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Importance: Functional movement disorders (FMDs) are frequent and disabling neurological disorders with a substantial socioeconomic impact. Few randomized studies have analyzed the effectiveness of combined physiotherapy and psychotherapy in patients' quality of life. Objective: To assess the efficacy of multidisciplinary treatment (physiotherapy plus cognitive behavioral therapy) in FMDs. Design, Setting, and Participants: This was a parallel, rater-blinded, single-center, randomized clinical trial. Recruitment took place from June 2022 to April 2023, and follow-up visits were performed at months 3 and 5, concluding in October 2023. Participants were recruited from a national referral center for movement disorders: the Movement Disorders Unit from the Hospital Universitario Virgen Rocio in Seville, Spain. Patients had to be 18 years or older with a confirmed FMD diagnosis and capable of giving consent to participate. Patients who did not meet eligibility criteria or refused to participate were excluded. Any uncontrolled psychiatric disorder was considered an exclusion criterion. Interventions: Patients were randomly assigned, in a ratio of 1:1 to multidisciplinary treatment (physiotherapy plus cognitive behavioral therapy), or a control intervention (psychological support intervention). Main Outcomes and Measures: Primary outcomes: between-group differences in changes from baseline to month 3 and month 5 in patients' quality of life (EQ-5D-5L score: EQ Index and EQ visual analog scale [EQ VAS]; and 36-Item Short-Form Survey Physical Component Summary [SF-36 PCS] and SF-36 Mental Component Summary [MCS]). Linear mixed models were applied, controlling by baseline severity and applying Bonferroni correction. Results: Of 70 patients screened with an FMD, 40 were enrolled (mean [SD] age, 43.5 [12.8] years; age range, 18-66 years; 32 female [80%]; mean [SD] age at FMD onset, 38.4 [12.1] years), and 38 completed all the follow-up visits and were included in the analysis for primary outcomes. Multidisciplinary treatment improved SF-36 PCS with a mean between-group difference at 3 months of 4.23 points (95% CI, -0.9 to 9.4 points; P = .11) and a significant mean between-group difference at 5 months of 5.62 points (95% CI, 2.3-8.9 points; P < .001), after multiple-comparisons adjustment. There were no significant differences in other quality-of-life outcomes such as SF-36 MCS (mean between-group difference at 3 and 5 months: 0.72 points; 95% CI, -5.5 to 7.0 points; P = .82 and 0.69 points; 95% CI, 2.3-8.9 points; P = .83, respectively), EQ VAS (9.34 points; 95% CI, -0.6 to 19.3 points; P = .07 and 13.7 points; 95% CI, -1.7 to 29.0 points; P = .09, respectively) and EQ Index (0.001 point; 95% CI, -0.1 to 0.1 point; P = .98 and 0.08 points; 95% CI, 0-0.2 points; P = .13, respectively). At months 3 and 5, 42% and 47% of patients, respectively, in the multidisciplinary group reported improved health using the EQ-5D system, compared with 26% and 16% of patients, respectively, in the control group. Conclusions and Relevance: Results show that multidisciplinary treatment (physiotherapy plus cognitive behavioral therapy) effectively improves FMD symptoms and physical aspects of patients' quality of life. Further studies must be performed to evaluate the potential cost-effectiveness of this approach in FMD. Trial Registration: ClinicalTrials.gov Identifier: NCT05634486.
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There is increasing evidence that supports the role of the cerebellum in the pathophysiology of dystonia. We used transcranial magnetic stimulation to test the hypothesis that patients with cervical dystonia may have a disrupted cerebellar cortical connectivity at rest, and that cerebellar plasticity is altered too. We enrolled 12 patients with isolated cervical dystonia and 13 controls. A paired-pulse transcranial magnetic stimulation protocol was applied over the right cerebellum and the left primary motor area. Changes in the amplitude of motor evoked potentials were analysed. Continuous and intermittent Theta Burst Stimulation over the cerebellum was also applied. The effects of these repetitive protocols on cortical excitability, on intra-cortical circuits and on cerebellar cortical inhibition were analysed. In healthy subjects, but not in dystonic patients, a conditioning stimulus over the cerebellum was able to inhibit the amplitude of the motor evoked potentials from primary motor cortex. In healthy subjects continuous and intermittent cerebellar Theta Burst Stimulation were able to decrease and increase respectively motor cortex excitability. Continuous Theta Burst Stimulation was able to abolish the cerebellar cortical inhibition observed in basal condition. These effects were not observed in patients with cervical dystonia. Cerebellar cortical connectivity and cerebellar plasticity is altered at rest in patients with cervical dystonia.
