A new automated implementation of the Posturo-Locomotion-Manual (PLM) method for movement analysis in patients with parkinson's disease.

OBJECTIVE: The Posturo-Locomotion-Manual (PLM) test, which uses an optoelectronic laboratory system, has here been further developed into an automated, more user-friendly, standardized tool for movement analysis named the QbTestMotus. This paper compares the accuracy of QbTestMotus to the PLM test, in particular the automated data analysis. METHODS: Both QbTestMotus and the PLM recorded data simultaneously from the same 61 patients. The correlation coefficients of movement time (MT), postural time (P), locomotion time (L), and manual time (M) were calculated between the systems. The absolute differences between the result parameters for each patient were also studied. Finally, the differences in MT between the systems were compared with the positive responses in the levodopa (L-dopa) challenges as measured in the PLM test for 11 patients. RESULTS: The comparisons in all the 61 patients showed high correlation coefficients for all four parameters. The absolute differences between the parameters were small and had small standard deviations, and the decreases in MT because of L-dopa in the positive L-dopa responders were much larger than the absolute difference between the systems. CONCLUSION: The PLM test and QbTestMotus are equivalent along all parameters, thus indicating that the test quality is equivalent between the PLM test and the automated QbTestMotus system.

Light subunit of neurofilament triplet protein in the cerebrospinal fluid after subthalamic nucleus stimulation for Parkinson's disease.

OBJECTIVES: Cerebrospinal fluid (CSF) levels of neurofilament triplet protein (NFL), a non-specific marker of neuronal damage, are normal in Parkinson's disease (PD) but increased after brain trauma and in several neurological disorders. Using longitudinal CSF-NFL measurements as an indicator of neuronal damage, this study investigated the impact of deep brain stimulation (DBS) of the subthalamic nucleus (STN) on the brain, directly following the surgical intervention and in chronically treated patients with PD. MATERIALS AND METHODS: CSF-NFL levels were measured consecutively in eight patients with PD before and after STN-DBS treatment. RESULTS: CSF-NFL levels were normal prior to STN-DBS and increased sharply during the first 2 weeks post-operatively, but normalized after 12 months or more. CONCLUSION: The STN-DBS procedure leads to an acute but limited neuronal damage, as expected. However, normal CSF-NFL levels at 12 months post-operatively and beyond suggest the absence of any long-term neuronal damage caused by long-term STN-DBS stimulation.

Multicentre European study of thalamic stimulation for parkinsonian tremor: a 6 year follow-up.

AIM: To evaluate the results of ventral intermediate (Vim) thalamic deep brain stimulation (DBS) in patients with tremor predominant Parkinson's disease (PD) at 6 years post surgery. METHODS: This was a prolonged follow-up study of 38 patients from eight centres who participated in a multicentre study, the 1 year results of which have been published previously. Total scores as well as scores for individual items of the motor part and the disability part of the Unified Parkinson's Disease Rating Scale were used for evaluation. RESULTS: Tremor was still effectively controlled by DBS and appendicular rigidity and akinesia remained stable compared with baseline. Axial scores (speech, gait and postural instability), however, worsened, and in parallel the initial improvement in activities of daily living scores at the 1 year follow-up had disappeared at 6 years, despite sustained improvement of tremor. Remarkably, neither daily doses of dopaminergic medication nor fluctuations and dyskinesias had changed at 6 years compared with baseline in this particular patient group. CONCLUSION: This study confirms that patients with tremor dominant PD who do not present with fluctuations and dyskinesias may have a relatively benign progression of the disease. Vim DBS, although having no effect on akinesia and rigidity, is a relatively lenient surgical procedure and may still have a place for long term symptomatic control of PD tremor in selected patients.

Patients with hyperhidrosis have changed grip force, coefficient of friction and safety margin.

