RESUMEN
BACKGROUND: How the joints exactly move and interact and how this reflects PD-related gait abnormalities and the response to dopaminergic treatment is poorly understood. A detailed understanding of these kinematics can inform clinical management and treatment decisions. The aim of the study was to investigate the influence of different gait speeds and medication on/off conditions on inter-joint coordination, as well as kinematic differences throughout the whole gait cycle in well characterized pwPD. METHODS: 29 controls and 29 PD patients during medication on, 8 of them also during medication off walked a straight walking path in slow, preferred and fast walking speeds. Gait data was collected using optical motion capture system. Kinematics of the hip and knee and coordinated hip-knee kinematics were evaluated using Statistical Parametric Mapping (SPM) and cyclograms (angle-angle plots). Values derived from cyclograms were compared using repeated-measures ANOVA for within group, and ttest for between group comparisons. RESULTS: PD gait differed from controls mainly by lower knee range of motion (ROM). Adaptation to gait speed in PD was mainly achieved by increasing hip ROM. Regularity of gait was worse in PD but only during preferred speed. The ratios of different speed cyclograms were smaller in the PD groups. SPM analyses revealed that PD participants had smaller hip and knee angles during the swing phase, and PD participants reached peak hip flexion later than controls. Withdrawal of medication showed an exacerbation of only a few parameters. CONCLUSIONS: Our findings demonstrate the potential of granular kinematic analyses, including > 1 joint, for disease and treatment monitoring in PD. Our approach can be extended to further mobility-limiting conditions and other joint combinations. TRIAL REGISTRATION: The study is registered in the German Clinical Trials Register (DRKS00022998, registered on 04 Sep 2020).
Asunto(s)
Dopaminérgicos , Enfermedad de Parkinson , Rango del Movimiento Articular , Humanos , Enfermedad de Parkinson/tratamiento farmacológico , Enfermedad de Parkinson/fisiopatología , Masculino , Femenino , Estudios de Casos y Controles , Fenómenos Biomecánicos , Persona de Mediana Edad , Anciano , Dopaminérgicos/uso terapéutico , Rango del Movimiento Articular/fisiología , Articulación de la Rodilla/fisiopatología , Marcha/fisiología , Marcha/efectos de los fármacos , Articulación de la Cadera/fisiopatología , Trastornos Neurológicos de la Marcha/fisiopatología , Trastornos Neurológicos de la Marcha/tratamiento farmacológico , Trastornos Neurológicos de la Marcha/etiología , Articulaciones/fisiopatologíaRESUMEN
Numerous studies have established a robust body of evidence for botulinum toxin A (BoNT-A) therapy as a treatment for upper motor neuron syndrome. These studies demonstrated improvements in spasticity, range of joint motion, and pain reduction. However, there are few studies that have focused on improvement of paralysis or functional enhancement as the primary outcome. This paper discusses the multifaceted aspects of spasticity assessment, administration, and rehabilitation with the goal of optimising the effects of BoNT-A on lower-limb spasticity and achieving functional improvement and gait reconstruction. This paper extracts studies on BoNT-A and rehabilitation for the lower limbs and provides new knowledge obtained from them. From these discussion,, key points in a walking reconstruction strategy through the combined use of BoNT-A and rehabilitation include: (1) injection techniques based on the identification of appropriate muscles through proper evaluation; (2) combined with rehabilitation; (3) effective spasticity control; (4) improvement in ankle joint range of motion; (5) promotion of a forward gait pattern; (6) adjustment of orthotics; and (7) maintenance of the effects through frequent BoNT-A administration. Based on these key points, the degree of muscle fibrosis and preintervention walking speed may serve as indicators for treatment strategies. With the accumulation of recent studies, a study focusing on walking functions is needed. As a result, it is suggested that BoNT-A treatment for lower limb spasticity should be established not just as a treatment for spasticity but also as a therapeutic strategy in the field of neurorehabilitation aimed at improving walking function.
Asunto(s)
Toxinas Botulínicas Tipo A , Marcha , Espasticidad Muscular , Fármacos Neuromusculares , Humanos , Espasticidad Muscular/tratamiento farmacológico , Espasticidad Muscular/rehabilitación , Marcha/efectos de los fármacos , Toxinas Botulínicas Tipo A/uso terapéutico , Toxinas Botulínicas Tipo A/administración & dosificación , Fármacos Neuromusculares/uso terapéutico , Terapia Combinada , Enfermedad de la Neurona Motora/tratamiento farmacológico , Enfermedad de la Neurona Motora/rehabilitaciónRESUMEN
BACKGROUND: Multiple sclerosis (MS) is the most common neurologic disease in young adults. Spasticity is one of its most disabling symptoms, with botulinum toxin A type A (BoNT-A) being one of the treatments of choice for this symptom. OBJECTIVE: We assessed the response to abobotulinumtoxinA in improving walking ability and fatigue in patients with spastic paraparesis caused by MS. METHODS: We performed a real-world, multicenter, prospective, open-label low-intervention trial in 84 patients with MS and spastic paraparesis of the lower limbs infiltrated with abobotulinumtoxinA (LINITOX study). The response of spasticity, walking ability and fatigue is analyzed in 4 cycles of ultrasound-guided injection in the lower limbs. RESULTS: The patients improved their walking ability by an average of 11.34% meters measured with 6-Minute Walk Test (6MWT), and decreased the percentage of fatigue by 6.86% (4.66 percentage points less), in the 12-Item Multiple Sclerosis Walking Scale (MSWS-12) 4 weeks after abobotulinumtoxinA injection, both values are statistically significant. This improvement seems to persist over time, throughout the cycles. CONCLUSION: We found improved walking ability and less fatigue in patients with MS-related spastic paresis of the lower limbs after injection of abobotulinumtoxinA.
