Geste Antagoniste Effects on Motor Performance in Dystonia-A Kinematic Study.

Background: The kinematic effects of gestes have not previously been studied. The mechanism(s) by which these sensory tricks modify dystonic movement is not well understood. Objectives: A kinematic investigation of the geste phenomenon in patients with dystonia. Methods: Twenty-three patients with dystonia associated with a geste were studied. Twenty-nine healthy controls also participated. Fifteen seconds of finger tapping was recorded by electromagnetic sensors, and the task was repeated with geste. Separable motor components were extracted using a custom-written MATLAB script. Performance with and without geste was compared using Wilcoxon signed ranks testing. Results: Speed and fluency of finger tapping is impaired in dystonia. When patients executed their geste, speed of movement (amplitude × frequency) increased (P < 0.0001), and halts decreased (P = 0.007). Conclusions: That gestes improve not only dystonic muscle contraction but also the efficiency of voluntary movement suggests a broad influence at the premotor control stage.

Surgical treatment for chronic thromboembolic pulmonary hypertension: an historical perspective.

Chronic thrombotic occlusion of the pulmonary arteries that results in pulmonary hypertension is now recognized as being relatively common, and surgical treatment of the condition is being increasingly applied throughout the world. However, the condition was not described until 90 years ago, and just 60 years ago less than 200 cases of the syndrome had been reported. At that time the condition was thought to be inoperable. Surgery for the acute phase of pulmonary embolism was attempted beginning 100 years ago, with minimal success until cardiopulmonary bypass was developed and could be used to stabilize the patient during induction of anesthesia and the surgical removal of the embolus. Pulmonary endarterectomy was suggested as a possible surgical approach to the chronic condition in 1956, and the first planned pulmonary endarterectomy was performed in 1957. Over the next thirty years several operations were attempted in Europe and the United States. By 1989 it is likely that fewer than 250 cases of pulmonary endarterectomy had been attempted, with a mortality rate of greater than 20%. Some cases of pulmonary endarterectomy had been carried out successfully at the University of California, San Diego (UCSD), beginning in 1970. The technique of the operation was refined, and in 2003 the results of 1,500 of these operations performed at UCSD were described, with a mortality rate of less than 5%. The good results obtained in San Diego encouraged other groups internationally to start their own programs and the operation is now well established, with good results. The following discourse traces the development of surgery, first for acute pulmonary embolism, and also, growing out of that experience, an operation for chronic pulmonary embolism.

Significant cognitive decline in Parkinson's disease exacerbates the reliance on visual feedback during upper limb reaches.

While upper limb reaches are often made in a feed-forward manner, visual feedback during the movement can be used to guide the reaching hand towards a target. In Parkinson's disease (PD), there is evidence that the utilisation of this visual feedback is increased. However, it is unclear if this is due solely to the characteristic slowness of movements in PD providing more opportunity for incorporating visual feedback to modify reach trajectories, or whether it is due to cognitive decline impacting (feed-forward) movement planning ability. To investigate this, we compared reaction times and movement times of reaches to a target in groups of PD patients with normal cognition (PD-NC), mild cognitive impairment (PD-MCI) or dementia (PD-D), to that of controls with normal cognition (CON-NC) or mild cognitive impairment (CON-MCI). Reaches were undertaken with full visual feedback (at a 'natural' and 'fast-as-possible' pace); with reduced visual feedback of the reaching limb to an illuminated target; and without any visual feedback to a remembered target with eyes closed. The PD-D group exhibited slower reaction times than all other groups across conditions, indicative of less efficient movement planning. When reaching to a remembered target with eyes closed, all PD groups exhibited slower movement times relative to their natural pace with full visual feedback. Crucially, this relative slowing was most pronounced for the PD-D group, compared to the PD-MCI and PD-NC groups, suggesting that substantial cognitive decline in PD exacerbates dependence on visual feedback during upper limb reaches.

Objective assessment of bradykinesia in Parkinson's disease using evolutionary algorithms: clinical validation.

