1. Higher Efficacy of Modified Constraint Induced Movement Therapy versus Conventional Rehabilitation Therapy in Acute Stroke Patients

2. Annually, there are approximately 15 million people worldwide suffering from cerebrovascular stroke. Of these, 5 million are permanently disabled Thus stroke represents one of the leading causes of disability among all CNS disorders. One of the disabling consequences of cerebrovascular stroke is functional impairment of the affected upper extremity since its recovery is often delayed than that of the lower extremity.

3. Rehabilitation Options For Individuals With Acute Stroke Most rehabilitation strategies of acute hemiplegic patients focus on compensation rather than restoration of upper extremity function since patients use the unaffected upper extremity for activities of daily living. Recently, new treatment strategies were introduced that might be more effective than conventional rehabilitation treatment. Promising approaches include practice with robotic devices or use of a virtual environment with electrical stimulation to increase cortical excitability during training. One potential method to improve sensorimotor recovery after acute stroke is constraint induced movement therapy (CIMT), often labeled “forced use” treatment which is a currently popular therapy with a sound theoretical foundation. Many reports are available about its effectiveness on cortical reorganization and there is mounting evidence for the efficiency of CIMT protocols.

4. CIMT is a behavioural approach in neurorehabilitation based on the principle of ‘learned non-use’. The term is derived from studies of non-human primates in which somatosensory deafferentation of a single forelimb was performed, after which the animal failed to use that limb. The major components of CIMT include: intense, repetitive (task oriented) training and behavioral shaping of the impaired limb with immobilization of the unimpaired arm. Intensive CIMT involves constraint of the unaffected arm for at least 90% of the waking hours whilst modified CIMT (m-CIMT) consists of constraint of the unaffected arm with a padded mitt or arm sling for a minimum of 6 hours per day.

5. In contrast to conventional therapy in acute stroke, CIMT discourages the use of the unaffected extremity and encourages the active use of the hemiplegic arm in order to restore the motor function16. CIMT can be thought to exert an indirect effect on the paretic limb use by preventing compensatory use of the less-affected limb for some tasks. On the other hand, the task-specific training with the paretic limb can be thought to exert a direct effect on paretic limb use. There are numerous studies that have suggested that CIMT can lead to considerable improvement in hand function which lasts for more than a year after training.

6. identification of the patient potentials for motor recovery is important in order to avoid “learned disuse’’ and to be able to initiate appropriate therapy with realistic goals Recovery is due to brain plasticity which occurs through cortical reorganization. Three major mechanisms for this plastic reorganization: 1.unmasking of existing but functionally inactive pathways, 2.sprouting of fibers from surviving neurons and 3.formation of new synapses and redundancy of CNS circuits allowing alternative pathways to take over functions

7. An essential question is "Does modified constraint induced movement therapy has higher efficacy than conventional rehabilitation therapy in management of acute stroke patients?".Consequently, in this article, the authors assessed functionally and neurophysiologically the efficacy of modified constraint induced movement therapy on functional recovery of upper extremity (UE) in acute stroke patients, as compared to conventional therapy with the same total rehabilitation peroid..

8. Objective To assess the efficacy of modified CIMT on functional recovery of upper extremity (UE) in acute stroke patients, as compared to conventional rehabilitation therapy

9. Methodology This study included twenty six acute stroke patients. Inclusion criteria included the following: patients within two weeks from the onset of stroke, persistent hemiparesis leading to impaired upper extremity function, evidence of preserved cognitive function and a minimum of 10 degrees of active finger extension and 20 degrees of active wrist extension.

10. Exclusion criteria included the following: intracerebral hemorrhage, previous stroke on the same side, presence of neglect or a degree of aphasia impeding understanding of instructions and patients with conditions that limit the use of the upper limb before the stroke..

11. The patients were divided into two groups. Group A: 13 patients were given a conventional rehabilitation program for two weeks. Group B: 13 patients were subjected to the modified CIMT for two consecutive weeks. Total treatment time was kept identical in both groups

12. Patients were assessed by Brunstrom- Fugl Meyer test Motor Assessment test (FMA), Action Research Arm Test (ARAT) and Motor evoked potentials (MEPs) recorded from the abductor pollicis brevis of the affected hand. The clinical and neurophysiological tests were performed pre and post rehabilitation

13. FMA upper extremity motor section of Brunstrom-Fugl Meyer Assessment (FMA) to evaluate motor performance and function of the upper extremity where 0= cannot perform and 2= can perform fully It includes: Reflex activity, flexor synery, extensor synergy, combining synergies, out of synergy, wrist, hand, coordination

