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Comparing Children and NPC Patient Group on Posture and Balance Measure

Comparing children and NPC patient group on posture and balance measure  


Niemann-Pick disease (NPC) is a natural mistake of metabolism connected with sphingomyelin accumulation and sphingomyelin inadequacy, which cause balance impairment leading to fall. This study compares NPC patients and healthy controls on a standing task to measure the difference of jerk and sway value in two conditions of eyes open and close for 3 trials each. Accelerometer was used to measure sway and jerk value, then was analyse by opals measure, in which measurement of the participant’s age, leg length, weight and height was measured and inserted to the PKMAS software to have information about each person’s physical attributes and data base within Excel then analysed on SPSS.  Overall controls and NPC patients have similar jerk and sway value on eyes open condition, but there was a significance difference on eyes close condition suggesting the stage of the disease may be more severe regarding of the age group of patients. Contents Abstract Introduction Rationale and Scientific Background Long-Term Objective Parkinson Disease similar disease to NPC Current Study Method Participants Resources Experimental Approach Data Analysis Predicted Result Results Average and Standard Deviation of Controls and Patients Intercept Value of Control Range Controls Influence of posture by using age and height as covariate Patients and controls individual Value Discussion Bibliography Appendices Appendix 1: SPSS Output (Control Range Intercept) Linear Regression Appendix 2: SPSS Output (Control individual value ANCOVA) Appendix 3: SPSS Output (Controls and NPC patients Individual Value ANCOVA) Appendix 4: Adult Consent Form        


Rationale and Scientific Background

Niemann-Pick disease (NPC) is considered a natural mistake of metabolism connected with sphingomyelin accumulation and sphingomyelin inadequacy (Passini et al, 2005). NPC generally have two patterns, types A and B, produce primary lysosomal storage disorders of sphingomyelin lead by the effect of serious failure of sphingomyelinase activity. A different group of NPC patients (types E, D and C) does not show clear and regular inadequacy of sphingomyelinase has been record for these unique phenotypes. The more apparent characteristic within this latter group are chronic neurological deterioration connected with hepatomegaly, alongside with foamy macrophage intrusion of tissues, bone marrow being stained by histiocyte, and a prudent amassing of sphingomyelin in a secure tissue. From recent study by Crocker and Farber (1958) revealed data collected from 18 cases, as five NPC patients didn’t survive between the age range of 3-6 years old, and three between the range of 12-20 years old and only one patient was able to reach 18 years, with the diagnosis conducted during 4 months of age. They have highlighted the critical of identifying that NPC disease biological behavior does equip with a boarder range than is normally stated, and that this might not possibly have a constantly quick and deadly course with death during early infancy. The importance of this showing if the beginning fatal phase of NPC disease can be remaining a non-progressive state this can entered with durable survival. The advancement and developing of the human brain is exposed to disease from a full range of causes and this mutation usually may lead to neurodegeneration. Where this kind of disease will be able to cause more progressive deficit of developmental skills and reduced social skills, i.e. impaired motor skills and language. Developmental deficit is a   common paediatric clinical problem, that causes up to 3-5% of the UK paediatric population (Tzika et al, 1993). In children, the development of NPC (Niemann Pick Type C) can be inherited or genetic basis leading the brain insult, including the inherited metabolic disease (Zhang et al, 2001). NPC belongs to a large class of heterogenous genetic disorders that are caused by dysfunction inside a single pathway of intermediary metabolism. For most of this disease, the dysfunction of metabolic enzymes is produced by toxic metabolites, which affects the usual development of the central nervous system. Depending on the unique role of the dysfunctional enzymes, the consequences associated NPCs can differ broadly. In stage 0 of NPC there are generally no apparent symptoms or disability, less serious symptoms can include physiological abnormalities such as impaired endurance, skeletal dysplasia and unclear speech are generally seen on stage 1 and 2. (Griffths, 2004). While more serious symptoms can include central nervous system complications, mental retardation, speech are very limited, need assistance in everyday activity and reduced life expectancy are seen on stage 3 & 4 of NPC (Liberman, 1999). Children with NPC are vulnerable to development regression/delay and chronic brain degeneration. Neurodegenerative disease is uncommon in children, as this lead to the fact poor movement and manipulation skills compared to atypically developing children, and can be related to cerebral palsy (CP) (Fay,1950). In which balance control are important for competence in performance of everyday functional skills, assisting children to heal from unpredicted balance interferences, wither due to slips or to self-induced instability when attempting a movement that drags them closer to the edge of their limit of stability. NPC are predicted to developed in approximately 1 in 150000 people in Western Europe (Al-Sarraf and Reddy 2002). Although currently it is still not completely known how disease development across NPC affects cognitive function, and why are distinctly cognitive function domains affected more consequently than others? Over 90% of patients with NPC harbor flaw in the NPC1 (Niemann Pick C1) protein. (Carstea et al, 1997). The NPC1 protein is known as a low affinity cholesterol-binding protein responsible for the act in cholesterol export (Landrigan, 2005). Patient display a variety range of clinical features, such as lung, bone marrow and liver dysfunction. Understanding of the system fundamentally the growth developing to brain damage in the metabolic disease still requires many research to it is complete, and in an abundance amount of child with assumed metabolic neurodegenerative disease no precise analysis is concluded. As mentioned, stage 4 NPC patients are generally affected by temporal lobe necrosis. Neuroimaging technique are limited to distinguishing visible structural changes in the brain only in the late stage of the disease development, and are not sufficient for monitoring and diagnosing these conditions.

