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Objective: Spinal and bulbar muscular atrophy is characterized by slow-progressive muscle weakness, decreased functional performance and falls. Research into the use of exercise in spinal and bulbar muscular atrophy has shown equivocal to negative results, although authors suggest that patients with spinal and bulbar muscular atrophy may benefit from both increased exercise intensity and shorter bout duration. The aim of this case report is to explore the safety of a moderate intensity strength training programme coupled with dynamic balance and function-specific training in a patient with spinal and bulbar muscular atrophy. Case report: A 56-year-old man with spinal and bulbar muscular atrophy presented with multiple falls and declining performance in physical, vocational, and recreational activities. Examination revealed several musculoskeletal impairments that were sub-clinical to mild compared with an SBMA natural history cohort. Intervention and outcome: A 15-week moderate intensity exercise programme combining weight-lifting and functional exercises was performed under clinical supervision. Exercise volume, frequency and intensity were adjusted based on patient-reported outcomes and muscle damage blood markers. Performance-based and self-reported functional improvements occurred that exceeded the minimal clinically important difference. The intervention was well tolerated and the patient nearly doubled his baseline 10-repetition maximums for weight-lifting exercises. Conclusion: Exercise therapy combining weight-lifting and upright functional training led to meaningful performance improvements in this case of a patient with spinal and bulbar muscular atrophy and relatively low disease burden.
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OBJECTIVE: To compare muscle ultrasound (MUS) parameters in patients with juvenile JDM and healthy controls, and examine their association with JDM disease activity measures and MRI. METHODS: MUS of the right mid-rectus femoris was performed in 21 patients with JDM meeting probable or definite Bohan and Peter criteria and 28 demographically matched healthy control subjects. MUS parameters were quantitated by digital image processing and correlated with JDM disease activity measures and semi-quantitative thigh MRI short tau inversion recovery (STIR) and T1 scores. RESULTS: Rectus femoris MUS echogenicity was increased (median 47.8 vs 38.5, P = 0.002) in patients with JDM compared with controls. Rectus femoris MUS echogenicity correlated with Physician Global Activity (PGA), Manual Muscle Testing (MMT), and Childhood Myositis Assessment Scale (CMAS) (rs 0.4-0.54). Some MUS parameters correlated with functional quantitative measures of muscle strength: resting RF area on MUS strongly correlated with knee extension quantitative muscle testing (rs 0.76), and contracted area correlated with proximal MMT, knee extension quantitative muscle testing, and CMAS (rs 0.71-0.80). MUS echogenicity correlated with both STIR and T1 MRI (rs 0.43), and T1 MRI correlated inversely with RF contracted area (rs -0.49) on MUS. There were differences in pre- and post-exercise vascular power and colour Doppler on MUS in patients with JDM vs controls, with the percentage change of post-exercise vascular power Doppler lower in JDM compared with controls (7.1% vs 100.0%). CONCLUSIONS: These data suggest MUS may be a valuable imaging modality to assess JDM disease activity and damage.
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Dermatomiositis , Niño , Dermatomiositis/complicaciones , Humanos , Imagen por Resonancia Magnética/métodos , Fuerza Muscular , Músculo Esquelético/diagnóstico por imagen , UltrasonografíaRESUMEN
INTRODUCTION: Spinal and bulbar muscular atrophy (SBMA) is a neuromuscular disorder that leads to progressive weakness of bulbar and extremity muscles. Dynamic balance during functional tasks has not been reported in people with SBMA. OBJECTIVES: (1) To evaluate the ability to safely complete a forward lunge (FL), step quick turn (SQT), and step up and over (SUO), (2) to determine the presence and severity of dynamic balance impairments by comparing performance to normative data, and (3) to investigate the relationship between lower extremity strength and ability to complete each task. DESIGN: Cross-sectional analysis. Participants. Fifty-three people with SBMA were included in a cross-sectional analysis. Normative datasets provided by the NeuroCom manufacturer and isometric strength literature facilitated patient comparisons. Outcome Measures. Force plate-based dynamic balance measures included FL (distance, impact index, contact time, and force impulse), SQT (turn time and turn sway), and SUO (lift up index, movement time, and impact index). Maximal isometric contractions of knee extensors, ankle dorsiflexors, ankle plantar flexors, and hip extensors were measured with fixed frame dynamometry. RESULTS: The most difficult test, per completion rate, was SUO (52%), followed by FL (57%) and SQT (65%). t-tests revealed significant abnormalities in eight of nine balance variables (p < 0.05) accompanied by large Cohen's D effect sizes ≥ 0.8. Receiver operating characteristics analysis showed knee extensor (SUO 95% CI =0.78-1.00, SQT 95% CI =0.64-0.92) and ankle plantar flexor strength (SUO 95%CI = 0.75-0.99, SQT 95%CI = 0.64 - 0.92) significantly discriminated the ability to perform SUO and SQT tests with acceptable to excellent areas under the curve. CONCLUSIONS: Considerable dynamic balance abnormalities were observed. Lower extremity strength helps explain low test completion rates. Patients modified task movement patterns, enabling safe task performance. Study results can help direct patient care and future protocol design for people with SBMA.