BACKGROUND: There is an urgent need for developing objective, effective and convenient measurements to help clinicians accurately identify bradykinesia. The purpose of this study is to evaluate the accuracy of an objective approach assessing bradykinesia in finger tapping (FT) that uses evolutionary algorithms (EAs) and explore whether it can be used to identify early stage Parkinson's disease (PD). METHODS: One hundred and seven PD, 41 essential tremor (ET) patients and 49 normal controls (NC) were recruited. Participants performed a standard FT task with two electromagnetic tracking sensors attached to the thumb and index finger. Readings from the sensors were transmitted to a tablet computer and subsequently analyzed by using EAs. The output from the device (referred to as "PD-Monitor") scaled from - 1 to + 1 (where higher scores indicate greater severity of bradykinesia). Meanwhile, the bradykinesia was rated clinically using the Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) FT item. RESULTS: With an increasing MDS-UPDRS FT score, the PD-Monitor score from the same hand side increased correspondingly. PD-Monitor score correlated well with MDS-UPDRS FT score (right side: r = 0.819, P = 0.000; left side: r = 0.783, P = 0.000). Moreover, PD-Monitor scores in 97 PD patients with MDS-UPDRS FT bradykinesia and each PD subgroup (FT bradykinesia scored from 1 to 3) were all higher than that in NC. Receiver operating characteristic (ROC) curves revealed that PD-Monitor FT scores could detect different severity of bradykinesia with high accuracy (≥89.7%) in the right dominant hand. Furthermore, PD-Monitor scores could discriminate early stage PD from NC, with area under the ROC curve greater than or equal to 0.899. Additionally, ET without bradykinesia could be differentiated from PD by PD-Monitor scores. A positive correlation of PD-Monitor scores with modified Hoehn and Yahr stage was found in the left hand sides. CONCLUSIONS: Our study demonstrated that a simple to use device employing classifiers derived from EAs could not only be used to accurately measure different severity of bradykinesia in PD, but also had the potential to differentiate early stage PD from normality.

Chronic Thromboembolic Pulmonary Hypertension.

Chronic thromboembolic pulmonary hypertension occurs when acute thromboemboli fail to dissolve completely. The resulting fibrotic scar tissue within the pulmonary arteries is obstructive and eventually leads to right heart failure. Medical therapy for this condition is supportive, but surgery with pulmonary artery endarterectomy is curative, and carries a low mortality at experienced centers.

A New Evolutionary Algorithm-Based Home Monitoring Device for Parkinson's Dyskinesia.

Parkinson's disease (PD) is a neurodegenerative movement disorder. Although there is no cure, symptomatic treatments are available and can significantly improve quality of life. The motor, or movement, features of PD are caused by reduced production of the neurotransmitter dopamine. Dopamine deficiency is most often treated using dopamine replacement therapy. However, this therapy can itself lead to further motor abnormalities referred to as dyskinesia. Dyskinesia consists of involuntary jerking movements and muscle spasms, which can often be violent. To minimise dyskinesia, it is necessary to accurately titrate the amount of medication given and monitor a patient's movements. In this paper, we describe a new home monitoring device that allows dyskinesia to be measured as a patient goes about their daily activities, providing information that can assist clinicians when making changes to medication regimens. The device uses a predictive model of dyskinesia that was trained by an evolutionary algorithm, and achieves AUC>0.9 when discriminating clinically significant dyskinesia.

Using epigenetic networks for the analysis of movement associated with levodopa therapy for Parkinson's disease.

Levodopa is a drug that is commonly used to treat movement disorders associated with Parkinson's disease. Its dosage requires careful monitoring, since the required amount changes over time, and excess dosage can lead to muscle spasms known as levodopa-induced dyskinesia. In this work, we investigate the potential for using epiNet, a novel artificial gene regulatory network, as a classifier for monitoring accelerometry time series data collected from patients undergoing levodopa therapy. We also consider how dynamical analysis of epiNet classifiers and their transitions between different states can highlight clinically useful information which is not available through more conventional data mining techniques. The results show that epiNet is capable of discriminating between different movement patterns which are indicative of either insufficient or excessive levodopa.

