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BACKGROUND & OBJECTIVE: Cervical Spondylotic Myelopathy (CSM) is one of the most serious spinal cord disorders in adults. Pharmacological modulation of ion channels is a common strategy to interfere with CSM and prevent neuronal damage. METHODS: Here, we investigated the effects of Jingshu Keli (JSKL), a traditional Chinese herbal formula, on CSM-related gait abnormality, mechanical allodynia and thermal hyperalgesia, and assessed the neuronal mechanisms of JSKL on cultured brainstem cells. Behavioral tests and patch clamp recordings were performed to make this assessment. RESULTS: In our study, we found that JSKL significantly recovered the gait performance (P<0.001) and decreased the levels of mechanical pain in 18.9% (P<0.01) and thermal pain in 18.1% (P<0.05). Further investigation suggested that JSKL and its containing ginsenoside Rb1 (GRb1), notoginsenoside R1 (NGR1) reduced the action potential frequency in 38.5%, 27.2%, 25.9%, and hyperpolarized resting membrane potential in 15.0%, 13.8%, 12.1%, respectively. Kir channels, not KV channels and KCa channels, were the major intermediate factors achieving treatment effects. Finally, immunostaining results showed that the phosphorylation of Kir3.1 was promoted, whereas the total expression level did not change. CONCLUSION: Our study reveals a novel strategy of treating CSM by using Traditional Chinese Medicines (TCMs) containing active components.
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Medicamentos Herbarios Chinos/uso terapéutico , Canales de Potasio Rectificados Internamente Asociados a la Proteína G/metabolismo , Marcha/efectos de los fármacos , Ginsenósidos/uso terapéutico , Hiperalgesia/tratamiento farmacológico , Enfermedades de la Médula Espinal/tratamiento farmacológico , Animales , Modelos Animales de Enfermedad , Medicamentos Herbarios Chinos/farmacología , Ginsenósidos/farmacología , Hiperalgesia/metabolismo , Masculino , Medicina Tradicional China , Dimensión del Dolor , Ratas , Ratas Sprague-Dawley , Enfermedades de la Médula Espinal/metabolismoRESUMEN
OBJECTIVE: To determine the changes in fractional anisotropy (FA) at the proximal spinal cord and in magnetic resonance spectroscopy (MRS) of the precentral gyrus in patients with cervical spondylotic myelopathy (CSM) with respect to clinical symptoms and their duration. MATERIAL AND METHODS: 20 patients with CSM (7 female; mean age 64.6 ± 10.5 years) and 18 age/sex matched healthy controls (9 female; mean age 63.5 ± 6.6 years) were prospectively included. Clinical data (modified Japanese Orthopaedic Association Score (mJOA) and Neck Disability Index (NDI)) and 3T MR measurements including DTI at the spinal cord (level C2/3) with FA and MRS of the left and right precentral gyrus were taken. Clinical correlations and regression analyses were performed. RESULTS: Mean clinical scores of patients were significantly different to controls (mJOA; CSM: 10.2 ± 2.9; controls: 18.0 ± 0.0, p < 0.001; NDI; CSM: 41.4±23.5; controls: 4.4±6.6, p<0.001); FA was significantly lower in patients (CSM: 0.645 ± 0.067; controls: 0.699 ± 0.037, p = 0.005). MRS showed significantly lower metabolite concentrations between both groups: creatine (Cr) (CSM: 46.46±7.64; controls: 51.36±5.76, p = 0.03) and N-acetylaspartate (NAA) (CSM: 93.94±19.22; controls: 107.24±20.20, p = 0.05). Duration of symptoms ≤6 months was associated with increased myo-inositol (Ins) (61.58±17.76; 44.44±10.79; p = 0.02) and Ins/Cr ratio (1.36±0.47; 0.96±0.18; p = 0.014) compared to symptoms >6 months. CONCLUSION: Metabolic profiles of the precentral gyrus and FA in the uppermost spinal cord differ significantly between patients and healthy controls. Ins, thought to be a marker of endogenous neuroinflammatory response, is high in the early course of CSM and normalizes over time.
