RESUMEN
BACKGROUND: Spasticity is a common and potentially debilitating symptom of multiple sclerosis (MS) with a highly variable presentation. Understanding, quantifying, and managing MS-associated spasticity (MSS) is a challenge for research and in clinical practice. The tetrahydrocannabinol:cannabidiol oromucosal spray nabiximols has demonstrated beneficial effects in the treatment of MSS in clinical studies as well as real-world observational studies, and is approved for the treatment of MSS in 29 countries globally. Most randomized studies evaluated the efficacy of nabiximols using the change in average daily spasticity scores reported by patients using the spasticity Numeric Rating Scale as a primary endpoint. This study, RELEASE MSS1 (NCT04657666), was conducted using a prespecified primary endpoint of change in spastic muscle tone (Modified Ashworth Scale Lower Limb Muscle Tone-6 [MAS LLMT-6]) to corroborate the efficacy of nabiximols as adjunctive therapy observed with the patient-measured spasticity Numeric Rating Scale primary endpoint in the previous pivotal studies. METHODS: This was a phase 3, multicenter, randomized, double-blind, placebo-controlled, 2-treatment, 2-period, crossover trial. Because of the prevalence and functional impact of lower limb spasticity on the individual patient's overall experience of MS spasticity, the MAS LLMT-6 was derived from the clinician-rated MAS. The MAS LLMT-6 is the average transformed MAS score of 6 muscle groups (knee flexors, knee extensors, and ankle plantar flexors; all assessed bilaterally). Secondary measures included MAS LLMT-4 scores, defined as the average of the 4 individual MAS-transformed scores of knee flexors and knee extensors bilaterally. Patients had a diagnosis of MS and an untransformed MAS score of at least 2 in ≥2 of 6 LLMT-6 muscle groups despite current treatment with ≥1 of the following oral antispasticity agents: baclofen, tizanidine, or dantrolene. Eligible participants were randomly assigned to 1 of 2 treatment sequences. Each treatment sequence consisted of two treatment periods, each consisting of a 14-day dose titration phase followed by a 7-day dose maintenance phase. RESULTS: Of 68 patients enrolled, 33 were assigned to nabiximols followed by placebo and 35 were assigned to placebo followed by nabiximols. Least squares mean changes in MAS LLMT-6 scores from baseline to day 21 were -0.23 for nabiximols and -0.26 for placebo; the least squares mean treatment difference in MAS LLMT-6 scores for nabiximols versus placebo was 0.04, which was not statistically significant (P = 0.7152). Mean changes in MAS LLMT-4 scores from baseline to day 21 also were not significantly different between the nabiximols and placebo groups. Safety results in this study were consistent with the known safety profile of nabiximols in patients with MSS. CONCLUSION: Despite the established efficacy of nabiximols in MSS observed using patient-reported measures, the primary endpoint was not met in this study. The findings from this study reflect and emphasize some of the challenges in the evaluation and treatment of MS spasticity. CLINICAL TRIAL REGISTRATION NUMBER (CLINICALTRIALS.GOV): : NCT04657666.
Asunto(s)
Cannabidiol , Dronabinol , Combinación de Medicamentos , Esclerosis Múltiple , Espasticidad Muscular , Humanos , Espasticidad Muscular/tratamiento farmacológico , Espasticidad Muscular/etiología , Cannabidiol/administración & dosificación , Cannabidiol/farmacología , Dronabinol/administración & dosificación , Dronabinol/farmacología , Método Doble Ciego , Esclerosis Múltiple/complicaciones , Esclerosis Múltiple/tratamiento farmacológico , Adulto , Masculino , Vaporizadores Orales , Femenino , Persona de Mediana Edad , Evaluación de Resultado en la Atención de SaludRESUMEN
Background: The growing trend in providing palliative care and end-of-life services has dictated that healthcare providers be adequately trained to care for people with serious illnesses, such as multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD). These progressive inflammatory diseases lead to physical, cognitive and emotional deficits and have exceptionally high care demands leading to high levels of distress. Because the impact on the delivery of patient care is influenced by the specialists' knowledge and comfort discussing end-of-life issues, it is concerning that interventions to address unmet palliative care needs in MS and NMOSD rarely include clinician-patient dyads. Objectives: To evaluate the neurology clinicians' knowledge and level of comfort discussing palliative care and end-of-life issues. Design: A cross sectional survey was conducted. The statistical analyses included frequencies, chi square statistics and logistic regression. Setting/Subjects: 414 MS specialists answered an online anonymous survey. The survey was conducted using email distributions to MS professionals through the Consortium of MS Centers (CMSC), the International Organization of MS Nurses (IOMSN) and the UK Nurses' MS Organization. Measurement: The "End of Life Professional Caregiver Survey" (EPCS) was used to collect data. Results: The majority of the multidisciplinary professionals were female, white, nurses, and older than 40 years of age. 41% had their own advance directives and 57.6% had end-of-life basic training. There was a statistically significant association between end-of-life training or having advance directives and comfort discussing palliative care and end of life issues. Professionals that had basic end-of-life training and their own advance directives had higher comfort discussing code status, specific end-of-life issues, and advance directive planning. Conclusions: Basic end-of-life training and having advance directives among MS professionals were associated with better communication of palliative care and end-of-life domains with patients and their care partners.