Asunto(s)
Toxinas Botulínicas Tipo A , Fatiga , Esclerosis Múltiple , Fármacos Neuromusculares , Paraparesia Espástica , Humanos , Toxinas Botulínicas Tipo A/administración & dosificación , Toxinas Botulínicas Tipo A/uso terapéutico , Femenino , Masculino , Esclerosis Múltiple/complicaciones , Esclerosis Múltiple/tratamiento farmacológico , Adulto , Fármacos Neuromusculares/administración & dosificación , Fármacos Neuromusculares/uso terapéutico , Paraparesia Espástica/tratamiento farmacológico , Paraparesia Espástica/etiología , Persona de Mediana Edad , Estudios Prospectivos , Fatiga/tratamiento farmacológico , Fatiga/etiología , Marcha/efectos de los fármacos , Resultado del TratamientoRESUMEN
OBJECTIVE: Cannabidiol-enriched oil (CBDO) is being used increasingly to improve seizure control in adult patients with drug-resistant epilepsy (DRE), despite the lack of large-scale studies supporting its efficacy in this patient population. We aimed to assess the effects of add-on CBDO on seizure frequency as well as on gait, cognitive, affective, and sleep-quality metrics, and to explore the electrophysiological changes in responder and non-responder DRE patients treated with add-on CBDO. METHODS: We prospectively recruited adult DRE patients who were treated with add-on CBDO. Patients were evaluated prior to treatment and following 4 weeks of a maintenance daily dose of ≈260 mg CBD and ≈12 mg Δ9-tetrahydrocannabinol (THC). The outcome measures included seizure response to CBDO (defined as ≥50% decrease in seizures compared to pre-CBDO baseline), gait testing, Montreal Cognitive Assessment (MoCA), Hospital Anxiety and Depression Scale (HADS), and sleep-quality questionnaire assessments. Patients underwent electroencephalography (EEG) recording during rest as well as event-related potentials (ERPs) during visual Go/NoGo task while sitting and while walking. RESULTS: Nineteen patients were recruited, of which 16 finished pre- and post-CBDO assessments. Seven patients (43.75%) were responders demonstrating an average reduction of 82.4% in seizures, and nine patients (56.25%) were non-responders with an average seizure increase of 30.1%. No differences in demographics and clinical parameters were found between responders and non-responders at baseline. However, responders demonstrated better performance in the dual-task walking post-treatment (p = .015), and correlation between increase in MoCA and seizure reduction (r = .810, p = .027). Post-CBDO P300 amplitude was lower during No/Go-sitting in non-responders (p = .028) and during No/Go-walking in responders (p = .068). SIGNIFICANCE: CBDO treatment can reduce seizures in a subset of patients with DRE, but could aggravate seizure control in a minority of patients; yet we found no specific baseline clinical or electrophysiological characteristics that are associated with response to CBDO. However, changes in ERPs in response to treatment could be a promising direction to better identify patients who could benefit from CBDO treatment.
Asunto(s)
Anticonvulsivantes , Cannabidiol , Epilepsia Refractaria , Electroencefalografía , Humanos , Masculino , Cannabidiol/uso terapéutico , Femenino , Epilepsia Refractaria/tratamiento farmacológico , Epilepsia Refractaria/fisiopatología , Adulto , Estudios Prospectivos , Anticonvulsivantes/uso terapéutico , Persona de Mediana Edad , Adulto Joven , Potenciales Evocados/efectos de los fármacos , Potenciales Evocados/fisiología , Resultado del Tratamiento , Dronabinol/uso terapéutico , Marcha/efectos de los fármacos , Marcha/fisiología , AceitesRESUMEN
Parkinson's Disease (PD) is a neurodegenerative movement disorder characterized by dopamine (DA) cell loss in the substantia nigra pars compacta (SNc). As PD progresses, patients display disruptions in gait such as changes in posture, bradykinesia, and shortened stride. DA replacement via L-DOPA alleviates many PD symptoms, though its effects on gait are not well demonstrated. This study aimed to assess the relationship between DA lesion, gait, and deficit-induced reversal with L-DOPA. To do so, Sprague-Dawley rats (N = 25, 14 males, 11 females) received unilateral medial forebrain bundle (MFB) DA lesions with 6-hydroxydopamine (6-OHDA). An automated gait analysis system assessed spatiotemporal gait parameters pre- and post-lesion, and after various doses of L-DOPA (0, 3, or 6 mg/kg; s.c.). The forepaw adjusting steps (FAS) test was implemented to evaluate lesion efficacy while the abnormal involuntary movements (AIMs) scale monitored the emergence of L-DOPA-induced dyskinesia (LID). High performance liquid chromatography (HPLC) assessed changes in brain monoamines on account of lesion and treatment. Results revealed lesion-induced impairments in gait, inclusive of max-contact area and step-sequence alterations that were not reversible with L-DOPA. However, the emergence of AIMs were observed at higher doses. Post-mortem, 6-OHDA lesions induced a loss of striatal DA and norepinephrine (NE), while prefrontal cortex (PFC) displayed noticeable reduction in NE but not DA. Our findings indicate that hemiparkinsonian rats display measurable gait disturbances similar to PD patients that are not rescued by DA replacement. Furthermore, non-DA mechanisms such as attention-related NE in PFC may contribute to altered gait and may constitute a novel target for its treatment.
