Adrenal spinal neuropathy (AMN) is a rare X-linked genetic disease caused by mutations in the ABCD1 gene, and belongs to a special type of adrenal leukodystrophy. The patient's lower limb strength is weakened, the range of motion of the ankle joint is reduced, the hip flexors are weak and affect walking, and the peripheral nerves and vibration sensation are damaged. As the condition worsens, the lower limb muscle tone changes from hyperactivity to decrease, ultimately transitioning from spastic paralysis to flaccid paralysis. At present, the treatment plan for AMN is not yet perfect, and effective therapies are urgently needed to alleviate symptoms. Spinal cord electrical stimulation (SCS) is the implantation of a thin electrode into the epidural space of the corresponding spinal segment within the spinal canal. Then connect the electrodes to a nerve stimulator implanted subcutaneously in the iliac region, and use electrical pulses to stimulate the conduction of sensory neurons in the posterior column and posterior horn of the spinal cord for treatment, which can achieve the goal of controlling pain. In addition, SCS has also conducted research on the recovery of lower limb function in paraplegic patients and upper limb function in post-stroke hemiplegic patients, and has improved corresponding motor dysfunction to a certain extent. Spinal cord stimulation may be a potential treatment for motor dysfunction in AMN. Based on the above, this study attempts to evaluate the efficacy of SCS in treating lower limb muscle tone and movement disorders in AMN patients, and explore the potential therapeutic effects and related mechanisms of SCS on AMN. In this study, 10 AMN patients will be recruited. After enrollment, preoperative evaluation will be conducted. After preliminary assessment of motor function, neurological evaluation, and other related examinations, lumbar spinal nerve stimulators and pulse generators were implanted in our hospital. After the implantation surgery is completed, depending on the patient's recovery status, they will be transferred to various centers for subsequent rehabilitation treatment within one to two weeks, and then turned on for treatment. Before starting up, a second corresponding inspection and evaluation will be conducted. The third and fourth corresponding inspections and evaluations will be conducted one week and four weeks after startup, respectively. The patient will be discharged 4 weeks after starting up, and then return to the hospital for the fifth and sixth corresponding examinations and evaluations at 4 weeks and 6 months after discharge. Evaluate the effectiveness and safety of SCS in improving lower limb motor dysfunction in AMN patients through statistical analysis.
Adrenomyeloneuropathy (AMN) is an X-linked inherited metabolic rare disease caused by mutations in the ABCD1 gene, with an incidence rate of only 1 in 50,000. Currently, it is regarded as a special type of adrenoleukodystrophy (ALD), and AMN is the most dominant disease subtype affecting adult patients. Due to the special phenomenon of skewed X-inactivation, female heterozygotes may also have spinal cord neuropathy. Such mutations can lead to the accumulation of very long chain fatty acids (VLCFA) in the blood and organs, mainly resulting in demyelination of the central nervous system and lesions in the adrenal cortex. As the disease progresses, the strength of the lower limbs and the passive range of motion of the ankle joints of patients will gradually decline. The deterioration of hip flexor muscle weakness is closely associated with a slower walking speed and an increased degree of disability. Most patients will also experience peripheral nerve involvement and impairment of vibration sensation. Hypertonia of the lower limbs will gradually develop into a decline in both muscle strength and muscle tone, and finally progress from spastic paralysis to flaccid paralysis. However, the current commonly used treatment regimens for AMN still have deficiencies, and it is necessary to seek effective treatment methods to alleviate patients' symptoms and improve their quality of life. Spinal Cord Stimulation (SCS) involves implanting a thin electrode (either strip-shaped or needle-shaped) into the epidural space within the spinal canal at the corresponding spinal segments, adjacent to the posterior columns of the spinal cord. The electrode is then connected to a nerve stimulator implanted subcutaneously in the iliac region, and electrical pulses are used to stimulate the conduction of the posterior columns of the spinal cord and the sensory neurons in the posterior horns for treatment purposes. This blocks the transmission of pain signals from the spinal cord to the brain, preventing them from reaching the cerebral cortex, thereby achieving the goal of pain control. Previous studies have demonstrated that, in addition to having significant therapeutic effects in analgesia, SCS has also been investigated in aspects such as the recovery of lower limb function in paraplegia and the recovery of upper limb function in hemiplegia after stroke, and it has improved the corresponding motor dysfunctions to a certain extent. For the problem of motor dysfunction in AMN, there is currently no good treatment method, and spinal cord stimulation may serve as a potential treatment approach. Based on the above, this study attempts to further explore the potential therapeutic effect and related treatment mechanisms of SCS on AMN through evaluating the efficacy of SCS in treating motor disorders of muscle tone and strength in the lower limbs of patients with AMN. In the study, 10 patients with AMN