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Espectroscopía de Resonancia Magnética/métodos , Corteza Motora/diagnóstico por imagen , Corteza Motora/metabolismo , Enfermedades de la Médula Espinal/patología , Espondilosis/patología , Anciano , Anisotropía , Ácido Aspártico/análogos & derivados , Ácido Aspártico/metabolismo , Biomarcadores/metabolismo , Vértebras Cervicales/diagnóstico por imagen , Vértebras Cervicales/patología , Creatina/metabolismo , Femenino , Humanos , Inositol/metabolismo , Masculino , Persona de Mediana Edad , Corteza Motora/patología , Enfermedades de la Médula Espinal/metabolismo , Espondilosis/metabolismo , Factores de TiempoRESUMEN
OBJECTIVE In patients with cervical spondylotic myelopathy (CSM), the motor system may undergo progressive functional/structural changes rostral to the lesion, and these changes may be associated with clinical disability. The extent to which these changes have a prognostic value in the clinical recovery after surgical treatment is not yet known. In this study, magnetic resonance spectroscopy (MRS) was used to test 2 primary hypotheses. 1) Based on evidence of corticospinal and spinocerebellar, rubro-, or reticulospinal tract degeneration/dysfunction during chronic spinal cord compression, the authors hypothesized that the metabolic profile of the primary motor cortices (M1s) and cerebellum, respectively, would be altered in patients with CSM, and these alterations would be associated with the extent of the neurological disabilities. 2) Considering that damage and/or plasticity in the remote motor system may contribute to clinical recovery, they hypothesized that M1 and cerebellar metabolic profiles would predict, at least in part, surgical outcome. METHODS The metabolic profile, consisting of N-acetylaspartate (NAA; marker of neuronal integrity), myoinositol (glial marker), choline (cell membrane synthesis and turnover), and glutamate-glutamine (glutamatergic system), of the M1 hand/arm territory in each hemisphere and the cerebellum vermis was investigated prior to surgery in 21 patients exhibiting weakness of the upper extremities and/or gait abnormalities. Age- and sex-matched controls (n = 16) were also evaluated to estimate the pre-CSM metabolic profile of these areas. Correlation and regression analyses were performed between preoperative metabolite levels and clinical status 6 months after surgery. RESULTS Relative to controls, patients exhibited significantly higher levels of choline but no difference in the levels of other metabolites across M1s. Cerebellar metabolite levels were indistinguishable from control levels. Certain metabolites-myo-inositol and choline across M1s, NAA and glutamate-glutamine in the left M1, and myo-inositol and glutamate-glutamine in the cerebellum-were significantly associated with postoperative clinical status. These associations were greatly improved by including preoperative clinical metrics into the models. Likewise, these models improved the predictive value of preoperative clinical metrics alone. CONCLUSIONS These preliminary findings demonstrate relationships between the preoperative metabolic profiles of two remote motor areas and surgical outcome in CSM patients. Including preoperative clinical metrics in the models significantly strengthened the predictive value. Although further studies are needed, this investigation provides an important starting point to understand how the changes upstream from the injury may influence the effect of spinal cord decompression.
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Vértebras Cervicales/cirugía , Enfermedades de la Médula Espinal/metabolismo , Enfermedades de la Médula Espinal/cirugía , Espondilosis/metabolismo , Espondilosis/cirugía , Adulto , Factores de Edad , Anciano , Cerebelo/diagnóstico por imagen , Cerebelo/metabolismo , Vértebras Cervicales/diagnóstico por imagen , Estudios de Cohortes , Descompresión Quirúrgica , Femenino , Lateralidad Funcional , Humanos , Masculino , Persona de Mediana Edad , Corteza Motora/diagnóstico por imagen , Corteza Motora/metabolismo , Espectroscopía de Protones por Resonancia Magnética , Análisis de Regresión , Enfermedades de la Médula Espinal/diagnóstico por imagen , Espondilosis/diagnóstico por imagen , Resultado del TratamientoRESUMEN
OBJECTIVE The goal of this study was to compare the recovery of neuronal metabolism and functional reorganization in the primary motor cortex (M1) between mild and moderate cervical spondylotic myelopathy (CSM) following surgical intervention. METHODS Twenty-eight patients with CSM underwent 3-T MRI scans that included spectroscopy and functional MRI, before surgery and 6 months postsurgery. The classification of severity was based on the modified Japanese Orthopaedic Association questionnaire. Mild and moderate myelopathy were defined by modified Japanese Orthopaedic Association scores > 12 of 18 (n = 15) and 9-12 (n = 13), respectively. Ten healthy control subjects underwent 2 MRI scans 6 months apart. Metabolite levels were measured in the M1 contralateral to the greater deficit side in patients with CSM and on both sides in the controls. Motor function was assessed using a right finger-tapping paradigm and analyzed with BrainVoyager QX. RESULTS Patients with mild CSM had a lower preoperative N-acetylaspartate to creatine (NAA/Cr) ratio compared with moderate CSM, suggesting mitochondrial dysfunction. Postsurgery, NAA/Cr in moderate CSM decreased to the levels observed in mild CSM. Preoperatively, patients with mild CSM had a larger volume of activation (VOA) in the M1 than those with moderate CSM. Postoperatively, the VOAs were comparable between the mild and moderate CSM groups and had shifted toward the primary sensory cortex. CONCLUSIONS The NAA/Cr ratio and VOA size in the M1 can be used to discriminate between mild and moderate CSM. Postsurgery, the metabolite profile of the M1 did not recover in either group, despite significant clinical improvement. The authors proposed that metabolic impairment in the M1 may trigger the recruitment of adjacent healthy cortex to achieve functional recovery.
