Hyperbaric Oxygen Therapy Induced Neuroplasticity in Post Stroke Patients Suffering Chronic Neurological Deficiencies

Completed

Phase N/A Results N/A

Update History

28 Dec '11
The description was updated.
New
Objective: Evaluate the effect of hyperbaric oxygen therapy (HBOT) on patients with chronic neurological deficiency due to stroke. Methods: A prospective, randomized, control-crossed over trial including patients who had stroke 6-36 months prior to their inclusion. All patients had at least one motor dysfunction. After their inclusion patients were randomized to treated or cross group. The neurologic functions were evaluated by NIHSS, ADL, life quality and brain SPECT. Patients in the treated group were evaluated twice-at baseline and after HBOT. Patients in the cross group were evaluated three times-baseline, after 2 months control period of no treatment and after a consequent 2 month of HBOT. The following HBOT protocol was practice: 40 daily sessions, 90 minutes each, 100% oxygen at 2ATA, 5 days/week,. Results: The study included 74 patients (8 were excluded). During the control period, in the cross group, NIHSS and the ADL had not changed, while in the treated group both significantly improved. After the cross-over, when the cross group received HBOT, NIHSS and ADL had significantly improved. Same trend of changes were in life quality. The SPECT correlated with the clinical improvement. The improvements were mostly in territories where there was a noticeable discrepancy between the CT and SPECT. Interpretation: In this study, for the first time, it was demonstrated that HBOT can induce neuroplasticity in patients with chronic neurologic deficiencies due to stroke. The beneficial effect of the HBOT is mostly in territories where there is a brain SPECT/CT mismatch.
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Methods A prospective, randomized, control- crossed over trial. The study population included patients, age 18 years or older, who had either ischemic or hemorrhagic stroke 6-36 months prior to their inclusion in the study. All patients had to have stable neurologic deficiency that includes at least one motor dysfunction (paresis or plegia) without noticeable improvement during the last month prior to their enrolment. Patients were excluded if they had one of the following criteria: Dynamic neurologic improvement or worsening during the last month; had been treated with HBOT for any other reason prior to their inclusion; have any other indication for HBOT; chest pathology incompatible with pressure changes; inner ear disease; Patients suffering from claustrophobia; Inability to sign written informed consent. Smoking patients were not allowed to smoke during the study and if they did not comply with this demand they were excluded. All patients signed written informed consent before their inclusion and the study protocol was approved by the local Helsinki committee. The study was conducted in the hyperbaric chamber and in the research & development unit of Assaf Harofeh Medical Center, Israel. Study protocol After signing the informed consent, patients were invited for baseline evaluation that included full review of their medical status and complete physical examination. All patients had baseline CT scan. After their inclusion patients were randomized to control or treated group. At baseline and after 2 months, at the end of the HBOT or the control period, all patients had evaluation of their neurologic functions by physical examination, ability to perform activities of daily living, quality of life and brain metabolism (SPECT scan). The study was a cross-over trial and patients in the control group received HBOT after their second evaluation. The control group had a third neurological evaluation after the cross, when they have completed their HBOT. The following HBOT protocol was applied for the treated group at the beginning of the study and to the control group after the cross over (after the 2nd evaluation): 40 daily, 90 minutes sessions of 100% O2 at 2 ATA, 5 times per week. Neurologic evaluation The neurological evaluation was done at baseline and after 2 months for all patients. In the control group a 3rd evaluation was performed after 4 month (after crossing and completing HBOT). The stroke severity was assessed by trained physician according to the National Institutes of Health Stroke Scale (NIHSS)56,57. The activities of daily living (ADL) were evaluated by a questioner that cover the following functions: bathing, dressing, grooming, oral care, toileting, walking, climbing stairs, eating, shopping, cooking, managing medications, using phone, housework, doing laundry, driving and managing finances58. For each criterion the patient had to define whether he is independent, needs help, dependent or does not do (The range of the total score is from 0 (best) to 51 (worst)). Quality of life evaluation Quality of live was evaluated by the EQ-5D questioner58,59. EQ-5D essentially consists of 2 pages - the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS). The