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Cuidados Paliativos , Cuidado Terminal , Directivas Anticipadas , Estudios Transversales , Muerte , Femenino , Humanos , MasculinoRESUMEN
OBJECTIVES: Stiff-person syndrome (SPS) is associated with axial rigidity superimposed on sustained muscle spasms. These symptoms commonly interfere with the performance of activities of daily living including ambulation. This retrospective case series evaluates the outcomes of screening tests and chronic infusion of intrathecal baclofen (ITB) in patients diagnosed with SPS treated in our spasticity clinic. MATERIALS AND METHODS: Patients were identified from an institutional review board-approved clinical registry of ITB therapy. Data from clinical encounters were extracted from the registry and from the patients' electronic medical record. All patients with medically refractory spasticity related to SPS screened with an ITB injection were included. In addition to pertinent demographic and clinical information, data from validated outcome measures routinely used in the clinic were collected: pain Numeric Rating Scale, Spasm Frequency Scale, lower extremity Modified Ashworth Scale (MAS), and Timed 25 Foot Walk. Outcomes data for chronic ITB infusion were assessed at early (<6 months) and late follow-up (6-12 months) visits after surgery. RESULTS: Nine patients were included, and seven received chronic ITB infusion. MAS scores were improved at early and late follow-up, and five patients experienced a reduction in pain scores. Walking performance remained stable in previously ambulatory patients. Four patients experienced complications related to ITB implantation, which resolved with medical or surgical treatment. CONCLUSION: Consistent with other case series, our results suggest that ITB is an effective therapy for medically intractable spasticity due to SPS, and symptom reduction can be achieved without compromising ambulation.
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Baclofeno/uso terapéutico , Inyecciones Espinales/métodos , Relajantes Musculares Centrales/uso terapéutico , Síndrome de la Persona Rígida/tratamiento farmacológico , Adulto , Anciano , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Dimensión del Dolor , Índice de Severidad de la EnfermedadRESUMEN
The Timed 25 Foot Walk (T25FW), a test of maximum walking speed on a short distance, is commonly used to monitor ambulation status and to assess treatment outcomes in multiple sclerosis (MS). The main aim of this study was to determine how walking speed on the T25FW correlates with other clinician-reported and patient-reported measures in an outpatient MS rehabilitation clinic. We analyzed cross-sectional data systematically collected during a physiatry evaluation for the management of spasticity and walking limitations. In addition to demographic variables and the Expanded Disability Status Scale (EDSS), measures of body functions [lower extremity manual muscle testing (LE MMT), lower extremity Modified Ashworth Scale, Fatigue Severity Scale, leg pain], and measures of activity and quality of life (reported frequency of falls, Incapacity Status Scale, Rivermead Mobility Index, EQ5D health questionnaire, and Patient Health Questionnaire-9 items) were administered. A multivariate regression analysis was carried out. 199 patients were included in the analysis [age 49.41 (9.89) years, disease duration 15.40 (10.22) years, EDSS score 5.6 (1.2), and T25FW speed 70.93 (44.13) cm/s]. Both EDSS and LE MMT were correlated significantly with T25FW speed (R=0.692, P<0.001). After adjusting for EDSS and LE MMT, lower T25FW speed was associated with higher Incapacity Status Scale scores (R=0.316, P<0.001), lower Rivermead Mobility Index scores (R=0.540, P<0.001), and higher frequency of falls. EQ5D and Patient Health Questionnaire-9 items were not significantly associated with T25FW speed. Our findings support the clinical relevance of the T25FW in the rehabilitation of patients with MS.
