Potential Factors Of The Pigd Motor Phenotype
With univariate logistic regression, the following candidate factors of the PIGD motor phenotype were identified: UPDRS ADL , UPDRS motor , HAMD , HAMA , PDSS , NMSQuest , cardiovascular domain , sleep domain , mood/cognitive domain , weight change and pain . Then, with multivariable forward stepwise logistic regression, the following factors were excluded as potential risk and protective factors: the UPDRS ADL, UPDRS motor, HAMA, PDSS, NMSQuest, cardiovascular domain, sleep domain, mood/cognitive domain and weight change. The HAMD and pain had significant discriminative power in differentiating the PIGD group from the non-PIGD group . Patients with higher HAMD score and incidence of pain exhibited a positive correlation with the PIGD phenotype.
Table 3 Univariate Logistic Regression for Potential Factors of the Postural Instability and Gait Difficulty Phenotype in De Novo Parkinsons Disease
Table 4 Multivariable Forward Logistic Regression for Potential Factors of the Postural Instability and Gait Difficulty Phenotype in De Novo Parkinsons Disease
Quantitative Analysis Of Postural Instability In Patients With Parkinsons Disease
Siquan LiangJialing Wu
Parkinsons disease is a progressive and chronic neurodegenerative disorder. The main clinical manifestations include bradykinesia, tremor, rigidity, and gait/postural disturbance. Postural instability is commonly observed in patients with PD, leading to an increased risk of falling, which has a negative impact on the patients ability to perform daily activities . Like dysphagia, autonomic dysfunction, and cognitive impairment, postural instability is also one of the most important disease milestones in advanced Parkinsons disease, especially represented by the transition to Hoehn and Yahr staging 2 to 3 . Notably, due to the progressive nature of PD, these symptoms tend to gradually worsen over time. Therefore, early identification of PI in individuals with PD is important for further prevention. However, patients do not tend to consult the doctor unless PI is severe with frequent falls. From the standpoint of clinical, PI in PD is only noticed in middle and late stages stages IIIV), the phases in which significant disability generally occurs .
PD patients were classified based on H& Y staging score . Twelve healthy controls with no sign of parkinsonism and matched for the same parameters were also recruited.
2.2. Experimental Protocol
2.3. Statistical Analysis
All statistical analyses were performed in SPSS software . The level of significance was set to .
Postural Instability In Parkinson Disease: To Step Or Not To Step
Parkinson subjects and Controls required the same force to be pulled off-balance
All Controls took a step in direction of pull to maintain balance without falling
59% of the time Parkinson subjects did not take a step to maintain balance and fell
Parkinson subjects do not defend against sudden gravitational instability
Parkinson gait disorder may be due to subjects avoiding gravitational instability
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Balance Orientation And Postural Control
Balance is the ability to automatically and accurately maintain your center of mass over your base of support. Postural orientation is the ability to control the segments of your body in relation to one another and to gravity, taking into account the environment and whatever task is being performed. Postural control involves both balance and postural orientation.
Control of posture has both musculoskeletal components and motor processes, which organize the muscles into neuromuscular synergies. Balance also involves neural componentssensory and perceptual processesthat integrate input from the somatosensory, visual, and vestibular systems, as well as higher level processes that contribute to anticipatory and adaptive aspects of postural control .
Poor balance and unstable posture are commonly observed motor symptoms in those with PD. Until recently, it was thought to occur relatively late in the course of the disease. This is reflected by the Hoehn and Yahr scale, in which postural instability is represented only in the advanced stages of the disease . However, there is significant evidence that changes in postural control occur even in the early stages of Parkinsons and, although there is fluctuation, generally increase over time .
Tremor Rigidity Bradykinesia And Dyskinesia
One of the first visible motor symptoms to emerge in PD is resting tremor of a limb that is supported and at rest. Tremor typically begins on one side of the body with a tremor rate of 3 to 7 cycles per second. Tremors are usually less severe or even absent with voluntary movement and can increase during times of emotional stress. Tremor is considered one of the cardinal symptoms of Parkinsons diseasesome studies report it to be present in up to 80% of patients with autopsy-proven PD .
Rigidity is another common visible motor symptom associated with PD. It is a type of increased muscle tone generally defined as an increased resistance to passive movement of a joint. Rigidity tends to be more prominent in the flexor muscles of the trunk and limbs, causing a characteristic stooped posture. There are two types of rigidity: lead pipe and cogwheel. Lead pipe rigidity is defined as a constant resistance to motion throughout the entire range of movement. Cogwheel rigidity refers to resistance that stops and starts as the limb is moved through its range of motion.
Bradykinesia, another cardinal motor feature of PD, is of unknown cause and remains the subject of debate. It is defined as slowed voluntary movement, although we now know that rigidity also affects automatic movements such as arm and leg swing during gait.