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Vértebras Cervicales/cirugía , Corteza Motora/metabolismo , Enfermedades de la Médula Espinal/metabolismo , Enfermedades de la Médula Espinal/cirugía , Espondilosis/metabolismo , Espondilosis/cirugía , Ácido Aspártico/análogos & derivados , Ácido Aspártico/metabolismo , Creatina/metabolismo , Descompresión Quirúrgica , Femenino , Estudios de Seguimiento , Humanos , Imagen por Resonancia Magnética , Espectroscopía de Resonancia Magnética , Masculino , Persona de Mediana Edad , Actividad Motora , Corteza Motora/diagnóstico por imagen , Plasticidad Neuronal/fisiología , Estudios Prospectivos , Recuperación de la Función , Índice de Severidad de la Enfermedad , Corteza Somatosensorial/diagnóstico por imagen , Corteza Somatosensorial/metabolismo , Enfermedades de la Médula Espinal/diagnóstico por imagen , Espondilosis/diagnóstico por imagen , Encuestas y Cuestionarios , Resultado del TratamientoRESUMEN
Purpose To characterize longitudinal metabolite alterations in the motor cortex of patients with cervical spondylotic myelopathy (CSM) by using proton magnetic resonance (MR) spectroscopy and to evaluate white matter integrity with diffusion-tensor imaging in patients who are recovering neurologic function after decompression surgery. Materials and Methods Informed written consent was obtained for all procedures and the study was approved by Western University's Health Sciences Research Ethics Board. Twenty-eight patients with CSM and 10 healthy control subjects were prospectively recruited and underwent two separate 3-T MR imaging examinations 6 months apart. Patients with CSM underwent surgery after the first examination. N-acetylaspartate (NAA), an indicator of neuronal mitochondrial function, normalized to creatine (Cr) levels were measured from the motor cortex contralateral to the greater functional deficit side in the patient group and on both sides in the control group. Fractional anisotropy and mean diffusivity were measured by means of diffusion-tensor imaging in the white matter adjacent to the motor and sensory cortices of the hand and the entire cerebral white matter. Clinical data were analyzed by using Student t tests. Results In patients with CSM, NAA normalized to Cr (NAA/Cr) levels were significantly lower 6 months after surgery (1.48 ± 0.08; P < .03) compared with preoperative levels (1.73 ± 0.09), despite significant improvement in clinical questionnaire scores. Fractional anisotropy and mean diffusivity were the same (P > .05) between the patient and control groups in all measured regions at all time points. Conclusion NAA/Cr levels decreased in the motor cortex in patients with CSM 6 months after successful surgery. Intact white matter integrity with decreased NAA/Cr levels suggests that mitochondrial metabolic dysfunction persists after surgery. © RSNA, 2016 Online supplemental material is available for this article.
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Ácido Aspártico/análogos & derivados , Vértebras Cervicales/metabolismo , Creatina/metabolismo , Corteza Motora/metabolismo , Enfermedades de la Médula Espinal/metabolismo , Espondilosis/metabolismo , Anisotropía , Ácido Aspártico/metabolismo , Vértebras Cervicales/diagnóstico por imagen , Vértebras Cervicales/cirugía , Descompresión Quirúrgica , Imagen de Difusión Tensora , Femenino , Humanos , Espectroscopía de Resonancia Magnética , Masculino , Persona de Mediana Edad , Corteza Motora/diagnóstico por imagen , Periodo Posoperatorio , Estudios Prospectivos , Enfermedades de la Médula Espinal/diagnóstico por imagen , Enfermedades de la Médula Espinal/cirugía , Espondilosis/diagnóstico por imagen , Espondilosis/cirugíaRESUMEN
Nitrous oxide is commonly used as an analgesic and anaesthetic agent. Nitrous oxide is also in use in industry as an aerosol propellant and is now recognised as a recreational drug whose use is growing, especially among the young. Nitrous oxide from whipped cream canisters is inhaled to produce a dissociative, intoxicated state. Nitrous oxide is known to inactivate vitamin B12 via oxidation, which can precipitate a demyelinating myelopathy akin to the classical B12 deficiency syndrome, subacute combined degeneration of the spinal cord. This case describes a young woman with chronic pain and a poor nutritional state who took regular nitrous oxide as an opiate-sparing agent. She developed a progressive subacute myelopathy with a sensory level, profoundly impaired joint position sense, extensor plantars and required a wheelchair. Once diagnosed, she responded well to a regime of nitrous oxide withdrawal, high-dose B12 replacement and physiotherapy. The case illustrates the need for clinical teams to be able to dentify a nitrous oxide-precipitated myelopathy as its use as a drug of abuse increases; particularly in the case of malnourished patients who receive nitrous oxide surgically or obstetrically.