Asunto(s)
Trastornos Neurológicos de la Marcha , Levodopa , Oxidopamina , Ratas Sprague-Dawley , Animales , Levodopa/farmacología , Levodopa/efectos adversos , Masculino , Femenino , Ratas , Trastornos Neurológicos de la Marcha/inducido químicamente , Trastornos Neurológicos de la Marcha/tratamiento farmacológico , Trastornos Neurológicos de la Marcha/etiología , Antiparkinsonianos/farmacología , Modelos Animales de Enfermedad , Haz Prosencefálico Medial/efectos de los fármacos , Trastornos Parkinsonianos/inducido químicamente , Trastornos Parkinsonianos/tratamiento farmacológico , Trastornos Parkinsonianos/fisiopatología , Trastornos Parkinsonianos/patología , Dopamina/metabolismo , Relación Dosis-Respuesta a Droga , Lateralidad Funcional/efectos de los fármacos , Enfermedad de Parkinson/tratamiento farmacológico , Enfermedad de Parkinson/patología , Enfermedad de Parkinson/fisiopatología , Marcha/efectos de los fármacos , Discinesia Inducida por MedicamentosRESUMEN
Parkinson's disease (PD) is a progressive disorder characterized by the apoptosis of dopaminergic neurons in the basal ganglia. This study explored the potential effects of aminophylline, a non-selective adenosine A1 and A2A receptor antagonist, on catalepsy and gait in a haloperidol-induced PD model. Sixty adult male Swiss mice were surgically implanted with guide cannulas that targeted the basal ganglia. After seven days, the mice received intraperitoneal injections of either haloperidol (experimental group, PD-induced model) or saline solution (control group, non-PD-induced model), followed by intracerebral infusions of aminophylline. The assessments included catalepsy testing on the bar and gait analysis using the Open Field Maze. A two-way repeated-measures analysis of variance (ANOVA), followed by Tukey's post hoc tests, was employed to evaluate the impact of groups (experimental × control), aminophylline (60 nM × 120 nM × saline/placebo), and interactions. Significance was set at 5%. The results revealed that the systemic administration of haloperidol in the experimental group increased catalepsy and dysfunction of gait that paralleled the observations in PD. Co-treatment with aminophylline at 60 nM and 120 nM reversed catalepsy in the experimental group but did not restore the normal gait pattern of the animals. In the non-PD induced group, which did not present any signs of catalepsy or motor dysfunctions, the intracerebral dose of aminophylline did not exert any interference on reaction time for catalepsy but increased walking distance in the Open Field Maze. Considering the results, this study highlights important adenosine interactions in the basal ganglia of animals with and without signs comparable to those of PD. These findings offer valuable insights into the neurobiology of PD and emphasize the importance of exploring novel therapeutic strategies to improve patient's catalepsy and gait.
Asunto(s)
Aminofilina , Catalepsia , Modelos Animales de Enfermedad , Marcha , Haloperidol , Enfermedad de Parkinson , Animales , Catalepsia/tratamiento farmacológico , Catalepsia/inducido químicamente , Ratones , Masculino , Aminofilina/administración & dosificación , Aminofilina/farmacología , Aminofilina/uso terapéutico , Marcha/efectos de los fármacos , Haloperidol/administración & dosificación , Haloperidol/farmacología , Enfermedad de Parkinson/tratamiento farmacológicoRESUMEN
BACKGROUND: Quantitative 3D movement analysis using inertial measurement units (IMUs) allows for a more detailed characterization of motor patterns than clinical assessment alone. It is essential to discriminate between gait features that are responsive or unresponsive to current therapies to better understand the underlying pathophysiological basis and identify potential therapeutic strategies. OBJECTIVES: This study aims to characterize the responsiveness and temporal evolution of different gait subcomponents in Parkinson's disease (PD) patients in their OFF and various ON states following levodopa administration, utilizing both wearable sensors and the gold-standard MDS-UPDRS motor part III. METHODS: Seventeen PD patients were assessed while wearing a full-body set of 15 IMUs in their OFF state and at 20-minute intervals following the administration of a supra-threshold levodopa dose. Gait was reconstructed using a biomechanical model of the human body to quantify how each feature was modulated. Comparisons with non-PD control subjects were conducted in parallel. RESULTS: Significant motor changes were observed in both the upper and lower limbs according to the MDS-UPDRS III, 40 minutes after levodopa intake. IMU-assisted 3D kinematics detected significant motor alterations as early as 20 minutes after levodopa administration, particularly in upper limbs metrics. Although all "pace-domain" gait features showed significant improvement in the Best-ON state, most rhythmicity, asymmetry, and variability features did not. CONCLUSION: IMUs are capable of detecting motor alterations earlier and in a more comprehensive manner than the MDS-UPDRS III. The upper limbs respond more rapidly to levodopa, possibly reflecting distinct thresholds to levodopa across striatal regions.
