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.

Load force during manual transport in Parkinson's disease.

OBJECTIVES: To search for a physiological method for the measurement of upper extremity dexterity during activities of daily life in Parkinson's disease (PD). MATERIALS AND METHODS: We examined load force output during manual transport in seven patients with PD and 10 healthy controls. PD patients were measured in both the non-medicated and medicated states. The test movement included two continuous sub-movements: an upward-forward transport of an object from the table to the stand, and a downward-backward transport of the object from the stand to the table. Hand movements were recorded using an optoelectronic camera, and load force was measured using a force sensor installed in the test object. RESULTS: Compared with the controls, PD patients had a different pattern of load force output characterized by slower force development and release, lower peak force, and less dynamic force generation during movement. After medication, the speed of force development and the level of peak force increased in the patients. CONCLUSIONS: These findings suggest that PD impairs the production of preprogrammed movements. The movements observed in the PD patients may result from compensatory strategies relying more on feedback mechanisms.

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.

Cardiovascular reflex testing contributes to clinical evaluation and differential diagnosis of Parkinsonian syndromes.

The differentiation between Parkinson's disease (PD), progressive supranuclear palsy (PSP), and multiple system atrophy (MSA) may be difficult but is important for prognostic and therapeutic purposes. Varying degrees of autonomic failure have been described in PD and MSA, whereas its involvement in PSP remains controversial. The aim of this study was to investigate autonomic function in patients fulfilling strict clinical diagnostic criteria for the disorders above, to evaluate the diagnostic capacity of laboratory autonomic tests. The study group was consecutively recruited among patients referred to a movement disorder unit. Thirty-four patients with PD, 15 patients with PSP, and 47 patients with MSA were compared with 18 healthy age-matched controls. Autonomic tests included analysis of heart rate variability (HRV) in temporal domain, at rest and during forced respiration, as well as blood pressure (BP) changes during 75 degrees head-up tilt. HRV did not differ between groups during quiet breathing but was significantly reduced during forced respiration in MSA (P < 0.01), while PD and PSP groups did not differ from controls. Hypotensive responses during orthostatic provocation were seen in PD (P < 0.01) and MSA (P < 0.001), whereas BP remained stable in most PSP patients, not differing from the healthy control group. On an individual basis, decreased HRV and severe hypotensive responses were seen in MSA patients regardless of age and disease duration, whereas PD patients showed this combination only at high age and long duration. In PSP, only a few cases with decreased HRV and limited hypotensive responses were found. We conclude that cardiovascular reflex tests can supplement the clinical differentiation of Parkinsonian syndromes.

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.

Gender differences in Parkinson's disease symptom profile.

Gender symptom differences were studied in 948 subjects with Parkinson's disease (PD) using a questionnaire covering the most common symptoms associated with PD at debut (SP-1) and at present (SP-2). The symptoms most frequently reported by both genders were: tremor, fumblingness, writing problems, rigidity and fatigue. At SP-1 females reported neck-pain and low back pain more frequently than males. At SP-2 subjects reported an increased number of symptoms. The following symptoms were more frequent among males than females: writing difficulties, fumblingness, gait problems, speech problems, increased flow of saliva, lack of initiative. Sleep problems were common in both sexes with inability to turn in bed and calf muscle cramps in a high percentage. A majority of female subjects find their symptoms (e.g. depression) constantly distressing. Although depression is not one of primary reported symptoms (36%) attention is called for, due to the problem with compliance to treatment regimes. About 30% do not report having tremor and rigidity. This study indicates the usefulness of a symptom profile instrument capable of capturing the many symptoms involved in PD. Such an instrument could be used to detect apparent mistakes in medication and thereby increase the function and quality of life for the individual.

Increased cerebrospinal fluid levels of neurofilament protein in progressive supranuclear palsy and multiple-system atrophy compared with Parkinson's disease.