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Accidentes por Caídas , Analgésicos no Narcóticos/efectos adversos , Dolor Crónico/tratamiento farmacológico , Enfermedades Desmielinizantes/inducido químicamente , Óxido Nitroso/efectos adversos , Enfermedades de la Médula Espinal/inducido químicamente , Vitamina B 12/metabolismo , Adulto , Analgésicos no Narcóticos/uso terapéutico , Anestésicos por Inhalación/efectos adversos , Anestésicos por Inhalación/uso terapéutico , Enfermedades Desmielinizantes/complicaciones , Enfermedades Desmielinizantes/metabolismo , Femenino , Humanos , Óxido Nitroso/uso terapéutico , Manejo del Dolor/efectos adversos , Enfermedades de la Médula Espinal/complicaciones , Enfermedades de la Médula Espinal/metabolismo , Deficiencia de Vitamina B 12RESUMEN
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.
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Enfermedades Desmielinizantes/genética , Electroacupuntura , Expresión Génica , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas/metabolismo , Receptor trkC/genética , Enfermedades de la Médula Espinal/genética , Adenoviridae/genética , Animales , Diferenciación Celular , Enfermedades Desmielinizantes/metabolismo , Enfermedades Desmielinizantes/terapia , Modelos Animales de Enfermedad , Potenciales Evocados Motores , Vectores Genéticos/genética , Células Madre Mesenquimatosas/citología , Vaina de Mielina/metabolismo , Neurotrofina 3/genética , Neurotrofina 3/metabolismo , Oligodendroglía/citología , Oligodendroglía/metabolismo , Ratas , Receptor trkC/metabolismo , Recuperación de la Función , Enfermedades de la Médula Espinal/metabolismo , Enfermedades de la Médula Espinal/terapia , Transducción Genética , TransgenesRESUMEN
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.
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Enfermedad de Descompresión/patología , Imagen de Difusión por Resonancia Magnética/métodos , Animales , Anisotropía , Muerte Celular , Enfermedad de Descompresión/metabolismo , Enfermedad de Descompresión/mortalidad , Enfermedad de Descompresión/terapia , Femenino , Oxigenoterapia Hiperbárica/métodos , Vaina de Mielina/patología , Vaina de Mielina/fisiología , Ovinos , Enfermedades de la Médula Espinal/metabolismo , Enfermedades de la Médula Espinal/mortalidad , Enfermedades de la Médula Espinal/patología , Enfermedades de la Médula Espinal/terapia , Factores de TiempoRESUMEN
Alterations in motor function in cervical myelopathy secondary to degenerative disease may be due to local effects of spinal compression or distal effects related to cortical reorganization. This prospective study characterizes differences in metabolite levels in the motor cortex, specifically N-acetylaspartate, creatine, choline, myo-inositol and glutamate plus glutamine, due to alterations in cortical function in patients with reversible spinal cord compression compared with healthy controls. We hypothesized that N-acetylaspartate/creatine levels would be decreased in the motor cortex of patients with cervical myelopathy due to reduced neuronal integrity/function and myo-inositol/creatine levels would be increased due to reactive gliosis. Twenty-four patients with cervical myelopathy and 11 healthy controls underwent proton-magnetic resonance spectroscopy on a 3.0 Tesla Siemens Magnetom Tim Trio MRI. Areas of activation from functional magnetic resonance imaging scans of a finger-tapping paradigm were used to localize a voxel on the side of greater motor deficit in the myelopathy group (n = 10 on right side and n = 14 on left side of the brain) and on each side of the motor cortex in controls. Neurological function was measured with the Neck Disability Index, modified Japanese Orthopaedic Association and American Spinal Injury Association questionnaires. Metabolite levels were measured relative to total creatine within the voxel of interest. No metabolite differences were detected between the right side and left side of the motor cortex in controls. The myelopathy group had significantly decreased neurological function compared with the control group (Neck Disability Index: P < 0.001 and modified Japanese Orthopaedic Association: P < 0.001). There was a significant decrease in the N-acetylaspartate/creatine metabolite ratio in the motor cortex of the myelopathy group (1.21 ± 0.07) compared with the right (1.37 ± 0.03; P = 0.01) and left (1.38 ± 0.03; P = 0.007) motor cortex in controls suggesting neuronal damage or dysfunction distal to the lesion in the spine. No difference was observed in levels of myo-inositol/creatine. Thus, cortical levels of N-acetylaspartate/creatine may be a meaningful biomarker in cervical myelopathy, indicative of neuronal damage or dysfunction.