Asunto(s)
Antiparkinsonianos , Marcha , Levodopa , Enfermedad de Parkinson , Humanos , Levodopa/uso terapéutico , Levodopa/administración & dosificación , Enfermedad de Parkinson/tratamiento farmacológico , Enfermedad de Parkinson/fisiopatología , Masculino , Fenómenos Biomecánicos , Femenino , Anciano , Persona de Mediana Edad , Antiparkinsonianos/uso terapéutico , Antiparkinsonianos/administración & dosificación , Marcha/efectos de los fármacos , Trastornos Neurológicos de la Marcha/fisiopatología , Trastornos Neurológicos de la Marcha/tratamiento farmacológico , Trastornos Neurológicos de la Marcha/diagnóstico , Trastornos Neurológicos de la Marcha/etiología , Índice de Severidad de la EnfermedadRESUMEN
Parkinson's Disease (PD)-typical declines in gait coordination are possibly explained by weakness in bilateral cortical and muscular connectivity. Here, we seek to determine whether this weakness and consequent decline in gait coordination is affected by dopamine levels. To this end, we compare cortico-cortical, cortico-muscular, and intermuscular connectivity and gait outcomes between body sides in people with PD under ON and OFF medication states, and in older adults. In our study, participants walked back and forth along a 12 m corridor. Gait events (heel strikes and toe-offs) and electrical cortical and muscular activities were measured and used to compute cortico-cortical, cortico-muscular, and intermuscular connectivity (i.e., coherences in the alpha, beta, and gamma bands), as well as features characterizing gait performance (e.g., the step-timing coordination, length, and speed). We observe that people with PD, mainly during the OFF medication, walk with reduced step-timing coordination. Additionally, our results suggest that dopamine intake in PD increases the overall cortico-muscular connectivity during the stance and swing phases of gait. We thus conclude that dopamine corrects defective feedback caused by impaired sensory-information processing and sensory-motor integration, thus increasing cortico-muscular coherences in the alpha bands and improving gait.
Asunto(s)
Dopamina , Marcha , Enfermedad de Parkinson , Humanos , Enfermedad de Parkinson/fisiopatología , Enfermedad de Parkinson/tratamiento farmacológico , Masculino , Dopamina/metabolismo , Femenino , Anciano , Marcha/efectos de los fármacos , Persona de Mediana Edad , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/fisiopatologíaRESUMEN
OBJECTIVE: Individuals with Dravet syndrome (DS) exhibit progressive gait disturbance. No quantitative studies have been conducted to evaluate the effectiveness of medication for gait disturbance. Therefore, the aim of this study was to evaluate the effectiveness of levodopa for pathological gait in people with DS using three-dimensional gait analysis (3DGA). METHODS: Nine individuals with DS, ages 6-20 years, participated in a crossover study of levodopa and were randomly assigned to the levodopa precedence or no levodopa precedence group. Levodopa/carbidopa hydrate was prescribed at a dose of 5 mg/kg/day (body weight <60 kg) or 300 mg/day (body weight ≥60 kg). The medication was taken for 4-6 weeks (4-week washout period). 3DGA was performed three times before the study, with and without levodopa. A mixed-effects model was used to evaluate the effectiveness of levodopa. The primary outcome was the change in the Gait Deviation Index (GDI). In addition, spatiotemporal gait parameters, 6-minute walking distance (6MD), and balance were evaluated. The correlation between the effectiveness of levodopa and age or gait performance before starting levodopa was analyzed. RESULTS: Levodopa improved the GDI by 4.2 points, (p = .029), 6MD by 52 m (p = .002), and balance test result by 4.1 mm (p = .011) in participants with DS. No severe adverse events were observed, with the exception of one participant, who exhibited fever and consequently stopped taking levodopa. Levodopa was more effective in younger participants with a higher baseline gait performance. SIGNIFICANCE: Our randomized crossover trial showed that levodopa has the potential to improve gait disturbance in people with DS.
Asunto(s)
Estudios Cruzados , Epilepsias Mioclónicas , Trastornos Neurológicos de la Marcha , Levodopa , Humanos , Levodopa/uso terapéutico , Masculino , Femenino , Adolescente , Adulto Joven , Niño , Trastornos Neurológicos de la Marcha/tratamiento farmacológico , Trastornos Neurológicos de la Marcha/etiología , Epilepsias Mioclónicas/tratamiento farmacológico , Análisis de la Marcha , Resultado del Tratamiento , Carbidopa/uso terapéutico , Marcha/efectos de los fármacos , Combinación de MedicamentosAsunto(s)
Levodopa , Enfermedad de Parkinson , Ubiquitina-Proteína Ligasas , Humanos , Enfermedad de Parkinson/tratamiento farmacológico , Enfermedad de Parkinson/genética , Levodopa/uso terapéutico , Ubiquitina-Proteína Ligasas/genética , Ubiquitina-Proteína Ligasas/metabolismo , Distonía/genética , Distonía/tratamiento farmacológico , Distonía/inducido químicamente , Masculino , Femenino , Antiparkinsonianos/uso terapéutico , Antiparkinsonianos/farmacología , Adulto , Marcha/efectos de los fármacos , Trastornos Neurológicos de la Marcha/genética , Trastornos Neurológicos de la Marcha/etiología , Trastornos Neurológicos de la Marcha/tratamiento farmacológicoRESUMEN
AIM: To identify short-term effects of botulinum neurotoxin type A (BoNT) injections on gait and clinical impairments, in children with spastic cerebral palsy (CP), based on baseline gait pattern-specific subgroups. METHOD: Short-term effects of BoNT injections in the medial hamstrings and gastrocnemius were defined in a retrospective convenience sample of 117 children with CP (median age: 6 years 4 months; GMFCS I/II/III: 70/31/16; unilateral/bilateral: 56/61) who had received gait analyses before and 2 months post-BoNT. First, baseline gait patterns were classified. Statistical and meaningful changes were calculated between pre- and post-BoNT lower limb sagittal plane kinematic waveforms, the gait profile score, and non-dimensional spatiotemporal parameters for the entire sample and for pattern-specific subgroups. These gait waveforms per CP subgroup at pre- and post-BoNT were also compared to typically developing gait and composite scores for spasticity, weakness, and selectivity were compared between the two conditions. RESULTS: Kinematic improvements post-BoNT were identified at the ankle and knee for the entire sample, and for subgroups with apparent equinus and jump gait. Limbs with baseline patterns of dropfoot and to a lesser extent true equinus showed clear improvements only at the ankle. In apparent equinus, jump gait, and dropfoot, spasticity improved post-BoNT, without leading to increased weakness or diminished selectivity. Compared to typical gait, knee and hip motion improved in the crouch gait subgroup post-BoNT. CONCLUSION: This comprehensive analysis highlighted the importance of investigating BoNT effects on gait and clinical impairments according to baseline gait patterns. These findings may help identify good treatment responders.