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Are There Different Treatment Strategies For The Two Groups Of Patients
It appears that patients with IPD and PI have different presentations of PI. One might classify them as patients with more significant difficulties with movement initiation and velocity features and those with additional impairment of the sensory organizational component of postural control. For the first time, we have found that there was a dissociation between the effects of medication and the effects of pallidotomy on the motor and sensory aspects of postural control. Medication clearly improved the motor adjustment component of postural control but could be detrimental to the sensory organizational control of posture. Pallidotomy, on the other hand, could completely correct abnormalities in the sensory organizational component of postural control as well as improve the motor components of balance and mobility. It appeared that the patients whose SOT5 scores were the worst on medication stood to gain the most improvement in PIGD scores from pallidotomy. Those with normal or above normal SOT5 scores, however, still gained improvement in PIGD from medication, postpallidotomy
Properties Of The Epirs Scale
Properties of the ePIRS in the derivation sample and both validation samples and 141 subjects with genetic mutations associated with PD ) show that all individuals with PD, regardless of quartile, were more likely to develop postural instability than controlsbut quartile rank was a substantial additional predictor. Table shows Cox Proportional Hazard Ratio for development of disability by ePIRS Quartile in the full sample. KaplanMeier Survival Curves are shown in Fig. in the derivation sample , the IPD de-novo validation sample , and the GPD validation sample . Quartile 4 is associated in both the derivation and validation sets, with a highly significant increased likelihood of developing HY stage 3.
Table 3 Baseline ePIRS quartile ranking predicts likelihood of advancing HY status.Fig. 2: Survival plots by ePIRS quartile in PPMI.
Properties of the ePIRS are shown in the full sample and in two validation sets. In both validation sets, membership in ePIRS quartile 4 is a significant predictor of later development of postural instability compared to both controls, and membership in Quartile I.
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Enhancing Healthcare Team Outcomes
The multifactorial pathophysiology underlying postural instability necessitates a multidisciplinary team approach, to target patient risk factors. A wide breadth of clinical presentations can occur alongside postural instability. This requires specialists across different areas for an accurate diagnosis. Given the various treatment options, physicians, nurses, physical therapists, occupational therapists, psychologists, social workers, and caregivers may all have a role to play in managing this patient population. New studies need to be designed focusing on the costs and benefits of multidisciplinary interventions in this group. Multifactorial risk assessment has already been shown to be consistently successful in preventing falls in elderly populations. Hopefully, as more evidence-based research becomes available with information on plausible pathophysiological mechanisms behind postural instability and new treatments, patients with postural instability will be introduced to more treatment strategies with favorable outcomes.
Experimental Procedure And Data Collection
Representative examples of CoM and ankle trajectories for the three requested speeds of trial execution: slow, preferred, and fast. The COM trajectory and its velocity , together with the right and left ankle trajectory for a representative control subject a and a subject with PD b. Solid black line represents the path reference traced on the floor with direction of walking indicated by arrows and numbers. The box insert for the fast trajectory shows a zoomed 90° turn trajectory in which the subject with PD has the COM outside the base of support longer than the control subject
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Sensory Integration And Sensory Transitions
Our results demonstrate that subjects with PD are capable of re-weighting sensory information for postural control. This is consistent with a previous study concluding that subjects with PD can integrate sensory information to successfully perform a turning task before and after walking on a circular treadmill . However, previous findings from our laboratory show that subjects with PD take more trials than control subjects to switch postural synergies when sensory conditions change . For example, subjects with PD do not immediately inhibit ankle muscles when holding a handle or sitting on a stool during surface perturbations . In addition, on the first trial of each of the sensory organization tests, subjects with PD fall more often than controls . However, subjects with PD improve with repeated exposure to each sensory condition, such that by the third trial of a particular sensory condition, subjects with PD reach near control levels . The third trial of each sensory condition is most similar to the steady-state conditions of our experiment. Therefore, this previous result is consistent with the mostly appropriate steady-state performance of our subjects with PD when compared to age-matched controls.
Signs And Symptoms Of Parkinsons Disease
A tremor is a rhythmic shaking of the hands, arms, legs, or head caused by involuntary muscle contractions. While its normal to feel shaky after exercising or during a fever, a tremor that occurs suddenly and uncontrollably may be a warning sign of Parkinsons disease.
Usually, Parkinsons tremors are rhythmical and happen when you are at rest. They also tend to be asymmetrical, meaning they affect one side of your body and may gradually spread to the other side over time.
Most Parkinsons tremors are mild and may decrease when you are performing tasks. However, in some severe cases, the tremors can become so strong that they interfere with daily activities such as writing and eating.
Over time, you may start to develop slow movements known as bradykinesia. This occurs because the brain cannot produce enough dopamine to coordinate movement properly.
Parkinsons slowness happens in different ways. For example, some people may experience a reduction in automatic movements, such as blinking and swallowing. Others may find initiating simple movements like standing from a seated position challenging.
Though seldom, over time, you may develop a stiff, inflexible feeling in your muscles. Some people call this stiffness tightness because it can make it difficult to move your limbs.
The rigidity can affect one or both sides of your body and may lead to a decreased range of motion.
As a result, you may experience pain and muscle cramps when stretching or moving.