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Corteza Motora/metabolismo , Enfermedades de la Médula Espinal/metabolismo , Adulto , Anciano , Ácido Aspártico/análogos & derivados , Ácido Aspártico/metabolismo , Vértebras Cervicales , Femenino , Neuroimagen Funcional , Humanos , Espectroscopía de Resonancia Magnética , Masculino , Persona de Mediana Edad , Corteza Motora/fisiopatología , Enfermedades de la Médula Espinal/fisiopatologíaRESUMEN
We report two patients with myelopathy associated with copper deficiency and pancytopenia. Excessive intake of zinc can lead to a severe deficiency of copper reducing the absorption of ingested copper. The patients had in common consumption of denture adhesive paste containing zinc. In both patients, laboratory tests showed a combination of copper deficiency, hyperzincemia and increased urinary zinc level. The use of a denture cream was stopped. Copper supplementation, initially subcutaneously then oral corrected the copper deficiency and pancytopenia. Clinically, the pain faded but the gait disturbance persisted. Copper deficiency associated with the use of denture cream rich in zinc is an unrecognized cause of myelopathy associated with pancytopenia which should be diagnosed early to establish appropriate therapeutic measures to minimize neurological complications.
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Cobre/deficiencia , Cementos Dentales/efectos adversos , Dentaduras , Enfermedades de la Médula Espinal/inducido químicamente , Anciano , Electromiografía , Trastornos Neurológicos de la Marcha/inducido químicamente , Trastornos Neurológicos de la Marcha/diagnóstico , Trastornos Neurológicos de la Marcha/fisiopatología , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Examen Neurológico , Pancitopenia/inducido químicamente , Enfermedades de la Médula Espinal/metabolismo , Enfermedades de la Médula Espinal/patología , Columna Vertebral/patología , Zinc/efectos adversos , Zinc/sangre , Zinc/orinaRESUMEN
OBJECTIVE: To observe the effect of acupotomy lysis (AL) on hypothalamic proopiomelanocortin (POMO) mRNA and preproenkephalin (PPE) mRNA expression in rats with the third lumbar vertebrae transverse process syndrome (TLVTPS) so as to study its underlying mechanism in relieving symptoms of lumbar muscle strain. METHODS: Twenty-four SD rats were randomly divided into normal control group, model group, AL group and electroacupunture (EA) group. The TLVTPS model was established by inserting a piece of gelatin sponge into the posterior of the left 3rd lumbar vertebrae transverse process. AL and EA were applied to the left "Shenshu"(BL 23) and "Yaoyangguan" (GV 3) respectively. The POMC mRNA and PPE mRNA expression levels in the hypothalamus were detected by in situ hybridization. RESULTS: In comparison with the normal group, the integrated optical density (IOD) values of hypothalamic POMC mRNA and PPE mRNA positive cells in the model group were increased significantly (P < 0.01); while compared with the model group, those of POMC mRNA and PPE mRNA positive cells in both left and right hypothalamus were increased further considerably in both AL and EA groups (P < 0.01). No significant differences were found between AL and EA groups in POMC mRNA and PPE mRNA expression levels (P > 0.05). CONCLUSION: AL and EA therapies can increase the expression of POMC mRNA and PPE mRNA in hypothalamus in rats with TLVTPS, which may contribute to its effect in relieving pain in the treatment of lumbar muscle strain.
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Electroacupuntura , Encefalinas/genética , Expresión Génica , Hipotálamo/metabolismo , Vértebras Lumbares/metabolismo , Manejo del Dolor , Proopiomelanocortina/genética , Precursores de Proteínas/genética , Enfermedades de la Médula Espinal/terapia , Analgesia por Acupuntura , Puntos de Acupuntura , Animales , Encefalinas/metabolismo , Humanos , Masculino , Dolor/genética , Dolor/metabolismo , Proopiomelanocortina/metabolismo , Precursores de Proteínas/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Enfermedades de la Médula Espinal/genética , Enfermedades de la Médula Espinal/metabolismoRESUMEN
INTRODUCTION: Copper deficiency is an increasingly recognized cause of gait unsteadiness. Recognized causes of copper deficiency include excess zinc ingestion, and malabsorption. Although hematologic abnormalities have been attributed to copper deficiency in patients with celiac disease, myeloneuropathy due to copper deficiency has not been well described in patients with celiac disease. CASE REPORT: A 69-year-old woman was evaluated for a 5-year history of progressive gait unsteadiness and weight loss. She had no other gastrointestinal symptoms. Her neurologic examination revealed a sensory ataxia, and electrodiagnostic testing confirmed a myeloneuropathy. She had decreased serum copper levels and markedly elevated gliadin and tissue transglutaminase antibodies. Subsequent duodenal biopsy showed findings consistent with celiac disease. The patient was diagnosed with copper deficiency myeloneuropathy due to celiac disease. Adoption of a gluten-free diet along with copper supplementation resulted in significant clinical improvement, including improvement on electrodiagnostic testing. CONCLUSIONS: Celiac disease should be considered in patients found to have copper deficiency, even in patients without gastrointestinal symptoms. Furthermore, the authors suggest that some cases of ataxia associated with celiac disease are likely due to copper deficiency myeloneuropathy.
