EAN consensus statement for management of patients with neurological diseases during the COVID-19 pandemic.

BACKGROUND AND PURPOSE: The recent SARS-CoV-2 pandemic has posed multiple challenges to the practice of clinical neurology including recognition of emerging neurological complications and management of coexistent neurological diseases. In a fast-evolving pandemic, evidence-based studies are lacking in many areas. This paper presents European Academy of Neurology (EAN) expert consensus statements to guide neurologists caring for patients with COVID-19. METHODS: A refined Delphi methodology was applied. In round 1, statements were provided by EAN scientific panels (SPs). In round 2, these statements were circulated to SP members not involved in writing them, asking for agreement/disagreement. Items with agreement >70% were retained for round 3, in which SP co-chairs rated importance on a five-point Likert scale. Results were graded by importance and reported as consensus statements. RESULTS: In round one, 70 statements were provided by 23 SPs. In round two, 259/1061 SP member responses were received. Fifty-nine statements obtained >70% agreement and were retained. In round three, responses were received from 55 co-chairs of 29 SPs. Whilst general recommendations related to prevention of COVID-19 transmission had high levels of agreement and importance, opinion was more varied concerning statements related to therapy. CONCLUSION: This is the first structured consensus statement on good clinical practice in patients with neurological disease during the COVID-19 pandemic that provides immediate guidance for neurologists. In this fast-evolving pandemic, a rapid response using refined Delphi methodology is possible, but guidance may be subject to change as further evidence emerges.

A randomized controlled double-blind study of rotigotine on neuropsychiatric symptoms in de novo PD.

Management of apathy, depression and anxiety in Parkinson's disease (PD) represents a challenge. Dopamine agonists have been suggested to be effective. This multicenter, randomized (1:1), double-blind study assessed the 6-month effect of rotigotine versus placebo on apathy, depression and anxiety in de novo PD. The primary outcome was the change of apathy, measured with the LARS. The secondary outcomes were the change in depression and anxiety, measured with BDI-2 and STAI-trait and state. Forty-eight drug-naive PD patients were included. The primary outcome was not reached, with a surprisingly high placebo effect on apathy (60%). There was no significant difference in the change of depression at 6 months between rotigotine and placebo. Trait-anxiety was significantly improved by rotigotine compared to placebo (p = 0.04). Compared to placebo, low dose rotigotine significantly improved trait anxiety, but not apathy and depression. The major placebo effect on apathy points towards the importance of a multidisciplinary and tight follow-up in the management of neuropsychiatric symptoms.

The international European Academy of Neurology survey on neurological symptoms in patients with COVID-19 infection.

BACKGROUND AND PURPOSE: Although the main clinical features of COVID-19 infection are pulmonary, several associated neurological signs, symptoms and diseases are emerging. The incidence and characteristics of neurological complications are unclear. For this reason, the European Academy of Neurology (EAN) core COVID-19 Task Force initiated a survey on neurological symptoms observed in patients with COVID-19 infection. METHODS: A 17-question online survey was made available on the EAN website and distributed to EAN members and other worldwide physicians starting on 9 April 2020. RESULTS: By 27 April 2020, proper data were collected from 2343 responders (out of 4199), of whom 82.0% were neurologists, mostly from Europe. Most responders (74.7%) consulted patients with COVID-19 mainly in emergency rooms and in COVID-19 units. The majority (67.0%) had evaluated fewer than 10 patients with neurological manifestations of COVID-19 (neuro COVID-19). The most frequently reported neurological findings were headache (61.9%), myalgia (50.4%), anosmia (49.2%), ageusia (39.8%), impaired consciousness (29.3%) and psychomotor agitation (26.7%). Encephalopathy and acute cerebrovascular disorders were reported at 21.0%. Neurological manifestations were generally interpreted as being possibly related to COVID-19; they were most commonly recognized in patients with multiple general symptoms and occurred at any time during infection. CONCLUSION: Neurologists are currently and actively involved in the management of neurological issues related to the COVID-19 pandemic. This survey justifies setting up a prospective registry to better capture the prevalence of patients with neuro COVID-19, neurological disease characteristics and the contribution of neurological manifestations to outcome.