will be recruited. After patients are enrolled in the group, preoperative evaluations will be conducted. And after the first evaluations of motor function, neurological assessment and other relevant examinations, the implantation of lumbar spinal cord nerve stimulator and pulse generator will be carried out in our hospital. After the completion of the implantation surgery, depending on the patients' recovery status, they will be transferred to each center for subsequent rehabilitation treatment within one to two weeks, and then the electrical stimulation treatment will be initiated by turning on the device. Before turning on the device, the second corresponding examinations and evaluations will be conducted. The third and fourth corresponding examinations and evaluations will be carried out one week and four weeks after turning on the device, respectively. Patients will be discharged four weeks after turning on the device, and then return to the hospital for the fifth and sixth corresponding examinations and evaluations four weeks and six months after discharge, respectively. Through the statistical analysis of self-controlled comparison before and after the trial, the efficacy and safety of SCS in improving lower limb motor dysfunction in patients with AMN will be evaluated.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
10
Upon completion of the initial assessments, a lumbar spinal cord nerve stimulator and pulse generator will be implanted. Following surgery, based on the patient's recovery status, the patient will be transferred to the respective center for rehabilitation within one to two weeks. Afterward, electrical stimulation therapy will be initiated. Stimulation should be applied at least three days per week. Each day, the total stimulation time should be between 4 and 8 hours. Stimulation Modes: Continuous Stimulation: For example, if 6 hours of stimulation are prescribed, the stimulator will run uninterrupted for 6 hours. Intermittent Stimulation: For instance, a cycle of 40 seconds on and 20 seconds off. If a total of 6 hours of active stimulation is needed, the stimulator must remain on for 9 hours in total to accommodate rest intervals.The ranges for each parameter are as follows:Stimulation Frequency: 2 Hz - 2000 Hz, Pulse Width: 20 μs - 1000 μs, Stimulation Amplitude:Voltage: 0 V - 10 v
Beijing TianTan Hospital
Beijing, Beijing Municipality, China
ACTIVE_NOT_RECRUITINGThe 958 Hospital of Chinese People's Liberation Army, The Jiangbei Campus of Southwest Hospital, The First Affiliated Hospital of Army Medical University
Chongqing, Chongqing Municipality, China
RECRUITINGthe Southwest hospital
Chongqing, Chongqing Municipality, China
RECRUITINGJingmen No.1 People's Hospital
Jingmen, Hubei, China
ACTIVE_NOT_RECRUITING6-minute walk test (6MWT)
This evaluation is based on the walking distance that patients cover in six minutes when walking as fast as possible along a straight corridor, which is a indicator for assessing the lower limb motor function.
Time frame: Preoperative stage; One week after surgery; One week after device activation; Four weeks after device activation; Four weeks after discharge from hospital; Six months after discharge from hospital
Adverse event
Record the adverse reactions related to spinal cord stimulation (SCS), such as nerve injury, infection, hemorrhage, edema, poor wound healing, etc. These manifestations reflect the safety of spinal cord stimulation treatment.
Time frame: One week after surgery; One week after device activation; Four weeks after device activation; Four weeks after discharge from hospital; Six months after discharge from hospital; One year after discharge from hospital.
Discomfort and pain.
This assessment is based on the fact that after each stimulus training, patients need to use the Numerical Rating Scale (NRS) to report the degree of discomfort they perceive: NRS versions 0-10 were used in this study. Use 0-10 to represent different degrees of pain: 0 represents no pain, 1-3 represents mild pain (pain does not affect sleep), 4-6 represents moderate pain (mild affects sleep), 7-9 represents severe pain (inability to fall asleep or waking up during sleep), and 10 represents severe pain.
Time frame: Preoperative stage; One week after surgery; One week after device activation; Four weeks after device activation; Four weeks after discharge from hospital; Six months after discharge from hospital; One year after discharge from hospital.
Spinal cord and brain MRI
This evaluation is based on the atrophy volume of each segment of the spinal cord and brain analyzed by artificial intelligence segmentation, so as to assess the progression degree of spinal cord and brain white matter injury in patients.
Time frame: Preoperative stage; One week after surgery; One week after device activation; Four weeks after device activation; Four weeks after discharge from hospital; Six months after discharge from hospital
The degree of improvement in electrophysiological indicators of the muscles in the affected limbs
This assessment is an objective examination of muscle electrophysiology to evaluate the recovery of the patient's motor function.
Time frame: Preoperative stage; One week after surgery; One week after device activation; Four weeks after device activation; Four weeks after discharge from hospital; Six months after discharge from hospital
Qmax（The maximum flow rate）
Qmax is the peak of a continuous, immediate uroflow rate numerical curve traced with a uroflowmetry device during voiding, suggesting a combination of bladder and urethral function during the subject's voiding. It is calculated in milliliters per second.