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PURPOSE: To evaluate the safety and efficacy of N-acetylmannosamine (ManNAc) in GNE myopathy, a genetic muscle disease caused by deficiency of the rate-limiting enzyme in N-acetylneuraminic acid (Neu5Ac) biosynthesis. METHODS: We conducted an open-label, phase 2, single-center (NIH, USA) study to evaluate oral ManNAc in 12 patients with GNE myopathy (ClinicalTrials.gov NCT02346461). Primary endpoints were safety and biochemical efficacy as determined by change in plasma Neu5Ac and sarcolemmal sialylation. Clinical efficacy was evaluated using secondary outcome measures as part of study extensions, and a disease progression model (GNE-DPM) was tested as an efficacy analysis method. RESULTS: Most drug-related adverse events were gastrointestinal, and there were no serious adverse events. Increased plasma Neu5Ac (+2,159 nmol/L, p < 0.0001) and sarcolemmal sialylation (p = 0.0090) were observed at day 90 compared to baseline. A slower rate of decline was observed for upper extremity strength (p = 0.0139), lower extremity strength (p = 0.0006), and the Adult Myopathy Assessment Tool (p = 0.0453), compared to natural history. Decreased disease progression was estimated at 12 (γ = 0.61 [95% CI: 0.09, 1.27]) and 18 months (γ = 0.55 [95% CI: 0.12, 1.02]) using the GNE-DPM. CONCLUSION: ManNAc showed long-term safety, biochemical efficacy consistent with the intended mechanism of action, and preliminary evidence clinical efficacy in patients with GNE myopathy.
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Miopatías Distales , Enfermedades Musculares , Adulto , Hexosaminas , Humanos , Enfermedades Musculares/inducido químicamente , Enfermedades Musculares/tratamiento farmacológico , Enfermedades Musculares/genética , Ácido N-AcetilneuramínicoRESUMEN
OBJECTIVE: To characterize muscle involvement and evaluate disease severity in patients with GNE myopathy using skeletal muscle MRI and proton magnetic resonance spectroscopy (1H-MRS). METHODS: Skeletal muscle imaging of the lower extremities was performed in 31 patients with genetically confirmed GNE myopathy, including T1-weighted and short tau inversion recovery (STIR) images, T1 and T2 mapping, and 1H-MRS. Measures evaluated included longitudinal relaxation time (T1), transverse relaxation time (T2), and 1H-MRS fat fraction (FF). Thigh muscle volume was correlated with relevant measures of strength, function, and patient-reported outcomes. RESULTS: The cohort was representative of a wide range of disease progression. Contractile thigh muscle volume ranged from 5.51% to 62.95% and correlated with thigh strength (r = 0.91), the 6-minute walk test (r = 0.82), the adult myopathy assessment tool (r = 0.83), the activities-specific balance confidence scale (r = 0.65), and the inclusion body myositis functional rating scale (r = 0.62). Four stages of muscle involvement were distinguished by qualitative (T1W and STIR images) and quantitative methods: stage I: unaffected muscle (T1 = 1,033 ± 74.2 ms, T2 = 40.0 ± 1.9 ms, FF = 7.4 ± 3.5%); stage II: STIR hyperintense muscle with minimal or no fat infiltration (T1 = 1,305 ± 147 ms, T2 = 50.2 ± 3.5 ms, FF = 27.6 ± 12.7%); stage III: fat infiltration and STIR hyperintensity (T1 = 1,209 ± 348 ms, T2 = 73.3 ± 12.6 ms, FF = 57.5 ± 10.6%); and stage IV: complete fat replacement (T1 = 318 ± 39.9 ms, T2 = 114 ± 21.2 ms, FF = 85.6 ± 4.2%). 1H-MRS showed a significant decrease in intramyocellular lipid and trimethylamines between stage I and II, suggesting altered muscle metabolism at early stages. CONCLUSION: MRI biomarkers can monitor muscle involvement and determine disease severity noninvasively in patients with GNE myopathy. CLINICALTRIALSGOV IDENTIFIER: NCT01417533.
