Background technology
Parkinson disease (Parkinson ' s disease PD) be a kind of more common nervous system degeneration disease, be one of middle-aged and elderly people major cause of morbidity.Increasing gradually with its prevalence of age growth, is to be 2% more than 1%, 60 years old among the old man more than 50 years old.Parkinsonian cause and onset of disease mechanism is unclear fully as yet so far, think at present wear out with heredity, environmental toxin, oxidative stress, excitotoxin, nervous system, factors such as autoimmune, natural death of cerebral cells are closely related.Therefore the main pathological change of parkinson disease is black substance-striatum dopaminergic neuronal degeneration, and the voluntomotory effect of its balance facilitation produces typical clinical motor symptomses such as stiff, static tremor and hypokinesia.For the diagnosis of this disease at present mainly according to medical history, clinical symptoms and sign, and the therapeutic response of anti-PD medicine.Parkinson disease clinical diagnosis standard sensitivity height, but specificity is no more than 75%.Other Parkinsonian diagnostic methods have gene studies (parkin, α-synuclein gene etc.), neural imageology (PET, SPECT, fMRI, MRS etc.), electrophysiology (visual evoked potential, electroretinogram, auditory evoked potential, event related potential etc.) and exercise test, measurement of olfaction, cognitive function inspection and some biochemical indicators such as platelet mitochondrion complex O and P MAO-B B depressant (FG7JP) activity etc.Genetic marker is applied to clinical still immature.Employing is present parkinson disease auxiliary diagnosis sensitive indicators to the detection of dopamine neuron tip function, has been used to detect those excessive risk individualities that family history is arranged abroad and whether has had preclinical dopamine dysfunction.This method specificity is higher, but the expense height has significant limitation in clinical practice.Therefore if can look for a kind of easy, easy row, objective, cheap methods for clinical diagnosis differentiates then the early stage neuroprotective treatment of disturbances in patients with Parkinson disease subclinical phase or clinical early stage parkinson disease, delaying that disease progression provides may.Parkinsonian main clinical manifestation is mainly the variation of motor function, and therefore the further investigation to the parkinson disease motor function has important effect to Parkinsonian early diagnosis.
It is not going down of muscular strength that the main motor function of parkinson disease changes, mainly be that sports coordination ability descends, main performance bradykinesia or motion can not, mainly comprise the startup difficulty of motion and slowing down of movement velocity, the multiformity movement defect, as the minimizing, poker-faced of twinkling, motion converter difficulty, the discontinuous or unexpected termination of moving.Think that in the past Parkinsonian bradykinesia mainly is because due to the myotonia, reality is noncausal relationship also.Prove tentatively that now Parkinsonian bradykinesia or motion can not be very complicated symptoms, mainly relevant with the driving device function or the extrapyramidal system downward movement active device obstacle of the outer system of cortex lower cone.Because the patient of bradykinesia is undergone surgery after the treatment, the myotonia symptom is obviously improved, but its movement velocity is not to resemble to become concordance to improve after taking the DOPA medicine.
There is the people that the detection method of parkinson patient motor function is explored and studied since the seventies in last century, begun to take shape the method that a series of motor functions detect, comprising foundation, the mensuration of movement velocity and the mensuration of muscular tension etc. at parkinson patient motor function different aspect motion scale.Reliabilities more commonly used clinically at present and validity are definite scale comes the parkinson disease motor function is detected, and it is comparatively comprehensively assessed the parkinson disease dyskinesia.Have characteristics separately again.Appraisal procedure has qualitative and quantitative.Qualitative is comparatively subjective assessment, quantitatively is objective assessment.It is comparatively accurate that two kinds of methods combine.At present generally adopt UPDRS to mark the detection of the parkinson patient being carried out motor function in the world, mainly comprise language performance, facial expression, static tremor, hand exercise or postural tremor, tetanic, finger is patted experiment, hands movement, diadochokinesia, shank motility, stand up, the stability of posture, gait, posture and body are moving less etc. from 0,1,2,3,4 five grade of score value motor function is detected from many aspects, it has reflected the situation of motor function comparatively all sidedly.Influence is bigger but its examined person is subjective, so score value can be offset to some extent, thereby influences accuracy.Referring to Lang AE, Fahn S.Assessment of Parkinson ' s disease.In:Munsat TL, ed.Quantification ofNeurological Deficit.Boston:Butterworth-Heinemann; 1989:285-309.