What to do when people with Parkinson's disease cannot take their usual oral medications.

People with Parkinson's disease have limited brain reserves of endogenous dopamine; thus, their medications must not be omitted or delayed as this may lead to a significant drop in brain dopamine levels. This has two main clinical consequences: first, a deterioration in disease control, with distressing symptoms such as tremor, pain, rigidity, dysphagia and immobility, and second, an increased risk of developing the life-threatening complication of neuroleptic malignant-like syndrome. Common reasons for people with Parkinson's disease being unable to take their oral medications are neurogenic dysphagia from progressive disease or concurrent illness, gastroenteritis, iatrogenic 'nil by mouth' status especially perioperatively, and impaired consciousness level. Here we outline alternative methods to give dopaminergic drugs in the acute setting to people with Parkinson's disease who cannot take their usual oral treatment, namely using dispersible preparations in thickened fluids, an enteral tube, a transdermal patch or subcutaneous injections.

Which figure copy test is more sensitive for cognitive impairment in Parkinson's disease: Wire cube or interlocking pentagons?

BACKGROUND: Performance on figure copy tests has been shown to predict progressive cognitive decline in Parkinson's disease (PD). Historically, the interlocking pentagons from the Mini Mental State Exam (MMSE) have been the figure copy test most commonly used during cognitive screening evaluations. However, the wire cube from the Montreal Cognitive Assessment (MoCA) is increasingly being used. OBJECTIVE: To evaluate which of these figure copy tests is more sensitive for cognitive impairment in PD. METHODS: Sixty-three PD patients from UK and USA completed the MMSE and MoCA. Logistic regression and sensitivity/specificity analyses were used to evaluate the utility of each figure copy test for detecting global cognitive impairment. RESULTS: The wire cube was a significant indicator of cognitive impairment (OR=4.79, 95% CI=1.63-14.07, p=0.004), with a sensitivity/specificity of 0.74/0.63 in our sample. In contrast, interlocking pentagons were not a significant indicator of cognitive impairment (OR=1.88, 95% CI=0.54-6.50, p=0.32), with a sensitivity/specificity of 0.26/0.84. CONCLUSION: The wire cube is more sensitive to cognitive impairment in PD, most likely related to its greater complexity. The results have implications for clinicians who may have time for just one figure copying task as part of a brief screen for cognitive impairment in busy clinics and for researchers applying the PD mild cognitive impairment diagnostic criteria necessitating two tests of visuospatial function to be administered.

Efficacy of a Low-Tidal Volume Ventilation Strategy to Prevent Reperfusion Lung Injury after Pulmonary Thromboendarterectomy.

RATIONALE: Reperfusion lung injury is a postoperative complication of pulmonary thromboendarterectomy that can significantly affect morbidity and mortality. Studies in other postoperative patient populations have demonstrated a reduction in acute lung injury with the use of a low-tidal volume (Vt) ventilation strategy. Whether this approach benefits patients undergoing thromboendarterectomy is unknown. OBJECTIVES: We sought to determine if low-Vt ventilation reduces reperfusion lung injury in patients with chronic thromboembolic pulmonary hypertension undergoing thromboendarterectomy. METHODS: Patients undergoing thromboendarterectomy at one center were randomized to receive either low (6 ml/kg predicted body weight) or usual care Vts (10 ml/kg) from the initiation of mechanical ventilation in the operating room through Postoperative Day 3. The primary endpoint was the onset of reperfusion lung injury. Secondary outcomes included severity of hypoxemia, days on mechanical ventilation, and intensive care unit and hospital lengths of stay. MEASUREMENTS AND MAIN RESULTS: A total of 128 patients were enrolled and included in the analysis; 63 were randomized to the low-Vt group and 65 were randomized to the usual care group. There was no statistically significant difference in the incidence of reperfusion lung injury between groups (32%, n=20 in the low-Vt group vs. 23%, n=15 in the usual care group; P=0.367). Although differences were noted in plateau pressures (17.9 cm H2O vs. 20.1 cm H2O, P<0.001) and peak inspiratory pressures (20.4 cm H2O vs. 23.0 cm H2O, P<0.001) between the low-Vt and usual care groups, respectively, mean airway pressures, PaO2/FiO2, days on mechanical ventilation, and ICU and hospital lengths of stay were all similar between groups. CONCLUSIONS: In patients with chronic thromboembolic pulmonary hypertension undergoing pulmonary thromboendarterectomy, intra- and postoperative ventilation using low Vts (6 mg/kg) compared with usual care Vts (10 mg/kg) does not reduce the incidence of reperfusion lung injury or improve clinical outcomes. Clinical trial registered with www.clinicaltrials.gov (NCT00747045).

