Tremor assessment scales before, during and after MRgFUS for essential tremor - results, recommendations and implications.

BACKGROUND: neurosurgical interventions such as MR-guided focused ultrasound (MRgFUS) are increasingly deployed for treatment of essential tremor. OBJECTIVE: to make recommendations for monitoring treatment effects during and after MRgFUS based on our investigation of correlations between different scales of tremor severity. METHODS: twenty-five clinical assessments were collected from thirteen patients before and after unilateral MRgFUS sequential lesioning of the thalamus and posterior subthalamic area for alleviating essential tremor. Scales included Bain Findley Spirography (BFS), Clinical Rating Scale for Tremor (CRST), Upper Extremity Total Tremor Score (UETTS) and Quality of Life of Essential Tremor (QUEST), and were documented at baseline, while lying in the scanner with stereotactic frame attached (BFS), and at 24-month follow-up. RESULTS: the four different scales of tremor severity all correlated significantly. BFS and CRST showed a strong correlation of 0.833 (p < 0.001). BFS, UETTS and CRST correlated moderately with QUEST (ρ = 0.575-0.721, p < 0.001). BFS and UETTS correlated significantly with all CRST subparts, with the strongest correlation between UETTS and CRST part C (ρ = 0.831, p < 0.001). Moreover, BFS drawn sitting upright in an outpatient setting correlated with spirals drawn in a supine position on the scanner bed with the stereotactic frame attached. CONCLUSION: we recommend a combination of BFS & UETTS for intraoperative assessment of awake essential tremor patients and BFS & QUEST for pre-operative and follow-up assessments, as these scale sets are quick and simple to collect and provide meaningful information whilst meeting the practical constraints of intraoperative assessment.

Impulse control disorders are associated with lower ventral striatum dopamine D3 receptor availability in Parkinson's disease: A [11C]-PHNO PET study.

INTRODUCTION: Reduced postsynaptic D3 dopaminergic receptor availability has been reported in the ventral striatum of pathological gamblers without Parkinson's disease (PD) and in patients with PD and impulse control disorders (ICD). However, a direct relationship between ventral striatum D3 dopaminergic receptors and the severity of ICD in PD patients has not yet been proven using a validated tool for ICD in PD, such as the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's disease-Rating Scale (QUIP-RS). In this pilot study, we investigated the relationship between ventral striatum D3 dopamine receptor availability and severity of impulse control disorder (ICD) in Parkinson's disease (PD). METHODS: Twelve patients were assessed with PET and the high affinity dopamine D3 receptor radioligand [11C]-PHNO. Severity of ICD was assessed with the QUIP-RS. RESULTS: We found that lower ventral striatum D3 receptor availability measured with [11C]-PHNO PET was associated with greater severity of ICD, as measured by the QUIP-RS score (rho = -0.625, p = 0.03). CONCLUSION: These findings suggest that the occurrence and severity of ICD in Parkinson's disease may be linked to reductions in ventral striatum dopamine D3 receptor availability. Further studies in larger cohort of patients need to be performed in order to confirm our findings and clarify whether lower ventral striatum D3 receptor may reflect a pharmacological downregulation to higher dopamine release in ventral striatum of patients with ICD or a patients' predisposition to ICD.

A review of peer-assisted learning to deliver interprofessional supplementary image interpretation skills.

BACKGROUND: Peer-assisted learning provides a means through which individuals can learn from one another through a reciprocal process. Radiographic image interpretation skills are fundamental to both diagnostic radiography students and medical students due to their shared role in preliminary evaluation of conventional radiographic images. Medical students on graduation, may not be well prepared to carry out image interpretation, since evidence suggests that they perform less well than radiographers in e.g. Accident and Emergency situations. METHOD: A review of literature was conducted exploring the application of peer-assisted learning within diagnostic radiography and health education more widely as well as the practice of initial image interpretation. An extensive and systematic search strategy was developed which provided a range of material related to the areas. FINDINGS: An overview was obtained of the effectiveness of peer-assisted learning and the issues associated with development of image interpretation skills and a degree of discrepancy was identified between the two cohorts regarding their interpretative competence and confidence. This inconsistency may create an opportunity to apply peer-assisted learning, better preparing both disciplines for the practical application of image interpretation skills. CONCLUSION: The review identified the lack of a substantial evidence base relating to peer-assisted learning in radiography. Peer-assisted learning is not widely embraced in an interprofessional context. Multiple positive factors of such an intervention are identified which outweigh perceived negative issues. Student teacher and learner may benefit as should the clinical service from enhanced practitioner performance. The findings justify further research to develop the evidence base.

