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1.
PLoS One ; 17(10): e0266236, 2022.
Article in English | MEDLINE | ID: mdl-36197931

ABSTRACT

BACKGROUND: Significant reductions in ambient pressure subject an individual to risk of decompression illness (DCI); with incidence up to 35 per 10,000 dives. In severe cases, the central nervous system is often compromised (>80%), making DCI among the most morbid of diving related injuries. While hyperbaric specialists suggest initiating recompression therapy with either a Treatment Table 6 (TT6) or 6A (TT6A), the optimal initial recompression treatment for severe DCI is unknown. METHODS: Swine were exposed to an insult dive breathing air at 7.06 ATA (715.35 kPa) for 24 min followed by rapid decompression at a rate of 1.82 ATA/min (184.41 kPa/min). Swine that developed neurologic DCI within 1 hour of surfacing were block randomized to one of four United States Navy Treatment Tables (USN TT): TT6, TT6A-air (21% oxygen, 79% nitrogen), TT6A-nitrox (50% oxygen, 50% nitrogen), and TT6A-heliox (50% oxygen, 50% helium). The primary outcome was the mean number of spinal cord lesions, which was analyzed following cord harvest 24 hours after successful recompression treatment. Secondary outcomes included spinal cord lesion incidence and gross neurologic outcomes based on a pre- and post- modified Tarlov assessment. We compared outcomes among these four groups and between the two treatment profiles (i.e. TT6 and TT6A). RESULTS: One-hundred and forty-one swine underwent the insult dive, with 61 swine meeting inclusion criteria (43%). We found no differences in baseline characteristics among the groups. We found no significant differences in functional neurologic outcomes (p = 0.77 and 0.33), spinal cord lesion incidence (p = 0.09 and 0.07), or spinal cord lesion area (p = 0.51 and 0.17) among the four treatment groups or between the two treatment profiles, respectively. While the trends were not statistically significant, animals treated with TT6 had the lowest rates of functional deficits and the fewest spinal cord lesions. Moreover, across all animals, functional neurologic deficit had strong correlation with lesion area pathology (Logistic Regression, p < 0.01, Somers' D = 0.74). CONCLUSIONS: TT6 performed as well as the other treatment tables and is the least resource intensive. TT6 is the most appropriate initial treatment for neurologic DCI in swine, among the tables that we compared.


Subject(s)
Decompression Sickness , Diving , Hyperbaric Oxygenation , Spinal Cord Diseases , Animals , Decompression , Decompression Sickness/therapy , Helium , Nitrogen , Oxygen , Spinal Cord Diseases/therapy , Swine
2.
Zhongguo Gu Shang ; 35(8): 790-8, 2022 Aug 25.
Article in Chinese | MEDLINE | ID: mdl-35979776

ABSTRACT

Cervical spondylotic myelopathy (CSM) is the most serious subtype, which is characterized by severe clinical symptoms, a high disability rate, and poor prognosis. Traditional Chinese medicine and Western medicine have their own advantages in the diagnosis and treatment of CSM at different stages. In order to further standardize the clinical diagnosis and treatment of CSM and improve the clinical efficacy, based on previous experience and evidence-based medicine, after repeated discussions by the national expert group, the expert consensus on the diagnosis and treatment of integrated traditional Chinese and Western medicine was compiled. This consensus comprehensively introduces the definition, etiology, pathogenesis, diagnosis treatment principles, integrated traditional Chinese and Western medicine treatment, postoperative rehabilitation and nursing care of cervical spondylotic myelopathy, so as to provide reference for clinicians.


Subject(s)
Spinal Cord Diseases , Cervical Vertebrae , Consensus , Humans , Medicine, Chinese Traditional , Spinal Cord Diseases/diagnosis , Spinal Cord Diseases/therapy , Treatment Outcome
3.
Undersea Hyperb Med ; 48(3): 247-253, 2021.
Article in English | MEDLINE | ID: mdl-34390629

ABSTRACT

Demyelination throughout the brain stem and spinal cord caused by acute carbon monoxide (CO) poisoning has not been previously reported. Magnetic resonance imaging (MRI) has revealed that acute CO poisoning primarily affects the subcortical white matter of the bilateral cerebral hemispheres and basal ganglia. Here we report the case of a patient with delayed neuropsychological sequelae (DNS) due to acute CO poisoning. A 28-year-old man was admitted to our department following a suicide attempt by acute CO poisoning. After a six-month pseudo-recovery period, he was diagnosed with DNS, with MRI evidence of demyelinating change of the bilateral cerebral peduncles. Demyelination was identified throughout the brain stem, expanding from the bilateral cerebral peduncles to the medulla oblongata, occurring approximately six months after poisoning. One and a half years after acute CO poisoning, demyelination of the cervical and thoracic spine was observed, most notable in the lateral and posterior cords. It is evident that previously published research on this topic is extremely limited. Perhaps in severe cases of acute CO poisoning the fatality rate is higher, leading to fewer surviving cases for possible study. This may be because a more severe case of acute CO poisoning would result in the higher likelihood of secondary demyelination. This research indicates that clinicians should be aware of the risk of secondary demyelination and take increased precautions such as vitamin B supplementation and administration of low-dose corticosteroids for an extended period of time in order to reduce the extent and severity of demyelination.


