Sensor Array for Detection of Early Stage Parkinson's Disease before Medication.

Early diagnosis of Parkinson's disease (PD) is important because it affects the choice of therapy and is subject to a relatively high degree of error. In addition, early detection of PD can potentially enable the start of neuroprotective therapy before extensive loss of dopaminergic neurons of the substantia nigra occurs. However, until now, studies for early detection of PD using volatile biomarkers sampled only treated and medicated patients. Therefore, there is a great need to evaluate untreated patients for establishing a real world screening and diagnostic technology. Here we describe for the first time a clinical trial to distinguish between de novo PD and control subjects using an electronic system for detection of volatile molecules in exhaled breath (sensor array). We further determine for the first time the association to other common tests for PD diagnostics as smell, ultrasound, and nonmotor symptoms. The test group consisted of 29 PD patients after initial diagnosis by an experienced neurologist, compared with 19 control subjects of similar age. The sensitivity, specificity, and accuracy values of the sensor array to detect PD from controls were 79%, 84%, and 81% respectively, in comparison with midbrain ultrasonography (93%, 90%, 92%) and smell detection (62%, 89%, 73%). The results confirm previous data showing the potential of sensor arrays to detect PD.

Hot executive control and response to a stimulant in a double-blind randomized trial in children with ADHD.

Attention deficit hyperactivity disorder (ADHD) is thought to involve an executive inhibitory control (IC) deficit, yet it is not clear if this is a general deficit affecting both cold and hot EC, and if methylphenidate (MPH) affects both systems in treated children. We explored this by using a Stroop-like task in children with ADHD as compared to controls, containing different types of emotional stimuli (six levels), and we investigated the role of intervention with MPH on IC as compared to placebo. Children with ADHD and controls (N = 40; 7-13 years old) were tested with a hot and cold Stroop-like task. This was followed by a double-blind placebo-controlled crossover trial of the effect of MPH on these skills. Children with ADHD showed a specific difficulty inhibiting their responses, particularly to hot, angry and frustration-inducing stimuli. Further, treatment with MPH was effective in reducing errors toward frustration-inducing stimuli as compared to placebo (p < .05, η 2 = .347), particularly with repeated exposure to the stimuli. Results indicate that children with ADHD experience executive control difficulties, particularly in hot negative emotional contexts. These emotion regulation difficulties are amenable to stimulant intervention.

[An approach to non-motor symptoms of Parkinson's disease: an update on pathophysiology and treatment].

The diagnosis of Parkinson's disease (PD) is based on the identification of at least two of the cardinal motor signs of the disease: rest tremor, bradykinesia, rigidity, and in progressive state the loss of postural reflexes. The disease is manifested mainly by motor signs but several non-motor features are present in patients with PD. Often, these non-motor symptoms can precede the motor features of the disease. We review part of the different non-motor symptoms that can be present in patients with PD. In many cases, the non-motor symptoms could cause important Limitations in the functionality of the patients, no less than the motor symptoms, and they are often difficult to treat.

An approach to the continuous dopaminergic stimulation in Parkinson's disease.

Dopaminergic neurons in the basal ganglia normally fire in a continuous manner, maintaining the striatal dopamine concentration at a relatively constant level. In Parkinson's disease, dopaminergic treatment produces a discontinuous stimulation, inducing an intermittent pulsatile activation of the striatal receptors. It is likely that the oscillations in the dopamine level in the striatum contribute to the development of motor complications. Treatment with long-acting dopaminergic agents, or providing a more continuous dopaminergic effect in the striatum, has been associated with fewer clinical motor complications. This review describes the state-of-the-art approach to achieve the desired continuous dopaminergic stimulation, providing patients with the best clinical effect and probably minimal motor complications.

Adaptation to cyclic stance perturbations in Parkinson's disease depends on postural demands.

The postural reactions of 10 moderate PD patients and 10 age matched controls were studied during stance on a sinusoidally back and forth moving platform during 5 blocks of 10, 1-min trials. Free stance was followed by weight bearing, lowering or raising the center of gravity (COG) by 10%. Next, a book was balanced on the head and finally, forward inclination was constrained. Normal stance strategy, including predictive muscle responses was found during free stance. Modifying COG height caused little response changes. Stance strategy became abnormal when head trajectory or forward inclination was restricted, indicating that ability to generate a nonstandard multi-joint stance strategy, rather than production of adequate stabilizing forces, is impaired in moderate, medicated PD patients.

Recruitment of attentional resources during visuomotor tracking: effects of Parkinson's disease and age.

The ability to recruit attentional resources during distracted tracking was studied in 19 moderate PD patients, 21 healthy elderly subjects and 20 young controls. All subjects tracked a 1-cm circle that moved across a computer screen along a sinusoidal path (training) and along a circular path (testing). Tracking consisted of maintaining a dot cursor within the target by moving an unseen manipulandum across a digitizing tablet. Distraction consisted of adding one or three, colored 12-mm circles that moved around and intersected with the target circle, and one or three dots that moved around and intersected with the subject-controlled cursor. The performance of tasks with a low level of distraction (one dot and one circle distractor) and of tasks with a high level of distraction (three dot and three circle distractors) was compared to performance with no distraction. The elderly and young controls did not differ in the baseline task. Both groups surpassed the patients, who failed to keep pace with the target, despite preserved ability to attain the necessary movement speed. Under a low level of distraction, the ability to adjust the direction of hand movement diminished in both control groups, but task management was unaltered. In the patients adjustment of hand movement direction lowered, as in the controls, but task management reduced significantly. Under a high level of distraction, all groups showed further decrement in both aspects of task performance. We conclude that PD, but not age, significantly reduces the attentional resources required for administrative control of tracking, which are associated with prefrontal function.

