epidural spinal cord stimulation for lower-limb impairment in adrenomyeloneuropathy

Conditions: Adrenomyeloneuropathy Without Cerebral Involvement

Summary: 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.

Eligibility criteria:
inclusion criteria: * conforming to the diagnostic criteria of amn, with a definite genetic testing report, and complicated by lower limb motor function disorders; * capable of normal communication and able to complete scale tests independently (as determined by on-site scale tests); * willing to participate in this study after giving informed consent; * the muscle tone of the patient's bilateral lower extremities was elevated. exclusion criteria: * other inherited diseases; * other severe central nervous system diseases; * history of brain surgery; * psychiatric and psychological diseases such as depression and anxiety; * the presence of metallic foreign bodies or prostheses (such as cardiac pacemakers, insulin pumps) in the body, claustrophobia, and other contraindications for mri; * informed consent was not obtained; * unable to tolerate mri-related examinations; * received anticoagulant, antispasmodic or antiepileptic drug therapies throughout the entire study period; * postoperative wound infection; * other motor disorders, spinal cord pathologies, fractures, osteoarthritis, amputations, scoliosis and other movement-affecting diseases.

Keywords: genetic diseases rare diseases spinal cord stimulation motor function recovery multicenter study adrenomyeloneuropathy