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Enfermedad Celíaca/complicaciones , Cobre/deficiencia , Trastornos Neurológicos de la Marcha/complicaciones , Enfermedades de la Médula Espinal/etiología , Enfermedades de la Médula Espinal/metabolismo , Anciano , Anticuerpos/sangre , Femenino , Humanos , Examen Neurológico/métodos , Transglutaminasas/inmunologíaRESUMEN
BACKGROUND: Chronic, excess zinc intake can result in copper deficiency and profound neurologic disease. However, when hyperzincemia is identified, the source often remains elusive. We identified four patients, one previously reported, with various neurologic abnormalities in the setting of hypocupremia and hyperzincemia. Each of these patients wore dentures and used very large amounts of denture cream chronically. OBJECTIVE: To determine zinc concentration in the denture creams used by the patients as a possible source of excess zinc ingestion. METHODS: Detailed clinical and laboratory data for each patient were compiled. Tubes of denture adhesives were analyzed for zinc content using dynamic reaction cell-inductively coupled plasma-mass spectrometry. Patients received copper supplementation. Copper and zinc levels were obtained post-treatment at varying intervals. RESULTS: Zinc concentrations ranging from about 17,000 to 34,000 mug/g were identified in Fixodent and Poli-Grip denture creams. Serum zinc levels improved in three patients following cessation of denture cream use. Copper supplementation resulted in mild neurologic improvement in two patients who stopped using denture cream. No alternative source of excess zinc ingestion or explanation for hypocupremia was identified. CONCLUSION: Denture cream contains zinc, and chronic excessive use may result in hypocupremia and serious neurologic disease.
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Cobre/deficiencia , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Enfermedades de la Médula Espinal/inducido químicamente , Adhesivos Tisulares/envenenamiento , Zinc/envenenamiento , Adulto , Sistema Nervioso Central/efectos de los fármacos , Sistema Nervioso Central/metabolismo , Sistema Nervioso Central/fisiopatología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Sistema Nervioso Periférico/efectos de los fármacos , Sistema Nervioso Periférico/metabolismo , Sistema Nervioso Periférico/fisiopatología , Enfermedades del Sistema Nervioso Periférico/metabolismo , Enfermedades del Sistema Nervioso Periférico/fisiopatología , Enfermedades de la Médula Espinal/metabolismo , Enfermedades de la Médula Espinal/fisiopatología , Zinc/metabolismoRESUMEN
OBJECTIVE: To observe changes of SP and CCK-8 contents in the hypothalamus and spinal cord after performing acupotomy lysis so as to study its central analgesic effect in rats with transverse-process syndrome of the third lumbar vertebra. METHODS: Twenty-eight SD rats were randomly divided into normal control group, model group, acupotomy lysis group and electroacupuncture (EA) group, with 7 cases in each one. The model of the third lumbar vertebra transverse process syndrome was established by inserting a piece of gelatin sponge into the deep subfascial part of the 3rd lumbar transverse process. Acupotomy lysis was conducted 1 time/week for 2 weeks. EA (2/100 Hz, 1-2 mA) was applied to the left "Shenshu" (BL 23)-"Yaoyangguan"(GV 3) for 20 min/time, 3 times/week and for 2 weeks. SP and CCK-8 contents in the hypothalamus and spinal cord were detected with enzyme linked immunosorbent assay (ELISA). RESULTS: In model group, SP and CCK-8 contents in the hypothalamus and spinal cord were increased significantly in comparison with normal control group (P < 0.01). Compared with model group, both SP and CCK-8 contents in hypothalamus and SP content in spinal cord in acupotomy lysis and EA groups were apparently lower (P < 0.01, 0.05). CCK-8 content in spinal cord in cupotomy lysis group was lower markedly than that of model group (P < 0.01), while no significant difference was found between model group and EA group in CCK-8 level in spinal cord (P > 0.05). CONCLUSION: Acupotomy lysis can downregulate SP and CCK-8 contents in hypothalamus and spinal cord, which may contribute to its effect in relieving pain from transverse process syndrome of the third lumbar vertebra.