Long-Term Objective

Research in the last 20 years have reflected how neurodegenerative disease have a connection to posture and balance, and how balance in motored by the sensorimotor system. In the past, measuring balance are done on obtaining a set of reflex responses and on a postural sway in stance (Snijders et al, 2007). Presently, balance control is classified to be a complex motor skill that requires the assimilation of multiple types of sensory information and the execution and planning of flexible movement pattern to reach different potential postural goals. Through years of clinical assessments of balance which relates into account of new findings about the control of balance gives a powerful evidence to clinicians for concerned in the rehabilitation of patients that are suffering from orthopedic and neurological deficits. Present balance examination should include observations that the goals and implementation of postural control can change relying upon the environmental circumstances, aim of the object and specific tasks (Nielsen, 2003). Thus, assessment of the achievement of postural control requires the context and task-specific goals of posture. Balance assessment should also be able to differentiate among different types of balance control including the capability to react to external perturbations, and can predict postural demands connected with voluntary movements, and the capability to willingly and efficiently move the center of body mass through space because every patient may have already been affected from different types of balance control (Hackney and Earhart, 2008). With children that have cerebral palsy (CP) shows symptoms of poor manipulation skills and walking abilities. As this is an essential features of NPC patients as they have delayed neurodegeneration and dementia, which alongside displays impaired logical thinking and impaired motor skills(Patterson and Platt 2004). One of the main factor to their difficult with gait and reaching movement is poor balance control because the maintenance of stability is essential to operate all movements. Balance control is critical for ability in the performance of a lot of functional skills, assisting a child to heal from accidental balance disturbances, cause by either trips and slips bring them close to the edge of their limit of stability (Riach and Starkes, 1994). Research conducted by Nashner et al (1983) has discovered that children with CP requires a step at lower platform displacement velocities than typically growing children of the same age, they take a longer period to heal stability, and revealed more center of pressure movement during the recovery period. Burtner et al (1998) conducted a similar experiment comparing the postural responses of children with spastic diplegia a type of brain damage inhibits the proper development of upper motor neuron function that influence the motor cortex of three developmental levels (pre-walkers, early walkers and experienced walkers), with those of usually developing children of similar developmental levels. Found that that timing of neuromuscular responses in these children was revealed to be more disorganized, and unlike normal developing children who shown signs of improvement with developmental level, timing was not a factor that help improve children with spastic diplegia. Walking experiment conducted on NPC children found that 75% of them generally have gait ataxia (Fink et al, 1989). Although posturography can measure performance up to the point as functional scales for balance tasks are needed. Balance monitoring with sensor are mostly used by rehabilitation therapists although the effectiveness of these scales for estimating the liability of recession in neurological population are not completely evaluated (Giladi et al, 2005). Prosperous, functional balance scales that are included into the account of sensory environmental context. Postural adaptation, the influence of cognitive predictive and distractors as well as reactive postural control have not been fully developed. The goal of a clinical assessment of balance is not commonly used to diagnose a disease, although types of balance disorders are frequently related with a specific neuropathology such as Parkinson’s disease (Horak and Mancini, 2013). Most musculoskeletal and neurological diagnoses caused into impaired balance. However, the problem in applying balance assessments to diagnose is that patients with different diagnoses can sometime carry the identical balance impairments and on the other side patients that have the same diagnosis may show different balance impairments. For example, NPC patients may reveal an impaired ability to conduct vestibular information used for postural orientation in clinical assessment due to the fact of a different range of neuropathology including eighth nerve tumors, degenerative loss of vestibular receptors and from a central nervous system lesion in the cerebellum and the brainstem which causes vestibular processing (Woollacott and Shumway-Cook, 2005). Nasher et al (1983) have shown in previous research that children that children that are classified with spastic hemiplegia displayed issues with the timing of accurate muscle responses. Such factors include late onset of contraction in the ankle musculature, a proximal-to-distal muscle response sequence (such as quadriceps and hamstrings muscles activated before tibialis anterior/gastrocnemius) and co-contraction of antagonist and agonist muscle at a joint. Such differences in neuromuscular response attribute would cause to a late and less organized recovery of balance.  Although NPC includes an expand phenotypic spectrum, starting from early-onset in infancy with continuous deterioration, advancing to late-onset in teenage or adulthood with delayed symptoms advancement (Campo et al, 1998), movement impairment is mostly considered an important factor of the disease. As NPC children are seen with deliberate tremor and slow motor movement, while juvenile outset shows gait impairment and dysfunction on smooth motor control. The variety of movement impairment are more obvious in adulthood (Pick, 1933). This shows how NPC patients are distinguishable in terms of movement when in comparison of normal healthy people.

