Alison D. Murray

Efficacy and safety of sacral nerve stimulation for urinary urge incontinence: a systematic review.

PURPOSE We systematically reviewed the evidence on the efficacy and safety of sacral nerve stimulation (SNS) for severe urge incontinence. MATERIALS AND METHODS A systematic review was performed of primary studies of SNS for urge incontinence published in English between 1966 and May 2003, and identified in major electronic databases. Two reviewers independently selected studies, assessed their methodological quality and extracted data. RESULTS Four randomized controlled trials and 30 case series were identified. Evidence from the randomized controlled trials, involving approximately 120 patients, showed that about 80% achieved continence or greater than 50% improvement in their main incontinence symptoms after SNS compared with about 3% of controls receiving conservative treatments while waiting for an implant. While case series were larger, they were methodologically less reliable. However, they showed similar results with 67% of patients becoming dry or achieving a greater than 50% improvement in symptoms after implantation. Incontinence episodes, leakage severity, voiding frequency and pad use were significantly lower after implantation. Benefits were reported to persist 3 to 5 years after implantation. Adverse events were documented in 27 studies. Overall the reoperation rate in implanted cases was 33%. The most common reason for surgical revision was relocation of the generator because of pain and infection. Common complications were pain at the implant or lead site in 25% of patients, lead related problems such as lead migration in 16%, replacement and repositioning of the implanted pulse generator in 15%, wound problems in 7%, adverse effects on bowel function in 6%, infection in 5% and generator problems in 5%. Permanent removal of the electrodes was reported in 9% of patients. Technical changes with time have been associated with decreased complication rates. CONCLUSIONS There is evidence indicating that SNS is effective for decreasing symptoms in patients with urge incontinence. Adverse events occurred in about half of the implanted cases and surgical revision was performed in 33%. No major irreversible complications were reported in the studies reviewed. Further research is required on the long-term effects of and quality of life in patients with SNS.

Brain white matter lesions detected by magnetic resosnance imaging are associated with balance and gait speed

Objective: To investigate the relations between premorbid and current mental ability, mood, and white matter signal abnormalities detected by T2 weighted brain magnetic resonance imaging (MRI) and impairment of balance and mobility in older adults. Methods: 97 subjects from the Aberdeen 1921 birth cohort underwent brain MRI, evaluation of balance, and measurement of gait speed. White matter hyperintensities detected on T2 weighted MRI scans were rated by three independent raters on three variables: white matter lesions; periventricular lesions; and brain stem lesions. Results: Decreased gait speed was correlated with impaired visual acuity (p = 0.020), shorter stature (p = 0.008), a lower childhood IQ (p = 0.030), a lower current Raven’s progressive matrices score (Raven score) (p < 0.001), a higher hospital anxiety and depression scale (HADS) score (p = 0.004), and an increased grade of brain stem lesions on MRI. Inability to balance was correlated with Raven score (p = 0.042), brain stem lesions (p = 0.003), white matter lesions (p = 0.003), and periventricular lesions (p = 0.038). Binary logistic regression identified brain stem lesions (odds ratio (OR) 0.22; 95% confidence interval 0.09 to 0.54) and HADS depression score (OR 0.75; 0.58 to 0.97) as the only significant associations with balance. Structural equation modelling detected an association between two latent traits representing white matter disease and an integrating function, respectively. Conclusions: In this cohort, white matter lesions, periventricular lesions, and brain stem lesions were associated with impaired balance. Current mental ability was strongly related to gait speed. There appears to be a concordance between motor skills and intellect in old age, which is degraded by white matter disease.

Structural white matter deficits in high-functioning individuals with autistic spectrum disorder: a voxel-based investigation.

A number of imaging and neuropathological studies have reported structural abnormalities in white matter areas such as the corpus callosum in autism spectrum disorder (ASD). Differences in both global brain volume and the size of specific neural structures have been reported. In order to expand these previously reported findings and to describe more precisely the nature of such structural changes, we performed a voxel-based morphometric whole brain analysis, using a group-specific template, in male adolescents with ASD. Fifteen individuals with normal intelligence and ASD, and a group of 16 controls, matched for age, sex, and IQ, were investigated. High-resolution T1-weighted 3D data sets were acquired and analysed. Local white matter volume deficits were found in the corpus callosum, particularly in the anterior splenium and isthmus, and right hemisphere. White matter volume deficits were also found in the left middle temporal, right middle frontal, and left superior frontal gyri. No significant areas of increased white matter volume were found. Our findings support the hypothesis that reduced white matter volume in the corpus callosum and right hemisphere may play a role in the pathophysiology of ASD.

Accuracy of T1 measurement in dynamic contrast-enhanced breast MRI using two- and three-dimensional variable flip angle fast low-angle shot

In vivo T1 measurements, used to monitor the uptake of contrast agent by tissues, are typically performed as a first step in implementing compartmental analysis of contrast‐enhanced breast magnetic resonance imaging (MRI) data. We have extended previously described methodology for in vivo T1 measurement (using a variable flip‐angle gradient‐recalled echo technique) to two‐dimensional (2D), fast low‐angle shot (FLASH). This approach requires computational modeling of slice‐selective radiofrequency (RF) excitation to correct for nonrectangular slice profiles. The accuracy with which breast tissue T1 values can be measured by this approach is examined: T1 measurements from phantom and in vivo image data acquired with 2D and 3D FLASH imaging sequences are presented. Significant sources of error due to imaging pulse sequence quality and RF transmit field nonuniformity in the breast coil device that will have detrimental consequences for compartmental analysis are identified. Rigorous quality assurance programs with calibrated phantoms are thus recommended, to verify the accuracy with which T1 measurements are obtained. J. Magn. Reson. Imaging 1999;9:163–171.