OBJECTIVE: To evaluate whether subjects with palmar hyperhidrosis have functional problems with the handgrip caused by the wet slippery surface of palm and fingertips. We used two different dosages of botulinum toxin to explore its impact on sweating and on muscle strength in the hand. METHOD: Using an object equipped with force sensors we measured the muscle strength and calculated the coefficients of friction and safety margin (SM) in the precision grip before and 2, 4, 6, 8 10-12 weeks and 6 months after treatment of 13 patients with two different doses of botulinum toxin. Sweat evaporation was measured simultaneously. RESULTS: A significant decrease in evaporation and a parallel reduction of grip force in the dominant hand of the patients were observed. The SM used by the patients was significantly lower after the treatment, and increased gradually when sweating reappeared. CONCLUSION: These measurements showed, for the first time, that hyperhidrosis of the palms may cause an objective perturbation of the hand function which may be partially corrected by botulinum toxin treatment.

Objective measurement of motor disability in Parkinson's disease.

A kinesiological analysis of complex movement performance was carried out in patients with Parkinson's disease, and in healthy subjects of different ages, with a computer-assisted optoelectronic camera system. A lifting movement entailing simultaneous coordination of rising, walking some steps and a goal-directed manual movement, the PLM test, was used. Speed reduction through normal aging was greatest at higher ages, where the coordination deficits were also most prominent. The increased movement time in parkinsonian patients was due both to deficient simultaneous coordination of postural, locomotor and manual movement phases, and to varying increases in phase durations. It was possible to determine postural, locomotor and manual disability profiles quantitatively, in terms of the relative phase time values. The presented documentation of parkinsonian disability and single-dose effects of l-dopa indicates that the technique is applicable in the objective assessment of disability and pharmacotherapeutic efficacy.

Optoelectronic movement analysis in Parkinson's disease: effect of selegiline on the disability in de novo parkinsonian patients--a pilot study.

New opto-electronic camera systems permit easy quantification of the motor performance during natural acts in freely moving humans. We used a simple test movement (PLM test) to quantify the disturbance in the postural (P), locomotor (L) and manual (M) part of the body movement and the coordination of the different movement phases into a smooth motor act. The test movement time was used to quantify the overall performance. With this technique we have measured the effects of selegiline on the degree of parkinsonism in a double-blind, placebo-controlled pilot study of 5 de novo patients with Parkinson's disease. There was a clear trend that selegiline was superior to placebo in reducing the test movement time.

Physiological mechanisms and movement analysis in Parkinson's disease.

We present new ideas about motor control in the human central nervous system and about pathophysiological mechanisms of Parkinson's disease, and we describe the Posturo-Locomotion-Manual (PLM) method, which is a new technique utilizing optoelectronic camera recording for objective, fully quantitative, and standardized assessment of human motor performance. In the PLM test, recordings of body movements are made during a simple motor task, where the subject repeatedly moves a small object from its starting position on the floor to a shelf located at chin height a few steps forward. The duration of the postural (raising up), locomotor and the goal-directed manual phase of the forward directed body movement is automatically calculated by a small computer as well as the degree of coordination (simultaneity) of these phases. The technique has high resolution and has been used for clinical assessment of motor performance, drug testing, and so on, in neurological and geriatric practice.

Human fetal dopamine neurons grafted into the striatum in two patients with severe Parkinson's disease. A detailed account of methodology and a 6-month follow-up.

By using stereotaxic surgical techniques, ventral mesencephalic tissues from aborted human fetuses of 8 to 10 weeks' gestational age were implanted unilaterally into the striata in two patients with advanced Parkinson's disease. The patients were treated with a cyclosporine, azathioprine, and steroid regimen to minimize the risk for graft rejection. They were examined for 6 months preoperatively and 6 months postoperatively and continued to receive the same doses of antiparkinsonian medication. There were no significant postoperative complications. No major therapeutic effect from the operation was observed. However, in the clinical tests, both patients showed small but significant increases of movement speed for repeated pronation-supination, fist clenching, and foot lifting. The rate of walking also increased in the one patient tested. For both patients, there was an initial worsening postoperatively, followed by improvement vs preoperative performance at 1 to 3 months. Both patients also showed significant improvement in the magnitude of response to a single dose of levodopa (L-dopa), but there was no increase in the duration of drug action. The motor readiness potential increased in both patients postoperatively, primarily over the operated hemisphere. Neurophysiological measurements also showed a more rapid performance of simple and complex arm and hand movements on the side contralateral to transplantation in one patient at 5 months postoperatively. Positron emission tomography demonstrated no increased uptake of 6-L-(18F)-fluorodopa in the transplanted striatum at 5 and 6 months. Taken together, these results suggest that the fetal nigral implants may have provided a modest improvement in motor function, consistent with the presence of small surviving grafts. Although our results support further scientific experimentation with transplantation in Parkinson's disease, widespread clinical trials with this procedure are probably not warranted at this time.

