Objective To assess the diagnostic accuracy of fetal fibronectin (fFN), fetal breathing movements (FBM), and cervical length (CL) for the short-term prediction of preterm birth in symptomatic ...patients. Study Design Diagnostic metaanalysis using bivariate methods. Results Pooled sensitivities for fFN, FBM, and CL for delivery within 48 hours of testing were 0.62 (95% confidence interval CI, 0.43–0.78), 0.75 (95% CI, 0.57–0.87) and 0.77 (95% CI, 0.54–0.90), respectively. Pooled specificities for fFN, FBM, and CL for delivery within 48 hours were 0.81 (95% CI, 0.74–0.86), 0.93 (95% CI, 0.75–0.98) and 0.88 (95% CI, 0.84–0.91). Pooled sensitivities for fFN, FBM, and CL for delivery within 7 days were 0.75 (95% CI, 0.69–0.80), 0.67 (95% CI, 0.43–0.84), and 0.74 (95% CI, 0.58–0.85). Pooled specificities for fFN, FBM, and CL for delivery within 7 days were 0.79 (95% CI, 0.76–0.83), 0.98 (95% CI, 0.83–1.00) and 0.89 (95% CI, 0.85–0.92). Based on a pretest probability of 10% for delivery within 48 hours, posttest probabilities (positive and negative) were 27% and 5% for fFN, 54% and 3% for fFN, and 42% and 3% for CL. For a pretest probability of 20% for delivery within 7 days, posttest probabilities (positive and negative) were 48% and 7% for fFN, 89% and 8% for FBM, and 63% and 7% for CL. Conclusion In symptomatic patients, for fFN, absence of FBM, and CL have diagnostic use as predictors of delivery within 48 hours and within 7 days of testing. Absence of FBM appears to be the best test for predicting preterm birth.
To report the results of 'responsive' deep brain stimulation (DBS) for Tourette syndrome (TS) in a National Institutes of Health funded experimental cohort. The use of 'brain derived physiology' as a ...method to trigger DBS devices to deliver trains of electrical stimulation is a proposed approach to address the paroxysmal motor and vocal tic symptoms which appear as part of TS. Ten subjects underwent bilateral staged DBS surgery and each was implanted with bilateral centromedian thalamic (CM) region DBS leads and bilateral M1 region cortical strips. A series of identical experiments and data collections were conducted on three groups of consecutively recruited subjects. Group 1 (n = 2) underwent acute responsive DBS using deep and superficial leads. Group 2 (n = 4) underwent chronic responsive DBS using deep and superficial leads. Group 3 (n = 4) underwent responsive DBS using only the deep leads. The primary outcome measure for each of the 8 subjects with chronic responsive DBS was calculated as the pre-operative baseline Yale Global Tic Severity Scale (YGTSS) motor subscore compared to the 6 month embedded responsive DBS setting. A responder for the study was defined as any subject manifesting a ≥ 30 points improvement on the YGTSS motor subscale. The videotaped Modified Rush Tic Rating Scale (MRVTRS) was a secondary outcome. Outcomes were collected at 6 months across three different device states: no stimulation, conventional open-loop stimulation, and embedded responsive stimulation. The experience programming each of the groups and the methods applied for programming were captured. There were 10 medication refractory TS subjects enrolled in the study (5 male and 5 female) and 4/8 (50%) in the chronic responsive eligible cohort met the primary outcome manifesting a reduction of the YGTSS motor scale of ≥ 30% when on responsive DBS settings. Proof of concept for the use of responsive stimulation was observed in all three groups (acute responsive, cortically triggered and deep DBS leads only). The responsive approach was safe and well tolerated. TS power spectral changes associated with tics occurred consistently in the low frequency 2-10 Hz delta-theta-low alpha oscillation range. The study highlighted the variety of programming strategies which were employed to achieve responsive DBS and those used to overcome stimulation induced artifacts. Proof of concept was also established for a single DBS lead triggering bi-hemispheric delivery of therapeutic stimulation. Responsive DBS was applied to treat TS related motor and vocal tics through the application of three different experimental paradigms. The approach was safe and effective in a subset of individuals. The use of different devices in this study was not aimed at making between device comparisons, but rather, the study was adapted to the current state of the art in technology. Overall, four of the chronic responsive eligible subjects met the primary outcome variable for clinical effectiveness. Cortical physiology was used to trigger responsive DBS when therapy was limited by stimulation induced artifacts.