The effect of pedunculopontine nucleus deep brain stimulation on postural sway and vestibular perception.

BACKGROUND AND PURPOSE: Deep brain stimulation (DBS) of the pedunculopontine nucleus (PPN) reduces the number of falls in patients with Parkinson's disease (PD). It was hypothesized that enhanced sensory processing contributes to this PPN-mediated gait improvement. METHODS: Four PD patients (and eight matched controls) with implanted bilateral PPN and subthalamic nucleus DBS electrodes were assessed on postural (with/without vision) and vestibular perceptual threshold tasks. RESULTS: Pedunculopontine nucleus ON stimulation (compared to OFF) lowered vestibular perceptual thresholds but there was a disproportionate increase in the normal sway increase on going from light to dark. CONCLUSIONS: The disproportionate increased sway with PPN stimulation in the dark may paradoxically improve balance function since mechanoreceptor signals rapidly adapt to continuous pressure stimulation from postural akinesia. Additionally, the PPN-mediated vestibular signal enhancement also improves the monitoring of postural sway. Overall, PPN stimulation may improve sensory feedback and hence balance performance.

Symptoms of depression and rates of neurocognitive impairment in HIV positive patients in Beijing, China.

BACKGROUND: In China an estimated 780,000 people are living with HIV (PLWH). In high-income countries PLWH are at increased risk of depression, with subsequent adverse consequences for quality of life, and HIV-related morbidity and mortality. There are few data from low-and middle-income countries. The aims of this country-specific investigation of the Asia Pacific NeuroAIDS Consortium (APNAC) study were to establish the point prevalence, severity and HIV-related and non-HIV related correlates of depressive symptoms in PLWH, in Beijing, China. METHOD: PLWH attending an outpatient clinic at Ditan Hospital, Beijing were recruited consecutively. Data sources were: study-specific questions about demographic characteristics, and health behaviours, the Centre for Epidemiological Studies Depression Scale (CES-D), the World Health Organisation Self-Reporting Questionnaire (SRQ-20) translated into Mandarin and administered as structured individual interviews, and a screen battery of four standard neuropsychological tests. RESULTS: In total 50/51 (98%) eligible patients agreed to participate. Overall 28% scored CES-D≥16 or SRQ20≥10 and 18% in these clinical ranges on both measures; 69% were classified as being neuropsychologically impaired (scoring below 1 SD of the control value on at least two tests). Higher depressive symptom scores were associated with lower education, alcohol overuse and diminished motor ability (all p<0.05), but not neuropsychological impairment CONCLUSION: Clinically significant depressive symptoms among this cohort of PLWH in Beijing occurred at 5 times the rate reported among a general Chinese urban population. No participants had been assessed for depression prior to the study and none were treated, indicating that consideration of psychological morbidity and its consequences for health behaviours should be incorporated into routine HIV care in China.

High precision isotope measurements reveal poor control of copper metabolism in parkinsonism.

Disordered copper metabolism may be important in the aetiology of Parkinsonism, as caeruloplasmin is a key enzyme in handling oxidative stress and is involved in the synthesis pathway of dopamine. The human Cu metabolism of ten Parkinsonism patients was compared to ten healthy controls with the aid of a stable (65)Cu isotope tracer. The analyses of blood serum (65)Cu/(63)Cu ratios yielded individual isotopic profiles, which indicate that the Cu metabolism is less controlled in patients with Parkinsonism. Modelling based on both isotope tracer and total Cu concentrations suggests that 30% of the subjects affected by Parkinsonism have abnormally large Cu stores in tissues. To detect the small differences in Cu metabolism between Parkinsonism and controls, the analysis of stable isotope composition must be performed using multiple-collector inductively coupled plasma mass spectrometry and the associated sample preparation techniques. This pilot investigation supports full-scale medical studies into the Cu metabolism of those with Parkinsonism.