A mechanographic method for measurement of muscle tone in the conscious rat. The calf muscle stretch response in reserpine-induced rigidity.

A simple mechanographic method for the measurement of muscle tone in awake rats is presented. It utilizes principles corresponding to those in clinical assessment of tone and it has been applied to an animal model of Parkinson's disease: the reserpine-treated rat. The rat was restrained by a plastic cylinder and by metal cuffs at the ankles. The hind feet were repeatedly dorsiflexed by an electromechanical manipulator and the resulting calf muscle tension was indirectly measured with a strain-gauge system. The relative contributions to the stretch response from the different muscle groups acting on the ankle joint in the awake and untreated rat and during reserpine-induced rigidity are described. Very little active tension was found in the untreated rat. After treatment with reserpine, continuous activation of the muscle was found in EMG recordings and there was a sharp increase in the tension recorded during stretch. The static response to the increased isometric stretch was augmented. An additional, tonic response to ramp stretch was elicited at all stretch velocities. There was no evidence for phasic responses to rapid stretch in reserpine-induced rigidity. The amplitude of the myomechanogram was thus found to be independent of the ramp stretch velocity. Subsequent injection of apomorphine abolished the increased stretch response. It is demonstrated that changes in muscle tone could be followed during drug treatment and that the method can be used in investigations of the pathophysiological mechanisms behind the disorders of muscle tone.

A mechanographic method for measurement of locomotor activity in rats. Effects of dopaminergic drugs and electric stimulation of the brainstem.

A simple treadmill arrangement has been developed to quantify the quadruped or hindleg locomotor activity in rats. The method provides information on the accumulated distance passed by the rat in the treadmill but also on the temporal distribution of locomotion and the stepping cycle. It can be used with intact rats but also during stereotaxically guided electric stimulation of the brain. The accumulated locomotion produced by apomorphine showed a partly linear relation to the dose and the results were comparable to those found with other methods. The locomotor effect of brainstem stimulation was enhanced by apomorphine. This method combines the advantages of several other methods and is well suited as a tool for the analysis of nervous regulation of locomotor activity.

On automatic determination of movement phases in manual transport during the precision grip.

Integrated movement and force analysis of the precision grip-lift sequence (grasping an object between index finger and thumb) is a useful tool in studies on manipulative hand functions. The everyday Manual Transport tasks, moving objects from one place to another, exhibits powerful test possibilities because it includes the precision grip. In this study, as a step towards the exploitation of these possibilities, we created an algorithm that extracts sequence of phases in this task. The mathematical and dynamical properties of the movement and force signals were used to determine the start and the end of each phase. The grip-lift synergy was quantified by the correlation coefficient during each phase. Eight patients with Parkinson's Disease (PD) and 10 healthy persons were studied. The PD patients were tested both in the medicated (ON) and the unmedicated (OFF) state. The object was lifted with the index finger and the thumb, moved a short distance, and put down on a shelf. The preliminary results of these experiments displayed significantly higher coordination between the grip and load forces in the initial phases, before the lift was completely established, than during the transport phases. This was evident both in PD patients and healthy subjects. This method provides an automatic analysis of the motor performance during an arm-hand movement that is important in daily life to aid in clinical diagnosis.

Is parkinsonian gait caused by a regression to an immature walking pattern?

The gait of 6 patients with Parkinson's disease was analyzed by movement, EMG, and force recordings. In certain important details, a regression towards a more immature walking pattern was seen. It is suggested that the characteristic parkinsonian gait in addition to hypokinesia is caused by deficits in the neural circuits controlling plantigrade locomotion.