14. ARAT ): quantitative test for the upper extremity function. There are four subsets: Grasp, Grip, Pinch and Gross movement. Items in each are ordered in such a way that if the patient performed the most difficult item (the first item of each subscale), then this predicts success with all less difficult subscale items. Thus, the patient is scored with the maximum score for that subscale for that limb. On the other hand, failure with the easiest item (the second item of the first three subscales and the first item of the fourth subscale) predicts failure with all items of greater difficulty on that subscale and the patient is scored zero and again no more tests needed to be performed in that subset. Otherwise the patient needs to complete all tasks within the subset. Materials needed to perform the test: Wood blocks, a ball, a stone, two different sizes of alloy tubes, a washer and bolt, two glasses, a marble and a 6-mm ball bearing. Scoring: The test is a four point scale ranging from 0 to 3 with maximum score =57. 0= Can perform no part of the test. 1= Perform test partially. 2= Complete test but takes abnormally long time or has great difficulty. 3= Perform test normally. Items of the Action Research Arm Test.

15. 1- Grasp subscale. Grasp and lift blocks, a ball and a stone from one shelf of a table to another. i– Pick up a block wood of 10 cm diameter (if score =3, total = 18 and go to grip). ii– Pick up a block wood of 2.5 cm diameter ( if score =0, total =0 and go to grip). Iii– Pick up a block wood of 5 cm diameter. iv– Pick up a block wood of 7.5 cm diameter. v– Pick up a ball of 7.5 cm diameter. vi– Pick up a stone 10X2.5X1 cm. 2- Grip subscale. i– Pour water from glass to another (if score =3, total=12 and go to pinch). ii– Displace an alloy tube (diameter 2.5 cm) from one side of the table to the other (if score = 0, total =0 and go to pinch). iii– Displace an alloy tube (diameter 1 cm) from one side of the table to the other. iv– Put washer over a bolt.

16. 3- Pinch subscale. Pinch and lift the ball and block from one shelf of a table to another (lift over 37 cm). i– Ball bearing of 6mm diameter between 3rd finger and thumb (if score =3, total = 18 and go to gross movement). ii– Marble bearing of 1.5 cm diameter between first finger and thumb (if score = 0, total = 0 and go to gross movement). iii– Ball bearing between 2nd finger and thumb. iv– Ball bearing between 1st finger and thumb. v– Marble bearing between 3rd finger and thumb. vi– Marble bearing between 2nd finger and thumb. 4- Gross movement subscale. i– Place hand behind head (If score =3, total=9 and finish), (If score = 0, total = 0 and finish). ii– Place hand on top of head. iii– Hand to mouth.

17. Neurophysiological evaluation Transcranial magnetic stimulation (TMS) was used as a diagnostic tool for estimation of resting motor threshold (RMT), motor evoked potential (MEPs) amplitude, central motor conduction time (CMCT)). TMS was performed initially and repeated after completion of the rehabilitation program. The clinical neurophysiologist was masked to the results of the clinical assessments. A Dantec keypoint EMG was utilized to collect the signal. Maglit Model 200 stimulator with 90 mm a figure of 8 coil. Stimuli were given on the infarcted side. Coil placement was performed as described by Malcolm et al.39 Motor response was recorded by surface electrodes placed over contralateral abductor pollicis brevis (APB). After recording RMT, the stimulus intensity was increased until potentials with the largest amplitude and shortest latency were obtained. The stimulus intensity was increased to the maximum before a response was considered absent. Resting motor threshold was defined as the lowest intensity necessary to produce motor evoked potential> 50 uV in at least 5 out of 10 consecutive stimulations. 40 The motor evoked potential amplitude was determined as peak to peak amplitude (mV). MEPs were considered absent if no response could be obtained with 4 stimulations at maximum intensity.41 CMCT was calculated as the latency difference between responses to stimulation of the motor cortex (TMCT) and the cervical ventral roots (peripheral latency). 41

18. Schematic representation of the calculation of CMCT. A- Motor evoked potential induced by TMS, TMCT is calculated (T1). B- MEP after cervical spinal root stimulation, peripheral latency is calculated (T2). CMCT= T1-T2

19. Recording: from the abductor pollicis brevis muscle by surface electrodes using Dantec keypoint EMG apparatus. Resting motor threshold: is defined as the lowest stimulus intensity evoking a MEP> 50 uv recorded from thenar muscle after magnetic stimulation of the motor cortex. MEP amplitude: peak to peak amplitude (mV). CMCT: latency difference between responses to stimulation of the motor cortex (TMCT) and the ventral roots (peripheral latency).i.e. subtracting peripheral latency from TMCT MEPs were considered absent if no response could be obtained with 4 stimulations at 100% intensity.