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Miopatías Distales/diagnóstico por imagen , Metabolismo de los Lípidos , Fuerza Muscular , Músculo Esquelético/diagnóstico por imagen , Adulto , Anciano , Progresión de la Enfermedad , Miopatías Distales/metabolismo , Miopatías Distales/patología , Miopatías Distales/fisiopatología , Femenino , Músculos Isquiosurales/diagnóstico por imagen , Músculos Isquiosurales/metabolismo , Músculos Isquiosurales/patología , Músculos Isquiosurales/fisiopatología , Humanos , Pierna , Lípidos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Complejos Multienzimáticos/genética , Músculo Esquelético/metabolismo , Músculo Esquelético/patología , Músculo Esquelético/fisiopatología , Tamaño de los Órganos , Medición de Resultados Informados por el Paciente , Espectroscopía de Protones por Resonancia Magnética , Músculo Cuádriceps/diagnóstico por imagen , Músculo Cuádriceps/metabolismo , Músculo Cuádriceps/patología , Índice de Severidad de la Enfermedad , Muslo , Prueba de Paso , Adulto JovenRESUMEN
Cancer-related fatigue (CRF) is commonly reported by patients both during and after receiving treatment for cancer. Current CRF diagnoses rely on self-report questionnaires which are subject to report and recall biases. Objective measurements using a handheld dynamometer, or handgrip device, have been shown in recent studies to correlate significantly with subjective self-reported fatigue scores. However, variations of both the handgrip fatigue test and fatigue index calculations exist in the literature. The lack of standardized methods limits the utilization of the handgrip fatigue test in the clinical and research settings. In this study, we provide detailed methods for administering the physical fatigue test and calculating the fatigue index. These methods should supplement existing self-reported fatigue questionnaires and help clinicians assess fatigue symptom severity in an objective and quantitative manner.
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Fatiga/diagnóstico , Fuerza de la Mano , Prostatectomía/efectos adversos , Neoplasias de la Próstata/cirugía , Índice de Severidad de la Enfermedad , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Fatiga/etiología , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Neoplasias de la Próstata/patología , Adulto JovenRESUMEN
INTRODUCTION: Spinal and bulbar muscular atrophy is a progressive neuromuscular disease that leads to muscle weakness and reduced physical function. Benefits of physical therapy for people with spinal and bulbar muscular atrophy have not been reported in the literature. CASE REPORT: A 62-year-old male patient with spinal and bulbar muscular atrophy reported falling, difficulty walking and completing upright tasks, and showed clinical signs of low baseline function on examination. Transportation challenges made it difficult for this patient to attend frequent one-on-one physical therapy sessions. INTERVENTIONS AND OUTCOMES: A minimally supervised home-based exercise intervention was chosen with the goal of safely improving his functional capacity. The 5-visit clinical intervention, spread over 10 months, provided 3 exercise modules: seated-to-standing postural alignment and core muscle activation; upright functional and endurance training; and balance training and rhythmic walking. Post-intervention the patient had increased lower extremity muscle strength, improved balance, and reduced self-reported fatigue. CONCLUSION: Home-based exercises were well tolerated with no increase in creatine kinase. Multiple clinical measures of strength and function improved, possibly related to the patients' excellent motivation and compliance with the programme. Promising utilization of a minimally supervised home-based programme is described here.