Asunto(s)
Toxinas Botulínicas Tipo A , Parálisis Cerebral , Fármacos Neuromusculares , Humanos , Parálisis Cerebral/tratamiento farmacológico , Parálisis Cerebral/fisiopatología , Parálisis Cerebral/complicaciones , Toxinas Botulínicas Tipo A/administración & dosificación , Toxinas Botulínicas Tipo A/farmacología , Toxinas Botulínicas Tipo A/uso terapéutico , Niño , Masculino , Femenino , Fármacos Neuromusculares/administración & dosificación , Fármacos Neuromusculares/farmacología , Estudios Retrospectivos , Preescolar , Fenómenos Biomecánicos/efectos de los fármacos , Trastornos Neurológicos de la Marcha/tratamiento farmacológico , Trastornos Neurológicos de la Marcha/etiología , Trastornos Neurológicos de la Marcha/fisiopatología , Músculo Esquelético/fisiopatología , Músculo Esquelético/efectos de los fármacos , Adolescente , Resultado del Tratamiento , Espasticidad Muscular/tratamiento farmacológico , Espasticidad Muscular/fisiopatología , Espasticidad Muscular/etiología , Marcha/efectos de los fármacos , Marcha/fisiologíaRESUMEN
There is growing interest in the use of natural products for the treatment of Parkinson's disease (PD). Mucuna pruriens has been used in the treatment of humans with PD. The goal of this study was to determine if daily oral treatment with an extract of Mucuna pruriens, starting after the MPTP-induced loss of nigrostriatal dopamine in male mice, would result in recovery/restoration of motor function, tyrosine hydroxylase (TH) protein expression in the nigrostriatal pathway, or glutamate biomarkers in both the striatum and motor cortex. Following MPTP administration, resulting in an 80 % loss of striatal TH, treatment with Mucuna pruriens failed to rescue either striatal TH or the dopamine transporter back to the control levels, but there was restoration of gait/motor function. There was an MPTP-induced loss of TH-labeled neurons in the substantia nigra pars compacta and in the number of striatal dendritic spines, both of which failed to be recovered following treatment with Mucuna pruriens. This Mucuna pruriens-induced locomotor recovery following MPTP was associated with restoration of two striatal glutamate transporter proteins, GLAST (EAAT1) and EAAC1 (EAAT3), and the vesicular glutamate transporter 2 (Vglut2) within the motor cortex. Post-MPTP treatment with Mucuna pruriens, results in locomotor improvement that is associated with recovery of striatal and motor cortex glutamate transporters but is independent of nigrostriatal TH restoration.
Asunto(s)
Mucuna , Enfermedad de Parkinson , Extractos Vegetales , Enfermedad de Parkinson/tratamiento farmacológico , Enfermedad de Parkinson/patología , Ácido Glutámico/metabolismo , Biomarcadores/metabolismo , Corteza Motora/efectos de los fármacos , Corteza Motora/metabolismo , Corteza Motora/patología , Mucuna/química , Extractos Vegetales/administración & dosificación , Marcha/efectos de los fármacos , Porción Compacta de la Sustancia Negra/metabolismo , Porción Compacta de la Sustancia Negra/patología , Ganglios Basales/metabolismo , Ganglios Basales/patología , Animales , RatonesRESUMEN
RATIONALE: This paper reports on a chronic hemiparetic stroke patient who showed delayed gait recovery due to resolution of limb-kinetic apraxia (LKA). PATIENT CONCERNS: A 49-year-old man underwent comprehensive rehabilitation at a local rehabilitation hospital since 3 weeks after spontaneous intracerebral haemorrhage. However, he could not walk independently because of severe motor weakness in his right leg until 19âmonths after the onset. DIAGNOSIS: At the beginning of rehabilitation at our hospital (19âmonths after onset), we thought that he had the neurological potential to walk independently because the unaffected (right) corticospinal tract and corticoreticulospinal tract were closely related to the gait potential, representing intact integrities. As a result, we assumed that the severe motor weakness in the right leg was mainly ascribed to LKA. INTERVENTIONS: At our hospital, he underwent comprehensive rehabilitation including increased doses of dopaminergic drugs (pramipexole, ropinirole, amantadine, and carbidopa/levodopa). OUTCOMES: After 10âdays to our hospital, he could walk independently on an even floor with verbal supervision, concurrent with motor recovery of the right leg. After 24âdays after hospital admission, he could walk independently on an even floor. LESSONS: We believe that the resolution of LKA in his right leg by the administration of adequate doses of dopaminergic drugs was the main reason for the delayed gait recovery in this patient. The results suggest the importance of detecting the neurological potential for gait ability of a stroke patient who cannot walk after the gait recovery phase and the causes of gait inability for individual patients.