20. III) Medical treatment according to the guidelines of the Ain Shams University stroke group. IV) Rehabilitation program Group A, the patients were subjected to a standard conventional one to one rehabilitation program for two hours per day, 5 days per week for 2 consecutive weeks. The prescription of the program was tailored according to each patient’s clinical and functional assessment and modified according to the development of his condition. It included traditional positioning, management of spasticity, standard occupational therapy, compensatory techniques in activities of daily living (ADL), strengthening exercises and range of motion exercises..

21. Group B, the patients were subjected to CIMT. CIMT consisted of 2 main elements; movement restriction and shaping: Restriction of movement of the unaffected extremity was achieved by asking the patient to wear a mitten on the unaffected hand for at least 6 hours per day during the 2 week treatment period. Onsite training of the affected arm was done in the rehabilitation outpatient department by a procedure termed "shaping" for two hours per day, 5 days per week for 2 consecutive weeks. Shaping (adapted task practice) is a method in which motor task difficulty is adjusted in small steps to the patient motor capabilities. Shaping was carried out for various tasks related to (ADL) and routine home activities. Task objects frequently used were children’s toys (e.g. building blocks, marbles). A formal behavioral contract with the patient was set up detailing the agreed-upon activities the patient would carry out alone, after the session in hospital or at home, with the mitten on.

22. Results

23. Table 1: Demographic data of all patient groups AgeDisease duration RangeMean ± SDRangeMean ± SD Group A43-7453.90 ± 10.87 5-118.60±2.71 Group B49-7055.70 ± 6.585-129.00 ± 2.67 P. value >0.05

24. Table 2: Baseline assessment between both groups Group AGroup BP value FMA35.70 ±9.4434.30 ±10.37 >0.05 ARAT29.3 ±10.3230.20 ±10.54 >0.05 RMT (% of output) 70.1±9.9369.80±12.38 >0.05 Amplitude of MEPs (mV) 0.64±0.410.63±0.32 >0.05 CMCT (msec)9.65±1.9610.82±1.71 >0.05

25. Table3: Comparison between clinical assessment scales in both groups before and after rehabilitation. GroupBefore Mean ±SD After Mean ±SD FMA ABAB 35.70 ±9.44 34.30±10.37 36.78±9.18 51.20±6.83 >0.05 <0.05* ARAT ABAB 29.3 ±10.32 30.20±10.54 32.80±9.46 48.00±6.34 >0.05 <0.05*

26. Table (4 ): Comparison between both groups as regards FMA & ARAT scale mean improvement in each group after end of rehabilitation therapy Group AGroup B Mean ±SD Z-test)Sig.(p ) FMA.Change 1.08±0.2116.90±9.93-4.322<0.05 ARAT.Change 3.50±1.2217.80±6.75-3.723<0.05

29. Table 5: Comparison between MEPs parameters in both groups before and after rehabilitation MEP Parameter GroupBefore Mean ± SD After Mean ± SD P value RMT (% of output) ABAB 70.1±9.93 69.80±12.38 67.82±5.74 62.80±11.85 >0.05 0.008* Amplitude of MEPs (mV) ABAB 0.64±0.41 0.63±0.32 0.96±0.36 1.25±0.53 >0.05 0.000* CMCT (msec) ABAB 9.65±1.96 10.82±1.71 9.38±2.44 8.91±2.30 >0.05 0.000*

30. MEPs after cortical and cervical motor root stimulation of both sides in a patient with left cerebral infarction. Affected side CMCT=26.7 -15.6 =11.1 msec (C &D) and normal side CMCT=22-14.1=7.9 msec (A & B). (A) TMCT of normal side (C) TMCT of affected side (B) Peripheral latency of normal side(D) Peripheral latency of affected side

31. Conclusion On the contrary to conventional rehabilitation therapy, the modified CIMT revealed a significant functional improvement in acute stroke patients denoting that m-CIMT might be a more efficient treatment strategy. Furthermore, improvement of MEP parameters reflects the impact of training on cortical plasticity.

32. Thank you