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BACKGROUND: Cancer-related fatigue (CRF) is a debilitating symptom frequently reported by patients during and after treatment for cancer. CRF is a multidimensional experience and is often solely assessed by self-report measures. The goal of the study is to examine the physical and cognitive aspects of self-reported CRF using a cognitive function test and a physical fatigue index in order to provide objective measures that can characterize the CRF phenotype. METHODS: A total of 59 subjects with nonmetastatic prostate cancer receiving external beam radiation therapy were included in the study. Fatigue was measured using the Functional Assessment of Cancer Therapy-Fatigue (FACT-F) questionnaire. Cognitive characteristics of CRF was measured using the Stroop Color-Word Interference computerized test and the motor aspect of fatigue was measured using the static fatigue test using a handgrip dynamometer. FINDINGS: Functional Assessment of Cancer Therapy-Fatigue scores significantly correlated with the Stroop Interference score, but not performance accuracy in all test conditions. Fatigued subjects exhibited a more rapid decline to 50% of maximal strength and increased static fatigue index in the handgrip test, whereas maximal grip strength was not affected. CONCLUSIONS: The results suggest that CRF exhibits both cognitive and physical characteristics. Subjective fatigue was associated with increased time required to overcome cognitive interference, but not cognitive performance accuracy. Fatigued patients exhibited decreased physical endurance and the ability to sustain maximal strength over time. These objective measures may serve as valuable tools for clinicians to detect cognitive and physical impairment associated with CRF.
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Cognición , Fatiga/psicología , Fuerza de la Mano , Neoplasias de la Próstata/psicología , Anciano , Humanos , Masculino , Persona de Mediana Edad , Fenotipo , Neoplasias de la Próstata/radioterapia , Test de StroopRESUMEN
OBJECTIVE: To investigate in a pilot study the safety and efficacy of infliximab in patients with refractory dermatomyositis (DM) and polymyositis (PM). METHODS: A randomized, double-blind, placebo-controlled trial including subjects with active DM or PM. Participants had stable doses of immunosuppressive medication and prednisone (≤0.5mg/kg/day), and exhibited clinical signs of muscle weakness for at least 4 weeks prior to study entry. Participants received infusions of either placebo or infliximab 5mg/kg at 0, 2, 6, and 14 weeks in blinded manner. The primary outcome was a ≥15% manual muscle strength (MMT) improvement at week 16 compared to week 0. The secondary outcome measures were improvement defined by the International Myositis Assessment and Clinical Studies Group (IMACS) criteria. At week 16, responders in each arm had the option of either continuing the same treatment or changing to the non-responder treatment for that study arm. Non-responders in the 5mg/kg infliximab arm were increased to infliximab 7.5mg/kg for weeks 22, 30, and 38. Non-responders in the placebo arm at week 16 received infliximab 5mg/kg at weeks 16, 18, 22, 30, and 38. Outcomes were reassessed at week 40. RESULTS: Twelve subjects completed the study to week 16. Six of the 12 subjects received infliximab treatment at the dose of 5mg/kg with only one subject meeting the responder criteria at that dose. Of the remaining five subjects on infliximab, three crossed over to the infliximab 7.5mg/kg dose. One of those three subjects responded. All six patients in the placebo arm crossed over to the 5mg/kg dosing regimen after week 16, and two of those responded to infliximab. CONCLUSIONS: Infliximab therapy for patients with refractory PM and DM was well tolerated and may benefit a subset of patients.