Asunto(s)
Apraxia Ideomotora/tratamiento farmacológico , Marcha/efectos de los fármacos , Rehabilitación de Accidente Cerebrovascular , Accidente Cerebrovascular/complicaciones , Daño Encefálico Crónico , Imagen de Difusión Tensora , Dopaminérgicos/uso terapéutico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recuperación de la FunciónRESUMEN
Manganese (Mn) is required for normal brain development and function. Excess Mn may trigger a parkinsonian movement disorder but the underlying mechanisms are incompletely understood. We explored changes in the brain proteomic profile and movement behavior of adult Sprague Dawley (SD) rats systemically treated with or without 1.0 mg/mL MnCl2 for 3 months. Mn treatment significantly increased the concentration of protein-bound Mn in the external globus pallidus (GP), as demonstrated by inductively coupled plasma mass spectrometry. Behavioral study showed that Mn treatment induced movement deficits, especially of skilled movement. Proteome analysis by two-dimensional fluorescence difference gel electrophoresis coupled with mass spectrometry revealed 13 differentially expressed proteins in the GP of Mn-treated versus Mn-untreated SD rats. The differentially expressed proteins were mostly involved in glycolysis, metabolic pathways, and response to hypoxia. Selected pathway class analysis of differentially expressed GP proteins, which included phosphoglycerate mutase 1 (PGAM1), primarily identified enrichment in glycolytic process and innate immune response. In conclusion, perturbation of brain energy production and innate immune response, in which PGAM1 has key roles, may contribute to the movement disorder associated with Mn neurotoxicity.
Asunto(s)
Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Globo Pálido/metabolismo , Manganeso/toxicidad , Animales , Marcha/efectos de los fármacos , Proteoma/metabolismo , Proteómica , Ratas , Ratas Sprague-DawleyRESUMEN
Patients with multiple sclerosis (MS) are characterized by, among other symptoms, impaired functional capacity and walking difficulties. Polyunsaturated fatty acids (PUFAs) have been found to improve MS patients' clinical outcomes; however, their effect on other parameters associated with daily living activities need further investigation. The current study aimed to examine the effect of a 24-month supplementation with a cocktail dietary supplement formula, the NeuroaspisTM PLP10, containing specific omega-3 and omega-6 PUFAs and specific antioxidant vitamins on gait and functional capacity parameters of patients with MS. Fifty-one relapsing-remitting MS (RRMS) patients with low disability scores (age: 38.4 ± 7.1 years; 30 female) were randomized 1:1 to receive either a 20 mL daily dose of the dietary formula containing a mixture of omega-3 and omega-6 PUFAs (12,150 mg), vitamin A (0.6 mg), vitamin E (22 mg), and γ-tocopherol (760 mg), the OMEGA group (n = 27; age: 39 ± 8.3 years), or 20 mL placebo containing virgin olive oil, the placebo group (n = 24; age: 37.8 ± 5.3 years). The mean ± SD (standard deviation) Expanded Disability Status Scale (EDSS) score for the placebo group was 2.36 and for the OMEGA group 2.22. All enrolled patients in the study were on Interferon-ß treatment. Spatiotemporal gait parameters and gait deviation index (GDI) were assessed using a motion capture system. Functional capacity was examined using various functional tests such as the six-minute walk test (6MWT), two sit-to-stand tests (STS-5 and STS-60), and the Timed Up and Go test (TUG). Isometric handgrip strength was assessed by a dynamometer. Leg strength was assessed using an isokinetic dynamometer. All assessments were performed at baseline and at 12 and 24 months of supplementation. A total of 36 patients completed the study (18 from each group). Six patients from the placebo group and 9 patients from the OMEGA group dropped out from the study or were lost to follow-up. The dietary supplement significantly improved the single support time and the step and stride time (p < 0.05), both spatiotemporal gait parameters. In addition, while GDI of the placebo group decreased by about 10% at 24 months, it increased by about 4% in the OMEGA group (p < 0.05). Moreover, performance in the STS-60 test improved in the OMEGA group (p < 0.05) and there was a tendency for improvement in the 6MWT and TUG tests. Long-term supplementation with high dosages of omega-3 and omega-6 PUFAs (compared to previous published clinical studies using PUFAs) and specific antioxidant vitamins improved some functional capacity and gait parameters in RRMS patients.
