Rosalind Mitchell

Deep brain stimulation plus best medical therapy versus best medical therapy alone for advanced Parkinson's disease (PD SURG trial): a randomised, open-label trial

Summary Background Surgical intervention for advanced Parkinsons disease is an option if medical therapy fails to control symptoms adequately. We aimed to assess whether surgery and best medical therapy improved self-reported quality of life more than best medical therapy alone in patients with advanced Parkinsons disease. Methods The PD SURG trial is an ongoing randomised, open-label trial. At 13 neurosurgical centres in the UK, between November, 2000, and December, 2006, patients with Parkinsons disease that was not adequately controlled by medical therapy were randomly assigned by use of a computerised minimisation procedure to immediate surgery (lesioning or deep brain stimulation at the discretion of the local clinician) and best medical therapy or to best medical therapy alone. Patients were analysed in the treatment group to which they were randomised, irrespective of whether they received their allocated treatment. The primary endpoint was patient self-reported quality of life on the 39-item Parkinsons disease questionnaire (PDQ-39). Changes between baseline and 1 year were compared by use of t tests. This trial is registered with Current Controlled Trials, number ISRCTN34111222. Findings 366 patients were randomly assigned to receive immediate surgery and best medical therapy (183) or best medical therapy alone (183). All patients who had surgery had deep brain stimulation. At 1 year, the mean improvement in PDQ-39 summary index score compared with baseline was 5·0 points in the surgery group and 0·3 points in the medical therapy group (difference −4·7, 95% CI −7·6 to −1·8; p=0·001); the difference in mean change in PDQ-39 score in the mobility domain between the surgery group and the best medical therapy group was −8·9 (95% CI −13·8 to −4·0; p=0·0004), in the activities of daily living domain was −12·4 (−17·3 to −7·5; p<0·0001), and in the bodily discomfort domain was −7·5 (−12·6 to −2·4; p=0·004). Differences between groups in all other domains of the PDQ-39 were not significant. 36 (19%) patients had serious surgery-related adverse events; there were no suicides but there was one procedure-related death. 20 patients in the surgery group and 13 in the best medical therapy group had serious adverse events related to Parkinsons disease and drug treatment. Interpretation At 1 year, surgery and best medical therapy improved patient self-reported quality of life more than best medical therapy alone in patients with advanced Parkinsons disease. These differences are clinically meaningful, but surgery is not without risk and targeting of patients most likely to benefit might be warranted. Funding UK Medical Research Council, Parkinsons UK, and UK Department of Health.

Acute management of pituitary apoplexy – surgery or conservative management?

background and objectiveu2002 The rarity of pituitary apoplexy renders it a difficult subject for audit; hence there are no evidence‐based standards of optimum care for such patients. The key controversy in management relates to the role of acute neurosurgical intervention. In recent years we have adopted a relatively conservative approach towards patients presenting with pituitary apoplexy. Against this background, we aimed to determine whether our less‐interventional approach affected long‐term clinical outcome in these patients.

Cost-utility analysis of deep brain stimulation surgery plus best medical therapy versus best medical therapy in patients with Parkinson's: Economic evaluation alongside the PD SURG trial.

Williams and colleagues reported that DBS surgery for patients with advanced PD improves motor function and quality of life compared to best medical therapy alone at 1 year, but with surgery‐related side effects in a minority. This article reports on the economic evaluation alongside this trial.

Outcome of Nonfunctioning Pituitary Adenomas That Regrow After Primary Treatment: A Study From Two Large UK Centers

ContextnDespite the major risk of regrowth of clinically nonfunctioning pituitary adenomas (CNFAs) after primary treatment, systematic data on the probability of further tumor progression and the effectiveness of management approaches are lacking.nnnObjectivenTo assess the probability of further regrowth(s), predictive factors, and outcomes of management approaches in patients with CNFA diagnosed with adenoma regrowth after primary treatment.nnnPatients, Design, and SettingnRetrospective cohort study of 237 patients with regrown CNFA managed in two UK centers.nnnResultsnMedian follow-up was 5.9 years (range, 0.4 to 37.7 years). The 5-year second regrowth rate was 35.3% (36.2% after surgery; 12.5% after radiotherapy; 12.7% after surgery combined with radiotherapy; 63.4% with monitoring). Of those managed with monitoring, 34.8% eventually were offered intervention. Type of management and sex were risk factors for second regrowth. Among those with second adenoma regrowth, the 5-year third regrowth rate was 26.4% (24.4% after surgery; 0% after radiotherapy; 0% after surgery combined with radiotherapy; 48.3% with monitoring). Overall, patients with a CNFA regrowth had a 4.4% probability of a third regrowth at 5 years and a 10.0% probability at 10 years; type of management of the first regrowth was the only risk factor. Malignant transformation was diagnosed in two patients.nnnConclusionsnPatients with regrown CNFA after primary treatment continue to carry considerable risk of tumor progression, necessitating long-term follow-up. Management approach to the regrowth was the major factor determining this risk; monitoring had >60% risk of progression at 5 years, and a substantial number of patients ultimately required intervention.