EQ-5D descriptive system comprises the following 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 3 levels: no problems, some problems, extreme problems. The EQ VAS records the respondent's self-rated health on a vertical, visual analogue scale where the endpoints are labelled 'Best imaginable health state' and 'Worst imaginable health state' (0 denoting the worst imaginable health state and 100 denoting the best imaginable health state). The validity and reliability of the EQ-5D questionnaire have been tested 60,61. Brain metabolism- SPECT imaging and Analysis Single photon emission computed tomography (SPECT) was conducted before and after HBOT. Subjects lay supine in a quiet dimly lit room for 20 min prior to injection of the radiopharmaceutical. Apart from administration of the injection by a physician, they remained alone in the room during this period. Subjects were asked to remain at rest for 10 min after the injection of the radiopharmaceutical to allow uptake of the radiopharmaceutical in the brain. An injection of 925-1110 MBq (25-30 mCi) of technetium-99m ethyl cysteinate dimmer (Tc-99m-ECD) was given into an arm vein through a previously placed intravenous cannula. SPECT imaging of the brain was performed, at 40-60 min post injection, with the subject's head supported by a headrest, using a dual detector gamma camera (ECAM or Symbia T, Siemens Medical Systems) equipped with high resolution collimators. Data were acquired in the step-and-shoot mode, using a 360 degree circular orbit, with the detectors of the gamma camera as close as possible to the subject's head. The camera used for imaging was noted for each subject and the same camera was used for the follow-up study. Data were acquired using a 128׳128 image matrix in 3 degree steps of 20 seconds per step. Data were reconstructed by iterative reconstruction with no filtering. The Chang method (μ=0.12/ cm) was used for attenuation correction (Chang, 1978). The final reconstructed voxel size was 3.3x3.3x3.3 mm3. Visual analysis was carried out by two nuclear medicine physicians who compared the scans independently and graded them as either: 1=no change, 2=mild change and 3=significant change. Where, no change was assigned when no visual difference was noted in the number or size of perfusion deficits, mild change was given when a reduced number of perfusion defects were noted or the size of the perfusion defects were reduced. Significant change was attributed when a global perfusion increment was observed in addition to diminution of defect numbers or size. Differences in evaluation were resolved after reviewing the images together. Scan visual interpretation was carried out while blinded to any laboratory or clinical data. A comparison of the SPECT results with anatomical imaging (CT or MRI) was conducted in order to evaluate the extent of perfusion deficit in relation to the anatomical lesion.
5 Nov '11
Trial name was updated.
New
Hyperbaric Oxygen Therapy Induced Neuroplasticity in Post Stroke Patients Suffering Chronic Neurological Deficiencies
The Summary of Purpose was updated.
New
The aim of the current work was to evaluate, for the first time in a prospective randomized study, the effect of HBOT on patients with chronic neurological deficiency due to stroke.
Old
The aim of the study is to evaluate the effect of HBO therapy on patients suffering from chronic neurological deficient due to stroke. Patients will be evaluated by clinical neurologic examination and by SPECT imaging of the brain. A prospective, randomized cross over study on patients with chronic neurologic deficiency due to stroke. The study population will include 60 patients, age 18 years or older, who had ischemic stroke and 60 patients who had hemorrhagic stroke 6-36 months prior to their inclusion in the study. All patients should have stable neurologic condition that includes at least one motor dysfunction (paresis or plegia) that has not improved during the last 4 weeks before their enrolment. All the participants will undergo a complete physical examination, and their medical history and medications will be recorded. All patients will undergo baseline CT scan baseline SPECT imagining, baseline carotid artery Doppler evaluation and chest X-ray before the HBOT. The study is a cross-over trial and patients will be randomized to receive the HBOT at the beginning of the trial or 2 months later. The HBOT procedure will be performed in a hyperbaric chamber at Assaf Harofeh Medical Center, Israel. The following HBOT protocol will be applied for the treated group: 8-week, 5 times a week administration of 100% O2 for 90 minutes at a pressure of 2 ATA. After 8 weeks the control group, that did not received HBOT, will receive the same HBOT protocols. At baseline, after 2 months and after 4 months all patients will undergo complete neurologic evaluation and brain SPECT scan (3 evaluation and scan per patient). Moreover, at baseline, 2 and 4 months 5 cc of blood will be withdrawn for evaluation of oxidative stress parameters (SOD, MDA and F2-Isoprostanes).