There is the people the detection by quantitative of motor function to be built up an experiment sequence set in conjunction with olfactory sensation and cognitive function detection at present.Its early diagnosis and discriminating to parkinson has very high sensitivity and specificity.Exercise testing comprises quick carpal joint flexion and extension assaying reaction time and movement velocity.Olfactory sensation detects by UPSIT (University of Pennsylvania SmellIdentification Test). and it comprises 40 standardization abnormal smells from the patients.Can give scoring to the selection situation of the abnormal smells from the patient that smelt according to the experimenter.Mental status is measured by the scoring of BDI (BeckDepression Inventory) scale.Confirmed its meaning by regression analysis to parkinson disease early diagnosis and Differential Diagnosis.Commute is suffered from Parkinsonian high-risk group also certain break-up value.But because its detection method is comparatively numerous and diverse, and adaptability still has certain limitation, therefore up to the present still do not obtain general application aspect clinical diagnosis.Referring to Montgomery EB Jr, Koller WC, et al.Early detection of probableidiopathic Parkinson ' s disease:I.Development of a diagnostic testbattery.Mov Disord.2000May; 15 (3): 467-73; With Montgomery EB Jr, Lyons K, Koller WC.Early detection of probable idiopathic Parkinson ' sdisease:II.A prospective application of a diagnostic test battery.MovDisord.2000May; 15 (3): 474-8.
Therefore, the someone utilizes keyboard to carry out the detection of hands movement function, but there are some defectives in traditional computer keyboard or typewriter keyboard.Owing to have a plurality of buttons on traditional keyboard, usually do not need too complicated operations when carrying out the detection of motor function, and for the poor slightly people of vision, need spend the regular hour owing in numerous buttons, seek the button that to push, cause test result can't reflect the problem of motor function aspect.And traditional keyboard is bigger, carries inconvenience and need be placed on the bigger plane.During test, tested person person will take seat, and upper body loosens straight and upright, knocks keyboard then, and this exists dyskinetic patient to have certain degree of difficulty to part.
Therefore, need a kind of simple keyboard or device to be used to carry out the detection of motor function.
The specific embodiment
Now in conjunction with the accompanying drawings detailed content of the present invention is described as follows:
Fig. 1 shows the structural representation according to device of the present invention.The device 1 that is used to detect the hands movement function according to the present invention comprises main frame 3, keyboard 2 and output device 4.In one embodiment of the invention, this main frame 3 comprises frequency generator 31, timer 32, memorizer 33, controller 34.When work, frequency generator 31 produces a frequency, and timer is based on this frequency signal timing.Knock keyboard 2 and produce an input signal, timer 32 picks up counting, and with corresponding data storage in memorizer 33, when when this knocks keyboard 2, produce second input signal, timer 33 stops timing, and controller 34 is according to the time between two input signals of the data computation in the memorizer, and the time between two input signals is exported by output device.When tested person person's motor function was tested, the time between two input signals was twice time of knocking between the keyboard, i.e. tested person person's arm or finger motion institute's elapsed time once.Need to prove, can use existing computer as the main frame that is used to detect the device of hands movement function of the present invention, but there is the problem of aspects such as costing an arm and a leg, volume is big in existing comparatively speaking computer.Main frame 3 in the foregoing description has advantage simple in structure, that volume is little, cost is low.
This output device is existing output device.In one embodiment, this output device is a display.This display can various existing display, owing to need the data owner of output to want the time, this display can be a simple LED or small-sized liquid crystal display.Certainly, this display can adopt computer monitor, and as cathode ray tube, liquid crystal display, plasma display etc., but these computer monitors are too expensive.For the consideration of cost, display of the present invention only need have simple numerical and the literal Presentation Function gets final product.And small-sized display is light small and exquisite, easy to carry, and relative computer monitor has advantage aspect volume and weight.In another embodiment, this output device is a printer, and perhaps display and printer are provided with simultaneously.
Fig. 2,3, the 4 multi-form keyboards that show according to device of the present invention.In keyboard shown in Figure 2, button 21,22 and button 23,24 are separately positioned on the two parallel line.Button 21 and button 22 be certain distance (from the button center position measurement) apart, preferred 4-20 centimetre of this distance.Spacing between the two is 9.5 centimetres in this embodiment.This distance is in order to measure the testee moves horizontally forearm under the motionless situation of ancon distance.If distance is too small, the testee only needs mobile wrist or finger can knock two buttons, so just can't measure the motor function of testee's forearm exactly.If distance is excessive, can cause the oversize of keyboard.Button 23 and button 24 adjacent settings are so that measure the motor function of adjacent two fingers (as forefinger and middle finger).In this embodiment, button 21,22 and button 23,24 are separated by far away, in order to avoid push the wrong button.