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Atención Ambulatoria , Evaluación de la Discapacidad , Esclerosis Múltiple/diagnóstico , Esclerosis Múltiple/rehabilitación , Centros de Rehabilitación , Prueba de Paso/métodos , Velocidad al Caminar , Adulto , Anciano , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Evaluación de Resultado en la Atención de Salud , Calidad de Vida , Estadística como AsuntoRESUMEN
OBJECTIVE: To evaluate the efficacy and safety of a hip flexion assist orthosis (HFAO) in ambulatory patients with multiple sclerosis (MS). DESIGN: Fourteen week pre- and postintervention uncontrolled trial. SETTING: Outpatient rehabilitation clinic within an MS center. PARTICIPANTS: Ambulatory MS patients (N=21) with unilateral (or unilateral predominant) hip flexor weakness. INTERVENTION: Subjects were fitted with the HFAO on the weaker side, trained to use the device, and given a wear schedule. Subjects completed 2 baseline evaluations and follow-up testing at 8 and 12 weeks. MAIN OUTCOME MEASURES: Lower-extremity manual muscle testing, pain, and gait performance (Timed 25-Foot Walk, Timed Up & Go, 6-minute walk test, Mellen Center Gait Test). Subject satisfaction was evaluated by using a 9-item custom questionnaire. RESULTS: There was a statistically significant improvement of strength in the affected lower extremity at 8 and 12 weeks (effect size [ES]=0.63; ES=1.32, respectively), of pain at 12 weeks only (ES=-0.64), and of all gait tests at 8 and 12 weeks (ES range, 0.38-1.33). The overall mean satisfaction score at 12 weeks was 39 (maximum score, 45). No serious adverse events were recorded during the study. The most frequent side effect of the HFAO was low back pain (19%). No side effects led to discontinuation of the HFAO use during the study. CONCLUSIONS: The HFAO was safe and well tolerated. HFAO use was associated with significant improvement of gait performance as well as improvement of strength in the lower extremity fitted with the HFAO. Subjective reports suggest that there was an increase in daily life activity level.
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Trastornos Neurológicos de la Marcha/rehabilitación , Articulación de la Cadera/fisiopatología , Esclerosis Múltiple/fisiopatología , Esclerosis Múltiple/rehabilitación , Aparatos Ortopédicos , Actividades Cotidianas , Diseño de Equipo , Femenino , Marcha , Trastornos Neurológicos de la Marcha/etiología , Trastornos Neurológicos de la Marcha/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Esclerosis Múltiple/complicaciones , Fuerza Muscular , Satisfacción del Paciente , Rango del Movimiento ArticularRESUMEN
Clinical signs and symptoms of spasticity include hypertonia, involuntary movements (spasms, clonus), decreased range of motion, contractures, and often spasm-related pain. When spasticity is refractory to medical management, patients may be referred for intrathecal baclofen (ITB) pump placement. We reviewed a cohort of amyotrophic lateral sclerosis (ALS) patients with intractable spasticity requiring ITB to further define the impact of ITB on pain relief in this patient population. From 2003 to 2005, eight patients (mean age 43.8 years; 5 men, 3 women) with ALS received ITB for pain associated with intractable spasticity at our institution. Mean disease duration preoperatively was 47.4 months, mean follow-up was 9.8 months, and pain was evaluated using a 0-10 scoring system. All patients experienced spasticity relief in response to a preoperative bolus test injection of ITB (25-50 microg) via lumbar puncture. Following ITB pump placement, the average reduction of pain was 54% (P = 0.0082). Six patients (75%) experienced pain score reduction, three of whom had complete pain relief. Postoperative pain reduction was predicted by the degree of pain reduction following preoperative ITB test injection. These results support ITB as a treatment modality for pain associated with spasticity in ALS.
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Esclerosis Amiotrófica Lateral/complicaciones , Baclofeno/administración & dosificación , Relajantes Musculares Centrales/administración & dosificación , Espasticidad Muscular/complicaciones , Espasticidad Muscular/etiología , Dolor/tratamiento farmacológico , Adulto , Anciano , Esclerosis Amiotrófica Lateral/tratamiento farmacológico , Estudios de Cohortes , Femenino , Humanos , Bombas de Infusión Implantables , Inyecciones Espinales/métodos , Masculino , Persona de Mediana Edad , Dolor/etiología , Dimensión del Dolor , Estudios RetrospectivosRESUMEN
Multiple sclerosis (MS) has protean manifestations, and the care of people with MS presents many unique challenges. Clinicians can have an important impact on health, quality of life, and daily functioning by participating in open dialogue, tailoring focused treatment plans, and anticipating general medical needs.