The description was updated.
New
Methods A prospective, randomized, control- crossed over trial. The study population included patients, age 18 years or older, who had either ischemic or hemorrhagic stroke 6-36 months prior to their inclusion in the study. All patients had to have stable neurologic deficiency that includes at least one motor dysfunction (paresis or plegia) without noticeable improvement during the last month prior to their enrolment. Patients were excluded if they had one of the following criteria: Dynamic neurologic improvement or worsening during the last month; had been treated with HBOT for any other reason prior to their inclusion; have any other indication for HBOT; chest pathology incompatible with pressure changes; inner ear disease; Patients suffering from claustrophobia; Inability to sign written informed consent. Smoking patients were not allowed to smoke during the study and if they did not comply with this demand they were excluded. All patients signed written informed consent before their inclusion and the study protocol was approved by the local Helsinki committee. The study was conducted in the hyperbaric chamber and in the research & development unit of Assaf Harofeh Medical Center, Israel. Study protocol After signing the informed consent, patients were invited for baseline evaluation that included full review of their medical status and complete physical examination. All patients had baseline CT scan. After their inclusion patients were randomized to control or treated group. At baseline and after 2 months, at the end of the HBOT or the control period, all patients had evaluation of their neurologic functions by physical examination, ability to perform activities of daily living, quality of life and brain metabolism (SPECT scan). The study was a cross-over trial and patients in the control group received HBOT after their second evaluation. The control group had a third neurological evaluation after the cross, when they have completed their HBOT. The following HBOT protocol was applied for the treated group at the beginning of the study and to the control group after the cross over (after the 2nd evaluation): 40 daily, 90 minutes sessions of 100% O2 at 2 ATA, 5 times per week. Neurologic evaluation The neurological evaluation was done at baseline and after 2 months for all patients. In the control group a 3rd evaluation was performed after 4 month (after crossing and completing HBOT). The stroke severity was assessed by trained physician according to the National Institutes of Health Stroke Scale (NIHSS)56,57. The activities of daily living (ADL) were evaluated by a questioner that cover the following functions: bathing, dressing, grooming, oral care, toileting, walking, climbing stairs, eating, shopping, cooking, managing medications, using phone, housework, doing laundry, driving and managing finances58. For each criterion the patient had to define whether he is independent, needs help, dependent or does not do (The range of the total score is from 0 (best) to 51 (worst)). Quality of life evaluation Quality of live was evaluated by the EQ-5D questioner58,59. EQ-5D essentially consists of 2 pages - the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS). The EQ-5D descriptive system comprises the following 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 3 levels: no problems, some problems, extreme problems. The EQ VAS records the respondent's self-rated health on a vertical, visual analogue scale where the endpoints are labelled 'Best imaginable health state' and 'Worst imaginable health state' (0 denoting the worst imaginable health state and 100 denoting the best imaginable health state). The validity and reliability of the EQ-5D questionnaire have been tested 60,61. Brain metabolism- SPECT imaging and Analysis Single photon emission computed tomography (SPECT) was conducted before and after HBOT. Subjects lay supine in a quiet dimly lit room for 20 min prior to injection of the radiopharmaceutical. Apart from administration of the injection by a physician, they remained alone in the room during this period. Subjects were asked to remain at rest for 10 min after the injection of the radiopharmaceutical to allow uptake of the radiopharmaceutical in the brain. An injection of 925-1110 MBq (25-30 mCi) of technetium-99m ethyl cysteinate dimmer (Tc-99m-ECD) was given into an arm vein through a previously placed intravenous cannula. SPECT imaging of