Individual differences in expert motor coordination associated with white matter microstructure in the cerebellum.

Recent investigations into the neural basis of elite sporting performance have focused on whether cortical activity might characterize individual differences in ability. However, very little is understood about how changes in brain structure might contribute to individual differences in expert motor control. We compared the behavior and brain structure of healthy controls with a group of karate black belts, an expert group who are able to perform rapid, complex movements that require years of training. Using 3D motion tracking, we investigated whether the ability to control ballistic arm movements was associated with differences in white matter microstructure. We found that karate experts are better able than novices to coordinate the timing of inter-segmental joint velocities. Diffusion tensor imaging revealed significant differences between the groups in the microstructure of white matter in the superior cerebellar peduncles (SCPs) and primary motor cortex-brain regions that are critical to the voluntary control of movement. Motor coordination, the amount of experience, and the age at which training began were all associated with individual differences in white matter integrity in the cerebellum within the karate groups. These findings suggest a role for the white matter pathways of the SCPs in motor expertise.

Accuracy of subjective and objective handwriting assessment for differentiating Parkinson's disease from tremulous subjects without evidence of dopaminergic deficits (SWEDDs): an FP-CIT-validated study.

Handwriting examinations are commonly performed in the analysis of tremor and Parkinson's disease (PD). We analyzed the accuracy of subjective and objective assessment of handwriting samples for distinguishing 27 PD cases, 22 with tremulous PD, and five with akinetic-rigid PD, from 39 movement-disorder patients with normal presynaptic dopamine imaging (subjects without evidence of dopamine deficiency or SWEDDs; 31 with dystonic tremor (DT), six indeterminate tremor syndrome, one essential tremor, one vascular parkinsonism). All handwriting analysis was performed blind to clinical details. Subjective classification was made as: (1) micrographia, (2) normal, or (3) macrographia. In addition, a range of objective metrices were measured on standardized handwriting specimens. Subjective assessments found micrographia more frequently in PD than SWEDDs (p = 0.0352) and in akinetic-rigid than tremulous PD (p = 0.0259). Macrographia was predominantly seen in patients with dystonic tremor and not other diagnoses (p = 0.007). Micrographia had a mean sensitivity of 55 % and specificity of 84 % for distinguishing PD from SWEDDs and mean sensitivity of 90 % and specificity of 55 % for distinguishing akinetic-rigid PD from tremulous PD. Macrographia had a sensitivity of 26 % and specificity of 96 % for distinguishing DT from all other diagnoses. The best of the objective metrices increased sensitivity for the distinction of SWEDDs from PD with a reduction in specificity. We conclude that micrographia is more indicative of PD than SWEDDs and more characteristic of akinetic-rigid than tremulous PD. In addition, macrographia strongly suggests a diagnosis of dystonic tremor.

The role of the subthalamic nucleus in response inhibition: evidence from deep brain stimulation for Parkinson's disease.

We measured reaction times during a stop-signal task while patients with Parkinson's disease were on and off unilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN). While reaction times to a "go" stimulus improved, there was no change in reaction times to the "stop" stimulus (SSRTs). However, changes in SSRTs induced by DBS were highly dependent on baseline SSRTs (measured off stimulation), with the greatest improvements being achieved by those with particularly slow reaction times. We therefore selected only those patients whose baseline SSRTs were within the limits of a control sample (N=10). In this group, SSRTs became slower when DBS was on. This finding suggests a role for the STN in response inhibition, which can be interrupted by DBS, observable only when more general improvements in Parkinson's function are minimised. We also compared the effects of unilateral left and right sided stimulation. We found a greater increase in SSRTs after DBS of the left STN.

Deep brain stimulation: a new treatment for hypertension?

We report a 61-year-old hypertensive man who underwent deep brain stimulation of the periventricular/periaqueductal grey area for the relief of chronic neuropathic pain affecting his oral cavity and soft palate. During intraoperative stimulation, we were able to modulate his blood pressure up or down, depending on electrode location. This is the first evidence that hypertension could be effectively treated with electrical stimulation of the midbrain.

Operative and hardware complications of deep brain stimulation for movement disorders.