When myopathy breaks the rules: a late-onset distal presentation.

Myopathies typically present with proximal or generalised muscle weakness, but it is important for clinicians to recognise they may also have other distributions. This paper describes a case of distal myopathy that was confirmed genetically as ZASP (Z-band alternatively spliced PDZ motif-containing protein) myofibrillar myopathy (MFM). MFMs are particularly topical because the genetic basis of several have recently been established, enabling diagnosis of conditions previously labelled 'idiopathic myopathy', and shedding new light on their pathophysiology. This paper describes a purely distal lower limb phenotype of ZASP MFM, the pathophysiology of ZASP and other MFMs, and the differential diagnosis of late-onset distal symmetrical weakness. The case includes several learning points: ZASP MFM is a new diagnosis; it should be included in differential diagnoses for late-onset myopathy, especially if there is a distal pattern or autosomal dominant inheritance; testing for cardiomyopathy is recommended, and a genetic test is now available.

Cognitive impairment in Parkinson's disease.

Cognitive impairment is a significant non-motor symptom of Parkinson's disease (PD). Longitudinal cohort studies have demonstrated that approximately 50% of those with PD develop dementia after 10 years, increasing to over 80% after 20 years. Deficits in cognition can be identified at the time of PD diagnosis in some patients and this mild cognitive impairment (PD-MCI) has been studied extensively over the last decade. Although PD-MCI is a risk factor for developing Parkinson's disease dementia there is evidence to suggest that PD-MCI might consist of distinct subtypes with different pathophysiologies and prognoses. The major pathological correlate of Parkinson's disease dementia is Lewy body deposition in the limbic system and neocortex although Alzheimer's related pathology is also an important contributor. Pathological damage causes alteration to neurotransmitter systems within the brain, producing behavioural change. Management of cognitive impairment in PD requires a multidisciplinary approach and accurate communication with patients and relatives is essential.

Baseline body mass index does not significantly affect outcomes after pulmonary thromboendarterectomy.

BACKGROUND: Obesity is a common comorbidity of patients with chronic thromboembolic pulmonary hypertension referred for pulmonary thromboendarterectomy, yet the effect of obesity on pulmonary thromboendarterectomy outcomes has not been well described. METHODS: We conducted a retrospective cohort study in which 476 consecutive operations over a 3.5-year period were examined to determine the effects of obesity on outcomes. Patients were grouped into four categories based on body mass index (BMI): less than 22 kg/m2, 22 to 30 kg/m2, 30 to 40 kg/m2, and more than 40 kg/m2. RESULTS: There were important differences in baseline pulmonary hemodynamics, with obese patients having significantly lower pulmonary vascular resistances than nonobese patients. All patients achieved a significant reduction in pulmonary vascular resistance, although the improvement was greatest in the lower BMI groups. The overall in-hospital mortality was 0.8%, and there were no differences in risk among BMI groups. Among the BMI groups, there were no differences in incidence of postoperative complications, including atrial fibrillation (overall 24.8%), reperfusion lung injury (overall 23.1%), and surgical site infection (overall 4.4%) or in median lengths of stay (including ventilator days, intensive care unit days, and postoperative length of stay). CONCLUSIONS: Pulmonary thromboendarterectomy outcomes have continued to improve, and this surgery can safely be completed in obese patients, previously deemed to be at high risk for poor outcomes.