Parkinson Disease similar disease to NPC

In NPC patients, motor activities in daily routine requires a lot more intricated motor control than that needed for the adjustment of easy single movements of one joint. Most goal-directed motor movement need the accomplishment of an order of movements, simultaneously or constantly, located at certain joints and of distinctive limbs. For example, when we drink we use one or both arms to hold the cup, then lift it towards our lips, before advancing to either sucking and swallowing system. Everyone detail of these movement comprise an individual motor activities plan, to accomplish a correct and effortless overall movement. This can be used on an example on standing still, as it requires our eye to compensate the ankle of our body to recover from swaying and prevent falling. Like NPC, Parkinson disease are neurodegenerative disease that displays symptoms of irregular motor movement, caused by the effect of majority to a continuous loss of dopamine neurons in the susbtantia nigra. The substantia nigra is a basal ganglion build structure found in the midbrains that is responsible for movement and reward (Rascol et al, 2002). Parkinson patient, on average requires longer period to move to a peripheral kinesthetic stimulus, which is a relative position located of our skeletal body parts to control by the directions of their legs.  Visual cues, provides a mental image of our body. Introspective attention transferring to the body reveals that sensory information makes an impact to our leg when conducting an action: first of knowledge, the angle both during our leg is performing stationary and movement, second awareness, which is the direction and third the speed of recovery from sway and smoothness of jerk. All three types of information are different independently when provided a position can be stretch by movements (Burgess et al, 1982). Different from normal subjects, Parkinson patient are less capable to conduct advance information to start the reaction to a clear cue. It is common for normal controls understanding what is needed can prepare and initiate the movement to carry it faster than Parkinson patients. However, the magnitude of impairment of clear reaction times are not usually correlated similar with clinical akinesia. NPC patients during their childhood, displays features of gait problems, continuous falls and maladroitness between the age of 3 to 5 years, due to ataxia (presented within 60% to 70& of cases found). They experience school issues such as writing difficulty and unable to focus on attention are frequent and may cause misdiagnosis. Similar in Parkinson’s case child are clumsier, show increase of learning disabilities, and ataxia are apparent (irregular movement and frequent fall) (Rottach et al, 1997).  Language delay is also seen usually. Motor movements declines, and cognitive dysfunction symptoms are displayed. During juvenile age, a preexisting temperate splenomegaly is frequent, although unseen viewable organomegaly which is the abnormal increase of organs, has been recorded to show in at least 15% of the cases. Apparent neurological symptoms are seen between the age starting from 6 and 12 to 15 years, but onset is subtle and volatile. Deuschl et al (2001) have found that the motor physiologic findings of NPC are distinguished predominantly by low frequency and variable inconsistent movements that are not present during rest, occasionally shown when keeping a posture, but is most serious with action. This was revealed with sEMG movements and accelerometric accurately measure muscle activity and movement most regular with cerebellar tremor, myoclonus, choreiform movement and dystonia. This have overall identified that NPC action tremor had significantly increase amplitudes, also lightly more frequencies, than postural tremor. Because more amplitude tremor is commonly connected with decrease frequency movements, this sequence of physiologic results signifies more asperity with action, as this would have been revealed with a predominantly cerebellar disorder. When compared to healthy patient is it more likely to observe more swaying due to their muscle tremor when standing. As NPC patients are generally required longer period to return to their most stable state.  

Current Study

As NPC patients ages, the change in posture is an essential significant factor of changes in activity. On a stereotypical frame of old people as an example. is one of a paused-over torso along an exaggerated kyphosis that are caused by poor posture that might lead to fall. Osteoporosis are factors that cause these changes, because compression fractures cause ‘wedging’ located on the anterior side of the vertebrae, leading both growth kyphosis and lessening lumbar lordosis (Giansircusa and Kantrowitz, 1982).  As mentioned, NPC children are seen with deliberate tremor and slow motor movement, while juvenile outset shows gait impairment and dysfunction on smooth motor control. The variety of movement impairment are more obvious in adulthood (Pick, 1933). The changes in lumbar can directly cause changes in knee position and pelvic tilt. Muscle weakness, and additional circumstances may also provide to alternative postural changes. In NPC patients, ataxic symptoms are regularly decayed over period, postulating from mild upper limb direct from moderate to serious full body involvement as age increase from the age of 5-7 years of onset. Intention tremor and dysmetria relate to NPC patients during infantile and juvenile (Fink et al, 1989). Past studies regarding posture within the elderly are concentrated on postural sway. This is a general focus since increased sway is a symptom of generalized instability, and signifies the risk of increased risk of falling (Woollacott et al, 1986). Notability, sway was discovered to increase with age and elderly people who experience fall are connected to rise postural sway. Changes in gait could be influence in this research. Possible suggestion that more forward leaning of head, trunk and arm is a factor of an intricated of changes in gait connected with instability (Wolfson et al, 1990). In terms of standing posture, including the static balance of body segments, there are not many study regarding, even though it might be vital in understanding the possibility for postural instability. When posture moves, then there will be changes following the biomechanics of standing and of locomotion, which can lead to mechanical insecurity and instability. Brocklehurst el al (1982) study correlated few measures of skeletal change to postural sway, and discover that more sway related to factors such as more knee flexion, less grip strength and larger loss of height. In adults, the skeleton is coordinate for maximal stability in multiple methods. Even though not always linear, the joint centers are adjusting quite linearly above and forward of the angle joint. The center of gravity of the whole body drop relatively near to the midpoint of the base of support, to keep stability, preserve (Hellebrandt, 1938). The balance regarding the hip joints and knees in adults also increases stability. Seen in the sagittal plane, the centers of gravity of the ration of the body above hip and knee fall almost upon these joints, but on common a minimal towards the knee and behind the hip, therefore inclining to hyperextend each joint and expand its stability (Akerblom, 1991); this type of balanced alignment shoes that postural muscles require only to apply slightest force to accomplish an upright posture. As this research focuses on observing jerk and sway of NPC and controls, by how they could recover from their normal standing posture. Generally, it is proposed that the inner ear is not contaminated by radiation at the dosage frequently conducted for therapy, information proposed that radiation-induced inner ear injury does happen in animals and NPC patients being treated (Chao et al, 1998). In the inner ear, the vestibular apparatus functions for body balance, it is likely that NPC patient’s survivors after being treated with radiotherapy get vestibular dysfunction leading to postural control problems. In a study, irradiated NPC patients was observed through a standing balance performance task. Using standard Romberg position and posturography, bipedal stance of postural sway was evaluated, and the results shows that NPC patients could have their postural control retain (Marieb and Hoehn, 2010). But, the researcher selects a double leg standing posture, as this may not have been difficult for the participants due to their wide base of support. They tried to block their visual input by having them stand on an eyes close condition, therefore suggesting that functional balance in NPC patients will be less superior to healthy controls. Results have shown that healthy control generally have a better performance than NPC patients, this may possibly because that NPC patients may not have been used their other sensory input well, usually, impairment of not being able to see of the other three senses NPC patients are not able to use the remaining two sensory input to compensate balance as well, thus there was obvious more irregular movement when trying to keep the double leg standing posture. For instance, impairment of the vestibular system may be adjusted by increasing somatosensory alertness and visual attention to better control, when control have one of their sensory system in this condition. It will be apparent, when NPC patient are tested by standing vs the controls, if one of  their sensory information are removed, more sway and increase jerk will be observed  The aims of the study were to compare the similarities and difference of child and patient group through conditions of their posture and balance, and was to determine if standing balance was abnormal in patients to healthy children and adults by using accelerometer for research, and if so, what factors of postural balance were affected by measuring them in two conditions of (eyes close/open) when measured by an accelerometer to look for posture deficits. Therefore, it will be hypothesized that NPC patients will have an inferior performance to recover from jerk and more sway in the eyes close condition conducted in this experiment and in controls younger participants will have an increase in jerk and sway compared to older participants, but similar value with NPC patients.