In keyboard shown in Figure 3, button 21 ' is similar to Fig. 2 with 22 ' set-up mode.Button 23 ' and button 21 ' adjacent setting.
Under the situation of keyboard shown in Figure 3, there is the possibility that pushes the wrong button.For fear of producing rub-out signal, can a switch key (mode key) 26 be set at this keyboard one jiao, as shown in Figure 4.This mode key can be made of touch-tone permutator.Under first pattern (M1), button 21 ' and 22 ' circuit are connected, and the signal that produces when pushing them can be transferred to the timer of main frame, timing is begun or finish.Under this first pattern, the circuit of button 23 ' is cut off, even therefore having pushed button 23 ' can not produce signal yet.Under second pattern (M2), button 21 ' and 23 ' circuit are connected, and the circuit of button 22 ' is cut off, and in the case, has only pressing keys 21 ' and 23 ' just can produce signal.
Referring to Fig. 5, in the figure, keyboard 2 is divided into two keypads that separate, and two adjacent buttons is set on the keyboard 2A, and a button is set on the keyboard 2B.Like this, when measuring the motor function of forearm, the distance that forearm moves can not be subjected to the restriction of keyboard size, and can be according to the length corresponding adjustment keyboard 2A of tested person person's forearm and the distance between the keyboard 2B.
, then each several part is fitted together for making each ingredient respectively according to the manufacture method of device of the present invention, constitute device of the present invention.
Be divided into the experiment of rotating of upper limb horizontal movement experiment and finger according to the test of device of the present invention.Upper limb horizontal movement experiment is meant that specifically the forefinger continuous several times beats two buttons of the apart from each other of keyboard 2, button 21,22 for example shown in Figure 2, button 21 ', 22 ' shown in Fig. 3,4, shown in Figure 5 21 ", 22 ", show its mean motion time, this time is mainly represented the speed and the sensitivity of tested person person's upper limb forearm motion; The finger experiment of rotating is meant that forefinger and middle finger alternately repeatedly push two adjacent in the keyboard 2 buttons, button 21 ', 23 ' shown in button 23,24 for example shown in Figure 2 or Fig. 3,4, button 21 perhaps shown in Figure 5 ", 23 ", show its mean motion time, this time is mainly represented the speed and the sensitivity of tested person person's finger motion.
For keyboard shown in Figure 4, the using method that this is used to detect the device of hands movement function may further comprise the steps: mode key 26 is arranged on first pattern, first group of button 21 ', 22 ' is connected with main frame; Push first button 21 ' in first group of button, the time that described first button is depressed was stored in the storage device as the motion time started, push second button 22 ' in first group of button, the time that described second button is depressed was stored in the storage device as the motion concluding time; Deduct the motion time started concluding time with motion and obtain movement time, store described movement time, and export described movement time by output device.This time is tested person person's upper limb antetheca motion time once.Repeat repeatedly calculating mean value.Then, mode key 26 is arranged on second pattern, second group of button 21 ', 23 ' is connected with main frame; Push first button 21 ' in second group of button, the time that described first button is depressed was stored in the storage device as the motion time started, push second button 23 ' in second group of button, the time that described second button is depressed was stored in the storage device as the motion concluding time; Deduct the motion time started concluding time with motion and obtain movement time, store described movement time, and export described movement time by output device.This time is tested person person's forefinger and middle finger alternating movement time once.Repeat repeatedly calculating mean value.The occupation mode of other keyboard is identical therewith, does not just have the process of switch mode button.
Utilization is tested tested person person's grouping according to device of the present invention.
1. the evaluation of determinator reliability
At first this experimental provision is carried out the test and appraisal of reliability.60 normal health persons (wherein the male is 32,28 of women, age 26-76 year) are carried out the mobile experiment of non-dominant hand and dominant hand and the experiment of rotating respectively, detected movement time.Dominant hand is meant dextromanuality experimenter's the right hand, and the experimenter is meant left hand for left handedness.Non-dominant hand is the hands of the former opposite side just.Repeat above-mentioned experiment after 24 hours again, come twice experiment of comparison to evaluate and test the degree that motor function repeats reliability.Use existing statistical package SPSS11.0 and carry out statistical analysis, with 95% as the confidence interval, when the P value is thought the difference significance less than 0.05 the time.Test that non-dominant hand between twice and dominant hand move experiment and the experiment concrete condition comparable situation of rotating sees Table 1:
Table 1 mean, standard deviation, the comparison of testing reliability again
Annotate: the equal value difference of twice experiment of aberration rate %=| |/twice experiment grand mean * 100%
Twice experiment grand mean=twice experiment average and/2
R
2The percentage ratio that can explain by the variation of independent variable in the variation of expression dependent variable, in general, R
2Big more, regression equation is meaningful more.