Subject(s)
Brain Diseases/etiology , Brain Stem , Carbon Monoxide Poisoning/complications , Demyelinating Diseases/etiology , Spinal Cord Diseases/etiology , Adult , Brain Diseases/diagnostic imaging , Brain Diseases/therapy , Brain Stem/diagnostic imaging , Cognition Disorders/etiology , Cognition Disorders/therapy , Demyelinating Diseases/diagnostic imaging , Demyelinating Diseases/therapy , Humans , Magnetic Resonance Imaging , Male , Mental Disorders/etiology , Mental Disorders/therapy , Spinal Cord Diseases/diagnostic imaging , Spinal Cord Diseases/therapy , Suicide, Attempted , Time Factors
4.
Rev Neurosci ; 32(3): 275-287, 2021 04 27.
Article in English | MEDLINE | ID: mdl-33661584

ABSTRACT

Degenerative cervical myelopathy (DCM) presents insidiously during middle-age with deterioration in neurological function. It accounts for the most common cause of non-traumatic spinal cord injury in developed countries and disease prevalence is expected to rise with the aging population. Whilst surgery can prevent further deterioration, biological therapies may be required to restore neurological function in advanced disease. Cell replacement therapy has been inordinately focused on treatment of traumatic spinal cord injury yet holds immense promise in DCM. We build upon this thesis by reviewing the pathophysiology of DCM as revealed by cadaveric and molecular studies. Loss of oligodendrocytes and neurons occurs via apoptosis. The tissue microenvironment in DCM prior to end-stage disease is distinct from that following acute trauma, and in many ways more favourable to receiving exogenous cells. We highlight clinical considerations for cell replacement in DCM such as selection of cell type, timing and method of delivery, as well as biological treatment adjuncts. Critically, disease models often fail to mimic features of human pathology. We discuss directions for translational research towards clinical application.


Subject(s)
Spinal Cord Diseases , Spinal Cord Injuries , Aged , Aging , Biological Therapy , Cervical Vertebrae , Humans , Spinal Cord Diseases/therapy
5.
PLoS One ; 14(12): e0214351, 2019.
Article in English | MEDLINE | ID: mdl-31821342

ABSTRACT

OBJECTIVE: Erythropoietin (EPO) is a clinically available hematopoietic cytokine. EPO has shown beneficial effects in the context of spinal cord injury and other neurological conditions. The aim of this study was to evaluate the effect of EPO on a rat model of spinal cord compression-induced cervical myelopathy and to explore the possibility of its use as a pharmacological treatment. METHODS: To develop the compression-induced cervical myelopathy model, an expandable polymer was implanted under the C5-C6 laminae of rats. EPO administration was started 8 weeks after implantation of a polymer. Motor function of rotarod performance and grip strength was measured after surgery, and motor neurons were evaluated with H-E, NeuN and choline acetyltransferase staining. Apoptotic cell death was assessed with TUNEL and Caspase-3 staining. The 5HT, GAP-43 and synaptophysin were evaluated to investigate the protection and plasticity of axons. Amyloid beta precursor protein (APP) was assessed to evaluate axonal injury. To assess transfer of EPO into spinal cord tissue, the EPO levels in spinal cord tissue were measured with an ELISA for each group after subcutaneous injection of EPO. RESULTS: High-dose EPO maintained motor function in the compression groups. EPO significantly prevented the loss of motor neurons and significantly decreased neuronal apoptotic cells. Expression of 5HT and synaptophysin was significantly preserved in the EPO group. APP expression was partly reduced in the EPO group. The EPO levels in spinal cord tissue were significantly higher in the high-dose EPO group than other groups. CONCLUSION: EPO improved motor function in rats with compression-induced cervical myelopathy. EPO suppressed neuronal cell apoptosis, protected motor neurons, and induced axonal protection and plasticity. The neuroprotective effects were produced following transfer of EPO into the spinal cord tissue. These findings suggest that EPO has high potential as a treatment for degenerative cervical myelopathy.


Subject(s)
Disease Models, Animal , Erythropoietin/administration & dosage , Motor Neurons/physiology , Recombinant Proteins/administration & dosage , Recovery of Function , Spinal Cord Compression/complications , Spinal Cord Diseases/therapy , Animals , Humans , Male , Rats , Rats, Wistar , Spinal Cord Diseases/etiology , Spinal Cord Diseases/pathology
6.
Spine (Phila Pa 1976) ; 44(22): 1606-1612, 2019 Nov 15.
Article in English | MEDLINE | ID: mdl-31205181