The objective of this study was to test the hypothesis that apathy and depression are dissociable in Parkinson disease (PD) by conducting a confirmatory factor analysis (CFA) of items from two ...commonly used mood scales. A total of 161 non-demented PD patients (age = 64.1; ± 8.4 years) were administered the Apathy Scale and the Beck Depression Inventory-II. Items were hypothesized to load onto four factors: (1) an apathy factor representing loss of motivation, (2) dysphoric mood factor representing sadness and negativity, (3) loss of interest/pleasure factor representing the features common to both apathy and depression, and (4) a somatic factor representing bodily complaints. Results indicated a good fit for the overall CFA model, χ² (128, N = 146) = 194.9; p<.01. RMSEA was .060 (p = .16). The four-factor model was significantly better than all alternative nested models at p < .001, including an overarching single factor model, representing "depression." Results support the concept that apathy and depression are discrete constructs. We suggest a "factor based" scoring of the Apathy Scale and Beck Depression Inventory-II that disentangles symptoms related to apathy, depression, overlapping symptoms, and somatic complaints. Such scoring may be important in providing useful information regarding differential treatment options.
Summary Background Efficacy in previous studies of surgical treatments of refractory multiple sclerosis tremor using lesioning or deep brain stimulation (DBS) has been variable. The aim of this study ...was to investigate the safety and efficacy of dual-lead thalamic DBS (one targeting the ventralis intermedius–ventralis oralis posterior nucleus border the VIM lead and one targeting the ventralis oralis anterior–ventralis oralis posterior border the VO lead) for the treatment of multiple sclerosis tremor. Methods We did a single centre, single-blind, prospective, randomised pilot trial at the University of Florida Center for Movement Disorders and Neurorestoration clinic (Gainesville, FL, USA). We recruited adult patients with a clinical diagnosis of multiple sclerosis tremor refractory to previous medical therapy. Before surgery to implant both leads, we randomly assigned patients (1:1) to receive 3 months of optimised single-lead DBS—either VIM or VO. We did the randomisation with a computer-generated sequence, using three blocks of four patients, and independent members of the Center did the assignment. Patients and all clinicians other than the DBS programming nurse were masked to the choice of lead. Patients underwent surgery 1 month after their baseline visit for implantation of the dual lead DBS system. A pulse generator and two extension cables were implanted in a second surgery 3–4 weeks later. Patients then received an initial 3-month period of continuous stimulation of either the VIM or VO lead followed by blinded safety assessment of their tremor with the Tolosa-Fahn-Marin Tremor Rating Scale (TRS) during optimised VIM or VO lead stimulation at the end of the 3 months. After this visit, both leads were activated in all patients for an additional 3 months, and optimally programmed during serial visits as dictated by a prespecified programming algorithm. At the 6-month follow-up visit, TRS score was measured, and mood and psychological batteries were administered under four stimulation conditions: VIM on, VO on, both on, and both off (the order of testing was chosen by a computer-generated random sequence, assigned by independent members of the centre, and enacted by an unmasked DBS programming nurse). Each of four stimulation settings were tested over 4 consecutive days, with stimulation settings held constant for at least 12 h before testing. The primary outcome was change in mean total TRS score at the 6-month postoperative assessment with both leads activated, compared with the preoperative baseline mean TRS score. Analysis was by intention to treat. Safety was analysed in all patients who received the surgical implantation except in one patient who discontinued before the safety assessment. This trial is registered with ClinicalTrials.gov , number NCT00954421. Findings Between Jan 16, 2007, and Dec 17, 2013, we enrolled 12 patients who were randomly assigned either to 3 initial months of VIM-only or VO-only stimulation. One patient from the VO-only group developed an infection necessitating DBS explantation, and was excluded from the assessment of the primary outcome. Compared with the mean baseline TRS score of 57·0 (SD 10·2), the mean score at 6 months decreased to 40·1 (17·6), −29·6% reduction; t =–0·28, p=0·03. Three of 11 patients did not respond to surgical intervention. One patient died suddenly 2 years after surgery, but this was judged to be unrelated to DBS implantation. Serious adverse events included a superficial wound infection in one patient that resolved with antibiotic therapy, and transient altered mental status and late multiple sclerosis exacerbation in another patient. The most common non-serious adverse events were headache and fatigue. Interpretation Dual lead thalamic DBS might be a safe and effective option for improving severe, refractory multiple sclerosis tremor. Larger studies are necessary to show whether this technique is widely applicable, safe in the long-term, and effective in treating multiple sclerosis tremor or other severe tremor disorders. Funding US National Institutes of Health, the Cathy Donnellan, Albert E Einstein, and Birdie W Einstein Fund, and the William Merz Professorship.