This experiment recruited 63 participants from one primary school (within the range of year 1, year 3 and year 5) to participate in this study and 93 older participants from the age range of 12-25 was recruited through research participant scheme recruiting software. Before being able to conduct the research a DBS Form (Disclosure and Baring Service Form) was collected from The University of Birmingham, to gain permission to conduct the study with children (age range of: 6 to 12) and older participant was required to complete a consent form. The experimenter will meet in and guide the children about the instruction and design of the study. The guardian of the children will be given an information form, which allows them to acknowledge the study and children participation will be granted from their parents. Approval will be obtained through the consent form and primary school. The experiment also recruited 16 postgraduate participants from the University of Birmingham, they were recruited by the research participant scheme webpage. Consent was obtained directly from the participant through a consent form. Debrief and information sheet was given to them to understand the purpose of the experiment.


Opals provides a suite of plugin for mobility lab that are created to measure and analyze a person posture and gait movement generally used in clinical rehabilitation of NPC and Parkinson patients. Participants were attached with accelerometer on the participant waist, the velocity, sway and jerk can be measure. The PKMAS software system will be installed in laptops, this advanced and modern software will be used to predict center of mass, provide a more efficient flexible use of the sensor mat (static and turn analyses, etc.), and bring several significant parameters to the equation. While undergoing test with children and patients in (eyes closed and open condition) blindfold will be needed for the closed condition, and a picture frame to get the participants focus of attention when conducting measures. Tripods was used for video recording each walk and sway measurement during the experiment. Excel software will be used for data transfer after collected from the PKMAS software.          

Experimental Approach

For the opals measure, measurement of the participant’s age, leg length, weight and height was measured and inserted to the PKMAS software to have information about each person’s physical attributes and data base within Excel. Participants were tested 6 trials in total in this experiment (eyes open: 3 trials) and (eyes close: 3 trials) and iPad was used to record every trial that with the time range of 30 seconds. All participants will be given a blindfold for the eyes close condition. Participants will be instructed to look at a picture frame placed at eye level, this will be used for swaying of children. It provides children something to concentrate on while standing quietly otherwise they might start to move around, this countermeasure was used to minimize errors of possibly inconsistent data collection. Parameter collected from the PKMAS software will include jerk, sway and velocity of each participants. Sway area and jerk were the two main measures from the standing task. This experiment is interested to know the difference of jerk and area and sway on controls and patients during eyes open and close conditions. Video recording was used as a countermeasure during data cleaning to ensure that unwanted movement could be observed and removed All results was analyzed in SPSS statistical software (version 16) to conduct statistical test by ANCOVA and linear regression.    

Data Analysis

Opal data will first be transferred to Excel from the PKMAS software. Pivot table will be created with the average, standard deviation and count of jerk and sway between two conditions (eyes open and close). Data collected will be cleaned in order to remove large irregular movement to avoid outliers from spreading on overall result on data analysis. All results will be analyzed in SPSS statistical software (version 24.0). The continuous data result will be presented as standard deviation, median, range and mean, and 95% confidence interval of the mean will be calculated. Linear regression was conducted using age and height as independent variables, fixed factors will be the two conditions of eyes open/close, and jerk/sway will be the dependent variable. Repeated measure with ANOCOVA are conducted between the two conditions of eyes open/close, as age was the co-variate. The purpose of this is to see are there an effect of NPC patients sways and jerk movement in two conditions when compared with normal patients in different age range. How large was the group difference and are variance among patients higher than controls? ANCOVA was conducted on within only control group to observe whether age or height has significant difference of jerk and sway on both condition. The primary interest for this research is the test interaction between the two-groups of children and healthy patients and to report the number of patient that are inside or outside of the control range. When looking at results through individual on NPC patients, we attempted to observed how spread the disease will be through scatterplot graph  