the brain was performed, at 40-60 min post injection, with the subject's head supported by a headrest, using a dual detector gamma camera (ECAM or Symbia T, Siemens Medical Systems) equipped with high resolution collimators. Data were acquired in the step-and-shoot mode, using a 360 degree circular orbit, with the detectors of the gamma camera as close as possible to the subject's head. The camera used for imaging was noted for each subject and the same camera was used for the follow-up study. Data were acquired using a 128׳128 image matrix in 3 degree steps of 20 seconds per step. Data were reconstructed by iterative reconstruction with no filtering. The Chang method (μ=0.12/ cm) was used for attenuation correction (Chang, 1978). The final reconstructed voxel size was 3.3x3.3x3.3 mm3. Visual analysis was carried out by two nuclear medicine physicians who compared the scans independently and graded them as either: 1=no change, 2=mild change and 3=significant change. Where, no change was assigned when no visual difference was noted in the number or size of perfusion deficits, mild change was given when a reduced number of perfusion defects were noted or the size of the perfusion defects were reduced. Significant change was attributed when a global perfusion increment was observed in addition to diminution of defect numbers or size. Differences in evaluation were resolved after reviewing the images together. Scan visual interpretation was carried out while blinded to any laboratory or clinical data. A comparison of the SPECT results with anatomical imaging (CT or MRI) was conducted in order to evaluate the extent of perfusion deficit in relation to the anatomical lesion.
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Introduction Stroke (cerebrovascular disease) is one of the leading causes for death and disability in elder population worldwide. In the united states stroke is the third leading cause of death accounting for 1 out of every 15 deaths and in most cases it sequel includes neurological deficit such as weakness, hemiplegia or paralysis1-3. The direct and indirect costs associated with stroke are about $56.8 billion in the united states 4-6. This number is relevant only for treatment and rehabilitation; it doesn't contain the economical damage of patients themselves while this loss can be huge. Stroke is classified into two major types: ⠢ Brain ischemia due to thrombosis, embolism, or systemic hypoperfusion ⠢ Brain hemorrhage due to intracerebral hemorrhage or subarachnoid hemorrhage with the consequent compression of the surrounding tissue and reduction of perfusion pressure. Stroke is a neurologic injury that occurs as a result of one of these pathologic processes. Approximately 80 percent of strokes are due to ischemic cerebral infarction and 20 percent to brain hemorrhage. In both cases, ischemic and hemorrhagic shock, the pathophysiology includes impairment in cerebral blood perfusion (CBF) and as a consequence lack of oxygen (hypoxia) and disturbed glucose transport, which are the main elements of brain metabolism. Under this deficient environment the function of the ATP- driven ion pumps is decreased leading to leakage of potassium outside and entry of calcium and sodium with excess water into the cells, resulting in membrane damage and extensive edema. If sever, the edema may end up with death in first 24 to 72 hours. If the patient survived, it may take up to 12 month to reabsorb this edema. During this time, the perfusion pressure is reduced and brain tissue continues to suffer from relatively hypoxia. Even at the end of the reabsorbing process only part of compressed blood vessels return to their baseline functioning so a large part of the affected area is still suffering from ischemia 7-9. The reduction of CBF, cerebral oxygenation, below critical thresholds discriminates between irreversible infarct core, penumbra, and benign oligemia (penumbra that recovers spontaneously) (Figure 1)7, 8. A transition from reversible to irreversible injury is dependent primarily on the severity and duration of ischemia9. The ischemic penumbra is defined as functionally impaired yet still viable tissue surrounding the ischemic core7, 8. Rate of progression to infarction (Figure 1, area c) depends on parameters that affect brain oxygenation such as the degree of collateral arterial circulation, duration of insult, and functional and metabolic cellular state7, 8. Peripheral penumbra