RESUMEN
Strokes are feared complications of sickle cell disease (SCD) and yield significant neurologic and neurocognitive deficits. However, even without detectable strokes, SCD patients have significant neurocognitive deficits in domains of learning and memory, processing speed and executive function. In these cases, mechanisms unrelated to major cerebrovascular abnormalities likely underlie these deficits. While oxidative stress and stress-related signaling pathways play a role in SCD pathophysiology, their role in cerebral injury remains unknown. We have shown that Townes and BERK SCD mice, while not having strokes, recapitulate neurocognitive deficits reported in humans. We hypothesized that cognitive deficits in SCD mice are associated with cerebral oxidative stress. We showed that SCD mice have increased levels of reactive oxygen species, protein carbonylation, and lipid peroxidation in hippocampus and cortex, thus suggesting increased cerebral oxidative stress. Further, cerebral oxidative stress was associated with caspase-3 activity alterations and vascular endothelial abnormalities, white matter changes, and disruption of the blood brain barrier, similar to those reported after ischemic/oxidative injury. Additionally, after repeated hypoxia/reoxygenation exposure, homozygous Townes had enhanced microglia activation. Our findings indicate that oxidative stress and stress-induced tissue damage is increased in susceptible brain regions, which may, in turn, contribute to neurocognitive deficits in SCD mice.
Asunto(s)
Anemia de Células Falciformes/patología , Células Endoteliales/patología , Estrés Oxidativo , Sustancia Blanca/patología , Anemia de Células Falciformes/metabolismo , Animales , Encéfalo/metabolismo , Encéfalo/patología , Cognición , Células Endoteliales/metabolismo , Femenino , Humanos , Masculino , Ratones , Sustancia Blanca/metabolismoRESUMEN
BACKGROUND AND OBJECTIVE: Destruction of large segments of peripheral nerves results in chronic loss of sensation and paralysis. For this type of severe injury, the defect can be bridged by nerve grafts. However, even with state-of-the-art microsurgical techniques, there is minimal recovery of sensation and motor function. Light therapy (LT) has been shown to improve functional outcome after surgical intervention to repair injured nerves using different techniques. Our objective was to investigate the effect of LT on peripheral nerve regeneration and function after severe median nerve injury and microsurgical autologous nerve graft repair using fibrin glue. STUDY DESIGN/MATERIALS AND METHODS: Adult female Sprague Dawley rats were used for this study. A 6-7 mm segment of the median nerve was excised and sural nerve segments from the same animal were used to bridge the gap using fibrin-based sealant. There were three experimental groups: control, autograft (AG), and autograft + LT (AG + LT). The AG + LT group received LT at the surgery site for 14 consecutive days using an 810 nm wavelength diode laser. Functional recovery was assessed bi-weekly by the grip strength test. Compound muscle action potential (CMAP) measurements were taken pre-injury and at 16 weeks post-surgery. Optical density measurement of S-100 immunoreactivity was done on the transplanted segment of the nerve. RESULTS: The AG + LT group had faster functional recovery of grip strength (P < 0.05), shorter CMAP latency (P < 0.05), and higher S-100 immunoreactivity (P = 0.0213) when compared to the AG group. However, at 15 weeks, grip strength in both the AG and AG + LT groups, while significantly improved, were still below control levels. CONCLUSION: These results suggest that LT can accelerate functional recovery and improve the quality of nerve regeneration after autograft repair of severely injured peripheral nerves.
Asunto(s)
Láseres de Semiconductores/uso terapéutico , Nervio Mediano/lesiones , Nervio Mediano/cirugía , Regeneración Nerviosa/efectos de la radiación , Nervios Periféricos/trasplante , Animales , Femenino , Puntaje de Gravedad del Traumatismo , Ratas , Ratas Sprague-DawleyRESUMEN
BACKGROUND AND OBJECTIVE: Familial amyotrophic lateral sclerosis (FALS) is a neurodegenerative disease characterized by progressive loss of motor neurons and death. Mitochondrial dysfunction and oxidative stress play an important role in motor neuron loss in ALS. Light therapy (LT) has biomodulatory effects on mitochondria. Riboflavin improves energy efficiency in mitochondria and reduces oxidative injury. The purpose of this study was to examine the synergistic effect of LT and riboflavin on the survival of motor neurons in a mouse model of FALS. STUDY DESIGN/MATERIALS AND METHODS: G93A SOD1 transgenic mice were divided into four groups: Control, Riboflavin, Light, and Riboflavin+Light (combination). Mice were treated from 51 days of age until death. A single set of LT parameters was used: 810 nm diode laser, 140-mW output power, 1.4 cm(2) spot area, 120 seconds treatment duration, and 12 J/cm(2) energy density. Behavioral tests and weight monitoring were done weekly. At end stage of the disease, mice were euthanized, survival data was collected and immunohistochemistry and motor neuron counts were performed. RESULTS: There was no difference in survival between groups. Motor function was not significantly improved with the exception of the rotarod test which showed significant improvement in the Light group in the early stage of the disease. Immunohistochemical expression of the astrocyte marker, glial fibrilary acidic protein, was significantly reduced in the cervical and lumbar enlargements of the spinal cord as a result of LT. There was no difference in the number of motor neurons in the anterior horn of the lumbar enlargement between groups. CONCLUSIONS: The lack of significant improvement in survival and motor performance indicates study interventions were ineffective in altering disease progression in the G93A SOD1 mice. Our findings have potential implications for the conceptual use of light to treat other neurodegenerative diseases that have been linked to mitochondrial dysfunction.