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Fármacos Dermatológicos/uso terapéutico , Dermatomiositis/tratamiento farmacológico , Inmunosupresores/uso terapéutico , Infliximab/uso terapéutico , Adulto , Estudios Cruzados , Método Doble Ciego , Esquema de Medicación , Quimioterapia Combinada , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Prednisona/uso terapéutico , Resultado del TratamientoRESUMEN
BACKGROUND: The aim of this analysis was to evaluate the psychometric properties of three patient reported outcome (PRO) measures characterizing physical function in GNE myopathy: the Human Activity Profile, the Inclusion Body Myositis Functional Rating Scale, and the Activities-specific Balance Confidence scale. METHODS: This analysis used data from 35 GNE myopathy subjects participating in a natural history study. For construct validity, correlational and known-group analyses were between the PROs and physical assessments. Reliability of the PROs between baseline and 6 months was evaluated using the intra-class correlation coefficient model; internal consistency was tested with Cronbach's alpha. RESULTS: The hypothesized moderate positive correlations for construct validity were supported; the strongest correlation was between the human activity profile adjusted activity score and the adult myopathy assessment endurance subscale score (r = 0.81; p < 0.0001). The PROs were able to discriminate between known high and low functioning groups for the adult myopathy assessment tool. Internal consistency of the PROs was high (α > 0.8) and there was strong reliability (ICC >0.62). CONCLUSION: The PROs are valid and reliable measures of physical function in GNE myopathy and should be incorporated in investigations to better understand the impact of progressive muscle weakness on physical function in this rare disease population. Implications for Rehabilitation GNE myopathy is a rare muscle disease that results in slow progressive muscle atrophy and weakness, ultimately leading to wheelchair use and dependence on a caregiver. There is limited knowledge on the impact of this disease on the health-related quality of life, specifically physical function, of this rare disease population. Three patient reported outcomes have been shown to be valid and reliable in GNE myopathy subjects and should be incorporated in future investigations to better understand how progressive muscle weakness impacts physical functions in this rare disease population. The patient reported outcome scores of GNE myopathy patients indicate a high risk for falls and impaired physical functioning, so it is important clinicians assess and provide interventions for these subjects to maintain their functional capacity.
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Accidentes por Caídas/prevención & control , Evaluación de la Discapacidad , Miopatías Distales , Psicometría/métodos , Calidad de Vida , Actividades Cotidianas , Adulto , Progresión de la Enfermedad , Miopatías Distales/fisiopatología , Miopatías Distales/psicología , Miopatías Distales/rehabilitación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Debilidad Muscular/diagnóstico , Debilidad Muscular/etiología , Medición de Resultados Informados por el Paciente , Reproducibilidad de los Resultados , Medición de Riesgo , Silla de Ruedas/estadística & datos numéricosRESUMEN
BACKGROUND: GNE myopathy is a rare genetic disease characterized by progressive muscle atrophy and weakness. It is caused by biallelic mutations in the GNE gene that encodes for the bifunctional enzyme, uridine diphosphate (UDP)-N-acetylglucosamine (GlcNAc) 2-epimerase/N-acetylmannosamine (ManNAc) kinase. Typical characteristics of GNE myopathy include progressive myopathy, first involving anterior tibialis muscle and sparing the quadriceps, and rimmed vacuoles on muscle biopsy. Identifying biallelic mutations by sequencing of the GNE gene confirms the diagnosis of GNE myopathy. In a subset of patients, diagnostic confirmation is challenged by the identification of mutations in only one allele, suggesting mutations in deep intronic regions or regulatory regions. METHODS: We performed targeted sequencing and copy number variant (CNV) analysis of GNE in two siblings who clinically presented with GNE myopathy. Further molecular and biochemical studies were done to characterize the effect of a previously uncharacterized GNE mutation. RESULTS: We report two siblings of Indian descent with characteristic features of GNE myopathy, including progressive skeletal muscle weakness initially involving the anterior tibialis, and rimmed vacuoles on muscle biopsy, in which a heterozygous mutation, p.Val727Met, was identified in both affected siblings, but no other deleterious variants in either coding region or exon-intron boundaries of the gene. Subsequent insertion/deletion analysis identified a novel 11.3-kb deletion (Chr9 [GRCh37]: g.36257583_36268910del) encompassing the GNE promoter region, with breakpoints residing in Alu repeats. Gene expression analysis revealed reduced GNE mRNA and protein levels, confirming decreased expression of the deleted allele harboring the deletion. CONCLUSIONS: We have identified GNE as one of the genes susceptible to Alu-mediated recombination. Our findings suggest that the deletion may encompass the promoter or another region necessary for GNE expression. In patients with typical manifestations of GNE myopathy and a single GNE variant identified, copy number variant (CNV) analysis may be useful in arriving at the diagnosis.