cells are able to perform slow metabolic activities. The penumbra cells produce Adenosine (released after depletion of ATP molecule for repair needs) that acts as vasodilator and stimulate neovascularization (formation of new blood vessels). However, the cells located near the core of infarction still suffer from lack of oxygen and nutrients and because of that these cells are unable to produce enough ATP for process of neovascularization, thus ischemic tissue remain ischemic and natural healing process default 7-9. At the long term, about 20% of patients die in the first month after stroke, and more than half of the survivors will require specialist rehabilitation10. Once the patient's condition stabilizes medically, there is less need for the facilities of an acute hospital and the focus of the rehabilitation program moves to improving function and independence. The end of the formal rehabilitation program is usually signaled by a functional plateau after which little or no recovery occurs. This may be hard to pinpoint, but if no improvement occurs over a period of more than 3 weeks then further significant improvement of brain function is unlikely. With respect to post CVA functional recovery, no significant improvement is expected to occur after a period of 4 weeks to 3 months in the majority of patients 11-13. HBO has been available for more than 300 years and has been investigated as a treatment for numerous disease states. The principal effect of HBO is to increase the solubility of oxygen in plasma to a level sufficient to support tissues with minimal extraction of oxygen carried on by hemoglobin. Our interest in the benefic effects of hyperbaric oxygen in patients suffering from residual neurologic deficiency rose from an episode which took place in our unit a couple of years ago. A patient with hemiplegia was admitted for HBO treatment in our hyperbaric unit (admission was due to non-healing diabetic foot ulcer). The patient was suffering from hemiparesis as a result of stroke which took place several years before. During the course of the HBO treatment the hemiparesis significantly improved. After this first episode, we have notice a significant neurological improvement in other patients admitted for hyperbaric therapy. Currently, the neuroprotective mechanisms of HBO after ischemia are poorly understood. Originally, the rationale for the use of HBO in cerebral ischemia was centered upon increasing oxygenation to the ischemic penumbra zone and thus reducing the subsequent effects of the hypoxia. For a long time physicians followed the theory that the cause for impairment in brain functions in stroke and TBI (traumatic brain injury) is cell death in the brain tissue. This theory has been challenged by others that says that the death of brain tissue will appear only after serious interruption in blood flow (below 8-10ml/100gr./min), if not - the cells stays alive but are unable to function normally 7-9. Stroke and TBI and have some similarities: a wide spectrum of neurological damage, acute and chronic stages, changes in functional disabilities and a disappointing outcomes under conventional treatment. In animal studies, PaO2 was increased in plasma of rats treated with HBO when treated immediately or 1 h after ischemia and did correlated with improved outcome and decreased infarct size 14-17. However, initial efforts to use HBO in humans in the acute/sub acute setting of stroke were unsuccessful due to methodological problems and inconsistence with relation to dose, study cohort (for example control group treated with hyperbaric air18) and therapeutic time window15, 16, 19-21. The benefits of HBO is through to be mediated by an indirect neuroprotective effect22-25: ⠢ Decrease neuronal shrinkage and edema as well as decrease necrotic damage have been described histologically in animals treated with HBO after ischemia 15, 26-28. ⠢ Increases in activation and adhesion of leukocytes, especially neutrophils, have been well described after cerebral ischemia, and higher neutrophil counts have been associated with poor outcome15. HBO may exert its effects through this pathway since decreased levels of ICAM-129 in addition to decreased myeloperoxidase activity, a marker of neutrophil sequestration, which correlated with improved outcome30, 31 were seen in animals treated with HBO before and after ischemia. Moreover, HBO , may affect other inflammatory gene expression: reduction in COX-2 mRNA