Battery longevity of neurostimulators in Parkinson disease: A historic cohort study.

BACKGROUND: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a well-established treatment for motor complications in Parkinson disease (PD). Since 2012, the nonrechargeable dual-channel neurostimulator available in France seems to have shorter battery longevity compared to the same manufacturer's previous model. OBJECTIVE: The aim of this study was to evaluate the battery longevity of older and more recent neurostimulators from the same manufacturer and to explore factors associated with battery life variations. MATERIALS AND METHODS: We retrospectively studied our cohort of PD patients who underwent STN DBS between 1987 and 2017. We collected data concerning neurostimulator replacements and parameters. We compared the survival of the first device available, Kinetra® and the current one, Activa-PC® (Medtronic Inc.) and estimated the factors that had an impact on battery longevity through a Cox logistic regression. RESULTS: Three hundred sixty-four PD patients received a total of 654 DBS STN neurostimulators: 317 Kinetra® and 337 Activa-PC®. The survival analysis, using the Kaplan-Meier estimator, showed a difference between the curves of the two devices (log-rank test; p < 0.001). The median survival of an Activa-PC® neurostimulator was 1666 days, while it was 2379 days for a Kinetra®. After adjustment, according to the multivariate analysis, the main factors associated with battery lifetime were: the neurostimulator type; the number of subsequent neurostimulator implantations; the total electrical energy delivered (TEED); and sex. CONCLUSION: The Kinetra® neurostimulator lifetime is 2.5 years longer than the Activa-PC®. The type of the device, the high TEED and the number of subsequent neurostimulator implantations influence battery longevity most. These results have medical-economic implications since the survival of PD patients with DBS increases over years.

Ketamine does not enhance the quality of recovery following laparoscopic cholecystectomy: a randomized controlled trial.

BACKGROUND: Ketamine has been used as part of the multimodal analgesia technique in the acute perioperative period. The effect of perioperative intravenous small-dose ketamine on the quality of recovery from the patient point-of-view has not been assessed. We hypothesized that low-dose ketamine would enhance recovery following laparoscopic cholecystectomy under total intravenous anesthesia. METHODS: One hundred thirty five patients undergoing laparoscopic cholecystectomy were enrolled in this randomized, double-blind placebo-controlled trial. Subjects were randomly assigned to one of three groups: saline, ketamine 0.2 mg/kg, or ketamine 0.4 mg/kg immediately following the induction of anesthesia and before skin incision. The primary endpoint was assessed using the Quality of Recovery Questionnaire (QoR-40), a 40-item quality of recovery scoring system. In addition, early clinical recovery variables, such as time to eye opening, occurrence of nausea and vomiting, pain score, analgesic use, and length of PACU stay were assessed. RESULTS: No differences were detected in the total or individual dimension scores of the QoR-40 questionnaire. The incidence of nausea, vomiting, and other complications did not differ among the three groups. CONCLUSIONS: Small doses of ketamine do not improve the quality of recovery after remifentanil-based anesthesia for laparoscopic cholecystectomy.

Efficacy of pallidal stimulation in isolated dystonia: a systematic review and meta-analysis.

The aim of this review was to provide strong clinical evidence of the efficacy of deep brain stimulation (DBS) of the globus pallidus internus (GPi) in isolated inherited or idiopathic dystonia. Eligible studies were identified after a systematic literature review of the effects of bilateral GPi-DBS in isolated dystonia. Absolute and percentage changes from baseline in the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) motor and disability scores were pooled, and associations between treatment effect and patient characteristics were explored using meta-regression. In total, 24 studies were included in the meta-analysis, comprising 523 patients. The mean absolute and percentage improvements in BFMDRS motor score at the last follow-up (mean 32.5 months; 24 studies) were 26.6 points [95% confidence interval (CI), 22.4-30.8] and 65.2% (95% CI, 59.6-70.7), respectively. The corresponding changes in disability score at the last follow-up (mean 32.9 months; 14 studies) were 6.4 points (95% CI, 5.0-7.8) and 58.6% (95% CI, 50.3-66.9). Multivariate meta-regression of absolute scores indicated that higher BFMDRS motor and disability scores before surgery, together with younger age at time of surgery, were the main factors associated with significantly better DBS outcomes at the latest follow-up. Reporting of safety data was frequently inconsistent and could not be included in the meta-analysis. In conclusion, patients with isolated inherited or idiopathic dystonia significantly improved after GPi-DBS. Better outcomes were associated with greater dystonia severity at baseline. These findings should be taken into consideration for improving patient selection for DBS.