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Mechanisms For The Different Effects Of Medication And Surgery On The Motor And Sensory Components Of Postural Control
The basal ganglia are part of multiple segregated circuits that mediate motor, oculomotor, limbic and associative functions. Anatomical and physiological evidence suggests that the striatum is a site of spatiotemporal, contextdependent, sensorimotor integration, which is directly influenced by dopamine . Inhibitory output signals travel from GPi to the thalamus and from there are returned to the premotor cortex. GPi also directly inhibits brainstem targets and the PPN in particular . The PPN appears to be part of a parallel basal ganglia pathway with dense reciprocal connections with the subthalamic nucleus and with extensive output to the thalamus. The PPN appears to be integral to postural control and locomotion , and it has been proposed that the PPN may play an important role in conditioned sensorimotor performance .
Pallidotomy reduces the inhibitory effects on the thalamus by reducing pallidal neuronal firing rates. Contrary to the effect of medication on firing patterns, pallidotomy may normalize firing patterns in pallidothalamocortical and pallidoPPNthalamocortical pathways .
Motor Symptoms Postural Instability And Gait
In Parkinsons disease, the loss of dopaminergic cells in the substantia nigra affects the basal ganglias ability to coordinate inhibitory and excitatory neural motor signals . The net effect is an overall reduction in motor output, referred to as hypokinesia. Unfortunately, drugs used to treat PD can introduce too much dopamine, causing over-activation of the motor system and producing dyskinesias . The motor symptoms associated with PD affect all aspects of daily activities, gait, postural stability, and mobility.
Scale Development And Sample Selection
Hoehn and Yahr Stage , was dichotomized, with a score of 3 or higher indicating clinically detectable postural instability during stance, in the derivation set to categorize individuals who by year 5 had developed gait dysfunction and those who had not . We classified a subject as Y5_HY35 if at any time over the first 5 years a clinical rating of HY 3 was scored by any rater while on-medication. The classification of Y5_HY02 was given to any individual who was never classified by any rater as above HY stage 2. We also measured PIGD using the PIGD score derived by Jankovic and colleagues at each follow up visit,. Average year 5 PIGD scores were also derived from on-medication evaluations in years 4.56 averaged over 23 visits to calculate a year 5 outcome variable .
Nmss Between Td And Pigd Motor Subtypes
As the total NMSQuest score significantly differed between the TD and PIGD groups, the prevalence of symptoms corresponding to each domain and item of the NMSQuest in the two groups was further compared in Table 2. Orthostatic symptoms in the cardiovascular domain , vivid dream imagery in the sleep domain , low mood and anxiety in the mood domain , and pain in the miscellaneous domain were more prevalent in patients with the PIGD subtype compared with patients with the TD subtype. No differences between the TD and PIGD subtypes were noted in the remaining NMSQuest items.
Table 2 Comparison of Non-Motor Symptoms Between the Tremor Dominant and Postural Instability and Gait Difficulty Groups of Patients with De Novo Parkinsons Disease
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Development Of Emerging Gait Dysfunction Scale Factors
Logistic regression using all UPDRS items as regressors revealed 7 baseline UPDRS items that were associated at p< 0.01 with more rapid progression to HY stage 3 or higher within 5 years of disease diagnosis and were used to develop the ePIRS . These items consisted of 2 factors from UPDRS I , 3 factors from UPDRS II , and two factors from UPDRS 3 . Two other items , were significant at p< 0.05 after correction for multiple comparisons but were not included.
Table 2 Factors associated with progression to HY Stage 3 or worse within the first 5 years of disease.
The Effects Of Pallidotomy On The Motor And Sensory Components Of Postural Control
In contrast to the effects of medication, unilateral pallidotomy resulted in substantial improvements in both the SOT5 equilibrium score and the PIGD score. Both the SOTN and SOTABN groups demonstrated improvements in SOT5, but the improvements were especially significant in patients with abnormal SOT5 scores preoperatively, off medication. In these patients, SOT5 scores were brought into the normal range following pallidotomy and remained so over the 12 months of followup. The PIGD score improvements also tended to be greater and more sustained in the SOTABN group after pallidotomy.
Out of 24 studies reporting pallidotomy outcomes, 12 included postural control . Among these 12 studies, eight reported on clinical measures of postural stability using subscores from the UPDRS three from the same centre used the PIGD score, the remainder used the single postural stability score from item 30 of the UPDRS motor scale . Three reported measures of postural control using posturography. Only one of 12 studies reported no early improvement in postural control . Although the other studies reported early improvements, none saw longterm benefit of unilateral pallidotomy on postural control. Sustained improvements were seen in individual patients in one longterm study .
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Aging And Sensory Weighting
In response to a surface and visual stimuli, subjects with PD and age-matched controls show greater use of proprioceptive and visual information compared to younger control subjects from a previous study . For surface stimuli, greater sensitivity has been confirmed in more recent studies comparing younger and older adults with normal balance function . These results indicate that subject age, not PD, determined the extent to which subjects utilized visual and proprioceptive information for postural control.
The Effect Of Dopaminergic Medication On Postural Control
Dopaminergic medication improved the PIGD score in all but three patients. On the other hand, medication worsened SOT5 scores in 66% of the patient group. In at least 40% of the patients, the decreases in SOT5 equilibrium scores, on medication, could not be explained only on the basis of the decrease seen in SOT1.
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