Asunto(s)
Antioxidantes/farmacología , Ácidos Grasos Omega-3/farmacología , Ácidos Grasos Omega-6/farmacología , Marcha/fisiología , Esclerosis Múltiple Recurrente-Remitente/fisiopatología , Vitaminas/farmacología , Adulto , Composición Corporal/efectos de los fármacos , Femenino , Marcha/efectos de los fármacos , Fuerza de la Mano , Humanos , Rodilla/fisiopatología , Masculino , Factores de TiempoAsunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Vestibulopatía Bilateral/inducido químicamente , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Ipilimumab/efectos adversos , Nivolumab/efectos adversos , Equilibrio Postural/efectos de los fármacos , Vestíbulo del Laberinto/efectos de los fármacos , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Vestibulopatía Bilateral/diagnóstico , Vestibulopatía Bilateral/tratamiento farmacológico , Vestibulopatía Bilateral/fisiopatología , Marcha/efectos de los fármacos , Glucocorticoides/uso terapéutico , Humanos , Masculino , Recuperación de la Función , Resultado del Tratamiento , Vestíbulo del Laberinto/fisiopatologíaRESUMEN
The radionuclide 117mSn (tin-117m) embedded in a homogeneous colloid is a novel radiosynoviorthesis (RSO) device for intra-articular (IA) administration to treat synovial inflammation and mitigate osteoarthritis (OA) in dogs. A study to evaluate tin-117m colloid treatment response in dogs with OA was conducted at two centers, the School of Veterinary Medicine at Louisiana State University, and at a referral practice in Houston, Texas. The tin-117m colloid was administered per-protocol to 14 client-owned dogs with radiographically confirmed, grade 3 OA in one or both elbow joints. Dog owners and attending clinicians assessed the level of pain at baseline (BL) and the post-treatment pain response at 90-day intervals for one year. Owners assessed treatment response according to a pain severity score (PSS) and a pain interference score (PIS) as defined by the Canine Brief Pain Inventory. Clinicians reported a lameness score using a 0-5 scale, from no lameness to continuous non-weight bearing lameness, when observing dogs at a walk and a trot. The rate of treatment success as determined by improved mean PSS and PIS scores reported by dog owners was >70% at all time points. Clinicians reported an improved mean pain score from BL at post-treatment Days 90 (p<0.05), 180, and 270. The dog owner and clinician assessments of treatment success were significantly correlated (p>0.05) at Day 90 and Day 180 time points. Results indicated that a single IA dose of tin-117m colloid provided a significant reduction in pain and lameness and improved functionality for up to a full year, with no adverse treatment related effects, in a high percentage of dogs with advanced, clinical OA of the elbow joint.
Asunto(s)
Coloides/farmacología , Inflamación/tratamiento farmacológico , Osteoartritis/tratamiento farmacológico , Dolor/tratamiento farmacológico , Animales , Enfermedades de los Perros/diagnóstico por imagen , Enfermedades de los Perros/tratamiento farmacológico , Enfermedades de los Perros/patología , Perros , Marcha/efectos de los fármacos , Inflamación/diagnóstico por imagen , Inflamación/patología , Inflamación/veterinaria , Inyecciones Intraarticulares , Isótopos/farmacología , Osteoartritis/diagnóstico por imagen , Osteoartritis/patología , Osteoartritis/veterinaria , Dolor/diagnóstico por imagen , Dolor/patología , Dimensión del Dolor/métodos , Estaño/farmacología , Resultado del Tratamiento , Caminata/fisiologíaRESUMEN
ABSTRACT Racewalking fatigue is a kind of fatigue symptom after a period of racewalking, which may lead to limb weakness, mental fatigue, muscle fatigue and other phenomena. If we do not timely adjust the stretching and effective treatment after exercise, it is very easy to produce sports injury and seriously affect the athletes' physical function. In order to effectively alleviate the fatigue of racewalking, this study focused on the traditional Chinese medicine (TCM) compounded medication, analyzed the mechanism of action and medicinal effectiveness of the TCM compound, and carried out control experiment on 80 male ICR mice. The mice in the experimental group were given sedentary training and racewalking training in groups. The results showed that the two groups of ICR mice, after racewalking training, had exercise fatigue symptoms and a large amount of serum lactic acid and other substances, while mice in group D treated by gavage of traditional Chinese medicine compounded medication had the symptoms of exercise fatigue, but the contents of blood urea nitrogen and lactic acid were decreased, the gastrocnemius muscle fibers were evenly arranged, the transverse lines were neat, and a rebound of protein expression. This shows that Chinese medicine compound can play a significant role in relieving racewalking fatigue.
RESUMO A fadiga causada pela marcha atlética é um tipo de sintoma que acomete os atletas após um período de prática do exercício, que pode ocasionar fraqueza dos membros, fadiga mental, fadiga muscular e outros fenômenos. Na ausência de alongamento e tratamento eficaz após o exercício, as lesões causadas pelo esporte podem afetar seriamente a função física dos atletas. A fim de aliviar de maneira eficaz a fadiga causada pela marcha atlética, o presente estudo se concentrou nos medicamentos manipulados na medicina tradicional chinesa (MTC), analisou o mecanismo de ação e eficácia medicinal dos medicamentos da MTC, e realizou experimentos de controle em 80 camundongos do tipo ICR masculinos. Os camundongos do grupo experimental receberam treinamento sedentário e treinamento de corrida em grupo. Os resultados mostraram que os dois grupos de camundongos ICR, após treino de marcha atlética, apresentavam sintomas de fadiga, e grande quantidade de ácido láctico sérico, além de outras substâncias, enquanto os camundongos do grupo D tratados com gavagem do medicamento manipulado tiveram sintomas de fadiga, mas com redução do teor sanguíneo de ureia e ácido láctico, fibras musculares gastrocnêmias uniformemente arranjadas, linhas transversais regulares, e efeito rebote da expressão proteica. Isto mostra que os medicamentos manipulados da medicina chinesa podem desempenhar um papel significativo no alívio da fadiga causada pela marcha atlética.