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Acupuntura , Hipotálamo/metabolismo , Vértebras Lumbares , Sincalida/metabolismo , Enfermedades de la Médula Espinal/metabolismo , Médula Espinal/metabolismo , Sustancia P/metabolismo , Animales , Electroacupuntura , Masculino , Distribución Aleatoria , Ratas , Enfermedades de la Médula Espinal/terapiaAsunto(s)
Derivación Gástrica/efectos adversos , Desnutrición/diagnóstico , Complicaciones Posoperatorias/metabolismo , Enfermedades de la Médula Espinal/metabolismo , Análisis Químico de la Sangre/normas , Sistema Nervioso Central/metabolismo , Sistema Nervioso Central/fisiopatología , Cobre/deficiencia , Suplementos Dietéticos/normas , Humanos , Desnutrición/etiología , Desnutrición/fisiopatología , Ácido Metilmalónico/análisis , Ácido Metilmalónico/sangre , Apoyo Nutricional/normas , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/fisiopatología , Valor Predictivo de las Pruebas , Enfermedades de la Médula Espinal/etiología , Enfermedades de la Médula Espinal/fisiopatología , Deficiencia de Vitamina B 12/diagnóstico , Deficiencia de Vitamina B 12/etiología , Deficiencia de Vitamina B 12/fisiopatologíaRESUMEN
A previously healthy 27-year-old woman developed a subacute myeloneuropathy after receiving nitrous oxide anesthesia for dental procedures. Neurologic evaluation revealed that she was vitamin B(12) deficient due to underlying pernicious anemia. Discontinuation of nitrous oxide and supplementation with vitamin B(12) resulted in dramatic clinical improvement, with near-complete normalization of her neurologic examination. This case and published reports reviewed here emphasize that favorable outcomes are possible following prompt recognition and treatment of vitamin B(12) deficiency.
Asunto(s)
Anemia Perniciosa/fisiopatología , Anestésicos por Inhalación/efectos adversos , Óxido Nitroso/efectos adversos , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Enfermedades de la Médula Espinal/inducido químicamente , Deficiencia de Vitamina B 12/complicaciones , Adulto , Anemia Perniciosa/complicaciones , Anemia Perniciosa/tratamiento farmacológico , Femenino , Humanos , Pierna/inervación , Pierna/fisiopatología , Imagen por Resonancia Magnética , Fibras Nerviosas Mielínicas/metabolismo , Fibras Nerviosas Mielínicas/patología , Enfermedades del Sistema Nervioso Periférico/metabolismo , Enfermedades del Sistema Nervioso Periférico/fisiopatología , Médula Espinal/metabolismo , Médula Espinal/patología , Médula Espinal/fisiopatología , Enfermedades de la Médula Espinal/metabolismo , Enfermedades de la Médula Espinal/fisiopatología , Resultado del Tratamiento , Vitamina B 12/farmacología , Vitamina B 12/uso terapéutico , Deficiencia de Vitamina B 12/tratamiento farmacológico , Deficiencia de Vitamina B 12/metabolismoAsunto(s)
Avitaminosis/fisiopatología , Derivación Gástrica/efectos adversos , Enfermedades Neurodegenerativas/fisiopatología , Obesidad Mórbida/cirugía , Complicaciones Posoperatorias/fisiopatología , Avitaminosis/complicaciones , Avitaminosis/prevención & control , Suplementos Dietéticos/normas , Derivación Gástrica/métodos , Humanos , Enfermedades Neurodegenerativas/etiología , Enfermedades Neurodegenerativas/metabolismo , Obesidad Mórbida/fisiopatología , Enfermedades del Sistema Nervioso Periférico/etiología , Enfermedades del Sistema Nervioso Periférico/metabolismo , Enfermedades del Sistema Nervioso Periférico/fisiopatología , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/metabolismo , Medición de Riesgo , Enfermedades de la Médula Espinal/etiología , Enfermedades de la Médula Espinal/metabolismo , Enfermedades de la Médula Espinal/fisiopatología , Deficiencia de Tiamina/complicaciones , Deficiencia de Tiamina/fisiopatología , Deficiencia de Tiamina/prevención & control , Deficiencia de Vitamina B 12/complicaciones , Deficiencia de Vitamina B 12/fisiopatología , Deficiencia de Vitamina B 12/prevención & control , Encefalopatía de Wernicke/etiología , Encefalopatía de Wernicke/metabolismo , Encefalopatía de Wernicke/fisiopatologíaRESUMEN