expression and neutrophin-3 mRNA32. These findings suggest that HBO may produce lasting neuroprotection by inhibiting inflammation and late neuronal programmed cell death. ⠢ Wada et al.33 described increases in expression of the free-radical scavenger Mn-SOD, as well as Bcl-2, an inhibitor of apoptosis, after repeated HBO exposure in gerbils, which correlated with increased neuronal survival 34. ⠢ Furthermore, a recent study of subarachnoid hemorrhage in rats showed HBO to have protective effects on CBF, neuronal damage and neurologic function. These changes were associated with decreased expression of hypoxia-inducible factor-1 , a mediator of hypoxic responses leading to improved blood brain barrier function, mediated by decreased vascular endothelial growth factor expression and decreased apoptosis, through inhibition of the proapototic factor BNIP-135, 36. Research in rodent model revealed lower hypoxia-inducible factor-1(alpha) protein in the ischemic hemisphere of HBO-treated mice and lower expression of vascular endothelial growth factor in HBO group (and in normobaric hyperoxia group). This data indicates that HBO can improve penumbral oxygenation in focal ischemia 37. ⠢ HBO therapy may stimulate of angiogenesis38-40. In a rat model of cereberal ischemia HBO induce significant angiogensis. ⠢ Decreased cerebral edema and intracranial pressure41-44, have also been suggested as mechanisms of protection from cerebral ischemia. All of the above mention mechanisms produce evidences as to the neuroprotective role of HBOT for patients at the acute as well as at the late chronic phase of stroke. In 1998 Steenblock et al. have enrolled 50 patients (21 male and 29 female, mean age 61.8 years) who suffered from stroke (Hemorrhagic and ischemic) which took place one month to 10 years previously(average of 29 month post stroke) in a two month study. The treatment protocol included administration of HBO at pressure of 1.5 to 2.0 (ATA) in a sealed single person chamber and each patient breath 100% O2 through a plastic mask, 90 minutes per day, 6 times per week (some patients received HBOT twice a day), the average number of HBOT sessions was 55. The HBOT was accompanied with physical therapy and EEG bio feedback treatments. The evaluation of treatment was done by a patient's questionnaire (which included 16 different functions from motor ability to mental situations) and evaluation that was also done by a licensed physical therapist (the evaluation included 33 different functions from motor ability to cognitive functioning) this tests took place at the beginning of the program and at the end. The results demonstrated improvements, in groups, the post hemorrhage and the post cerebral ischemia/thrombosis/embolism groups. The conclusion was that chronic stroke and TBI patients, who had stable neurologic deficiency for a long time (month or years), can benefit from combined therapy with HBO, physical therapy and bio-feedback. There were no serious complications and according to the author the treatment was safe and effective. Another work was published by Neubauer and James in 1998 45. They reported three patients with different diagnoses who had been treated by HBOT: (1) 74 old white male patients after TIA (transient ischemic attack) -who received 16 total HBO treatments. A SPECT scan was made within 3 hours of the onset of the TIA (with quarter dose of the technicium administrated before HBO treatment and the remaining three-quarter dose after the first HBOT). A repeat scan was done at the end of treatments. They report a significant improvements without any neurological deficits; (2) The second report was a 14 years old juvenile diabetic girl with encephalopathy resulted from sever hypoglycemia, prolonged seizures which took place 6 month before the HBO administration. She didn't use her left hand and couldn't grasp with her right, speech was poor, she was aggressive and hyperactive with ''diffuse cerebral deficit pattern consistent with sever hypoxic effect'' in baseline SPECT. She underwent 88 HBOT with obvious improvements (calm in attitude, gets on school bus by herself, attends special school) and repeated SPECT revealed ''diffusely improved cerebral perfusion''; (3) 22 year old boy was admitted for HBOT almost a year after an episode of near drowning. He was in a state of ''persistent vegetable state", blind, with sever spastic on his left body side, low function of the right leg, got fed