Asunto(s)
Esclerosis Amiotrófica Lateral/tratamiento farmacológico , Esclerosis Amiotrófica Lateral/radioterapia , Láseres de Semiconductores/uso terapéutico , Terapia por Luz de Baja Intensidad , Riboflavina/uso terapéutico , Complejo Vitamínico B/uso terapéutico , Esclerosis Amiotrófica Lateral/etiología , Animales , Terapia Combinada , Modelos Animales de Enfermedad , Ratones , Ratones Transgénicos , Superóxido Dismutasa , Superóxido Dismutasa-1RESUMEN
BACKGROUND: Subacute combined degeneration is an acquired myelopathy caused by vitamin B12 deficiency. Therapy with B12 leads to improvement in most but to complete recovery in only a few patients. Prognostic indicators in subacute combined degeneration are unknown; therefore, predicting complete recovery of neurologic deficits is challenging. PURPOSE: To identify potential correlates of outcome and to generate hypotheses concerning predictors of complete resolution of neurologic deficits in subacute combined degeneration. DATA SOURCE: We searched EMBASE (1974 to October 2005), MEDLINE (1968 to October 2005), and references from identified reports. REPORTS SELECTION: Reports of patients with subacute combined degeneration containing results of magnetic resonance imaging (MRI) and description of outcome and 1 patient treated by the authors. DATA EXTRACTION, SYNTHESIS: We extracted data from 45 reports and 57 patients (36 males, 21 females; age range: 10 to 81) with a diagnosis of subacute combined degeneration, and estimated the strength of association between clinical, laboratory, and radiological factors and complete resolution of signs and symptoms. RESULTS: Eight patients (14%) achieved clinical resolution and 49 (86%) improved with B12 therapy. The absence of sensory dermatomal deficit, Romberg, and Babinski signs were associated with a higher complete resolution rate. Patients with MRI lesions in < or = 7 segments and age less than 50 also appear to have higher rates of complete resolution. CONCLUSIONS: B12 therapy is reported to stop progression and improve neurologic deficits in most patients with subacute combined degeneration. However, complete resolution only occurs in a small percentage of patients and appears to be associated with factors suggestive of less severe disease at the time of diagnosis.
Asunto(s)
Enfermedades de la Médula Espinal/diagnóstico por imagen , Deficiencia de Vitamina B 12/diagnóstico por imagen , Vitamina B 12/uso terapéutico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Intervalos de Confianza , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Radiografía , Estudios Retrospectivos , Enfermedades de la Médula Espinal/tratamiento farmacológico , Resultado del Tratamiento , Deficiencia de Vitamina B 12/tratamiento farmacológicoRESUMEN
OBJECTIVE: The Adult Myopathy Assessment Tool (AMAT) is a 13-item performance-based battery developed to assess functional status and muscle endurance. The purpose of this study was to determine the intrarater and interrater reliability of the AMAT in adults with myositis. METHODS: Nineteen raters (13 physical therapists and 6 physicians) scored videotaped recordings of patients with myositis performing the AMAT for a total of 114 tests and 1,482 item observations per session. Raters rescored the AMAT test and item observations during a followup session (mean ± SD 19 ± 6 days between scoring sessions). All raters completed a single, self-directed, electronic training module prior to the initial scoring session. RESULTS: Intrarater and interrater reliability correlation coefficients were ≥0.94 for the AMAT functional subscale, endurance subscale, and total score (all P < 0.02 for Ho , ρ ≤0.75). All AMAT items had satisfactory intrarater agreement (kappa statistics with Fleiss-Cohen weights, with values κw = 0.57-1.00). Interrater agreement was acceptable for each AMAT item (κ = 0.56-0.89) except the sit up (κ = 0.16). The standard error of measurement and 95% confidence interval range for the AMAT total scores did not exceed 2 points across all observations (AMAT total score range 0-45). CONCLUSION: The AMAT is a reliable, domain-specific assessment of functional status and muscle endurance for adult subjects with myositis. Results of this study suggest that physicians and physical therapists may reliably score the AMAT following a single training session. The AMAT functional subscale, endurance subscale, and total score exhibit interrater and intrarater reliability suitable for clinical and research use.