Predicted Result

The aims of the study were to compare the similarities and difference of child and patient group through conditions of their posture and balance, by measuring them in two conditions of (eyes close/open) when measured by. We hypothesized that deficits in postural control in patients with NPC will have a less sensitive movement than normal patients by the measures on the accerrometer. When testing children for gait measures, we believe that if there were long delays on movements, it is likely to increase new neurological symptoms. The (open eyes/close condition), movement and the onset of gait is most likely to be late in children that may be with NPC (Sutherland et al, 1980) and this influences advancement of postural control. Standing balance was found to have significant relationship with age in children (Wolff et al, 1998). In terms of height, eyes open and close are different when a person, interaction with condition are not affected by age and height, but the condition. Height will be a significant factor for jerk, the difficulty level in keeping a steady standing posture varies depending the movement of direction. We want to know what is the normal pattern and how different is eyes open and close during standing test. Another factor we are trying to understand what is the developmental trajectory, that is, do controls change with age? If they do change with age does this happen only when they are younger, so that the capacity is reached earlier than older participants? Possibly there will be a difference in value in both condition. Or does development occur across the full range? Line will be plot on scatterplot for the two conditions to see how development is occurring and if it is different for eyes open/close. Newton (2001) have found when older adults had less larger reach distance in the backward direction. This highlighted that with the position of angle joint are connected to the foot, suggesting there is more biochemical benefits for changing the bogy movement forward than backwards at the time of backward reaching. This highlights the fact that NPC patients will higher spread of activity of jerk and sway may be due to cerebella damage of unable to function their motor control movement as well thus leaving the control range through the increase of their age. For that we plot individual conditions of eyes open/close by themselves on the scatter graph, and put controls and patients on the same plot with different colour to observe the difference in standing balance.


Controls Age Range Average of Jerk EO Average of Jerk EC Average of Sway EO Average of Sway EC StdDev of Jerk EO StdDev of Jerk EC StdDev of Sway EO StdDev of Sway EC
6.5 0.008595374 0.009940768 0.001889141 0.002324737 0.003376027 0.004806077 0.00281051 0.002803898
8.5 0.007746111 0.009955389 0.00081126 0.001213583 0.001973724 0.007843886 0.000602505 0.00128233
10.5 0.007667589 0.008137656 0.000717589 0.001020261 0.001864412 0.002605339 0.000629559 0.00113921
12.5 0.007707576 0.007395091 0.00028173 0.000331818 0.002948149 0.002522863 0.000137135 0.000173552
14.5 0.008189233 0.008495812 0.000329767 0.000509733 0.002593252 0.002275187 0.000239929 0.000637491
17.5 0.006448758 0.007136121 0.000176064 0.000242576 0.003132625 0.00331038 0.000106209 0.000148288
25 0.006005104 0.011599844 0.000264269 0.000365615 0.001751541 0.02095421 0.000248427 0.000268951
Grand Total 0.007489386 0.009470274 0.00079616 0.00106272 0.002594736 0.010402502 0.001466514 0.00165735

Average and Standard Deviation of Controls and Patients

Table 1: Average and Standard Deviation of Controls of Jerk and Sway in eyes open and close conditions On average, it reported on table 1 that the youngest control of age range of 6.5 shows a higher average of sway in both conditions on eyes open (mean=0.001889141, SD=0.00281051) and eyes close condition (mean=0.002324737, SD=0.002803898). Following it was reported that age range of 17.5 shows the lowest average of sway on eyes open (mean=0.000176064, SD=0.000106209) and eyes close (mean=0.00024576, SD=0.000148288) condition. In Jerk eyes open condition, it was reported that that the age range of 6.5 have the most value of jerk (mean=0.008595374, SD= 0.003376027). In jerk eyes close condition, it was reported that controls of the age range of 25 have the highest value of jerk (mean=0.011599844, SD=0.002095421). While controls of age range 25 shows a lowest value of jerk (mean=0.006005104, SD=0.001751541). In eyes close condition, control of the age range of 17.5 have the lowest value of jerk (mean=0.007136121, SD=0.00331038).

Patient Age Jerk EO Jerk EC Sway EO Sway EC
3 0.0101865 0.0157105 0.001026 0.007313
4 0.0536483 0.086656667 0.04261 0.088213667
6 0.112067 0.105372333 0.091865667 0.091432433
8 0.0376 0.00508475 0.025324
10 0.0084968 0.0079038 0.0009438 0.0011048
10 0.005547 0.0080778 0.0010654 0.0016692
11 0.0048015 0.00508475 0.00069125 0.00128175
14 0.0278955 0.143759 0.0062705 0.1231025
Grand Total 0.260242633   0.3776496   0.169796617   0.31411735  
Average 0.032530329   0.0472062   0.021224577   0.044873907  
Standard Deviation 0.036631525   0.055905793   0.032371133   0.053633359  

Table 2: Average and Standard Deviation of Patients of Jerk and Sway in eyes open and close conditions On average, it reported on table 2 that on jerk eyes open condition NPC patient of age 6 have the highest value of jerk. While jerk value was reported to be highest on NPC patients of age 14. For the sway measure, NPC patients with age 6 have the highest value of sway value on eyes open condition. While on eyes close condition, NPC patient of age 14 have the most sway value throughout the experiment.