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Spinal and bulbar muscular atrophy is caused by polyglutamine expansion in the androgen receptor. As an X-linked disease dependent on androgens, symptoms and findings are only fully manifest in males. Here we describe a 40-year-old male-to-female transgender SBMA patient who developed full disease manifestations despite undetectable levels of androgens. We used cell culture and animal models to show that spironolactone, the anti-androgen she had taken for 15 years, promotes nuclear localization and toxicity of the mutant protein, which may explain the disease manifestations in this patient.
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Antagonistas de Andrógenos/farmacología , Atrofia Bulboespinal Ligada al X/prevención & control , Procedimientos de Reasignación de Sexo/métodos , Espironolactona/farmacología , Transexualidad/terapia , Antagonistas de Andrógenos/efectos adversos , Animales , Modelos Animales de Enfermedad , Drosophila , Femenino , Humanos , Masculino , Ratas , Espironolactona/efectos adversosRESUMEN
OBJECTIVE: This study examines the utility of MRI, including T2 maps and T2 maps corrected for muscle fat content, in evaluating patients with idiopathic inflammatory myopathy. METHODS: A total of 44 patients with idiopathic inflammatory myopathy, 18 of whom were evaluated after treatment with rituximab, underwent MRI of the thighs and detailed clinical assessment. T2, fat fraction (FF) and fat corrected T2 (fc-T2) maps were generated from standardized MRI scans, and compared with semi-quantitative scoring of short tau inversion recovery (STIR) and T1-weighted sequences, as well as various myositis disease metrics, including the Physician Global Activity, the modified Childhood Myositis Assessment Scale and the muscle domain of the Myositis Disease Activity Assessment Tool-muscle (MDAAT-muscle). RESULTS: Mean T2 and mean fc-T2 correlated similarly with STIR scores (Spearman rs = 0.64 and 0.64, P < 0.01), while mean FF correlated with T1 damage scores (rs = 0.69, P < 0.001). Baseline T2, fc-T2 and STIR scores correlated significantly with the Physician Global Activity, modified Childhood Myositis Assessment Scale and MDAAT-muscle (rs range = 0.41-0.74, P < 0.01). The response of MRI measures to rituximab was variable, and did not significantly agree with a standardized clinical definition of improvement. Standardized response means for the MRI measures were similar. CONCLUSION: Muscle T2, fc-T2 and FF measurements exhibit content validity with reference to semi-quantitative scoring of STIR and T1 MRI, and also exhibit construct validity with reference to several myositis activity and damage measures. T2 was as responsive as fc-T2 and STIR scoring, although progression of muscle damage was negligible during the study.
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Tejido Adiposo/patología , Interpretación de Imagen Asistida por Computador , Imagen por Resonancia Magnética/métodos , Músculo Esquelético/patología , Miositis/diagnóstico , Adolescente , Adulto , Estudios de Factibilidad , Femenino , Humanos , Modelos Lineales , Masculino , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Estadísticas no Paramétricas , Adulto JovenRESUMEN
OBJECTIVE: To determine the safety and efficacy of a home-based functional exercise program in spinal and bulbar muscular atrophy (SBMA). METHODS: Subjects were randomly assigned to participate in 12 weeks of either functional exercises (intervention) or a stretching program (control) at the National Institutes of Health in Bethesda, MD. A total of 54 subjects enrolled, and 50 completed the study with 24 in the functional exercise group and 26 in the stretching control group. The primary outcome measure was the Adult Myopathy Assessment Tool (AMAT) total score, and secondary measures included total activity by accelerometry, muscle strength, balance, timed up and go, sit-to-stand test, health-related quality of life, creatine kinase, and insulin-like growth factor-1. RESULTS: Functional exercise was well tolerated but did not lead to significant group differences in the primary outcome measure or any of the secondary measures. The functional exercise did not produce significantly more adverse events than stretching, and was not perceived to be difficult. To determine whether a subset of the subjects may have benefited, we divided them into high and low functioning based on baseline AMAT scores and performed a post hoc subgroup analysis. Low-functioning individuals receiving the intervention increased AMAT functional subscale scores compared to the control group. INTERPRETATION: Although these trial results indicate that functional exercise had no significant effect on total AMAT scores or on mobility, strength, balance, and quality of life, post hoc findings indicate that low-functioning men with SBMA may respond better to functional exercises, and this warrants further investigation with appropriate exercise intensity.