New approach for the strategic control of gastrointestinal nematodes in grazed beef cattle during the growing phase in central Brazil.

We evaluated the effect of different treatment protocols against gastrointestinal nematodes in Nelore beef cattle during the growing phase in the municipality of Terenos, MS, in central Brazil from May 2013 to April 2014 and from May 2014 to April 2015. Ninety-six Nelore calves were kept on Brachiaria brizantha grass during each trial period and were distributed into six experimental groups (replicate paddocks for each group) based on live weight and the number of eggs per gram of feces (EPG): T1 (control)-treated in May, July and September with a saline solution; T2-treated in May and November with 700 µg/kg doramectin; T3-treated in May (doramectin), July (4.7 mg/kg levamisole phosphate) and September (doramectin); T4-treated in May (doramectin), July (200 µg/kg moxidectin) and September (doramectin); T5-treated in May (doramectin), August (levamisole phosphate) and November (doramectin) and T6-treated in May (doramectin), August (moxidectin) and November (doramectin). The calves were weighed and feces were collected (for faecal culture and EPG counts) from calves every 28 days, concomitantly with the collection of forage samples. The efficacies of doramectin, moxidectin and levamisole were low, at 69.2, 65.9 and 69.4% in the first and 13.8, 92.6, and 76.5% in the second experimental periods, respectively, but only the untreated animals lost weight during the dry season. Final weight gains did not differ significantly (p>0.05) among the animals in T2 (120.8 kg), T3 (131.4 kg), T4 (131.2 kg) and T5 (134.4 kg). T6 was the only group with a significantly higher final weight gain (140.9 kg) compared to the protocol with two annual dosages (T2). The weight gain was 31.9% higher in T6 than in the untreated animals (T1). None of the protocols affected the number of larvae on the pasture. Body weight was significantly and negatively (r=-0.65) correlated with EPG counts, which were significantly lower in June (T2, T3, T4 and T6), August (T3), September (T5 and T6), October (T5) and November (T5 and T6). Haemonchus, Cooperia, Trichostrongylus and Oesophagostomum were identified. Treatments in May and November, the most common practice in Brazil, did not increase the final weight gain, so an additional and intermediate treatment during the dry season (August) is recommended.

Delivering a sustainable trauma management training programme tailored for low-resource settings in East, Central and Southern African countries using a cascading course model.

BACKGROUND: Injuries cause five million deaths and 279 Disability Adjusted Life Years (DALYS) each year worldwide. The COSECSA Oxford Orthopaedic Link (COOL) is a multi-country partnership programme that has delivered training in trauma management to nine sub-Saharan countries across a wide-cadre of health-workers using a model of "primary" courses delivered by UK instructors, followed by "cascading" courses led by local faculty. This study examines the impact on knowledge and clinical confidence among health-workers, and compares the performance of "cascading" and "primary" courses delivered in low-resource settings. METHODS: Data was collated from 1030 candidates (119 Clinical Officers, 540 Doctors, 260 Nurses and 111 Medical Students) trained over 28 courses (9 "primary" and 19 "cascading" courses) in nine sub-Saharan countries between 2012 and 2013. Knowledge and clinical confidence of candidates were assessed using pre- and post-course MCQs and confidence matrix rating of clinical scenarios. Changes were measured in relation to co-variants of gender, job roles and primary versus cascading courses. Multivariate regression modelling and cost analysis was performed to examine the impact of primary versus cascading courses on candidates' performance. FINDINGS: There was a significant improvement in knowledge (58% to 77%, p<0.05) and clinical confidence (68% to 90%, p<0.05) post-course. "Non-doctors" demonstrated a greater improvement in knowledge (22%) and confidence (24%) following the course (p<0.05). The degree of improvement of MCQ scores differed significantly, with the cascading courses (21%) outperforming primary courses (15%) (p<0.002). This is further supported by multivariate regression modelling where cascading courses are a strong predictor for improvement in MCQ scores (Coef=4.83, p<0.05). INTERPRETATION: Trauma management training of health-workers plays a pivotal role in tackling the ever-growing trauma burden in Africa. Our study suggests cascading PTC courses may be an effective model in delivering trauma training in low-resource settings, however further studies are required to determine its efficacy in improving clinical competence and retention of knowledge and skills in the long term.