Intercept Value of Control Range

Model Standardized Coefficient B (Std. Error) Sig
Jerk EO Constant .044(.015) .013
Jerk EO Age Value -.001(.001) .428
Jerk EC Constant .030(.026) .281
Jerk EC Age Value .002(.002) .346
Sway EO Constant .034(.013) .0.26
Sway EO Age Value -.002(.001) .115
Sway EC Constant .046(0.25) .091
Sway EC Age Value -002(.002) .383

*p < .05 Table 3: Linear Regression between controls and patient’s participants and age value In table 3, a simple linear regression was calculated to predict participant jerk and sway value on both conditions based on their age. Results have indicated that age predict participant value of jerk and sway on both condition (eyes open and close).  Graph 1: Controls (Normal Pattern) and NPC patients jerk eyes open value  Graph 2: Controls (Normal Pattern) and NPC patients jerk eyes close value  Graph 3: Controls (Normal Pattern) and NPC patients sway eyes open value  Graph 4: controls (Normal Pattern) and NPC patients sway eyes close value                            

Controls Influence of posture by using age and height as covariate

Controls Jerk EO (Sig) Jerk EC (Sig) Sway EO (Sig) Sway EC (Sig)
Height .982 .072 .007 .018
Age .021 .057 .936 .616

            *p < .05   Table 4: Controls Individual Values of between the influence of age and height of each variables In table 4, A one-way ANCOVA was conducted to compare the influence of how age and height would have an influence to jerk and sway in eyes open and close conditions of controls. There was a significance difference in age in influence on jerk condition in eyes open condition [F (1, 154) =5.398, p=0.021) but was not significant for jerk eyes close condition and both conditions of sway. Height was reported to have a significant difference on the influence of sway eyes open [F (1, 154) =7.345, p=0.007) and eyes close condition [F (1, 154) =5.708, p=0.018). There was no significant difference of height influencing jerk in both conditions.  Graph 5: Individual conditions of controls on jerk eyes open  Graph 6: Individual conditions of controls on jerk eyes close  Graph 7: Individual conditions of controls on sway eyes open  Graph 8: Individual conditions of controls on sway eyes close                          

Patients and controls individual Value

Between Subject Effect Jerk EO (Sig) Jerk EC (Sig) Sway EO (Sig) Sway EC (Sig)
Groups (Controls and NPC Patients) .000 .000 .000 .000
Age .079 .515 .130 .579

*p < .05 Table 5: Controls and NPC Patients Individual Values of between the using covariate as age on jerk and sway of both eyes open and close condition In table 5, A one-way ANCOVA was conducted to compare the influence of how age would have an influence to jerk and sway in eyes open and close conditions of controls and NPC patients. There was a significance difference (P <0.05) in groups that influence the outcome of all measure on jerk and sway measurement on both eyes open and close condition. No significant different on age was found between the two groups (P= 1.000).  Graph 9: Individual conditions comparing Controls and NPC patients on jerk eyes open  Graph 10: Individual conditions comparing Controls and NPC patients on jerk eyes close  Graph 11: Individual conditions comparing Controls and NPC patients on sway eyes open  Graph 12: Individual conditions comparing Controls and NPC patients on sway eyes close  


To summarize the result of the main finding, it was found that NPC patients does have a significant difference in terms of performance of jerk measure on both eyes open and close conditions (referring to graph 9 and 10). Significant difference was found of sway measure, participant have a higher value of sway when compare to controls. Especially on eyes close condition of both jerk and sway, it reported that NPC patient have a more increase value when compared to eyes open condition. Generally, controls have a better performance than NPC patients when maintaining a posture balance, as NPC patient may not have been able to use their sensory system well as control was able to compensate their surrounding better than patients (Marieb and Hoehn, 2010). Linear regression result (referring to table 3) shown that age was a significant predictor of jerk eyes open and sway eyes open on both controls and NPC patients. (Refer on graph 1) it was observed that there were 4 NPC patients that was out of the control range of the controls and (referring to graph 3) 4 other participant was out of the control range of the control. When observing the overall result (referring to table 2) NPC patients with the age of 6 have the highest value of jerk and sway when compared to other NPC patients. During the age range of 3 to 6, displays feature of gait problems and continuous falls are usually seen during this stage of the disease (Rottach et al, 1997). The NPC patient this age, might possibly have a later onset of muscle responses on accurate timing. Such factor may include slow contraction on the ankle musculature, a proximal to distal muscle response (Roncaesvalles et al 2002). But when observing NPC patients on the age range 10-11(refer to graph 1, 2, 3 and) jerk and sway value of both condition (eyes open and close) was lower than the control range, as this may explain that this NPC patients have less serious symptoms when compared to other of the same group. This may suggest that no regular inadequacy of sphingomyelins have been recorded during this stage, as apparent symptoms of posture disability is not apparent (Passini et al 2005). NPC patient of the age range of 14 (referring to table 2) had the highest jerk and sway value on eyes close condition. This provide possible evidence that inner ear of this NPC patients could have possibly been damage, referring to previous study of Chao et al (1998) poorer standing performance was seen when compare to healthy control. Therefore, this NPC patients have a more apparent neurological and psychiatric symptoms, when compare to early age group of NPC patients. Therefore, it was predicted that NPC patients have poorer performance to recover from jerk and more sway in the eyes close condition conducted in this experiment. When controls are observed individually, height was a major significant factor on controlling sway movement (refer to table 4) and age influence jerk values.  The significant negative decline of jerk can be influence by the effect of aging. When compared to previous study of Lewek et al (2010) jerk correlates with age, younger adult (age 20) have twice the amount of jerk value when compared to older adult (age 40). Suggesting jerk smoothness are decrease by the increase of age. Increase of sway movement was reported on (referring to graph 7 and 8) on younger control participants when compared to older participants. (Referring to table 4) there was a significant effect on height with increase of sway, in generally major factor this may suggest older participant may have a postural sway control method that can help them perform volitional movement when compared to younger children (Koceja et al, 2000). Another possible suggestion, younger children may lack knowledge in compensating their posture leading to an increase of fall when vision is removed leading to an increase in sway. Overall when younger controls were compared with NPC patients (referring to graph 8, 9, 10 and 11) there is a similar jerk and sway value on both eyes open and close condition, difference value was more apparent on older controls compared to NPC patients.   Conclusion Overall, this present study provide result indicating that NPC patient will generally have a late stage of fall risk and more time for correction when keeping a standing posture. From comparing children from primary school, and NPC patients, it can be observed that NPC disease are not apparent usually in this stage as both result on jerk and sway are similar. However, for this study, limited NPC patients was recruited for this study as this sample to be observed provided less outcome to observe are most NPC patient jerk and sway value are all range similarly on the graph. Effect of NPC patient result may have been influence by limited time of training, NPC patients usually have learning disability as one of the symptom of this disease during age range of 4-10. For future study, it is recommended more training can be conducted to NPC patients to allow them to understand the nature of the standing task they are participating, provide a more obvious standing platform point for participant will help in assisting them in knowing the point where they are supposed to remain in to avoid unwanted value of jerk and sway measure. More accurate description is also needed, so that experimenter can enhance their judgment of confirming the most common symptom of this disease. Lack of the understanding of this disease, such as treatment are needed increase understanding of the nature caused by this disease.


