement at 108-240 hours (n = 41). In all 3 groups, the CBF in girls was significantly lower than in boys (group 1: 11.5 +/- 2.8 ml/100 gm/min vs 14.0 +/- 4.1 ml/100 gm/min; group 2: 13.4 +/- 2.9 ml/100 gm/min vs 16.3 +/- 4.3 ml/100 gm/min; group 3: 12.9 +/- 3.2 ml/100 gm/min vs 15.3 +/- 3.1 ml/100 gm/min). In group 1, the CBF in neonates requiring mechanical ventilation was significantly lower (P < .05) than in patients who were spontaneously breathing (11.5 +/- 3.7 ml/100 gm/min vs 14.2 +/- 3.1 ml/100 gm/min), and the CBF in neonates who were too small for gestational age was significantly higher (P < .005) than in children with appropriate intrauterine growth (16.1 +/- 4.1 ml/100 gm/min vs 11.5 +/- 2.6 ml/100 gm/min). It is concluded that in preterm neonates CBF is substantially affected by sex, intrauterine growth retardation, and the need of mechanical ventilation.