As seen from the above table, there is not significant difference between twice experiment; It is very little that dominant hand and non-dominant hand repeat the aberration rate that moves the experiment and rotate the experiment, can show that therefore non-dominant hand still is that dominant hand moves experiment and the experiment of rotating all has the very high stability of repeated experiments, just has good validity.
2. the evaluation of determinator validity
The evaluation of determinator validity is a reliability of utilizing the result that this device detects in order to illustrate.Generally speaking, the movement time of dominant hand and non-dominant hand is different.Specific to this experiment be exactly the experimenter must clear and definite dominant hand and non-dominant hand use respectively and move experiment and the experiment of rotating is carried out motor function and detected.Owing to exist dominant hemisphere so dominant hand and non-dominant hand motor function to certainly exist difference, the experimenter has only the mobile experiment of carrying out dominant hand and non-dominant hand respectively and the experiment of rotating, and movement time detects just has comparability, and experimental result just has credibility.Use correlation analysis, the correlation analysis that utilization dominant hand and non-dominant hand move experiment and the experiment of rotating is carried out between the motor function detection sees Table 2:
Table 2 is tried factorial analysis
As seen from the above table, utilization dominant hand and non-dominant hand move experiment and rotate has significant difference between the detection of experiment motor function, still has certain dependency.
Move experiment and rotate experiment movement time and the relation between the age
Normal control group 60 examples, age 26-76 year, 54.97 ± 14.85 years old mean age.We the age according to being divided into 5 groups from small to large, be 26-40 year 14 examples, 41-50 year 4 examples, 51-60 year 16 examples, 61-70 year 15 examples, 71-80 year 11 examples.Use one factor analysis of variance, relatively whether the nigration and the trial movement time of rotating of normal control group age groups is variant.Concrete experimental result sees Table 4.
By between table 4 explanation normal control each age group moving movement time of group and diadochokinesia time significant difference being arranged.Just the motor function of normal control group changes relevant with the age.
Table 4 normal control group all ages and classes section motor function relatively
In the normal health matched group, whether there is significance to change for the mobile experiment and the experiment movement time of rotating of further clear and definite age in 40 years old later crowd, therefore, use one factor analysis of variance, relatively whether the nigration and the trial movement time of rotating of normal control group age groups after 40 years old is variant.Concrete experimental result sees Table 5.
The table 5 explanation normal control group age is there was no significant difference between 40 years old later each age group moving movement time and diadochokinesia time.Just the motor function of age normal control group after 40 years old changes with the age irrelevant.
Table 5 normal control group all ages and classes section motor function relatively
Foregoing proves that determinator according to the present invention has fine validity.Utilization determinator according to the present invention moves experiment and the result of experiment of rotating is reliable.This device can be used to detect experimenter's motor function.
3. the comparison of motor function between sporadic parkinson disease group, normal control group, the essential tremor group
For the value of further clear and definite motor function detection by quantitative experiment in sporadic parkinson disease diagnosis and differential diagnosis, we also utilize computer apparatus to compare the motor function of sporadic parkinson disease group, normal control group, essential tremor group in twos simultaneously.At first, must carry out the comparison of three groups of subject age, between clear and definite three groups of subject age whether significant difference being arranged, thereby whether clear and definite three groups of experimenters have comparability.Use one factor analysis of variance, concrete experimental result is as follows:
Table 19 is respectively organized subject age relatively
The age does not have significant difference between three groups of experimenters.Has comparability between three groups of experimenters.
Aforementioned result explanation utilizes apparatus and method provided by the invention, can detect the difference of motor function aspect between normal, parkinson, the essential tremor experimenter significantly, and apparatus and method of the present invention can be used for Parkinsonian early diagnosis.And these apparatus and method can also be used for the judgement of curative effect and disease process.
The above is the preferred embodiments of the present invention only, is not limited to the present invention, and for a person skilled in the art, the present invention can have various changes and variation.Within the spirit and principles in the present invention all, any modification of being done, be equal to replacement, improvement etc., all should be included within protection scope of the present invention.