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Appendix 1: SPSS Output (Control Range Intercept) Linear Regression

Model Summary
Model R R Square Adjusted R Square Std. Error of the Estimate Change Statistics
R Square Change F Change df1 df2 Sig. F Change
1 .221a .049 -.024 .026442486600 .049 .670 1 13 .428
  1. Predictors: (Constant), age

Sig.F Change: .428

Model Sum of Squares df Mean Square F Sig.
1 Regression .000 1 .000 .670 .428b
Residual .009 13 .001
Total .010 14
a. Dependent Variable: jerkopcutoff
b. Predictors: (Constant), age
Model Unstandardized Coefficients Standardized Coefficients t Sig. 95.0% Confidence Interval for B
B Std. Error Beta Lower Bound Upper Bound
1 (Constant) .044 .015 2.864 .013 .011 .076
age -.001 .001 -.221 -.818 .428 -.004 .002
a. Dependent Variable: jerkopcutoff
Model Summary
Model R R Square Adjusted R Square Std. Error of the Estimate Change Statistics
R Square Change F Change df1 df2 Sig. F Change
1 .273a .074 -.003 .044343324000 .074 .964 1 12 .346
  1. Predictors: (Constant), age

Sig.F Change: .346

Model Sum of Squares df Mean Square F Sig.
1 Regression .002 1 .002 .964 .346b
Residual .024 12 .002
Total .025 13
a. Dependent Variable: jerkeccutoff
b. Predictors: (Constant), age
Model Unstandardized Coefficients Standardized Coefficients t Sig. 95.0% Confidence Interval for B
B Std. Error Beta Lower Bound Upper Bound
1 (Constant) .030 .026 1.129 .281 -.028 .087
age .002 .002 .273 .982 .346 -.003 .007
a. Dependent Variable: jerkeccutoff
Model Summary
Model R R Square Adjusted R Square Std. Error of the Estimate Change Statistics
R Square Change F Change df1 df2 Sig. F Change
1 .424a .180 .117 .023218185000 .180 2.854 1 13 .115
  1. Predictors: (Constant), age

Sig.F Change: .115

Model Sum of Squares df Mean Square F Sig.
1 Regression .002 1 .002 2.854 .115b
Residual .007 13 .001
Total .009 14
a. Dependent Variable: swayeocutoff
b. Predictors: (Constant), age
Model Unstandardized Coefficients Standardized Coefficients t Sig. 95.0% Confidence Interval for B
B Std. Error Beta Lower Bound Upper Bound
1 (Constant) .034 .013 2.519 .026 .005 .062
age -.002 .001 -.424 -1.689 .115 -.004 .001
a. Dependent Variable: swayeocutoff


Model Summary
Model R R Square Adjusted R Square Std. Error of the Estimate Change Statistics
R Square Change F Change df1 df2 Sig. F Change
1 .253a .064 -.014 .042053951100 .064 .822 1 12 .383
  1. Predictors: (Constant), age

Sig.F Change: .383

Model Sum of Squares df Mean Square F Sig.
1 Regression .001 1 .001 .822 .383b
Residual .021 12 .002
Total .023 13
a. Dependent Variable: swayeccutoff
b. Predictors: (Constant), age

Model Unstandardized Coefficients Standardized Coefficients t Sig. 95.0% Confidence Interval for B
B Std. Error Beta Lower Bound Upper Bound
1 (Constant) .046 .025 1.837 .091 -.009 .100
age -.002 .002 -.253 -.906 .383 -.006 .003
a. Dependent Variable: swayeccutoff