More reliable tools are needed for the differentiation of Parkinson's disease (PD) from other parkinsonian disorders. The neurofilament protein (NFL) and the glial fibrillary acidic protein (GFAP) are main structural proteins of axons and fibrillary astroglial cells. By using enzyme-linked immunosorbent assays, these proteins were quantified in the cerebrospinal fluid (CSF) of 49 patients referred to the Department of Neurology for diagnostic consideration or treatment of parkinsonism of different etiologies. All patients were first diagnostically evaluated by strict clinical criteria. The procedure included a neurologic and neuro-ophthalmologic examination as well as computed tomography or magnetic resonance imaging. These were performed independently and in advance of the CSF analysis. A total of 19 patients were diagnosed as having PD, 12 had progressive supranuclear palsy (PSP), and 10 had multiple-system atrophy (MSA). Eight were diagnosed as having other diseases, such as arteriosclerotic parkinsonism and undefined parkinsonian syndromes. The content of NFL was significantly higher both in the PSP group (p < 0.001) and in the MSA group (p < 0.0001) compared with the PD group. The high values of NFL indicate an ongoing neuronal degeneration affecting mainly the axonal compartment in the PSP and MSA groups, whereas there was no difference in glial involvement as measured by GFAP in the PD, PSP, and MSA groups. There was a relation between high CSF levels of NFL in the various patient groups and the occurrence of pyramidal symptoms (p < 0.001), possibly reflecting the axonal damage to the corticospinal tract. Furthermore, mortality at 24-month follow up was associated with high NFL levels (p < 0.01). We conclude that analysis of NFL in CSF may become useful in the differential diagnosis of parkinsonian syndromes.

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.

Motor performance in normal pressure hydrocephalus assessed with an optoelectronic measurement technique.

The motor performance of 10 patients with normal pressure hydrocephalus (NPH) was clinically assessed with the aid of a computer assisted optoelectronic movement analysis system (Mac Reflex). We used the Posturo Locomotion Manual (PLM) method that gives a quantitative estimation of the postural, locomotor and manual performance in freely moving humans. Measurements were done before intervention, after CSF tap test and 3 months post installation of a CSF ventriculo peritoneal shunt. Comparison was made to data from 10 matched normal subjects and 10 patients with Parkinson's disease (PD). Shunt operation of the NPH patients and l-dopa treatment of the Parkinson patients improved the motor performance to a comparable degree. However, while the NPH patients improved the speed in the PLM test after the operation, the PD patients also improved the co-ordination after l-dopa treatment. This could indicate a different mechanism behind the improvement of motor performance in NPH and PD after intervention.

Motor function in 90-year olds measured by optoelectronic kinesiology and activities of daily living.

Computer-assisted optoelectronic movement analysis using a Posturo-Locomotor-Manual (PLM) test, and assessment with an ADL (Activities of Daily Living) scale were performed in 36 (18 women and 18 men) 90-year-old subjects as part of a larger study. In the PLM test, the subjects were asked to pick up an object placed on the floor, and carry it to a shelf at the height of their chin and at a distance of 150 cm from the starting position. In the ADL assessment, the subjects were classified as ADL-dependent or independent in each of 4 instrumental (cleaning, shopping, transport and cooking) and 5 personal activities (bathing, dressing, going to the toilet, transfer and feeding). ADL independence was defined as being able to perform ADL activities without assistance from another person. In this study, ADL-dependent subjects performed the PLM test considerably more slowly than the ADL-independent group. A correlation was found in females between poorer ADL performance and slower and less co-ordinated PLM test results. Particularly, the Postural and Locomotor phases representing lower limb mobility correlated to the ADL steps. In males, no such correlation was found, indicating that factors other than mobility were important for ADL performance in this group, e.g., cooking skills. The relationships between the PLM test and the ADL assessment estimating practical motor function could be an indication that the PLM test is not only a strict laboratory method, but also measures components of everyday motor activities. Combined use of optoelectronic measurements and ADL scales will improve measurements of motor performance in elderly persons.

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.

Single-dose L-dopa response in early Parkinson's disease: measurements with optoelectronic recording technique.

Twenty-five patients with suspected Parkinson's disease were submitted to optoelectronic movement analysis with the Posturo-Locomotor-Manual (PLM) test before and 60 min after a single dose of L-Dopa. They were then examined clinically for diagnosis. Two patients were excluded due to L-Dopa intolerance. Seventeen of the remaining patients were classified as having Parkinson's disease. The movement time (MT) in the PLM test was increased for all these patients, and they improved their performance after L-Dopa. The degree of improvement was roughly proportional to the pretreatment augmentation of MT in comparison to healthy subjects of the same age. The PLM phase analysis showed a specific disability profile for each individual. Six patients were given diagnoses other than PD. Some improvement was found in one patient with suspected olivopontocerebellar atrophy and one patient with multiple brain injury. Two patients with progressive supranuclear palsy, one with suspected striatonigral degeneration, and one with functional disturbance deteriorated after L-Dopa. In conclusion, truly objective and fully reproducible evaluation of the motor performance before and after a single L-Dopa dose is easily accomplished with computer-assisted modern optoelectronic recording equipment. The technique is a valuable tool for the quantitative measurement of treatment effects and contributes to the differential diagnosis.