ABSTRACT

STUDY DESIGN: Prospective Cohort OBJECTIVE.: The aim of this study was to evaluate which demographic, clinical, or radiographic factors are associated with selection for surgical intervention in patients with mild cervical spondylotic myelopathy (CSM). SUMMARY OF BACKGROUND DATA: Surgery has not been shown superior to best conservative management in mild CSM comparative studies; trials of conservative management represent an acceptable alternative to surgical decompression. It is unknown what patients benefit from surgery. METHODS: This is a prospective study of patients with mild CSM, defined as modified Japanese Orthopaedic Association Score (mJOA) ≥15. Patients were recruited from seven sites contributing to the Canadian Spine Outcomes Research Network. Demographic, clinical, radiographic and health related quality of life data were collected on all patients at baseline. Multivariate logistic regression modeling was used to identify factors associated with surgical intervention. RESULTS: There were 122 patients enrolled, 105 (86.0%) were treated surgically, and 17 (14.0%) were treated nonoperatively. Overall mean age was 54.8 years (SD 12.6) with 80 (65.5%) males. Bivariate analysis revealed no statistically significant differences between surgical and nonoperative groups with respect to age, sex, BMI, smoking status, number of comorbidities and duration of symptoms; mJOA scores were significantly higher in the nonoperative group (16.8 [SD 0.99] vs. 15.9 [SD 0.89], P < 0.001). There was a statistically significant difference in Neck Disability Index, SF12 Physical Component, SF12 Mental Component Score, EQ5D, and PHQ-9 scores between groups; those treated surgically had worse baseline questionnaire scores (P < 0.05). There was no difference in radiographic parameters between groups. Multivariable analysis revealed that lower quality of life scores on EQ5D were associated with selection for surgical management (P < 0.018). CONCLUSION: Patients treated surgically for mild cervical myelopathy did not differ from those treated nonoperatively with respect to baseline demographic or radiographic parameters. Patients with worse EQ5D scores had higher odds of surgical intervention. LEVEL OF EVIDENCE: 3.


Subject(s)
Cervical Vertebrae , Spinal Cord Diseases , Adult , Aged , Cervical Vertebrae/diagnostic imaging , Cervical Vertebrae/surgery , Conservative Treatment/statistics & numerical data , Decompression, Surgical/statistics & numerical data , Female , Humans , Male , Middle Aged , Prospective Studies , Quality of Life , Spinal Cord Diseases/diagnostic imaging , Spinal Cord Diseases/epidemiology , Spinal Cord Diseases/therapy , Treatment Outcome
7.
Turk Neurosurg ; 29(5): 789-792, 2019.
Article in English | MEDLINE | ID: mdl-29757450

ABSTRACT

Intradural spinal cord abscesses are rare infections in early childhood and usually result from pre-existing congenital anomalies of the spinal column. The formation of abscess may be the result of hematogenous spread. It is treated by surgical and parenteral antibiotic treatment, but some special cases may require additional treatments. This article presents a 4-year-old male patient who was previously operated on for spina bifida (meningocele and tethered cord syndrome) at another hospital. Upon complaints of not being able to walk after one month, he was operated on with the diagnosis of spinal intradural abscess and referred to our clinic to continue his treatment. The patient underwent an emergency operation when his new spinal magnetic resonance imaging (MRI) at our hospital showed progression of intradural abscess. Due to no regression of neurological deficits in the follow-up and the risk of another operation, antimicrobial treatment as well as hyperbaric oxygen therapy (HBOT) was planned. At the end of 20 HBOT treatment sessions, the patient started to walk with support and the antibiotic treatment was completed in six weeks. In cases where surgical and antimicrobial treatments have failed, HBOT should be considered as an additional treatment method in children with spinal abscess.


Subject(s)
Abscess/therapy , Hyperbaric Oxygenation/methods , Postoperative Complications/therapy , Spinal Cord Diseases/therapy , Abscess/etiology , Child, Preschool , Humans , Male , Meningomyelocele/surgery , Neural Tube Defects/surgery , Neurosurgical Procedures/adverse effects , Postoperative Complications/etiology , Spinal Cord Diseases/etiology
8.
Medicine (Baltimore) ; 97(49): e13541, 2018 Dec.
Article in English | MEDLINE | ID: mdl-30544463

ABSTRACT

RATIONALE: Nocardial spinal epidural abscess is rare. The diagnosis is often difficult to make and, if delayed, poses a high risk of long-term disability. Nocardial spinal epidural abscess with severe lumbar disc herniation has not previously been reported. PATIENT CONCERNS: A 50-year-old man presented with progressive lumbago and leg pain for 6 weeks after receiving acupuncture therapy, and then the patient suddenly occurred urine retention after walking. DIAGNOSES: Clinical examination revealed sign of cauda equina syndrome. Magnetic resonance imaging (MRI) revealed a Lumbar(L)4 to L5 disc herniation, L3 to Sacrum(S)1 epidural abscess, and L2 to S1 paravertebral abscess. The causative organism was Nocardia farcinica. INTERVENTIONS: An urgent paravertebral abscess debridement and right L4 to L5 laminectomy were performed. Simultaneously, the disc tissue protruding into the spinal canal was removed, as well as irrigation and drainage. And antimicrobial treatment was continued for 12 months. OUTCOMES: Fortunately, the patient was able to walk with a cane and urinate autonomously without a catheter, although this remained difficult 7 days after surgery. After 1 year of treatment, the patient has recovered completely and returned to work. LESSONS: Nocardial spinal epidural abscess with severe lumbar disc herniation is extremely rare. Pain from spinal degenerative diseases often masks the early symptoms of spinal infection. It's worth noting that invasive treatment of spine is a way of causing spinal nocardial infection.