Time frame: Preoperative stage; One week after surgery; One week after device activation; Four weeks after device activation; Four weeks after discharge from hospital; Six months after discharge from hospital
Filling bladder pressure
Filling cystometry is a method of measuring the pressure-volume correlation of the bladder under specific media perfusion in order to understand the function of the urethra and urethra during the storage phase.
Time frame: Preoperative stage; One week after surgery; One week after device activation; Four weeks after device activation; Four weeks after discharge from hospital; Six months after discharge from hospital
Urethral pressure
Urethral pressure is the fluid pressure required just to open and close the urethra during urodynamics, and is an important indicator for evaluating the functional status of the urethra.
Time frame: Preoperative stage; One week after surgery; One week after device activation; Four weeks after device activation; Four weeks after discharge from hospital; Six months after discharge from hospital
Residual urine volume
Bladder residual urine volume is the amount of urine still remaining in the bladder after the end of urination. It is an important indicator for assessing bladder voiding function. Under normal circumstances, the residual urine volume in a healthy adult should be less than 10 milliliters. When the residual urine volume exceeds 10 milliliters, it may indicate impaired bladder voiding function.
Time frame: Preoperative stage; One week after surgery; One week after device activation; Four weeks after device activation; Four weeks after discharge from hospital; Six months after discharge from hospital
Evaluation of erectile function (International Index of Erectile Function-5 (IIEF-5) score)
This evaluation is based on the International Index of Erectile Function (IIEF) scores. The total score of the IIEF-5 ranges from 0 to 25, and a higher score indicates that the patient has better erectile function.
Time frame: Preoperative stage; One week after surgery; One week after device activation; Four weeks after device activation; Four weeks after discharge from hospital; Six months after discharge from hospital
Stool scoring (Wexner Incontinence Scale, Bristol Stool Scale (BSFS))
This evaluation is based on the Wexner Incontinence Scale and the Bristol Stool Form Scale. The Wexner Incontinence Scale is a scale used to assess the severity of defecation in patients and is applicable to patients with fecal incontinence caused by various reasons. The Bristol Stool Form Scale is a classification system based on the shape of feces, which is used to evaluate the characteristics of feces and possible health problems.
Time frame: Preoperative stage; One week after surgery; One week after device activation; Four weeks after device activation; Four weeks after discharge from hospital; Six months after discharge from hospital
Somatosensory evoked potential, visual evoked potential, auditory evoked potential, motor evoked potential.
Evoked potentials are generated by stimulating any structures related to sensory organs, nerves, pathways or systems, resulting in measurable potential changes in the central nervous system. They can be used to assess the functional integrity of the central and peripheral nervous systems.
Time frame: Preoperative stage; One week after surgery; One week after device activation; Four weeks after device activation; Four weeks after discharge from hospital; Six months after discharge from hospital
Motion capture (gait test)
This evaluation is based on the range of motion of joints and spatio-temporal parameters of gait.
Time frame: Preoperative stage; One week after surgery; One week after device activation; Four weeks after device activation; Four weeks after discharge from hospital; Six months after discharge from hospital
Short Physical Performance Battery (SPPB)
This evaluation is based on a comprehensive score, which includes walking speed, balance tests and the chair stand test. The higher the score is, the better the physical condition will be.
Time frame: Preoperative stage; One week after surgery; One week after device activation; Four weeks after device activation; Four weeks after discharge from hospital; Six months after discharge from hospital
Very-long-chain fatty acid (VLCFA)
This evaluation is based on detecting the levels of very-long-chain fatty acids (VLCFAs) in plasma and cerebrospinal fluid, analyzing the specific metabolic changes of this disease, so as to conduct disease monitoring and efficacy evaluation.
Time frame: Preoperative stage; One week after surgery; One week after device activation; Four weeks after device activation; Four weeks after discharge from hospital; Six months after discharge from hospital
Cerebrospinal fluid (CSF)
The cerebrospinal fluid was examined by means of biochemical, transcriptomic, epigenetic and other methods.
Time frame: Preoperative stage; One week after surgery; One week after device activation; Four weeks after device activation; Four weeks after discharge from hospital; Six months after discharge from hospital
Fugl-Meyer assessment scale (FMA)
The Fugl-Meyer Assessment (FMA) is a method used to evaluate the motor function status of patients of various ages. It is applicable in both clinical settings and research to determine the severity of diseases, describe motor recovery, and formulate plans as well as evaluate treatments.
Time frame: Preoperative stage; One week after surgery; One week after device activation; Four weeks after device activation; Four weeks after discharge from hospital; Six months after discharge from hospital
Cranial MRI
Utilize 3T and 7T magnetic resonance imaging to examine the resting state, occipital radiation spectroscopy, quantitative susceptibility mapping (QSM), and subvoxel imaging of the enrolled patients.
Time frame: Preoperative stage; One week after surgery; One week after device activation; Four weeks after device activation; Four weeks after discharge from hospital; Six months after discharge from hospital
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.