OBJECTIVE: To describe a patient with idiopathic zinc overload without an identifiable source and secondary copper deficiency causing myelopolyneuropathy and pancytopenia. DESIGN: Case report. PATIENT AND RESULTS: A 46-year-old man presented with severe bone marrow suppression and subsequently developed progressive myelopathy with sensory ataxia. No identifiable cause of myelopathy was detected, and his neuroimaging findings were unremarkable. Plasma analysis demonstrated a low copper level and an increased zinc level (<10 micro g/dL [<12.6-18.9 micro mol/L] and 184 micro g/dL [28.2 micro mol/L], respectively; normal range for both, 80-120 micro g/dL [12.6-18.9 micro mol/L and 12.3-18.4 micro mol/L, respectively) and a low level of ceruloplasmin. There was no evidence for an external source of zinc. Daily oral supplementation with 2 mg resulted in the prompt reversal of hematologic abnormalities, improved but still subnormal plasma copper levels, and normalization of ceruloplasmin values. The patient's neurologic condition deteriorated further, with worsening of myelopathy and development of polyneuropathy. Analyses of plasma copper and zinc levels demonstrated persisting hyperzincemia and subnormal copper levels during 4 years of follow-up. Increased copper supplementation to 8 mg/d partially reversed his neurologic signs. A clinical investigation of 6 siblings and 1 surviving parent did not identify family members with similar abnormalities. CONCLUSIONS: Persistent hyperzincemia without an identifiable external source appears to be a primary metabolic defect, while copper deficiency is a secondary phenomenon, causing hematologic and neurologic abnormalities. Two unrelated patients with similar idiopathic hyperzincemia and hypocupremia have been recently described. This suggests the existence of a new metabolic disorder with idiopathic zinc overload.
Asunto(s)
Cobre/deficiencia , Pancitopenia/complicaciones , Polineuropatías/complicaciones , Polineuropatías/metabolismo , Enfermedades de la Médula Espinal/complicaciones , Enfermedades de la Médula Espinal/metabolismo , Zinc/sangre , Cobre/sangre , Cobre/uso terapéutico , Humanos , Masculino , Persona de Mediana Edad , Polineuropatías/tratamiento farmacológicoRESUMEN
Degenerative Myelopathy (DM) is a progressive neurological disorder of the spinal cord preferentially occurring in German shepherd dogs. The pathogenesis of the disease is unknown. However, there are indications that vitamin E deficiency may be involved in the pathogenesis of DM. Therefore, we analyzed the expression and the nucleotide sequence of the canine alpha-tocopherol transfer protein (alpha Ttp) of German shepherd dogs with DM in order to determine whether a deficiency or a defect of the alpha Ttp could be a primary factor in the pathogenesis of DM, as found in human patients with Ataxia with vitamin E deficiency (AVED). The cDNA of the coding region of the canine alpha Ttp-mRNA was generated from total liver RNA using RT-PCR and 5' RACE technique. We determined the sequence of 707 out of 834 base pairs or 84.8% of the canine alpha Ttp coding region. Sequence comparison of canine alpha Ttp between affected and control dogs revealed no differences in either nucleotide or predicted amino acid sequence. Using Northern blot analysis alpha Ttp-mRNA expression was solely found in the liver of the dogs, rats and humans, while various other organs showed no alpha Ttp-mRNA expression. No significant differences in expression levels of canine alpha Ttp mRNA were found between DM and control dogs. Our data suggest that the canine alpha Ttp gene is unlikely to be involved in the pathogenesis of DM in German shepherd dogs.
Asunto(s)
Proteínas Portadoras/genética , Enfermedades de los Perros/genética , Enfermedades de la Médula Espinal/veterinaria , Deficiencia de Vitamina E/veterinaria , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Proteínas Portadoras/química , Proteínas Portadoras/metabolismo , ADN Complementario/química , ADN Complementario/genética , Enfermedades de los Perros/metabolismo , Perros , Femenino , Expresión Génica , Hígado/metabolismo , Masculino , Datos de Secuencia Molecular , ARN Mensajero/biosíntesis , ARN Mensajero/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/veterinaria , Homología de Secuencia , Enfermedades de la Médula Espinal/genética , Enfermedades de la Médula Espinal/metabolismo , Deficiencia de Vitamina E/complicaciones , Deficiencia de Vitamina E/genéticaRESUMEN
The ability of serotonin derivatives to stimulate cAMP accumulation in isolated nerve terminals and lumbar enlargement of the spinal cord of normal rats was compared. The effect of the compounds on the intensity of spinal pain syndrome was also assessed. It has been established that substitutes injected into NH2-group of serotonin in 5-OH position attenuate the ability to stimulate cAMP accumulation in synaptosomes, with the effect more pronounced with substitutes of larger volume. A certain correlation between the ability of serotonin derivatives to stimulate adenylate cyclase in vivo and in vitro, on the one hand, and their analgetic effect, on the other hand, is suggested.