Subjectively perceived personality and mood changes associated with subthalamic stimulation in patients with Parkinson's disease.

BACKGROUND: Clinical and ethical implications of personality and mood changes in Parkinson's disease (PD) patients treated with subthalamic deep brain stimulation (STN-DBS) are under debate. Although subjectively perceived personality changes are often mentioned by patients and caregivers, few empirical studies concerning these changes exist. Therefore, we analysed subjectively perceived personality and mood changes in STN-DBS PD patients. METHOD: In this prospective study of the ELSA-DBS group, 27 PD patients were assessed preoperatively and 1 year after STN-DBS surgery. Two categories, personality and mood changes, were analysed with semi-structured interviews. Patients were grouped into personality change yes/no, as well as positive/negative mood change groups. Caregivers were additionally interviewed about patients' personality changes. Characteristics of each group were assessed with standard neurological and psychiatric measurements. Predictors for changes were analysed. RESULTS: Personality changes were perceived by six of 27 (22%) patients and by 10 of 23 caregivers (44%). The preoperative hypomania trait was a significant predictor for personality change perceived by patients. Of 21 patients, 12 (57%) perceived mood as positively changed. Higher apathy and anxiety ratings were found in the negative change group. CONCLUSIONS: Our results show that a high proportion of PD patients and caregivers perceived personality changes under STN-DBS, emphasizing the relevance of this topic. Mood changed in positive and negative directions. Standard measurement scales failed to adequately reflect personality or mood changes subjectively perceived by patients. A more individualized preoperative screening and preparation for patients and caregivers, as well as postoperative support, could therefore be useful.

Fully nonlinear dynamics of stochastic thin-film dewetting.

The spontaneous formation of droplets via dewetting of a thin fluid film from a solid substrate allows materials nanostructuring. Often, it is crucial to be able to control the evolution, and to produce patterns characterized by regularly spaced droplets. While thermal fluctuations are expected to play a role in the dewetting process, their relevance has remained poorly understood, particularly during the nonlinear stages of evolution that involve droplet formation. Within a stochastic lubrication framework, we show that thermal noise substantially influences the process of droplets formation. Stochastic systems feature a smaller number of droplets with a larger variability in size and space distribution, when compared to their deterministic counterparts. Finally, we discuss the influence of stochasticity on droplet coarsening for asymptotically long times.

Macroscopic response to microscopic intrinsic noise in three-dimensional Fisher fronts.

We study the dynamics of three-dimensional Fisher fronts in the presence of density fluctuations. To this end we simulate the Fisher equation subject to stochastic internal noise, and study how the front moves and roughens as a function of the number of particles in the system, N. Our results suggest that the macroscopic behavior of the system is driven by the microscopic dynamics at its leading edge where number fluctuations are dominated by rare events. Contrary to naive expectations, the strength of front fluctuations decays extremely slowly as 1/logN, inducing large-scale fluctuations which we find belong to the one-dimensional Kardar-Parisi-Zhang universality class of kinetically rough interfaces. Hence, we find that there is no weak-noise regime for Fisher fronts, even for realistic numbers of particles in macroscopic systems.