Objective
Our aim was to compare in a prospective blinded study the cognitive and mood effects of subthalamic nucleus (STN) vs. globus pallidus interna (GPi) deep brain stimulation (DBS) in Parkinson ...disease.
Methods
Fifty‐two subjects were randomized to unilateral STN or GPi DBS. The co‐primary outcome measures were the Visual Analog Mood Scale, and verbal fluency (semantic and letter) at 7 months post‐DBS in the optimal setting compared to pre‐DBS. At 7 months post‐DBS, subjects were tested in four randomized/counterbalanced conditions (optimal, ventral, dorsal, and off DBS).
Results
Forty‐five subjects (23 GPi, 22 STN) completed the protocol. The study revealed no difference between STN and GPi DBS in the change of co‐primary mood and cognitive outcomes pre‐ to post‐DBS in the optimal setting (Hotelling's T2 test: p = 0.16 and 0.08 respectively). Subjects in both targets were less “happy”, less “energetic” and more “confused” when stimulated ventrally. Comparison of the other 3 DBS conditions to pre‐DBS showed a larger deterioration of letter verbal fluency in STN, especially when off DBS. There was no difference in UPDRS motor improvement between targets.
Interpretation
There were no significant differences in the co‐primary outcome measures (mood and cognition) between STN and GPi in the optimal DBS state. Adverse mood effects occurred ventrally in both targets. A worsening of letter verbal fluency was seen in STN. The persistence of deterioration in verbal fluency in the off STN DBS state was suggestive of a surgical rather than a stimulation‐induced effect. Similar motor improvement were observed with both STN and GPi DBS. Ann Neurol 2009
To examine the utility of a novel "cognitive stress test" to detect subtle cognitive impairments and amyloid load within the brains of neuropsychologically normal community-dwelling elders.
...Participants diagnosed as cognitively normal (CN), subjective memory impairment (SMI), mild cognitive impairment (MCI), and preclinical mild cognitive impairment (PreMCI) were administered the Loewenstein-Acevedo Scale for Semantic Interference and Learning (LASSI-L), a sensitive test of proactive semantic interference (PSI), retroactive semantic interference, and, uniquely, the ability to recover from the effects of PSI. Ninety-three subjects (31 men and 62 women) were recruited from three academic institutions in a research consortium. A subset of these individuals underwent 18F florbetapir positron emission tomography scanning. Relative percentages of impairment for each diagnostic group on the LASSI-L were calculated by χ(2) and Fisher's exact tests. Spearman's rho was used to examine associations between amyloid load and different cognitive measures.
LASSI-L deficits were identified among 89% of those with MCI, 47% with PreMCI, 33% with SMI, and 13% classified as CN. CN subjects had no difficulties with recovery from PSI, whereas SMI, preMCI, and MCI participants evidenced deficits in recovery from PSI effects. Among a subgroup of participants with normal scores on traditional neuropsychological tests, the strong associations were between the failure to recover from the effects of PSI and amyloid load in the brain.
Failure to recover or compensate for the effects of PSI on the LASSI-L distinguishes the LASSI-L from other widely used neuropsychological tests and appears to be sensitive to subtle cognitive impairments and increasing amyloid load.