RESUMEN La fatiga causada por la marcha atlética es un tipo de síntoma que afecta los atletas después de un período de práctica del ejercicio, que puede ocasionar debilidad de los miembros, fatiga mental, fatiga muscular y otros fenómenos. En ausencia de elongación y tratamiento eficaz después del ejercicio, las lesiones causadas por el deporte pueden afectar seriamente la función física de los atletas. A fin de aliviar de manera eficaz la fatiga causada por la marcha atlética, el presente estudio se concentró en los medicamentos manipulados en la medicina tradicional china (MTC), analizó el mecanismo de acción y eficacia medicinal de los medicamentos da MTC, y realizó experimentos de control en 80 ratones del tipo ICR masculinos. Los ratones del grupo experimental recibieron entrenamiento sedentario y entrenamiento de carrera en grupo. Los resultados mostraron que los dos grupos de ratones ICR, después de entrenamiento de marcha atlética, presentaban síntomas de fatiga, y gran cantidad de ácido láctico sérico, además de otras sustancias, mientras que los ratones del grupo D tratados con gavaje del medicamento manipulado tuvieron síntomas de fatiga, pero con reducción del tenor sanguíneo de urea y ácido láctico, fibras musculares del gastrocnemio uniformemente arregladas, líneas transversales regulares, y efecto rebote de la expresión proteica. Esto muestra que los medicamentos manipulados de la medicina china pueden desempeñar un papel significativo en el alivio de la fatiga causada por la marcha atlética.
Asunto(s)
Animales , Masculino , Ratones , Condicionamiento Físico Animal , Fatiga/prevención & control , Atletas , Marcha/efectos de los fármacos , Medicina Tradicional ChinaRESUMEN
OBJECTIVE: Attentional deficits following degeneration of brain cholinergic systems contribute to gait-balance deficits in Parkinson disease (PD). As a step toward assessing whether α4ß2* nicotinic acetylcholine receptor (nAChR) stimulation improves gait-balance function, we assessed target engagement of the α4ß2* nAChR partial agonist varenicline. METHODS: Nondemented PD participants with cholinergic deficits were identified with [18 F]fluoroethoxybenzovesamicol positron emission tomography (PET). α4ß2* nAChR occupancy after subacute oral varenicline treatment was measured with [18 F]flubatine PET. With a dose selected from the nAChR occupancy experiment, varenicline effects on gait, balance, and cognition were assessed in a double-masked placebo-controlled crossover study. Primary endpoints were normal pace gait speed and a measure of postural stability. RESULTS: Varenicline doses (0.25mg per day, 0.25mg twice daily [b.i.d.], 0.5mg b.i.d., and 1.0mg b.i.d.) produced 60 to 70% receptor occupancy. We selected 0.5mg orally b.i.d for the crossover study. Thirty-three participants completed the crossover study with excellent tolerability. Varenicline had no significant impact on the postural stability measure and caused slower normal pace gait speed. Varenicline narrowed the difference in normal pace gait speed between dual task and no dual task gait conditions, reduced dual task cost, and improved sustained attention test performance. We obtained identical conclusions in 28 participants with treatment compliance confirmed by plasma varenicline measurements. INTERPRETATION: Varenicline occupied α4ß2* nicotinic acetylcholine receptors, was tolerated well, enhanced attention, and altered gait performance. These results are consistent with target engagement. α4ß2* agonists may be worth further evaluation for mitigation of gait and balance disorders in PD. ANN NEUROL 2021;90:130-142.
Asunto(s)
Trastornos Neurológicos de la Marcha/tratamiento farmacológico , Marcha/efectos de los fármacos , Agonistas Nicotínicos/uso terapéutico , Enfermedad de Parkinson/tratamiento farmacológico , Equilibrio Postural/efectos de los fármacos , Vareniclina/uso terapéutico , Anciano , Encéfalo/diagnóstico por imagen , Estudios Cruzados , Femenino , Trastornos Neurológicos de la Marcha/diagnóstico por imagen , Humanos , Masculino , Persona de Mediana Edad , Agonistas Nicotínicos/farmacología , Enfermedad de Parkinson/diagnóstico por imagen , Tomografía de Emisión de Positrones , Vareniclina/farmacologíaRESUMEN
Duchenne muscular dystrophy (DMD) is a genetic disease linked to the X chromosome induced by mutations in the dystrophin gene. Neuroprotective drugs, such as pregabalin (PGB), can improve motor function through the modulation of excitatory synapses, together with anti-apoptotic and anti-inflammatory effects. The present work studied the effects of PGB in the preservation of dystrophic peripheral nerves, allowing motor improvements in MDX mice. Five weeks old MDX and C57BL/10 mice were treated with PGB (30 mg/kg/day, i.p.) or vehicle, for 28 consecutive days. The mice were sacrificed on the 9th week, the sciatic nerves were dissected out and processed for immunohistochemistry and qRT-PCR, for evaluating the expression of proteins and gene transcripts related to neuronal activity and Schwann cell function. The lumbar spinal cords were also processed for qRT-PCR to evaluate the expression of neurotrophic factors and pro- and anti-inflammatory cytokines. Cranial tibial muscles were dissected out for endplate evaluation with α-bungarotoxin. The recovery of motor function was monitored throughout the treatment, using a spontaneous walking track test (Catwalk system) and a forced locomotion test (Rotarod). The results showed that treatment with PGB reduced the retrograde effects of muscle degeneration/regeneration on the nervous system from the 5th to the 9th week in MDX mice. Thus, PGB induced protein expression in neurons and Schwann cells, protecting myelinated fibers. In turn, better axonal morphology and close-to-normal motor endplates were observed. Indeed, such effects resulted in improved motor coordination of dystrophic animals. We believe that treatment with PGB improved the balance between excitatory and inhibitory inputs to spinal motoneurons, increasing motor control. In addition, PGB enhanced peripheral nerve homeostasis, by positively affecting Schwann cells. In general, the present results indicate that pregabalin is effective in protecting the PNS during the development of DMD, improving motor coordination, indicating possible translation to the clinic.