Dispersible levodopa has a fast and more reproducible onset of action than the conventional preparation in Parkinson's disease. A study with optoelectronic movement analysis.

In a crossover study we compared the single dose effect of 200mg levodopa (plus decarboxylase inhibitor) in the form of Madopar with that of Madopar Dispersible on the motor performance of eight patients with Parkinson's disease, after 12h without their ordinary anti-parkinsonian medication and food intake. Objective recording of their performance was done with an opto-electronic camera and automatic computerised treatment of the movement data and with scoring according to the United Parkinson's Disease Rating Scale. We conclude that Madopar Dispersible has a much faster and more constant onset of action than the standard preparation (25 vs 46min.). The effect duration and the effects on motor performance were otherwise the same.

CSF-neurofilament and levodopa tests combined with discriminant analysis may contribute to the differential diagnosis of Parkinsonian syndromes.

The differentiation between Parkinson's disease (PD), progressive supranuclear palsy (PSP) and multiple system atrophy (MSA) is important for prognostic and therapeutic purposes. In order to evaluate the diagnostic capability of two tests reflecting these items, patients fulfilling strict clinical criteria for PD (n=35), MSA (n=36) and PSP (n=14), were consecutively included. An analysis of neurofilament protein (NFL), a marker of axonal degeneration in the cerebrospinal fluid (CSF) and a levodopa test, recorded with optoelectronic technique were performed. Using discriminant analyses, the test's abilities to predict the clinical PD or non-PD (MSA and PSP) diagnoses were compared. Whereas the CSF-NFL and levodopa tests predicted 79 and 85% correct diagnoses respectively, the combined test predicted 90% correct diagnoses. We conclude that the CSF-NFL and levodopa tests provide detailed information of clinical variables on which the clinical diagnostic criteria are based. As they are pathologically unrelated, the diagnostic precision increases compared to clinical diagnoses when they are combined.

Locomotor hypokinesia in the reserpine-treated rat: drug effects from the corpus striatum and nucleus accumbens.

A mechanographic method was used to assess the locomotor performance induced by apomorphine or other dopaminergic drugs in reserpine-treated rats. Reserpine was found to induce locomotor hypokinesia. The hypokinesia was dose-dependently reversed by apomorphine (APO), bromocriptine and pergolide. Locomotion was induced by microinjection of APO into the nucleus accumbens. No locomotor effect was found after injection into corpus striatum. Injection into both nuclei was not superior to accumbens only. Intra-striatal or intraaccumbens injections of trifluoperazine blocked the effect on locomotion by systematic apomorphine. The results confirmed that reserpine-induced locomotor hypokinesia is reversed by dopaminergic stimulation in the nucleus accumbens. There were indications that blockade of striatal or accumbens' dopamine receptors counteracts apomorphine-induced locomotion presumably by interaction with postural motor control. Evidence was found for separate dopaminergic control of locomotion and muscletone. This may be of importance for the development of new antiparkinson drugs.

Reserpine-induced rigidity in rats: drug effects on muscle tone from corpus striatum and nucleus accumbens.

A study of the pathophysiological mechanisms of reserpine rigidity with the aid of a mechanographic method for the quantification of muscle tone. Apomorphine was used as a test substance to reduce reserpine rigidity by stimulation of dopamine receptors. Some experiments were made with additional drug treatment in an attempt to ascertain the dopaminergic specificity of the test. Apomorphine injected bilaterally to the corpus striatum has been shown to counteract the rigidity [6]. Microinjections of reserpine to corpus striatum induced rigidity with dominance in the hindleg ipsilateral to the side of injection. This rigidity was reduced by subcutaneous apomorphine. The effect of subcutaneous apomorphine on the rigidity was blocked by prior microinjection of trifluoperazine to the corpus striatum. Injections to nucleus accumbens were ineffective in all these respects. It is concluded that reserpine induces rigidity mainly by interference with the dopamine transmission in the corpus striatum.