Multiple studies have explored the relationship between MRI-based volumetric measurements of the hippocampus and amygdala, the degree of volumetric asymmetry of these structures, and symptom ...manifestation. However, considerable variability exists with regard to the reported volumetric values of these structures. The present study employed meta-analytic procedures to provide a systematic analysis of the normal population parameters of hippocampal and amygdala volumetric asymmetry as well as the absolute intrahemispheric volumes of these structures in normal adults. A literature review of studies published between 1990 and 2002 resulted in a representative sample of 82 studies (N = 3,564 participants) providing volumetric information of the hippocampus and 51 studies (N = 2,000 participants) providing volumetric information of the amygdala. Results revealed that both the hippocampus and the amygdala are reliably asymmetrical structures in normal adults, with larger right hippocampal (D = 0.21, p.001) and right amygdala (D = 0.09, p.01) volumes. Additional analyses indicated that differences in MRI magnet field strength and slice thickness values might differentially contribute to volumetric asymmetry estimates. These results expand on previous volumetric normative studies and may be relevant to investigators studying the clinical correlates of hippocampal and amygdala volumes.
Hedonic bias during free viewing of novel emotional and neutral scenes was investigated in older adults and college students. A neurophysiological index of emotional picture processing-the amplitude ...of the centroparietal late positive potential (LPP)-was recorded from the scalp using a dense sensor array while participants (29 older adults; 21 college students) viewed emotionally engaging or mundane natural scenes that varied in specific content. Both students and older adults showed LPP enhancement when viewing affective, compared to neutral, scenes, and there was no difference in LPP amplitude between older individuals and college students when viewing neutral everyday scenes. However, compared to the college students, older individuals showed attenuated LPP amplitude when viewing emotional scenes, regardless of hedonic valence or specific content. Age related differences could be mediated by a reduction in reactive emotional arousal with age, possible mediated by repeated life exposure to emotional stimuli.
Aging is associated with declines in mitochondrial efficiency and energy production which directly impacts the availability of adenosine triphosphate (ATP), which contains high energy phosphates ...critical for a variety of cellular functions. Previous phosphorous magnetic resonance spectroscopy (
31
P MRS) studies demonstrate cerebral ATP declines with age. The purpose of this study was to explore the functional relationships of frontal and posterior ATP levels with cognition in healthy aging. Here, we measured frontal and posterior ATP levels using
31
P MRS at 3 Tesla (3 T) and assessed cognition using the Montreal Cognitive Assessment (MoCA) in 30 healthy older adults. We found that greater frontal, but not posterior, ATP levels were significantly associated with better MoCA performance. This relationship remained significant after controlling for age, sex, years of education, and brain atrophy. In conclusion, our findings indicate that cognition is related to ATP in the frontal cortex. These preliminary findings may have important implications in the search for non-invasive markers of
in vivo
mitochondrial function and the impact of ATP availability on cognition. Future studies are needed to confirm the functional significance of regional ATP and cognition across the lifespan.
: Deep brain stimulation (DBS) targeted to the ventral intermediate (VIM) nucleus of the thalamus is effective for motor symptoms in essential tremor (ET), but there is limited data on cognitive ...outcomes. We examined cognitive outcomes in a large cohort of ET DBS patients (pre-DBS and 1+ year after DBS).
: In a retrospective analysis, we used repeated-measures ANOVA testing to examine whether the age of tremor onset, age at DBS surgery, hemisphere side implanted with lead, unilateral vs. bilateral implantations, and presence of surgical complications influenced the cognitive outcomes. Neuropsychological outcomes of interest were verbal memory, executive functioning, working memory, language functioning, visuospatial functioning, and general cognitive function.
: We identified 50 ET DBS patients; 29 (58%) males; the mean age of tremor onset was 35.84 (±21.50) years with a median age of 38 years. The mean age at DBS was 68.18 (±10.07) years. There were 37 unilateral 30 left, seven right, and 13 bilateral brain implantations. In the subgroup analysis, there was a significant interaction between assessment (pre vs. post) and age of tremor onset (<38 vs. >38 years);
= 4.47;
= 0.043 for working memory. The
testing found improvements for younger onset ET. Similarly, there was a significant interaction between assessment (pre vs. post) and complications vs. no complications subgroups;
= 4.34;
= 0.043 for verbal memory with worsening scores seen for ET patients with complications. The remaining tests were not significant.
: In this large cohort of ET patients with (>30% improvements), DBS was not accompanied by a significant decline in many cognitive domains. These outcomes were possibly related to the selection of patients with normal cognitive functioning before surgery, unilateral DBS implantations for the majority, and selection of patients with optimal response to DBS.
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