Estudio del papel de los miARN en células madre mesenquimales aisladas de pacientes artrósicos / Study of the role of miRNA in mesenchymal stem cells isolated from osteoarthritis patients

Objetivo: Los miARN actúan como silenciadores génicos que están implicados en la regulación de funciones celulares esenciales. El miR-335 participa regulando los procesos de diferenciación celular en células progenitoras. Las células madre mesenquimales (MSC) son células progenitoras de los condrocitos y osteoblastos encargados del mantenimiento homeostático del cartílago y hueso. El objetivo de este estudio era determinar una posible asociación entre la expresión de miR-335 y la enfermedad artrósica. Metodología: Las MSC obtenidas de la médula ósea de 3 pacientes artrósicos y 3 controles sin signos clínicos de artrosis ni osteoporosis se cultivaron y caracterizaron fenotípica y funcionalmente en el pase 3 de cultivo. Así mismo, mediante PCR cuantitativa se determinaron los niveles de expresión de miR-335 y del gen mesoderm-specific transcript ---MEST---, que controla su expresión. Resultados: Se detectaron diferencias entre las MSC aisladas de pacientes con artrosis y los controles en los niveles de expresión de miR-335 y de MEST (mediana [rango intercuartílico]: 1,69 [0,85-1,74]; 3,85 [3,20-5,67]). Aunque las diferencias detectadas no alcanzaron una significación estadística (p = 0,1), sí se apreció una clara tendencia a una menor expresión de miR-335 en las MSC de pacientes artrósicos. Conclusiones: Teniendo en cuenta que miR-335 tiene como dianas potenciales diferentes genes que participan en la vía de se˜nalización de la Wnt, la tendencia observada podría determinar, al menos en parte, algunas de las alteraciones que determinan el inicio o progresión de la artrosis, y puede, por lo tanto, servir en el diseño de futuras dianas terapéuticas para el tratamiento de esta enfermedad (AU)

Objective: MiRNAs act as gene silencers that are involved in the regulation of essential cell functions. miR-335 is involved in regulating cell differentiation processes in progenitor cells. Mesenchymal stem cells (MSCs) are progenitor cells of chondrocytes and osteoblasts responsible for homeostatic maintenance of cartilage and bone. The aim of this study was to determine a possible relationship between the expression of miR-335 and osteoarthritis. Methods: MSCs obtained from the bone marrow of 3 osteoarthritic patients and 3 controls with no clinical signs of osteoarthritis or osteoporosis were cultured and phenotypically and functionally characterised in a 3-step culture. Expression levels of miR-335 and the mesodermspecific transcript gene ---MEST--- that controls its expression were determined by quantitative PCR. Results: Differences in the expression levels of miR-335 and MEST (median [interquartile range]: 1.69 [0.85-1.74], and 3.85 [3.20-5.67] were detected between MSCs isolated from patients with osteoarthritis and controls. Although the differences detected did not reach statistical significance (P = .1), a clear trend towards lower expression of miR-335 in osteoarthritis MSCs was observed. Conclusions: Given that miR-335 has the different genes involved in the Wnt signalling pathway as potential targets, the observed trend may help to ascertain, at least partially, some of the alterations which determine the onset or progression of osteoarthritis, and can therefore serve for the design of future therapeutic targets for the treatment of this disease (AU)

[Study of the role of miRNA in mesenchymal stem cells isolated from osteoarthritis patients]. / Estudio del papel de los miARN en células madre mesenquimales aisladas de pacientes artrósicos.

OBJECTIVE: MiRNAs act as gene silencers that are involved in the regulation of essential cell functions. miR-335 is involved in regulating cell differentiation processes in progenitor cells. Mesenchymal stem cells (MSCs) are progenitor cells of chondrocytes and osteoblasts responsible for homeostatic maintenance of cartilage and bone. The aim of this study was to determine a possible relationship between the expression of miR-335 and osteoarthritis. METHODS: MSCs obtained from the bone marrow of 3 osteoarthritic patients and 3 controls with no clinical signs of osteoarthritis or osteoporosis were cultured and phenotypically and functionally characterised in a 3-step culture. Expression levels of miR-335 and the mesoderm-specific transcript gene -MEST- that controls its expression were determined by quantitative PCR. RESULTS: Differences in the expression levels of miR-335 and MEST (median [interquartile range]: 1.69 [0.85-1.74], and 3.85 [3.20-5.67] were detected between MSCs isolated from patients with osteoarthritis and controls. Although the differences detected did not reach statistical significance (P=.1), a clear trend towards lower expression of miR-335 in osteoarthritis MSCs was observed. CONCLUSIONS: Given that miR-335 has the different genes involved in the Wnt signalling pathway as potential targets, the observed trend may help to ascertain, at least partially, some of the alterations which determine the onset or progression of osteoarthritis, and can therefore serve for the design of future therapeutic targets for the treatment of this disease.