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OBJECTIVE: To determine the relationship between peak isometric muscle force and temporal characteristics of gait in individuals with sporadic inclusion body myositis (s-IBM). METHODS: An observational study of 42 individuals with s-IBM (12 women; mean ± SD age 61.8 ± 7.3 years and mean ± SD disease duration 8.9 ± 4.3 years) was conducted at a federal hospital. Peak isometric force measurements for lower extremity (LE) muscle groups were obtained using quantitative muscle testing. Temporal characteristics of gait during habitual and fast walking conditions were measured using a portable gait analysis system. RESULTS: All observed muscle force values were significantly lower than predicted values (P ≤ 0.001). During habitual walking, the subjects' gait speed and cadence were ≤83% of normative literature values. During fast walking, total gait cycle time was 133% of normal, while gait speed and cadence were 58% and 78% of normative literature values, respectively. Scaled LE peak muscle forces showed significant moderate correlations with temporal gait variables. Weaker subjects had greater limitations in gait speed and cadence compared with stronger subjects (P < 0.05). Peak isometric force of the knee flexors and ankle plantar flexors was significantly correlated with most temporal features of habitual gait. CONCLUSION: Muscle weakness associated with s-IBM disease activity may contribute to diminished gait kinematics. Temporal features of gait were not substantially influenced by knee extensor weakness alone, considering the knee flexors and ankle plantar flexors played a compensatory role in maintaining the walking ability of individuals with s-IBM.
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Marcha/fisiología , Extremidad Inferior/fisiología , Fuerza Muscular/fisiología , Miositis por Cuerpos de Inclusión/diagnóstico , Miositis por Cuerpos de Inclusión/fisiopatología , Rango del Movimiento Articular/fisiología , Anciano , Fenómenos Biomecánicos/fisiología , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
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
GNE myopathy is a rare autosomal recessive muscle disease caused by mutations in GNE, the gene encoding the rate-limiting enzyme in sialic acid biosynthesis. GNE myopathy usually manifests in early adulthood with distal myopathy that progresses slowly and symmetrically, first involving distal muscles of the lower extremities, followed by proximal muscles with relative sparing of the quadriceps. Upper extremities are typically affected later in the disease. We report a patient with GNE myopathy who presented with asymmetric hand weakness. He had considerably decreased left grip strength, atrophy of the left anterior forearm and fibro-fatty tissue replacement of left forearm flexor muscles on T1-weighted magnetic resonance imaging. The patient was an endoscopist and thus the asymmetric hand involvement may be associated with left hand overuse in daily repetitive pinching and gripping movements, highlighting the possible impact of environmental factors on the progression of genetic muscle conditions.
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Mano/fisiopatología , Complejos Multienzimáticos/genética , Debilidad Muscular/genética , Debilidad Muscular/fisiopatología , Enfermedades Musculares/genética , Enfermedades Musculares/fisiopatología , Adulto , Trastornos de Traumas Acumulados/genética , Trastornos de Traumas Acumulados/patología , Trastornos de Traumas Acumulados/fisiopatología , Estudios de Seguimiento , Mano/patología , Humanos , Imagen por Resonancia Magnética , Masculino , Debilidad Muscular/patología , Músculo Esquelético/patología , Músculo Esquelético/fisiopatología , Enfermedades Musculares/patologíaRESUMEN
Spinal and bulbar muscular atrophy (SBMA) is an X-linked neuromuscular disease caused by a trinucleotide (CAG) repeat expansion in the androgen receptor gene. Patients with SBMA have weakness, atrophy, and fasciculations in the bulbar and extremity muscles. Individuals with CAG repeat lengths greater than 62 have not previously been reported. We evaluated a 29year old SBMA patient with 68 CAGs who had unusually early onset and findings not seen in others with the disease. Analysis of the androgen receptor gene confirmed the repeat length of 68 CAGs in both peripheral blood and fibroblasts. Evaluation of muscle and sensory function showed deficits typical of SBMA, and in addition the patient had manifestations of autonomic dysfunction and abnormal sexual development. These findings extend the known phenotype associated with SBMA and shed new insight into the effects of the mutated androgen receptor.