by PEG tube. First SPECT demonstrated extensive and symmetrical deficit throughout frontal, temporal, pariental and occipital lobes'. Significant improvements was seen after the third HBO treatment and after a total of 154 treatments he was able to see clearly, speaks in two languages, able to stand and to take a few steps, eat and drink normally, much more alert, smiling, crying, sleeping much better. As a conclusion, those case reports shows the benefits of HBO in acute and chronic brain dysfunctions. In a trial that was mentioned before 122 patients with acute and chronic (completed) stroke received hyperbaric therapy21. Patients who had their stroke onset up to 4 weeks prior to therapy were considered as acute, and the rest of the patients who had their episode of stroke one month to 10 years prior to therapy, were considered as chronic (completed) stroke. The mean age was 66 (ranged from 44 to 88). All patients underwent CT scan, scull x-rays, EEGs and cerebral spinal fluid examinations. The treatment for the chronic patients was combined with standard therapies for their neurological handicaps. In patients with acute stroke the HBO protocol used were one session of HBO per week and then one session per month. Patients with completed stroke were treated with 10 to 90 sessions (most of them 10 sessions) of 2 ATA, O2 100%. The neurologic evaluation was based on neurologist, physical therapists, nurse technicians, and the attending physician examinations. The opinions of family members about effect of treatment were also considered. Each patient in the completed stroke group served as his own control. The patients were divided to three subgroups: (1) Bedridden (11 patients) - 6 had significant improvement: before the HBOT they were using wheelchair and afterwards they were able to walk by themselves ; (2) Wheelchair group (31 patient) - only 9 had no improvement, 8 responded with significant improvement in their ability to walk with assistance and 14 were able to walk without any assistance; (3) Walking with aids (48 patients) - 27 responded with improve ability toward independent walking and 21 didn't respond. At the end of the study the researches summarized the work and declare that even thought the HBO offers a good therapoetical option for patients with neurologic deficiency due to stroke, the protocols of treatments were not unified and the statistical evaluation was problematic21. The aim of the current study is to evaluate the effect of HBO therapy on patients suffering from chronic neurological deficient due to stroke. Patients will be evaluated by clinical neurologic examination and by SPECT imaging of the brain. . Methods A prospective, randomized cross over study on patients with chronic neurologic deficiency due to stroke. The study population will include 60 patients, age 18 years or older, who had ischemic stroke and 60 patients who had hemorrhagic stroke 6-36 months prior to their inclusion in the study. All patients should have stable neurologic condition that includes at least one motor dysfunction (paresis or plegia) that has not improved during the last 4 weeks before their enrolment. All patients will sign written informed consent before their inclusion and the study protocol will be approved by the local Helsinki committee. Patients will be excluded if they will have one of the following criteria: 1. Dynamic neurologic improvement or worsening during the last 4 weeks. 2. Had been treated with HBO for any other reason prior to their inclusion. 3. Have any other indication for HBOT 4. chest pathology incompatible with pressure changes 5. Inner ear disease 6. Patients suffering from claustrophobia. 7. Inability to give written informed consent. Study protocol All the participants will undergo a complete physical examination, and their medical history and medications will be recorded. All patients will undergo baseline CT scan baseline SPECT imagining, baseline carotid artery Doppler evaluation and chest X-ray before the HBOT. The study is a cross-over trial and patients will be randomized to receive the HBOT at the beginning of the trial or 2 months later. The HBOT procedure will be performed in a hyperbaric chamber at Assaf Harofeh Medical Center, Israel. The following HBOT protocol will be applied for the treated group: 8-week, 5 times a week administration of 100% O2 for 90 minutes at a pressure of 2 ATA. After 8 weeks the control group, that did not received HBOT, will