Apathy in patients with Parkinson’s disease following deep brain stimulation of the subthalamic nucleus

OBJECTIVEnApathy has been reported as a possible adverse effect of deep brain stimulation of the subthalamic nucleus (STN-DBS). We investigated the prevalence and severity of apathy in 22 patients with Parkinsons disease (PD) who underwent STN-DBS, as well as the effects of apathy on quality of life (QOL).nnnMETHODSnAll patients were assessed with the Lille Apathy Rating Scale (LARS), the Apathy Scale (AS), and the Parkinsons Disease Questionnaire and were compared to a control group of 38 patients on pharmacotherapy alone.nnnRESULTSnThere were no significant differences in the prevalence or severity of apathy between patients who had undergone STN-DBS and those on pharmacotherapy alone. Significant correlations were observed between poorer QOL and degree of apathy, as measured by the LARS (p<0.001) and the AS (p=0.021). PD-related disability also correlated with both apathy ratings (p<0.001 and p=0.017, respectively).nnnCONCLUSIONnOur findings suggest that STN-DBS is not necessarily associated with apathy in the PD population; however, more severe apathy appears to be associated with a higher level of disability due to PD and worse QOL, but no other clinico-demographic characteristics.

ACTH and gonadotropin deficiencies predict mortality in patients treated for nonfunctioning pituitary adenoma: long-term follow-up of 519 patients in two large European centres

Nonfunctioning pituitary adenomas (NFPAs) are the most common subtype of pituitary tumour. Hypopituitarism is observed in NFPAs due to tumour‐ or treatment‐related factors and may increase mortality risk. Here, we analysed the associations of hypopituitarism, hormone replacement and mortality in a large NFPA cohort derived from two large European centres.

Patients’ experiences of deep brain stimulation for Parkinson's disease: a qualitative systematic review and synthesis

Objective To review and synthesise qualitative research studies that have explored patients’ experience of deep brain stimulation (DBS) in advanced Parkinsons disease (PD). Design Systematic review and meta-synthesis of 7 original papers, using metaethnography. Setting Studies conducted in Denmark, France and Sweden. Participants 116 patients who had undergone DBS and 9 spouses of patients. Results Prior to surgery, the experience of advancing PD is one of considerable loss and a feeling of loss of control. There are significant hopes for what DBS can bring. Following surgery, a sense of euphoria is described by many, although this does not persist and there is a need for significant transitions following this. We suggest that normality as a concept is core to the experience of DBS and that a sense of control may be a key condition for normality. Experience of DBS for patients and spouses, and of the transitions that they must undertake, is influenced by their hopes of what surgery will enable them to achieve, or regain (ie, a new normality). Conclusions There is a need for further qualitative research to understand the nature of these transitions to inform how best patients and their spouses can be supported by healthcare professionals before, during and after DBS. In assessing the outcomes of DBS and other treatments in advanced PD, we should consider how to capture holistic concepts such as normality and control. Studies that examine the outcomes of DBS require longer term follow-up.

Use of a Pulsed Radiofrequency Energy Device (PEAK Plasmablade™) in Neuromodulation Implant Revisions

BACKGROUNDnBattery replacement or revision surgery for neuromodulation implants is conventionally performed using sharp dissection. Meticulous dissection within thick scar tissue is vital to avoid damage to surrounding lead(s), which could result in more extensive revision surgery. Traditional electrosurgery devices are contraindicated as the emitted energy can be transferred to the hardware, resulting in implant or tissue damage with severe consequent complications.nnnOBJECTIVEnWe report our experience and potential applications of a novel, pulsed monopolar radiofrequency energy device (PEAK PlasmaBlade, Medtronic PLC, Minneapolis, Minnesota, USA), which facilitates dissection around implants without the risk of damaging or transmitting energy through the system.nnnMETHODSnWe conducted a 2-center retrospective study to review the indications, safety, and efficacy of the PlasmaBlade in 57 cases requiring either neuromodulation system replacement or revision. Deep brain stimulator (DBS) battery replacements were undertaken in 45 cases, 8 vagal nerve stimulator battery revisions, 2 intrathecal baclofen system revision, 1 DBS extension revision, and 1 DBS scar revision around the cranial portion of the lead.nnnRESULTSnAll cases proceeded without adverse event or damage to lead/generator and with a subjective and objective impression of significant time savings. Average operating times for battery replacements were reduced from 37 to 26 minutes (Pxa0= 0.015).nnnCONCLUSIONnIn our experience, the PlasmaBlade is safe to use in revising/replacing neuromodulation implants. We observed no damage or transmission of energy to the implants or leads; additional advantages of the system include reduced operating times, less damage to surrounding tissue, and the potential to facilitate revision procedures in awake patients under local anesthesia.

Does stimulus predict the best candidates for deep brain stimulation for PD

Background Deep Brain Stimulation (DBS) is used for people with Parkinson’s disease (PwPD) who are experiencing motor complications that are not controlled by medication. To date, PD SURG is the largest trial to compare DBS to best medical therapy in PwPD. Outcomes to DBS for PwPD are varied and there is an ongoing question as whether patient selection can be improved. To date, subgroup analyses have not been powered to provide an answer. An algorithm (STIMULUS) was designed to try to identify suitable candidates for DBS for PD symptoms based on the clinical opinion of an expert panel. The PD SURG data set provides an opportunity to test the ability of STIMULUS to predict suitable candidates.

Resolution of third nerve palsy following treatment of prolactinoma with cabergoline

This report describes a case of prolactinoma that presented acutely with a third nerve palsy without evidence of apoplexy. The third nerve palsy resolved within 48xa0h on medical therapy. This is an atypical clinical presentation that highlights a successful and novel medical approach to treatment.