Subject(s)
Central Nervous System Bacterial Infections/complications , Epidural Abscess/complications , Intervertebral Disc Degeneration/complications , Intervertebral Disc Displacement/complications , Nocardia Infections/complications , Nocardia , Spinal Cord Diseases/complications , Central Nervous System Bacterial Infections/diagnostic imaging , Central Nervous System Bacterial Infections/therapy , Epidural Abscess/diagnostic imaging , Epidural Abscess/therapy , Humans , Intervertebral Disc Degeneration/diagnostic imaging , Intervertebral Disc Degeneration/therapy , Intervertebral Disc Displacement/diagnostic imaging , Intervertebral Disc Displacement/therapy , Lumbar Vertebrae/diagnostic imaging , Lumbar Vertebrae/surgery , Male , Middle Aged , Nocardia Infections/diagnostic imaging , Nocardia Infections/therapy , Spinal Cord Diseases/diagnostic imaging , Spinal Cord Diseases/therapy
9.
Medicine (Baltimore) ; 97(36): e12249, 2018 Sep.
Article in English | MEDLINE | ID: mdl-30200156

ABSTRACT

RATIONALE: Cervical spondylotic myelopathy (CSM) is the most common spinal cord disorder in older patients. The purpose of this case report is to introduce conservative treatment with integrative Korean medicine (KM) as a possible alternative to surgery in patients with mild CSM. PATIENT CONCERNS: An 81-year-old male with both hand weakness and dysesthesia was diagnosed with CSM and was recommended laminectomy. However, considering the patient's age and the underlying disease, he refused immediate surgery and preferred KM treatment DIAGNOSES:: The diagnosis of mild CSM was based on a modified Japanese Orthopedic Association (mJOA) score as well as the presence of compression on the spinal cord in magnetic resonance imaging findings INTERVENTIONS:: Integrative KM treatment consisting of acupuncture, acupotomy, Bee venom herbal acupuncture, cupping therapy, moxibustion, and herbal medicine was provided during the 12-week admission. OUTCOMES: Clinical improvement was detected with a mJOA score (11 to 17), a numerical rating scale for dysesthesia intensity (5 to 2), finger escape sign (+/+ to +/-), grip and release test (11/14 to 32/31) and grasp power measured by dynamometer (3.1/9.7 to 10.8/18.3 kg) at 12 weeks. This improvement was maintained without surgery until 1 year. LESSONS: This case suggests that integrative KM was a possible conservative management option for mild CSM.


Subject(s)
Conservative Treatment , Integrative Medicine , Medicine, Korean Traditional , Spinal Cord Diseases/therapy , Spondylosis/therapy , Aged, 80 and over , Cervical Vertebrae , Follow-Up Studies , Humans , Male , Spinal Cord Diseases/physiopathology , Spondylosis/physiopathology
10.
J Neurol ; 265(5): 1089-1095, 2018 May.
Article in English | MEDLINE | ID: mdl-29502317

ABSTRACT

BACKGROUND: Whilst the dangers of 'legal highs' have been widely publicised in the media, very few cases of the neurological syndrome associated with the inhalation of nitrous oxide (N2O) have been reported. Here we set out to raise awareness of subacute degeneration of the spinal cord arising from recreational N2O use so that formal surveillance programs and public health interventions can be designed. METHODS: Case series documenting the clinical and investigational features of ten consecutive cases of subacute degeneration of the spinal cord presenting to a hospital with a tertiary neurosciences service in East London. RESULTS: Sensory disturbance in the lower (± upper) limbs was the commonest presenting feature, along with gait abnormalities and sensory ataxia. MRI imaging of the spine showed the characteristic features of dorsal column hyperintensity on T2 weighted sequences. Serum B12 levels may be normal because subacute degeneration of the spinal cord in this situation is triggered by functional rather than absolute B12 deficiency. DISCUSSION: A high index of suspicion is required to prompt appropriate investigation, make the diagnosis and commence treatment early. This is the largest reported series of patients with subacute degeneration of the spinal cord induced by recreational use of N2O. However, the number of patients admitted to hospital likely represents the 'tip of the iceberg', with many less severe presentations remaining undetected. After raising awareness, attention should focus on measuring the extent of the problem, the groups affected, and devising ways to prevent potentially long-term neurological damage.


Subject(s)
Neurodegenerative Diseases/chemically induced , Nitrous Oxide/toxicity , Spinal Cord Diseases/chemically induced , Substance-Related Disorders/etiology , Adolescent , Adult , Ataxia/chemically induced , Ataxia/diagnostic imaging , Ataxia/physiopathology , Ataxia/therapy , Diagnosis, Differential , Female , Humans , Magnetic Resonance Imaging , Male , Neurodegenerative Diseases/diagnostic imaging , Neurodegenerative Diseases/physiopathology , Neurodegenerative Diseases/therapy , Retrospective Studies , Spinal Cord/diagnostic imaging , Spinal Cord Diseases/diagnostic imaging , Spinal Cord Diseases/physiopathology , Spinal Cord Diseases/therapy , Substance-Related Disorders/diagnostic imaging , Substance-Related Disorders/physiopathology , Substance-Related Disorders/therapy , Vitamin B 12/blood , Young Adult
11.
Zhongguo Gu Shang ; 31(1): 30-36, 2018 Jan 25.
Article in Chinese | MEDLINE | ID: mdl-29533034