receive the same HBOT protocols. At baseline, after 2 months and after 4 months all patients will undergo complete neurologic evaluation and brain SPECT scan (3 evaluation and scan per patient). Moreover, at baseline, 2 and 4 months 5 cc of blood will be withdrawn for evaluation of oxidative stress parameters (SOD, MDA and F2-Isoprostanes). Neurologic evaluation The neurological evaluation will be done by the same neurologist at baseline, 2 and 4 month. During the neurological evaluation the neurologist will be blinded as to whether the patients been receiving or not the HBOT during the last 2 months. The stroke severity will be assessed according to the National Institutes of Health Stroke Scale (NIHSS) as detailed in appendix 1. Functional brain imaging (rCBF-SPECT) Single Photon Emission CT (SPECT) scans will be performed as part of the clinical follow-up and investigation. In all cases regional cerebral blood flow (rCBF) SPECT will be done before and after completion of HBOT treatment. rCBF-SPECT will carried out using the freely permeable compound perfusion agent, 99mTc- ethyl cysteinate dimer (Tc-ECD) as a marker for tissue viability and function. All scan will be performed using a dual headed gamma camera (Varicam, Symbia or E-cam ). Acquisition mode: 128x128 pix matrix, 120 images- each image at 30. Dosage: Adults; 555-1110 MBq (15-30 mCi) ECD. Children; 7.4-11.1 MBq/kg (0.2-0.3 mCi/kg). Minimum dose is 5 mCi. Statistical analysis This is a pilot randomized crossover study. The sample size of 30 patients in each subgroup (total 60 patients) in the post ischemic stroke as well as in the post hemorrhagic stroke was determined in order to achieve 90% power based on the following assumption related to the expected change in neurologic evaluation: mean difference between the groups of at least 25% with drop rate of 16% and alpha 5% before the cross match period. Statistical analysis will be performed using the statistical software SPSS-version 13. Parametric data will be expressed as means ± standard deviations and compared by one way ANOVA. Non-parametric data will be compared using Kolmogorov-Smirnov test. Differences between the results yielding p values less than 0.05 (p<0.05) will be considered statistically significant. Reference List 1. Rosamond W, Flegal K, Furie K et al. Heart disease and stroke statistics--2008 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation 2008; 117(4):e25-146. 2. Rosamond W, Flegal K, Friday G et al. Heart disease and stroke statistics--2007 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation 2007; 115(5):e69-171. 3. Thom T, Haase N, Rosamond W et al. Heart disease and stroke statistics--2006 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation 2006; 113(6):e85-151. 4. Rosamond W, Flegal K, Furie K et al. Heart disease and stroke statistics--2008 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation 2008; 117(4):e25-146. 5. Rosamond W, Flegal K, Friday G et al. Heart disease and stroke statistics--2007 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation 2007; 115(5):e69-171. 6. Thom T, Haase N, Rosamond W et al. 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Measurement of motor recovery after stroke. Outcome assessment and sample size requirements. Stroke 1992; 23(8):1084-1089. 13. Kotila M, Waltimo O, Niemi ML, Laaksonen R, Lempinen M. The profile of recovery from stroke and factors influencing outcome. Stroke 1984; 15(6):1039-1044. 14. Chang CF, Niu KC, Hoffer BJ, Wang Y, Borlongan CV. Hyperbaric oxygen therapy for treatment of postischemic stroke in adult rats. Exp Neurol 2000; 166(2):298-306. 15. Helms AK, Whelan HT, Torbey MT. Hyperbaric oxygen therapy of cerebral ischemia. Cerebrovasc Dis 2005; 20(6):417-426. 16. Helms AK, Whelan HT, Torbey MT. Hyperbaric oxygen therapy of acute ischemic stroke. Stroke 2007; 38(4):1137-1139. 17. Sunami K, Takeda Y, Hashimoto M, Hirakawa M. Hyperbaric oxygen reduces infarct volume in rats by increasing oxygen supply to the ischemic periphery. Crit Care Med 2000; 28(8):2831-2836. 18. Anderson DC, Bottini AG, Jagiella WM et al. A pilot study of hyperbaric oxygen in the treatment of human stroke. 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A location was updated in Zerifin.
New
The overall status was removed for Research & Development unit, Asaf-Harofeh Medical Center.
A location was updated in Zerifin.
New
The overall status was removed for Asaf-Harofeh Medical Center.