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Trastornos Musculares Atróficos/genética , Receptores Androgénicos/genética , Repeticiones de Trinucleótidos/genética , Adulto , Humanos , Imagen por Resonancia Magnética , Masculino , Debilidad Muscular/etiología , Trastornos Musculares Atróficos/complicaciones , Fibras Nerviosas/patologíaRESUMEN
OBJECTIVES: We aimed to assess changes in myositis core set measures and ancillary clinical and laboratory data from the National Institutes of Health's subset of patients enrolled in the Rituximab in Myositis trial. METHODS: Eighteen patients (5 dermatomyositis, 8 polymyositis, 5 juvenile dermatomyositis) completed more in-depth testing of muscle strength and cutaneous assessments, patient-reported outcomes, and laboratory tests before and after administration of rituximab. Percentage change in individual measures and in the definitions of improvement (DOIs) and standardized response means were examined over 44 weeks. RESULTS: Core set activity measures improved by 18-70% from weeks 0-44 and were sensitive to change. Fifteen patients met the DOI at week 44, 9 patients met a DOI 50% response, and 4 met a DOI 70% response. Muscle strength and function measures were more sensitive to change than cutaneous assessments. Constitutional, gastrointestinal, and pulmonary systems improved 44-70%. Patient-reported outcomes improved up to 28%. CD20+ B cells were depleted in the periphery, but B cell depletion was not associated with clinical improvement at week 16. CONCLUSIONS: This subset of patients had high rates of clinical response to rituximab, similar to patients in the overall trial. Most measures were responsive, and muscle strength had a greater degree of change than cutaneous assessments. Several novel assessment tools, including measures of strength and function, extra-muscular organ activity, fatigue, and health-related quality of life, are promising for use in future myositis trials. Further study of B cell-depleting therapies in myositis, particularly in treatment-naïve patients, is warranted.
Asunto(s)
Antiinflamatorios/uso terapéutico , Anticuerpos Monoclonales de Origen Murino/uso terapéutico , Miositis/tratamiento farmacológico , Adolescente , Adulto , Linfocitos B/efectos de los fármacos , Linfocitos B/inmunología , Biomarcadores/sangre , Niño , Femenino , Indicadores de Salud , Humanos , Masculino , Persona de Mediana Edad , Fuerza Muscular/efectos de los fármacos , Miositis/sangre , Miositis/diagnóstico , Miositis/fisiopatología , Valor Predictivo de las Pruebas , Recuperación de la Función , Inducción de Remisión , Rituximab , Piel/efectos de los fármacos , Piel/patología , Encuestas y Cuestionarios , Factores de Tiempo , Resultado del TratamientoRESUMEN
Purpose. The adult myopathy assessment tool (AMAT) is a performance-based battery comprised of functional and endurance subscales that can be completed in approximately 30 minutes without the use of specialized equipment. The purpose of this study was to determine the construct validity and internal consistency of the AMAT with a sample of adults with spinal and bulbar muscular atrophy (SBMA). Methods. AMAT validity was assessed in 56-male participants with genetically confirmed SBMA (mean age, 53 ± 10 years). The participants completed the AMAT and assessments for disease status, strength, and functional status. Results. Lower AMAT scores were associated with longer disease duration (r = -0.29; P < 0.03) and lower serum androgen levels (r = 0.49-0.59; P < 0.001). The AMAT was significantly correlated with strength and functional status (r = 0.82-0.88; P < 0.001). The domains of the AMAT exhibited good internal consistency (Cronbach's α = 0.77-0.89; P < 0.001). Conclusions. The AMAT is a standardized, performance-based tool that may be used to assess functional limitations and muscle endurance. The AMAT has good internal consistency, and the construct validity of the AMAT is supported by its significant associations with hormonal, strength, and functional characteristics of adults with SBMA. This trial is registered with Clinicaltrials.gov identifier NCT00303446.