Appendix 2: SPSS Output (Control individual value ANCOVA)

Tests of Between-Subjects Effects
Dependent Variable:   jerkeo
Source Type III Sum of Squares df Mean Square F Sig.
Corrected Model .000a 2 5.718E-5 9.408 .000
Intercept .000 1 .000 19.934 .000
height 3.134E-9 1 3.134E-9 .001 .982
age 3.280E-5 1 3.280E-5 5.398 .021
Error .001 154 6.078E-6
Total .010 157
Corrected Total .001 156
a. R Squared = .109 (Adjusted R Squared = .097)
Tests of Between-Subjects Effects
Dependent Variable:   jerkec
Source Type III Sum of Squares df Mean Square F Sig.
Corrected Model .000a 2 .000 1.902 .153
Intercept .001 1 .001 7.439 .007
height .000 1 .000 3.273 .072
age .000 1 .000 3.672 .057
Error .016 154 .000
Total .031 157
Corrected Total .017 156
a. R Squared = .024 (Adjusted R Squared = .011)
Tests of Between-Subjects Effects
Dependent Variable:   swayeo
Source Type III Sum of Squares df Mean Square F Sig.
Corrected Model 4.517E-5a 2 2.259E-5 11.980 .000
Intercept 3.177E-5 1 3.177E-5 16.850 .000
height 1.385E-5 1 1.385E-5 7.345 .007
age 1.203E-8 1 1.203E-8 .006 .936
Error .000 154 1.885E-6
Total .000 157
Corrected Total .000 156
a. R Squared = .135 (Adjusted R Squared = .123)
Tests of Between-Subjects Effects
Dependent Variable:   swayec
Source Type III Sum of Squares df Mean Square F Sig.
Corrected Model 6.468E-5a 2 3.234E-5 13.688 .000
Intercept 3.841E-5 1 3.841E-5 16.260 .000
height 1.349E-5 1 1.349E-5 5.708 .018
age 5.974E-7 1 5.974E-7 .253 .616
Error .000 154 2.363E-6
Total .001 157
Corrected Total .000 156
a. R Squared = .151 (Adjusted R Squared = .140)

Appendix 3: SPSS Output (Controls and NPC patients Individual Value ANCOVA)

Tests of Between-Subjects Effects
Dependent Variable:   jerkeo
Source Type III Sum of Squares df Mean Square F Sig.
Corrected Model .005a 2 .002 39.032 .000
Intercept .009 1 .009 145.290 .000
age .000 1 .000 3.118 .079
groups .004 1 .004 68.814 .000
Error .010 161 6.354E-5
Total .028 164
Corrected Total .015 163
a. R Squared = .327 (Adjusted R Squared = .318)
Tests of Between-Subjects Effects
Dependent Variable:   jerkec
Source Type III Sum of Squares df Mean Square F Sig.
Corrected Model .013a 2 .007 29.414 .000
Intercept .016 1 .016 70.805 .000
age 9.423E-5 1 9.423E-5 .425 .515
groups .013 1 .013 58.652 .000
Error .035 160 .000
Total .069 163
Corrected Total .049 162
a. R Squared = .269 (Adjusted R Squared = .260)
Tests of Between-Subjects Effects
Dependent Variable:   swayeo
Source Type III Sum of Squares df Mean Square F Sig.
Corrected Model .003a 2 .002 34.957 .000
Intercept .003 1 .003 63.229 .000
age .000 1 .000 2.321 .130
groups .003 1 .003 62.425 .000
Error .008 161 4.697E-5
Total .011 164
Corrected Total .011 163
a. R Squared = .303 (Adjusted R Squared = .294)
Tests of Between-Subjects Effects
Dependent Variable:   swayec
Source Type III Sum of Squares df Mean Square F Sig.
Corrected Model .013a 2 .006 58.414 .000
Intercept .010 1 .010 90.130 .000
age 3.405E-5 1 3.405E-5 .309 .579
groups .012 1 .012 112.605 .000
Error .018 160 .000
Total .032 163
Corrected Total .031 162
a. R Squared = .422 (Adjusted R Squared = .415)

Appendix 4: Adult Consent Form

 Study Number: Participant Number: CONSENT FORM Project title:   Cognitive assessment of paediatric neurodegenerative disease   Name of Researcher:  Dr. Andrew Olson

Please initial each box
  1. I confirm that I have read and understood the information sheet dated 24 September 2016 (version 4) for the above study. I have had the opportunity to consider the information, ask questions and have had these answered satisfactorily.
  1. I understand that my participation is voluntary and that I am free to withdraw them at any time, without giving any reason and without my legal rights or NHS services being affected.
  1. I understand that data collected during the study may be looked at by individuals from regulatory authorities or from the NHS trust where it is relevant to my taking part in this research. Anonymized data will also be analysed by members of the research team and by students or researchers under their supervision. I give my permission for these individuals to have access to my data.
  1. I agree to take part in the above study.
  1. I agree to be videotaped for this project
  1. I agree that my video can be used in scientific presentations of the data from this project.
  1. I agree that I may be contacted regarding future research that follows up on this project (initial one box).

_______________________       ____________    ______________________ Name of Participant                     Date                    Signature _______________________       ____________    ______________________ Name of person taking consent   Date       Signature

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