ABSTRACT

OBJECTIVE: To compare the clinical effect between spinal card decompression combined with traditional Chinese medicine and simple spinal card decompression for cervical spondylotic myelopathy. METHODS: From June 2012 to June 2015, 73 patients with cervical spondylotic myelopathy were treated, including 42 males and 31 females, aged from 29 to 73 years old with a mean of 50.9 years old. The patients were divided into the simple operation group (34 cases) and the operation combined with traditional Chinese medicine group(39 cases) according to the idea of themselves. The anterior discectomy or subtotal corpectomy with internal fixation or posterior simple open-door decompression with lateral mass screw fixation were performed in the patients. Among them, 39 cases were treated with traditional Chinese medicine after surgery. The Japanese orthopedic association (JOA) score of spinal cord function, the improvement rate of neural function, the neck dysfunction index (NDI) score and the governor vessel stasis syndrome score were compared between two groups preoperative and postoperative 1 week, 1 month and the final follow-up respectively. The internal fixation and the condition of spinal cord decompression were observed by CT, MRI and X-rays before and after operation. RESULTS: All the operations were successful, no injuries such as dura mater, spinal cord and nerve root were found. All the wounds were healed without infection except one patient had a superficial infection. It was solved after intermittent debridement and anti-infective therapy. Hematoma occurred in 1 case, complicated with spinal cord compression, caused incomplete paralysis, and promptly performed the re-operation to remove the hematoma without any obvious sequelae. All the patients were followed up from 12 to 24 months, (14.6±0.8) months for simple operation group and (13.5±0.7) months for operation combined with traditional Chinese medicine group, and there was no significant difference(P>0.05). The scores of JOA, NDI and the governor's vessel stasis syndrome in simple operation group were 8.31±3.15, 29.91±4.52, 6.58±1.31 before operation, and 10.21±2.58, 18.67±4.31, 8.24±1.18 one week after operation, and 11.38±2.85, 16.11±3.18, 8.91±2.11 one month after operation, and 12.21±3.12, 14.61±3.28, 9.12±1.56 at final follow-up, respectively; and in operation combined with traditional Chinese medicine group were 8.29±3.47, 30.83±4.14, 6.38±1.81before operation, and 10.48±2.39, 17.59±5.14, 8.33±1.57 one week after operation, and 12.14±3.12, 13.14±3.21, 9.55±2.49 one month after operation, and 13.85±3.34, 12.11±2.51, 10.33±1.95 at final follow-up, respectively. Postoperative JOA , NDI, and the governor vessel stasis syndrome score of two groups were significantly higher than preoperativee(P<0.05). There was no significant difference in JOA, NDI, and the governor vessel stasis syndrome score between two groups one week after operation (P>0.05). The above items in operation combined with traditional Chinese medicine group was better than that of simple operation group one month and final follow-up after operation (P<0.05). The improvement rate of neural function in simple operation group was (67.59±10.78)%, and in operation combined traditional Chinese medicine group was (66.88±12.15)%, there was no significant difference between two groups(P>0.05). There were no complications such as internal fixation failure or re-dislocation of atlas by postoperative CT, MRI and X-rays examination. CONCLUSIONS: Spinal card decompression for the treatment of cervical spondylotic myelopathy can extend the spinal canal, relieve the compression of nerve, achieve the deoppilation of governor vessel, the regulation of qi and blood, the restore of Yangqi, combined with traditional Chinese medicine of activating blood removing stasis, warming yang and activating meridians, reinforcing liver benefiting kidney, which may obtain better clinical effect.


Subject(s)
Decompression, Surgical , Medicine, Chinese Traditional , Spinal Cord Diseases/surgery , Spondylosis/surgery , Adult , Aged , Cervical Vertebrae/surgery , Female , Humans , Male , Middle Aged , Retrospective Studies , Spinal Cord Diseases/therapy , Spinal Fusion , Spondylosis/therapy , Treatment Outcome , Young Adult
12.
Glia ; 66(3): 538-561, 2018 03.
Article in English | MEDLINE | ID: mdl-29148104