Wnt activation promotes neuronal differentiation of glioblastoma.

One of the biggest challenges in tumour research is the possibility to reprogram cancer cells towards less aggressive phenotypes. In this study, we reprogrammed primary Glioblastoma multiforme (GBM)-derived cells towards a more differentiated and less oncogenic phenotype by activating the Wnt pathway in a hypoxic microenvironment. Hypoxia usually correlates with malignant behaviours in cancer cells, but it has been recently involved, together with Wnt signalling, in the differentiation of embryonic and neural stem cells. Here, we demonstrate that treatment with Wnt ligands, or overexpression of ß-catenin, mediate neuronal differentiation and halt proliferation in primary GBM cells. An hypoxic environment cooperates with Wnt-induced differentiation, in line with our finding that hypoxia inducible factor-1α (HIF-1α) is instrumental and required to sustain the expression of ß-catenin transcriptional partners TCF-1 and LEF-1. In addition, we also found that Wnt-induced GBM cell differentiation inhibits Notch signalling, and thus gain of Wnt and loss of Notch cooperate in the activation of a pro-neuronal differentiation program. Intriguingly, the GBM sub-population enriched of cancer stem cells (CD133(+) fraction) is the primary target of the pro-differentiating effects mediated by the crosstalk between HIF-1α, Wnt, and Notch signalling. By using zebrafish transgenics and mutants as model systems to visualize and manipulate in vivo the Wnt pathway, we confirm that Wnt pathway activation is able to promote neuronal differentiation and inhibit Notch signalling of primary human GBM cells also in this in vivo set-up. In conclusion, these findings shed light on an unsuspected crosstalk between hypoxia, Wnt and Notch signalling in GBM, and suggest the potential to manipulate these microenvironmental signals to blunt GBM malignancy.

Role of neuronal and inducible nitric oxide synthases in the guinea pig ileum myenteric plexus during in vitro ischemia and reperfusion.

BACKGROUND: Intestinal ischemia and reperfusion (I/R) injury leads to abnormalities in motility, namely delay of transit, caused by damage to myenteric neurons. Alterations of the nitrergic transmission may occur in these conditions. This study investigated whether an in vitro I/R injury may affect nitric oxide (NO) production from the myenteric plexus of the guinea pig ileum and which NO synthase (NOS) isoform is involved. METHODS: The distribution of the neuronal (n) and inducible (i) NOS was determined by immunohistochemistry during 60 min of glucose/oxygen deprivation (in vitro ischemia) followed by 60 min of reperfusion. The protein and mRNA levels of nNOS and iNOS were investigated by Western-immunoblotting and real time RT-PCR, respectively. NO levels were quantified as nitrite/nitrate. KEY RESULTS: After in vitro I/R the proportion of nNOS-expressing neurons and protein levels remained unchanged. nNOS mRNA levels increased 60 min after inducing ischemia and in the following 5 min of reperfusion. iNOS-immunoreactive neurons, protein and mRNA levels were up-regulated during the whole I/R period. A significant increase of nitrite/nitrate levels was observed in the first 5 min after inducing I/R and was significantly reduced by N(ω) -propyl-l-arginine and 1400 W, selective inhibitors of nNOS and iNOS, respectively. CONCLUSIONS & INFERENCES: Our data demonstrate that both iNOS and nNOS represent sources for NO overproduction in ileal myenteric plexus during I/R, although iNOS undergoes more consistent changes suggesting a more relevant role for this isoform in the alterations occurring in myenteric neurons following I/R.

Reduced paired pulse depression in the basal ganglia of dystonia patients.