The objective of this investigation was to present the operative and hardware complications encountered during follow-up of patients with in situ deep brain stimulators. The study took the form of a retrospective chart review on a series of consecutive patients who were treated successfully with insertion of deep brain stimulators at a single centre by a single surgeon between 1999 and 2005. During the study period, a total of 60 patients underwent 96 procedures for implantation of unilateral or bilateral DBS electrodes. The mean follow-up period was 43.7 months (range 6-78 months) from the time of the first procedure. No patients were lost to follow-up or died. Eighteen patients (30%) developed 28 adverse events, requiring 28 electrodes to be replaced. Seven patients developed two adverse events and two patients developed three adverse events. The rate of adverse events per electrode-year was 8%. We observed a higher proportion of early complications (<6 months postoperatively) in patients with Parkinson's disease, while dystonic patients had more late complications (>6 months postoperatively) and no early complications. Thirty per cent of our patients developed an adverse event that could potentially lead to revision of the implanted hardware. In patients with Parkinson's disease most of the complications tend to occur during the first 6 months postoperatively, while in dystonic patients most occur between 12 and 24 months postoperatively.

A randomly assigned double-blind cross-over study examining the relative anti-parkinsonian tremor effects of pramipexole and pergolide.

This study examined the relative anti-Parkinson's disease (PD) tremor potencies of pergolide and pramipexole in people with PD, using a 3-month double-blind cross-over design. Patients were randomly assigned to receive either pergolide and then pramipexole (n=9) or vice versa (n=8). The dose of the respective dopamine agonist was increased according to a titration schedule up to a maximum 1.5 mg t.d.s., with cross-over at 10 weeks. Assessments were performed at baseline, 4, 8 and 12 weeks. The primary outcome measures were the differences in the clinical (rest and postural) tremor scores on pergolide versus pramipexole. Seventeen PD patients (11 females and six males) with a mean age 68.4 years (range: 55-84 years) and a mean disease duration of 3.9 years (range: 2 months to 13 years) participated in the study. Twelve of the patients were taking other anti-parkinsonian medications. Two patients dropped out of the study whilst on pergolide. Fifteen of 16 patients were able to cross-over from one dopamine agonist to the other, without major retitration. There were no significant differences between the effects of the two drugs on the primary outcome measures, suggesting that the anti-PD tremor efficacies of dopaminergic medications are not dependent on differential affinities for dopamine receptor types.

Cost analysis of unilateral and bilateral pallidotomy for Parkinson's disease.

With the rapid increase in provision of deep brain stimulation for Parkinson's disease, the efficacy of pallidotomy in symptom alleviation appears to be increasingly ignored. We demonstrate that lesional surgery is effective with benefit over a significant period of time with very significant societal cost savings. Such studies are essential for future planning of services so that maximum numbers of patients can benefit from surgery, both lesional and neuromodulation, as deemed appropriate.

Cannabis for dyskinesia in Parkinson disease: a randomized double-blind crossover study.

BACKGROUND: The long-term treatment of Parkinson disease (PD) may be complicated by the development of levodopa-induced dyskinesia. Clinical and animal model data support the view that modulation of cannabinoid function may exert an antidyskinetic effect. The authors conducted a randomized, double-blind, placebo-controlled crossover trial to examine the hypothesis that cannabis may have a beneficial effect on dyskinesia in PD. METHODS: A 4-week dose escalation study was performed to assess the safety and tolerability of cannabis in six PD patients with levodopa-induced dyskinesia. Then a randomized placebo-controlled crossover study (RCT) was performed, in which 19 PD patients were randomized to receive oral cannabis extract followed by placebo or vice versa. Each treatment phase lasted for 4 weeks with an intervening 2-week washout phase. The primary outcome measure was a change in Unified Parkinson's Disease Rating Scale (UPDRS) (items 32 to 34) dyskinesia score. Secondary outcome measures included the Rush scale, Bain scale, tablet arm drawing task, and total UPDRS score following a levodopa challenge, as well as patient-completed measures of a dyskinesia activities of daily living (ADL) scale, the PDQ-39, on-off diaries, and a range of category rating scales. RESULTS: Seventeen patients completed the RCT. Cannabis was well tolerated, and had no pro- or antiparkinsonian action. There was no evidence for a treatment effect on levodopa-induced dyskinesia as assessed by the UPDRS, or any of the secondary outcome measures. CONCLUSIONS: Orally administered cannabis extract resulted in no objective or subjective improvement in dyskinesias or parkinsonism.