ABSTRACT

Oligodendroglial cell death and demyelination are hallmarks of neurotrauma and multiple sclerosis that cause axonal damage and functional impairments. Remyelination remains a challenge as the ability of endogenous precursor cells for oligodendrocyte replacement is hindered in the unfavorable milieu of demyelinating conditions. Here, in a rat model of lysolecithin lysophosphatidyl-choline (LPC)-induced focal demyelination, we report that Neuregulin-1 (Nrg-1), an important factor for oligodendrocytes and myelination, is dysregulated in demyelinating lesions and its bio-availability can promote oligodendrogenesis and remyelination. We delivered recombinant human Nrg-1ß1 (rhNrg-1ß1) intraspinally in the vicinity of LPC demyelinating lesion in a sustained manner using poly lactic-co-glycolic acid microcarriers. Availability of Nrg-1 promoted generation and maturation of new oligodendrocytes, and accelerated endogenous remyelination by both oligodendrocyte and Schwann cell populations in demyelinating foci. Importantly, Nrg-1 enhanced myelin thickness in newly remyelinated spinal cord axons. Our complementary in vitro studies also provided direct evidence that Nrg-1 significantly promotes maturation of new oligodendrocytes and facilitates their transition to a myelinating phenotype. Nrg-1 therapy remarkably attenuated the upregulated expression chondroitin sulfate proteoglycans (CSPGs) specific glycosaminoglycans in the extracellular matrix of demyelinating foci and promoted interleukin-10 (IL-10) production by immune cells. CSPGs and IL-10 are known to negatively and positively regulate remyelination, respectively. We found that Nrg-1 effects are mediated through ErbB2 and ErbB4 receptor activation. Our work provides novel evidence that dysregulated levels of Nrg-1 in demyelinating lesions of the spinal cord pose a challenge to endogenous remyelination, and appear to be an underlying cause of myelin thinning in newly remyelinated axons.


Subject(s)
Demyelinating Diseases/therapy , Immunomodulation , Neuregulin-1/administration & dosage , Neuroprotective Agents/administration & dosage , Remyelination/physiology , Spinal Cord/immunology , Animals , Cells, Cultured , Chondroitin Sulfate Proteoglycans/metabolism , Demyelinating Diseases/immunology , Demyelinating Diseases/pathology , Disease Models, Animal , Drug Carriers , Extracellular Matrix/immunology , Extracellular Matrix/pathology , Female , Ganglia, Spinal/immunology , Ganglia, Spinal/pathology , Humans , Lactic Acid , Male , Neural Stem Cells/immunology , Neural Stem Cells/pathology , Oligodendroglia/immunology , Oligodendroglia/pathology , Polyglycolic Acid , Polylactic Acid-Polyglycolic Acid Copolymer , Rats, Sprague-Dawley , Recombinant Proteins/administration & dosage , Spinal Cord/pathology , Spinal Cord Diseases/immunology , Spinal Cord Diseases/pathology , Spinal Cord Diseases/therapy
13.
J Cell Physiol ; 233(4): 2705-2714, 2018 04.
Article in English | MEDLINE | ID: mdl-28594115

ABSTRACT

Ozone, one of the most important air pollutants, is a triatomic molecule containing three atoms of oxygen that results in an unstable form due to its mesomeric structure. It has been well-known that ozone has potent ability to oxidize organic compounds and can induce respiratory irritation. Although ozone has deleterious effects, many therapeutic effects have also been suggested. Since last few decades, the therapeutic potential of ozone has gained much attention through its strong capacity to induce controlled and moderated oxidative stress when administered in precise therapeutic doses. A plethora of scientific evidence showed that the activation of hypoxia inducible factor-1α (HIF-1a), nuclear factor of activated T-cells (NFAT), nuclear factor-erythroid 2-related factor 2-antioxidant response element (Nrf2-ARE), and activated protein-1 (AP-1) pathways are the main molecular mechanisms underlying the therapeutic effects of ozone therapy. Activation of these molecular pathways leads to up-regulation of endogenous antioxidant systems, activation of immune functions as well as suppression of inflammatory processes, which is important for correcting oxidative stress in diabetes and spinal pain. The present study intended to review critically the available scientific evidence concerning the beneficial properties of ozone therapy for treatment of diabetic complications and spinal pain. It finds benefit for integrating the therapy with ozone into pharmacological procedures, instead of a substitutive or additional option to therapy.


Subject(s)
Diabetes Mellitus/therapy , Ozone/therapeutic use , Pain Management , Spinal Cord Diseases/therapy , Animals , Clinical Trials as Topic , Humans , Oxidative Stress/drug effects , Ozone/pharmacology
14.
J Vet Sci ; 17(3): 337-45, 2016 Sep 30.
Article in English | MEDLINE | ID: mdl-26645331

ABSTRACT

This study was conducted to evaluate new acupuncture protocols for the clinical treatment of cervical spinal cord diseases in 19 dogs. Three treatment options containing Jing-jiaji (cervical jiaji) were developed to treat neck pain, hemiparesis, and tetraparesis depending on the severity. The interval between the neurological disease onset and treatment (duration of signs), time to improvement after treatment, and recovery time were compared in dogs by body weight, age, and dry needle acupuncture (AP) with or without electro-AP (EAP). The duration of signs was longer in dogs weighing greater than 10 kg than in those weighing less than 10 kg (p< 0.05). Improvement and recovery times did not vary by body weight. Additionally, improvement and recovery times did not vary by age. The improvement and recovery times were longer in the AP+EAP group than the AP group (p< 0.05). Acupuncture with Jing-jiaji was effective in cervical spinal cord diseases in different sized dogs and in middle-aged and senior dogs. This report standardized AP treatment containing Jing-jiaji for canine cervical problems and evaluated its effects. The newly standardized AP methodology offers clinical practitioners an effective way to improve the outcomes of cervical neurological diseases in dogs.