Decreased inhibition and aberrant plasticity are key features in the pathophysiology of dystonia. Impaired short interval cortical inhibition and resultant increased excitability have been described for various forms of dystonia using paired pulse methods with transcranial magnetic stimulation of motor cortex. It is hypothesized that, in addition to cortical abnormalities, impairments in basal ganglia function may lead to dystonia but a deficit of inhibition within the basal ganglia has not been demonstrated to date. To examine the possibility that impaired inhibition and synaptic plasticity within the basal ganglia play a role in dystonia, the present study used a pair of microelectrodes to test paired pulse inhibition in the globus pallidus interna (GPi) and substantia nigra pars reticulata (SNr) of dystonia and PD patients undergoing implantation of deep brain stimulating (DBS) electrodes. We found that there was less paired pulse depression of local field evoked potentials in the basal ganglia output nuclei of dystonia patients compared with Parkinson's disease patients on dopaminergic medication. Paired pulse depression could be restored following focal high frequency stimulation (HFS). These findings suggest that abnormalities exist in synaptic function of striatopallidal and/or striatonigral terminals in dystonia patients and that these abnormalities may contribute to the pathophysiology of dystonia, either independent of, or in addition to the increased excitability and plasticity observed in cortical areas in dystonia patients. These findings also suggest that HFS is capable of enhancing striatopallidal and striatonigral GABA release in basal ganglia output nuclei, indicating a possible mechanism for the therapeutic benefits of DBS in the GPi of dystonia patients.

Palliative care for advanced Parkinson disease: an interdisciplinary clinic and new scale, the ESAS-PD.

UNLABELLED: Palliative care provides a holistic approach to symptom relief using a multidisciplinary team approach to enhance quality of life throughout the entire course of a particular illness. The care team consists of movement disorders neurologist, a palliative care physician, a wound care nurse, a spiritual counselor and a care coordinator. Palliative care concepts were applied to a group of advanced Parkinson disease (PD) patients in a dedicated Palliative Care Clinic. METHODS: A modified Edmonton Symptom Assessment System Scale for PD (ESAS-PD) was developed and applied to 65 PD patients at their initial consultation and following recommended interventions. Scores were compared to those of metastatic cancer patients reported in the palliative care literature. RESULTS: The ESAS-PD scores significantly improved after the interventions (56 and 40 respectively, p = 0.0001). The most improved items were constipation, dysphagia, anxiety, pain and drowsiness. ESAS-PD scores were not significantly different from metastatic cancer patients' ESAS scores. CONCLUSIONS: ESAS-PD is a quick, effective scale for assessment of late stage PD symptoms. Scores are sensitive to intervention, and therefore have potential clinical utility for physicians and other healthcare providers. Advanced PD patients have a similar degree of symptoms as metastatic cancer patients, respond to treatment in a similar way, and therefore should have access to palliative care services.

Subthalamic deep brain stimulation at individualized frequencies for Parkinson disease.

OBJECTIVES: The oscillation model of Parkinson disease (PD) states that, in the subthalamic nucleus (STN), increased θ (4-10 Hz) and ß (11-30 Hz) frequencies were associated with worsening whereas γ frequencies (31-100 Hz) were associated with improvement of motor symptoms. However, the peak STN frequency in each band varied widely from subject to subject. We hypothesized that STN deep brain stimulation (DBS) at individualized γ frequencies would improve whereas θ or ß frequencies would worsen PD motor signs. METHODS: We prospectively studied 13 patients with PD. STN local field potential (LFP) was recorded after electrode implantations, in the OFF and then in ON dopaminergic medication states while patients performed wrist movements. Six individual peak frequencies of the STN LFP power spectra were obtained: the greatest decrease in θ and ß and greatest increase in γ frequencies in the ON state (MED) and during movements (MOVE). Eight DBS frequencies were applied including 6 MED and MOVE frequencies, high frequency (HF) used for chronic stimulation, and no stimulation. The patients were assessed using the motor Unified Parkinson's Disease Rating Scale (mUPDRS). RESULTS: STN DBS at γ frequencies (MED and MOVE) and HF significantly improved mUPDRS scores compared to no stimulation and both γ frequencies were not different from HF. DBS at θ and ß frequencies did not worsen mUPDRS scores compared to no stimulation. CONCLUSION: Short-term administration of STN DBS at peak dopamine-dependent or movement-related γ frequencies were as effective as HF for reducing parkinsonian motor signs but DBS at θ and ß frequencies did not worsen PD motor signs. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that STN DBS at patient-specific γ frequencies and at usual high frequencies both improved mUPDRS scores compared to no stimulation and did not differ in effect.