Externalising deep brain electrodes: an increased risk of infection?

It is the practice in many centres to externalise deep brain electrodes in functional neurosurgery to confirm efficacy of therapy prior to full implantation of the pacemaker. It has been a concern that such practice might lead to an increased rate of infection. We report a retrospective study of the rates of infection in two major centres where all electrodes are externalised in one centre and directly implanted in the other. We have not found an increased rate of infection as a result of externalisation and feel, particularly in pain patients, that doing so can lead to significant cost savings by avoiding ineffective implantations.

Electron microscopy of tissue adherent to explanted electrodes in dystonia and Parkinson's disease.

Deep brain stimulation (DBS) is used to treat a variety of severe medically intractable movement disorders, including Parkinson's disease, tremor and dystonia. There have been few studies examining the effect of chronic DBS on the brains of Parkinson's disease patients. Most of these post mortem studies concluded that chronic DBS caused mild gliosis around the lead track and did not damage brain tissue. There have been no similar histopathological studies on brains from dystonic patients who have undergone DBS. In this study, our objective was to discover whether tissue would be attached to DBS electrodes removed from patients for routine clinical reasons. We hoped that by examining explanted DBS electrodes using scanning (SEM) and/or transmission (TEM) electron microscopy we might visualize any attached tissue and thus understand the electrode-human brain tissue interaction more accurately. Initially, SEM was performed on one control DBS electrode that had not been implanted. Then 21 (one subthalamic nucleus and 20 globus pallidus internus) explanted DBS electrodes were prepared, after fixation in 3% glutaraldehyde, for SEM (n = 9) or TEM (n = 10), or both (n = 2), according to departmental protocol. The electrodes were sourced from two patients with Parkinson's disease, one with myoclonic dystonia, two with cervical dystonia and five with primary generalized dystonia, and had been in situ for 11 and 31 months (Parkinson's disease), 16 months (myoclonic dystonia), 14 and 24 months (cervical dystonia) and 3-24 months (primary generalized dystonia). Our results showed that a foreign body multinucleate giant cell-type reaction was present in all TEM samples and in SEM samples, prewashed to remove surface blood and fibrin, regardless of the diagnosis. Some of the giant cells were >100 microm in diameter and might have originated from either fusion of parenchymal microglia, resident perivascular macrophage precursors and/or monocytes/macrophages invading from the blood stream. The presence of mononuclear macrophages containing lysosomes and sometimes having conspicuous filopodia was detected by TEM. Both types of cell contained highly electron-dense inclusions, which probably represent phagocytosed material. Similar material, the exact nature of which is unknown, was also seen in the vicinity of these cells. This reaction was present irrespective of the duration of implantation and may be a response to the polyurethane component of the electrodes' surface coat. These findings may be relevant to our understanding of the time course of the clinical response to DBS in Parkinson's disease and various forms of dystonia, as well as contributing to the design characteristics of future DBS electrodes.

Bacteriophages that infect the cellulolytic ruminal bacterium Ruminococcus albus AR67.

AIM: To isolate bacterial viruses that infect the ruminal cellulolytic bacterium Ruminococcus albus. METHODS: Four phages infecting R. albus AR67 were isolated under anaerobic conditions using the soft-agar overlay technique. The phages were characterized on morphology, solvent stability, nucleic acid type and digestion characteristics. Two phages, phiRa02 and phiRa04 comprised icosahedral virions with linear double-stranded DNA and appeared to belong to the family Podoviridae [corrected] The other two phages are most likely filamentous phages with circular single-stranded DNA of the family Inoviridae. SIGNIFICANCE OF THE STUDY: Viruses of the family Inoviridae [corrected] have not previously been isolated from rumen bacteria. The phages isolated in this study are the first phages shown to infect the cellulolytic bacteria of the rumen. This suggests that the cellulolytic populations of the rumen are subject to lytic events that may impact on the ability of these bacteria to degrade plant fibre and on the nutrition of the animal.