Subject(s)
Acupuncture Therapy/veterinary , Dog Diseases/therapy , Neck Pain/veterinary , Paresis/veterinary , Spinal Cord Diseases/veterinary , Animals , Cervical Vertebrae/physiopathology , Dog Diseases/etiology , Dogs , Neck Pain/etiology , Neck Pain/therapy , Paresis/etiology , Paresis/therapy , Retrospective Studies , Spinal Cord Diseases/etiology , Spinal Cord Diseases/therapy
15.
Sci Rep ; 5: 9133, 2015 Mar 16.
Article in English | MEDLINE | ID: mdl-25779025

ABSTRACT

This study attempted to graft neurotrophin-3 (NT-3) receptor (TrkC) gene modified mesenchymal stem cells (TrkC-MSCs) into the demyelinated spinal cord and to investigate whether electroacupuncture (EA) treatment could promote NT-3 secretion in the demyelinated spinal cord as well as further enhance grafted TrkC-MSCs to differentiate into oligodendrocytes, remyelination and functional recovery. Ethidium bromide (EB) was microinjected into the spinal cord of rats at T10 to establish a demyelinated model. Six groups of animals were prepared for the experiment: the sham, PBS, MSCs, MSCs+EA, TrkC-MSCs and TrkC-MSCs+EA groups. The results showed that TrkC-MSCs graft combined with EA treatment (TrkC-MSCs+EA group) significantly increased the number of OPCs and oligodendrocyte-like cells differentiated from MSCs. Immunoelectron microscopy showed that the oligodendrocyte-like cells differentiated from TrkC-MSCs formed myelin sheaths. Immunofluorescence histochemistry and Western blot analysis indicated that TrkC-MSCs+EA treatment could promote the myelin basic protein (MBP) expression and Kv1.2 arrangement trending towards the normal level. Furthermore, behavioural test and cortical motor evoked potentials detection demonstrated a significant functional recovery in the TrkC-MSCs+EA group. In conclusion, our results suggest that EA treatment can increase NT-3 expression, promote oligodendrocyte-like cell differentiation from TrkC-MSCs, remyelination and functional improvement of demyelinated spinal cord.


Subject(s)
Demyelinating Diseases/genetics , Electroacupuncture , Gene Expression , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells/metabolism , Receptor, trkC/genetics , Spinal Cord Diseases/genetics , Adenoviridae/genetics , Animals , Cell Differentiation , Demyelinating Diseases/metabolism , Demyelinating Diseases/therapy , Disease Models, Animal , Evoked Potentials, Motor , Genetic Vectors/genetics , Mesenchymal Stem Cells/cytology , Myelin Sheath/metabolism , Neurotrophin 3/genetics , Neurotrophin 3/metabolism , Oligodendroglia/cytology , Oligodendroglia/metabolism , Rats , Receptor, trkC/metabolism , Recovery of Function , Spinal Cord Diseases/metabolism , Spinal Cord Diseases/therapy , Transduction, Genetic , Transgenes
16.
J Clin Gastroenterol ; 48(10): 862-5, 2014.
Article in English | MEDLINE | ID: mdl-24583748

ABSTRACT

Malabsorptive bariatric surgery is rapidly becoming a major cause of copper deficiency given the increasing prevalence of these procedures for morbid obesity. Acquired copper deficiency can present with clinically significant hematologic and neurological manifestations. Although hematologic manifestations of copper deficiency are rapidly reversible, significant neurological improvement after copper supplementation therapy is unusual and many patients remain debilitated and may only experience, at best, stabilization of the neurological manifestations. Here we present a case of an undiagnosed copper deficiency several years after bariatric gastric bypass surgery, in a patient who concomitantly used zinc-containing denture cream for several years, associated with anemia, neutropenia, myelopathy, respiratory failure, and bilateral optic neuropathy, which caused major vision loss. This patient was also a heterozygote carrier of the 5,10-methylenetetrahydrofolate reductase A1298C gene polymorphism, which may affect copper metabolism. Intravenous copper repletion resulted in rapid correction of hematologic indices. However, neurological manifestations, including vision loss responded only modestly to copper supplementation, despite achieving normal blood copper concentrations. Clinicians should consider copper deficiency in patients at risk, as in this case, as a delayed diagnosis can lead to irreversible disability due to neurological manifestations.


Subject(s)
Anemia/etiology , Copper/deficiency , Deficiency Diseases/etiology , Gastric Bypass/adverse effects , Neutropenia/etiology , Obesity, Morbid/surgery , Optic Nerve Diseases/etiology , Spinal Cord Diseases/etiology , Anemia/blood , Anemia/diagnosis , Anemia/therapy , Copper/blood , Copper/therapeutic use , Deficiency Diseases/blood , Deficiency Diseases/diagnosis , Deficiency Diseases/genetics , Deficiency Diseases/therapy , Female , Humans , Methylenetetrahydrofolate Reductase (NADPH2)/genetics , Methylenetetrahydrofolate Reductase (NADPH2)/metabolism , Middle Aged , Neutropenia/blood , Neutropenia/diagnosis , Neutropenia/therapy , Optic Nerve Diseases/blood , Optic Nerve Diseases/diagnosis , Optic Nerve Diseases/therapy , Polymorphism, Genetic , Risk Factors , Spinal Cord Diseases/blood , Spinal Cord Diseases/diagnosis , Spinal Cord Diseases/therapy , Time Factors , Treatment Outcome
17.
J Neurointerv Surg ; 6(9): 708-11, 2014 Nov.
Article in English | MEDLINE | ID: mdl-24151115