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Miositis/diagnóstico , Miositis/fisiopatología , Fisioterapeutas/normas , Médicos/normas , Adulto , Humanos , Enfermedades Musculares/diagnóstico , Enfermedades Musculares/fisiopatología , Reproducibilidad de los ResultadosRESUMEN
Analysis for GNE mutations was performed in an American, non-Iranian Jewish, family with quadriceps-sparing inclusion body myopathy (QS-IBM) and in 11 patients with sporadic IBM (s-IBM). Two novel nonallosteric site missense mutations were found in the QS-IBM kinship. No mutations were identified in s-IBM patients. After 8 years of follow-up and severe disease progression, the quadriceps muscle in the QS-IBM patient remains strong despite subclinical involvement documented with repeat MRI and muscle biopsy.
Asunto(s)
Carbohidrato Epimerasas/genética , Proteínas de Escherichia coli , Músculo Esquelético/patología , Mutación/genética , Miositis por Cuerpos de Inclusión/genética , Miositis por Cuerpos de Inclusión/patología , Adulto , Clonación Molecular , Progresión de la Enfermedad , Exones/genética , Femenino , Estudios de Seguimiento , Genotipo , Humanos , Imagen por Resonancia Magnética , Debilidad Muscular/genética , Debilidad Muscular/patología , Linaje , Polimorfismo Conformacional Retorcido-Simple , ARN/genética , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
Evidence suggests that sensory loss may occur in a proportion of patients affected by poliomyelitis. We hypothesize that sensory problems may be a lasting sequela in some polio survivors. Sensory pathways in polio survivors were evaluated clinically and electrophysiologically using sensory evoked potentials (SEPs). Patients with sensory deficits or abnormal SEPs were further evaluated by magnetic resonance imaging (MRI). Twenty-two patients were studied. The mean age was 64.7 years (age range: 56-81 years). Clinically, sensory impairments were found in 4 patients. Upper limb SEPs were normal. Lower limb SEPs were abnormal in 10 patients. In 1 patient, clinical and electrographic findings correlated with a patch of atrophy in the spinal cord, as shown by MRI. Sensory derangements may be found in a proportion of aging polio survivors. SEP studies may add sensitivity when evaluating sensory function in this cohort. It remains unclear whether these sensory abnormalities are related to remote poliomyelitis. Further studies are necessary.
Asunto(s)
Potenciales Evocados Somatosensoriales/fisiología , Poliomielitis/complicaciones , Síndrome Pospoliomielitis/diagnóstico , Trastornos de la Sensación/diagnóstico , Trastornos de la Sensación/etiología , Médula Espinal/fisiopatología , Sobrevivientes , Vías Aferentes/patología , Vías Aferentes/fisiopatología , Anciano , Anciano de 80 o más Años , Atrofia/etiología , Atrofia/patología , Atrofia/fisiopatología , Encéfalo/patología , Encéfalo/fisiopatología , Estudios de Cohortes , Evaluación de la Discapacidad , Progresión de la Enfermedad , Estimulación Eléctrica/métodos , Electroencefalografía/métodos , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Conducción Nerviosa/fisiología , Síndrome Pospoliomielitis/fisiopatología , Trastornos de la Sensación/fisiopatología , Células Receptoras Sensoriales/fisiología , Índice de Severidad de la Enfermedad , Médula Espinal/patologíaRESUMEN
We hypothesized that the corticospinal system undergoes functional changes in long-term polio survivors. Central motor conduction times (CMCTs) to the four limbs were measured in 24 polio survivors using transcranial magnetic stimulation (TMS). Resting motor thresholds and CMCTs were normal. In 17 subjects whose legs were affected by polio and 13 healthy controls, single- and paired-pulse TMS was used to assess motor cortex excitability while recording from tibialis anterior (TA) muscles at rest and following maximal contraction until fatigue. In polio survivors the slope of the recruitment curve was normal, but maximal motor evoked potentials (MEPs) were larger than in controls. MEPs were depressed after fatiguing exercise. Three patients with central fatigue by twitch interpolation had a trend toward slower recovery. There was no association with symptoms of post-polio syndrome. These changes occurring after polio may allow the motor cortex to activate a greater proportion of the motor neurons innervating affected muscles.