Cerebral blood flow and cognitive responses to rivastigmine treatment in Alzheimer's disease.

Twenty seven patients with mild AD were enrolled in a prospective open label controlled study of rivastigmine. Assessments included a range of neuropsychiatric and behavioural measures and rCBF using HMPAO SPECT at baseline, three and six months. Significant enhancement of frontal, parietal and temporal brain blood flow with related psychometric improvement was observed in twelve of the treated patients. A pattern of reduced rCBF and cognitive performance was observed in four unresponsive and eleven untreated patients. The results suggest that alterations in the clinical and cognitive status of patients receiving a cholinesterase inhibitor are paralleled by changes in rCBF. Longitudinal assessment with repeated imaging offers a method of better understanding the effects of cholinesterase inhibition on the AD brain.

Increased sensitivity after repeated stimulation of residual spatial channels in blindsight

Lesions of the occipital cortex result in areas of cortical blindness affecting the corresponding regions of the patients visual field. The traditional view is that, aside from some spontaneous recovery in the first few months after the damage, when acute effects have subsided the areas of blindness are absolute and permanent. It has been found, however, that within such field defects some residual visual capacities may persist in the absence of acknowledged awareness by the subject (blindsight type 1) or impaired awareness (type 2). Neuronal pathways mediating blindsight have a specific and narrow spatial and temporal bandwidth. A group of cortically blind patients (n = 12) carried out a daily detection “training” task over a 3-month period, discriminating grating visual stimuli optimally configured for blindsight from homogeneous luminance-matched stimuli. No feedback was given during the training. Assessment of training was by psychophysical measurements carried out before and after training and included detection of a range of spatial frequencies (0.5–7 cycles per degree), contrast detection at 1 cycle per degree, clinical perimetry, and subjective estimates of visual field defect. The results show that repeated stimulation by appropriate visual stimuli can result in improvements in visual sensitivities in the very depths of the field defect.

Cerebral White Matter Abnormalities and Lifetime Cognitive Change: A 67-Year Follow-Up of the Scottish Mental Survey of 1932

Cerebral white matter abnormalities relate to cognitive functioning in elders. We examine whether this association is (a) independent of mental ability in youth and (b) related to general and/or specific mental abilities. We retested 83 participants of the Scottish Mental Survey of 1932 on a battery of mental tests. Their brains were scanned by magnetic resonance imaging. Three independent ratings (Fazekas) were made of periventricular, and subcortical and deep white matter abnormalities. Structural equation models showed that, irrespective of brain location, white matter abnormalities contributed about 14% of cognitive function variance in old age. Some of this effect might be due to hypertension. This contribution is independent of mental function in early life and is associated with general cognitive ability.

Childhood Socioeconomic Status and Adult Brain Size: Childhood Socioeconomic Status Influences Adult Hippocampal Size

To investigate in older adults without dementia the relationships between socioeconomic status (SES) in childhood and magnetic resonance imaging (MRI)‐derived brain volume measures typical of brain aging and Alzheimers disease (AD).

Changes in the rCBF images of patients with Alzheimer's disease receiving Donepezil therapy

Alzheimers disease is associated with a loss in presynaptic cholinergic function. It has been suggested that cholinergic inhibitors such as donepezil hydrochloride (Donepezil) could restore this function and improve some of the symptoms of Alzheimers disease. Previous work has shown that Donepezil improves cognitive and global function in patients with mild to moderate Alzheimers disease. This study reviewed retrospectively 12 patients who had previously had a 99Tcm-hexamethylpropylene amine oxime (99Tcm-HMPAO) single photon emission tomography (SPET) regional cerebral blood flow (rCBF) examination and had gone on to receive Donepezil therapy. These patients were recalled for a further 99Tcm-HMPAO SPET rCBF examination and the image data sets were compared. The results showed an overall increase in global cerebral blood flow (P = 0.04) averaged over the group with a percentage change in blood flow ranging from −1.8% to 6.4%. However, some patients showed a slight decrease in blood flow. When the data were analysed in terms of regional cerebral blood flow, we found that the most significant increase in blood flow occurred in the frontal lobes (P = 0.02).

Age-, gender-, and socioeconomic status-specific incidence of Parkinson's disease and parkinsonism in North East Scotland: The PINE study

There have been few high quality incidence studies of Parkinsons disease (PD). We measured age-, gender- and socioeconomic-specific incidence rates for parkinsonism and PD in north-east Scotland, and compared our results with those of previous high quality studies. Incident patients were identified prospectively over three years by several overlapping methods from primary care practices (total population 311,357). Parkinsonism was diagnosed if patients had two or more cardinal motor signs. Drug-induced parkinsonism was excluded. Patients had yearly follow-up to improve diagnostic accuracy. Incidence rates using clinical diagnosis at latest follow-up were calculated for all parkinsonism and for PD by age, gender and socioeconomic status. Meta-analysis with similar studies was performed. Of 377 patients identified at baseline with possible or probable parkinsonism, 363 were confirmed as incident patients after median follow-up of 26 months (mean age 74.8 years, SD 9.8; 61% men). The crude annual incidence of parkinsonism was 28.7 per 100,000 (95% confidence interval (CI) 25.7-31.8) and PD 17.9 per 100,000 (95% CI 15.5-20.4). PD was more common in men (age-adjusted male to female ratio 1.87:1, 95% CI 1.55-2.23) but there was no difference by socioeconomic status. Meta-analysis of 12 studies showed an incidence of PD (adjusted to the 1990 Scottish population) of 14.6 per 100,000 (95% CI 12.2-17.3) with considerable heterogeneity (I(2) 95%), partially explained by population size and recruitment duration. The incidence of PD was similar to other high quality studies. The incidence of PD was not affected by socioeconomic status.