ABSTRACT

PURPOSE: Spinal cord stimulation is a known modality for the treatment of chronic back and neck pain. Traditionally, spine surgeons and pain physicians perform the procedures. We report our experience in performing neuromodulation procedures in an outpatient interventional neuroradiology practice. METHODS: A retrospective analysis of medical records of all trial and permanent implantation patients over a period of 4 years was performed. 45 patients (32 men) of median age 47 years were included in the study. The primary diagnoses were 23 cases of failed back or neck surgery syndrome, 12 cases of spinal stenosis, 4 cases of axial pain, 3 cases with reflex sympathetic dystrophy, 1 case of peripheral vascular disease, 1 case of phantom limb and 1 case of post-concussion syndrome. RESULTS: Thirty-four trials were performed in an outpatient clinic while 11 trials were performed in hospital outpatient settings. Trial periods were 3-7 days. 27 patients (60%) who reported ≥50% pain relief underwent a permanent implantation. An interventional neuroradiologist performed 17 implantations, while spine surgeons performed 10 implantations. 23 implants were epidural (19 lumbar and 4 cervical) and four implants were subcutaneous. During the follow-up period, three patients had infections (13%) and required removal of the device and two cases (8%) reported lead migration. CONCLUSIONS: Neuromodulation procedures can be performed safely in an outpatient interventional radiology setting. Although the infection rate was relatively higher in this study population, the other complication rates and trial-to-implant ratio are similar to published data.


Subject(s)
Electric Stimulation Therapy/methods , Pain Management/methods , Radiography, Interventional/methods , Spinal Cord Diseases/therapy , Spinal Cord Stimulation/methods , Ambulatory Care , Electrodes, Implanted , Female , Foreign-Body Migration , Humans , Infections/etiology , Male , Middle Aged , Retrospective Studies , Spinal Cord Stimulation/adverse effects , Spinal Cord Stimulation/instrumentation , Treatment Failure , Treatment Outcome
19.
Undersea Hyperb Med ; 41(6): 599-603, 2014.
Article in English | MEDLINE | ID: mdl-25562951

ABSTRACT

Decompression illness affecting the cervical spinal cord is uncommon. We report a case that presented with mixed signs and symptoms of cervical myelopathy and Type II neurological decompression sickness. This presented a diagnostic dilemma that required the use of magnetic resonance imaging (MRI) scan to elucidate the underlying cause. Cervical spine MRI revealed the presence of tiny hypointensities and edema within the spinal cord that corresponded to the clinical findings. The patient recovered with residual neurological deficits after hy-perbaric oxygen (HBO2) therapy. To our knowledge, these MRI findings have yet to been described in literature and we recommend the use of MRI to assist diving physicians in the management of complex cases as long as it does not delay recompression.


Subject(s)
Decompression Sickness/diagnosis , Magnetic Resonance Imaging , Spinal Cord Diseases/diagnosis , Adrenal Cortex Hormones/therapeutic use , Decompression Sickness/therapy , Edema/diagnosis , Edema/therapy , Female , Humans , Hyperbaric Oxygenation , Middle Aged , Spinal Cord Compression/diagnosis , Spinal Cord Diseases/therapy
20.
Undersea Hyperb Med ; 40(1): 23-31, 2013.
Article in English | MEDLINE | ID: mdl-23397865

ABSTRACT

In order to develop more sensitive imaging tools for clinical use and basic research of spinal decompression sickness (DCS), we used diffusion tensor MRI (DTI) validated by histology to assess DCS-related tissue injury in sheep spinal cords. DTI is based on the measurement of water diffusion indices, including fractional anisotropy (FA) and mean diffusion (MD) to detect tissue microstructural abnormalities. In this study, we measured FA and MD in white and gray matter spinal cord regions in samples taken from sheep following hyperbaric exposure to 60-132 fsw and 0-180 minutes of oxygen pre-breathing treatment before rapid decompression. The main finding of the study was that decompression from >60 fsw resulted in reduced FA that was associated with cell death and disrupted tissue microstructure in spinal cord white matter tracts. Additionally, animals exposed to prolonged oxygen pre-breathing prior to decompression demonstrated reduced MD in spinal cord gray matter regions regardless of dive depth. To our knowledge, this is the first study to demonstrate the utility of DTI for the investigation of DCS-related injury and to define DTI biomarkers of spinal DCS.


Subject(s)
Decompression Sickness/pathology , Diffusion Magnetic Resonance Imaging/methods , Animals , Anisotropy , Cell Death , Decompression Sickness/metabolism , Decompression Sickness/mortality , Decompression Sickness/therapy , Female , Hyperbaric Oxygenation/methods , Myelin Sheath/pathology , Myelin Sheath/physiology , Sheep , Spinal Cord Diseases/metabolism , Spinal Cord Diseases/mortality , Spinal Cord Diseases/pathology , Spinal Cord Diseases/therapy , Time Factors
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