Asunto(s)
Potenciales Evocados Motores/fisiología , Corteza Motora/fisiopatología , Síndrome Pospoliomielitis/patología , Anciano , Relación Dosis-Respuesta en la Radiación , Estimulación Eléctrica/métodos , Electromiografía , Fatiga , Femenino , Humanos , Masculino , Persona de Mediana Edad , Corteza Motora/virología , Músculo Esquelético/inervación , Conducción Nerviosa/fisiología , Conducción Nerviosa/efectos de la radiación , Inhibición Neural/fisiología , Inhibición Neural/efectos de la radiación , Resistencia Física , Estimulación Magnética Transcraneal/métodosRESUMEN
OBJECTIVE: To examine the applicability and validity of traditional fatigue questionnaires in postpoliomyelitis syndrome (PPS) patients with disabling fatigue. DESIGN: Cross-sectional study. PPS and disabling fatigue were ascertained according to published criteria. Descriptiveness was determined using the McNemar test, and interscale z-score agreement was estimated with Pearson's coefficients. SETTING: PPS clinic. PARTICIPANTS: Fifty-six survivors of poliomyelitis: 39 met criteria for PPS, 25 of whom met criteria for disabling fatigue. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The Fatigue Severity Scale (FSS), visual analog scale (VAS) for fatigue, and Fatigue Impact Scale (FIS). RESULTS: Twenty-four patients scored 50% or higher on the scale range for FSS, compared with 19 patients for VAS for fatigue (P=.042), and 7 patients for FIS (P<.001). Scores for patients with disabling fatigue averaged 81.5%, 62%, and 40.9% of the scale range for FSS, VAS for fatigue, and FIS, respectively. Agreement was moderate between the FSS and VAS for fatigue (r=.45, P=.02), but low between FSS and FIS (r=.29, P=.15), and FIS and VAS for fatigue (r=.20, P=.33). Two sample t tests showed significant differences between those with disabling fatigue and those without, based on FSS scores (t=3.8, P<.001), but not for VAS for fatigue or FIS scores. CONCLUSIONS: FSS was the most descriptive of the instruments tested. Scores generated by the scales were not interchangeable. Of the 3 scales, FFS seemed to be the most informative for the clinical assessment of fatigue in patients with PPS.
Asunto(s)
Fatiga/clasificación , Síndrome Pospoliomielitis/fisiopatología , Adulto , Anciano , Anciano de 80 o más Años , Estudios Transversales , Fatiga/etiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Dimensión del Dolor , Síndrome Pospoliomielitis/complicaciones , Índice de Severidad de la Enfermedad , Encuestas y CuestionariosRESUMEN
A patient developed an adult-onset dermatomyositis-like syndrome characterized by skin rash and progressive proximal muscle weakness concurrent with the intake of simvastatin. Despite discontinuation of the statin, symptoms progressed and required conventional steroid therapy for remission. The association between statins and the development of a musculocutaneous syndrome closely resembling dermatomyositis in susceptible subjects is poorly understood and has been reported rarely. The purpose of this report is to provide additional support for this pathological association. Since the population receiving statins is large and rapidly growing, caregivers are urged to be alert regarding the early recognition and proper care of the spectrum of neuromuscular complications linked to statin intake.
Asunto(s)
Dermatomiositis/inducido químicamente , Inhibidores de Hidroximetilglutaril-CoA Reductasas/efectos adversos , Anciano , Dermatomiositis/patología , Humanos , Masculino , SíndromeRESUMEN
Stiff-person syndrome (SPS) is a progressive neurologic disorder characterized by 1) stiffness that is prominent in axial muscles, with co-contraction of agonist and antagonist muscles; 2) sudden episodic spasms; and 3) absence of another disease that causes similar symptoms. The diagnosis of SPS is based on clinical grounds and requires a high degree of suspicion. The diagnosis is, however, aided by electromyography, which demonstrates motor unit firing at rest simultaneously from the agonist and antagonist muscles, and by high serum titers of antibodies against glutamic acid decarboxylase (GAD), the rate-limiting enzyme for the synthesis of gamma-aminobutyric acid (GABA), which is the brain's main inhibitory neurotransmitter. The reduced GABA level in the brain and cerebrospinal fluid explains the patients' stiffness and justifies the clinical improvement observed by drugs enhancing GABAergic transmission. The association of SPS with other autoimmune disorders or autoantibodies, the intrathecal GAD-specific immunoglobulin G antibody synthesis, and the suppression of GABA by the patient's antibodies supports the autoimmune nature of SPS and justifies the use of immunotherapies. At present, GABA-enhancing agents, such as benzodiazepines, valproate, vigabatrin, tiagabine, gabapentin, and baclofen, provide symptomatic relief. Plasmapheresis, steroids, and periodic intravenous immunoglobulin infusions provide additional and lasting benefit. In this article, the treatment options for patients with SPS are discussed based on the authors' experience and that of others. The beneficial effects from the first controlled study conducted in SPS using intravenous immunoglobulin are presented.