Dopamine-transporter imaging and visuo-motor testing in essential tremor, practical possibilities for detection of early stage Parkinson's disease.

BACKGROUND: Essential tremor (ET) is often an alternative diagnosis to Parkinson's disease (PD) and some ET patients may later develop PD. Unlike the former, PD patients have deficient visuo-motor coordination (VMC). Recently, we have attempted to exploit this difference in order to detect PD in ambiguous neurological cases. OBJECTIVE: To assess the possibility of using VMC testing for screening ET patients prior to [123I]-FP-CIT SPECT imaging. METHODS: Ten clinically diagnosed ET patients who showed deficient VMC were subjected to [123I-FP-CIT] SPECT imaging. We expected these patients to show subnormal striatal ligand uptake, as in PD. RESULTS: We found decreased [123I]-FP-CIT uptake in 80% of the patients. A significant correlation between ligand uptake and VMC was observed. CONCLUSIONS: Impaired VMC is a pertinent indication for further SPECT imaging in patients with ET, in order to establish a diagnosis of incipient PD.

Antipsychotic-induced rabbit syndrome: epidemiology, management and pathophysiology.

Rabbit syndrome is an antipsychotic-induced rhythmic motion of the mouth/lips, resembling the chewing movements of a rabbit. The movement consists of a vertical-only motion, at about 5Hz, with no involvement of the tongue. Usually, the involuntary movements associated with rabbit syndrome appear after a long period (in most cases months or years) of antipsychotic treatment; however, a few patients with the syndrome have had treatment histories with no antipsychotic involvement. The reported prevalence of rabbit syndrome ranges from 2.3 to 4.4% of patients treated with typical antipsychotics. There have been isolated reports of rabbit syndrome in patients treated with the atypical agents risperidone and clozapine. Patients with rabbit syndrome are most often misdiagnosed as having oral tardive dyskinesia. In such cases the key for correct diagnosis is the involvement of tardive tongue movements, which does not occur in rabbit syndrome. The treatment of rabbit syndrome is empirical, reflecting poor understanding of its neuropathology. The first step is to reduce the amount of antipsychotic treatment as much as possible. However, since, in most cases, full withdrawal of antipsychotic treatment is impossible, the syndrome cannot be completely abolished without additional measures. The next stage of treatment involves specific drugs that aim to control the syndrome. Anticholinergic drugs are the best known treatment. Rabbit syndrome does not respond to treatment with levodopa or dopamine agonists. The most striking aspect of this syndrome is its specificity. Rabbit syndrome affects only the buccal region, and within this area it involves a highly stereotyped involuntary movement. This immediately focuses attention on the basal ganglia, in particular the substantia nigra pars reticulata, which is also implicated in oral dyskinesia. Continuing neurophysiological and pharmacological research of the basal ganglia holds the key to better understanding and treatment of this syndrome in the coming years.

Response selection and execution in patients with Parkinson's disease.

Different studies report diverse, sometimes conflicting findings, regarding the ability of Parkinson's disease (PD) patients to benefit from advanced cuing in choice reaction time (RT). Thus, conclusions about the changed state of underlying processes such as set formation, motor programming and motor initiation are not certain. In the present study, visual choice RT testing that utilized brief (100 ms) color signals (red/blue), was followed by auditory choice reaction time (CRT) testing with brief (100 ms) low/high pitch sound stimuli. Response consisted of either index or middle finger flexion. The signals were then combined so that the color stimuli cued the sound stimuli with an 800-ms interstimuli interval. Cuing validity was reduced from 100% during training to 76% during final testing. In addition, the same sound stimuli were presented randomly, without visual cuing, in which case response should have been suppressed. Tested subjects include 19 moderate PD patients, 21 elderly controls and 20 young controls. The patients did not differ from the controls in error rate but were slower to respond, except under 100% congruent cuing, indicating that their extended RT in CRT results from slowed stimulus-response linking and not from impaired motor initiation/execution. In the final condition patients showed no perseverance and demonstrated normal speed of set shifting in incongruent trials.

Visuo-motor coordination is normal in patients with major depression.

Depression and Parkinson's disease (PD) are strongly associated with each other. Similarly, deficient visuo-motor coordination (VMC) accompanies PD from its earliest clinical stages. This double association suggests that a VMC dysfunction would be found in patients with major depression. Previous reports are ambiguous on this matter. Therefore, the present study was undertaken in order to determine whether MD patients pass or fail a VMC test on which PD patients are known to be deficient.Sixty-five MD patients were tested. Fifty-four (83%) had normal VMC. VMC was found to be independent of age, disease duration, severity of depression, or treatment. A deficit was found in 12 patients (17%). In this group too, VMC capabilities did not correlate with depression, or its treatment.These results negate an effect of depression, its accompanying frontal cortical changes, or its treatment on VMC. We propose that abnormal VMC in depression indicates coexisting illness, including possible preclinical PD.

Impaired visuomotor function in schizophrenic patients compared with control subjects.

Visuomotor function was studied in 36 schizophrenic patients treated with atypical antipsychotics and in 22 control subjects. Patients showed significant disturbances in ability to control movement direction when tracing objects on screen and in keeping pace with a moving target in tracking tests. The impairments were not related to medication dose or to extrapyramidal side effects. Visuomotor impairment may be part of illness-related pathology in schizophrenia.