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Cerebelo/fisiología , Trastornos Distónicos/fisiopatología , Adulto , Estudios de Casos y Controles , Potenciales Evocados Motores , Femenino , Humanos , Masculino , Persona de Mediana Edad , Corteza Motora/fisiología , Estimulación Magnética TranscranealAsunto(s)
Trastornos Cerebrovasculares/fisiopatología , Trastornos Cerebrovasculares/psicología , Cognición , Enfermedad de Parkinson Secundaria/fisiopatología , Enfermedad de Parkinson Secundaria/psicología , Corteza Sensoriomotora/fisiopatología , Vías Aferentes/fisiopatología , Anciano , Anciano de 80 o más Años , Electromiografía , Potenciales Evocados Motores , Potenciales Evocados Somatosensoriales , Femenino , Humanos , Masculino , Nervio Mediano/fisiopatología , Músculo Esquelético/fisiopatología , Inhibición Neural , Plasticidad Neuronal , Pruebas Neuropsicológicas , Estimulación Magnética TranscranealRESUMEN
OBJECTIVES: Euthymic patients with bipolar disorder (BD) have deficits in cortical inhibition. However, whether cortical inhibitory deficits are trait- or state-dependent impairments is not yet known and their relationship with psychiatric symptoms is not yet understood. In the present study, we examined trait- and state-dependent cortical inhibitory deficits and evaluated the potential clinical significance of these deficits. METHODS: Nineteen patients with bipolar I disorder were evaluated using the paired-pulse transcranial stimulation protocol, which assessed cortical inhibition during an acute manic episode. Cortical inhibition measures were compared with those obtained in 28 demographically matched healthy controls. A follow-up assessment was performed in 15 of these patients three months later, when there was remission from their mood and psychotic symptoms. The association between cortical inhibitory measures and severity of psychiatric symptoms was also studied. RESULTS: During mania, patients showed decreased short-interval intracortical and transcallosal inhibition, as well as a normal cortical silent period and long-interval cortical inhibition. These findings were the same during euthymia. Symptoms associated with motor hyperactivity were correlated negatively with the degree of cortical inhibition. These correlations were not significant when a Bonferroni correction was applied. CONCLUSIONS: The present longitudinal study showed cortical inhibitory deficits in patients with BD, and supports the hypothesis that cortical inhibitory deficits in BD are trait dependent. Further research is necessary to confirm the clinical significance of these deficits.
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Trastorno Bipolar/fisiopatología , Trastorno Bipolar/psicología , Corteza Cerebral/fisiopatología , Carácter , Inhibición Neural/fisiología , Adulto , Trastorno Bipolar/diagnóstico , Cuerpo Calloso/fisiopatología , Femenino , Humanos , Interneuronas/fisiología , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Actividad Motora/fisiología , Estimulación Transcraneal de Corriente Directa , Adulto Joven , Ácido gamma-Aminobutírico/fisiologíaRESUMEN
OBJECTIVES: Orthostatic tremor is a rare condition characterised by high-frequency tremor that appears on standing. Although the essential clinical features of orthostatic tremor are well established, little is known about the natural progression of the disorder. We report the long-term outcome based on the largest multicentre cohort of patients with orthostatic tremor. METHODS: Clinical information of 68 patients with clinical and electrophysiological diagnosis of orthostatic tremor and a minimum follow-up of 5 years is presented. RESULTS: There was a clear female preponderance (76.5%) with a mean age of onset at 54 years. Median follow-up was 6 years (range 5-25). On diagnosis, 86.8% of patients presented with isolated orthostatic tremor and 13.2% had additional neurological features. At follow-up, seven patients who initially had isolated orthostatic tremor later developed further neurological signs. A total 79.4% of patients reported worsening of orthostatic tremor symptoms. These patients had significantly longer symptom duration than those without reported worsening (median 15.5 vs 10.5 years, respectively; p=0.005). There was no change in orthostatic tremor frequency over time. Structural imaging was largely unremarkable and dopaminergic neuroimaging (DaTSCAN) was normal in 18/19 cases. Pharmacological treatments were disappointing. Two patients were treated surgically and showed improvement. CONCLUSIONS: Orthostatic tremor is a progressive disorder with increased disability although tremor frequency is unchanged over time. In most cases, orthostatic tremor represents an isolated syndrome. Drug treatments are unsatisfactory but surgery may hold promise.
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Temblor/epidemiología , Temblor/terapia , Edad de Inicio , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Progresión de la Enfermedad , Neuronas Dopaminérgicas , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Neuroimagen , Procedimientos Neuroquirúrgicos/métodos , Factores Sexuales , Estimulación de la Médula Espinal , Resultado del Tratamiento , Temblor/tratamiento farmacológicoRESUMEN
BACKGROUND: Recent studies have shown altered cortical plasticity in adult patients with Tourette syndrome. However, the clinical significance of this finding remains elusive. METHODS: Motor cortical plasticity was evaluated in 15 adult patients with severe Tourette syndrome and 16 healthy controls using the paired associative stimulation protocol by transcranial magnetic stimulation. Associations between paired associative stimulation-induced plasticity and relevant clinical variables, including cortical excitability, psychiatric comorbidities, drug treatment and tic severity, were assessed. RESULTS: Motor cortical plasticity was abnormally increased in patients with Tourette syndrome compared with healthy subjects. This abnormal plasticity was independently associated with tic severity. CONCLUSION: Patients with severe Tourette syndrome display abnormally increased cortical associative plasticity. This aberrant cortical plasticity was associated with tic severity, suggesting an underlying mechanism for tic pathophysiology.
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Potenciales Evocados Motores/fisiología , Corteza Motora/fisiopatología , Plasticidad Neuronal/fisiología , Síndrome de Tourette/patología , Adulto , Electromiografía , Humanos , Persona de Mediana Edad , Estimulación Magnética Transcraneal , Adulto JovenRESUMEN
BACKGROUND: The clinical profile in vascular parkinsonism (VP) patients is well described in the literature, but little is known about the neuropsychological features of this disease. The aim of our study was to evaluate the clinical characteristics and the profile of cognitive impairment in patients with VP. METHODS: We prospectively evaluated 12 patients with VP, 15 with Parkinson's disease (PD) and 13 healthy controls (HC) with similar age and sex distribution. Different clinical and demographic details were collected. All subjects underwent detailed neurological and neuropsychological examinations. The neuropsychological tests included analysis of global efficiency, executive function, verbal memory, language and visuospatial function. RESULTS: VP patients exhibited lower disease duration, older age at onset and higher frequency of cardiovascular risk factors. Non-motor symptoms were found to be more frequent in PD. We found that VP patients developed cognitive impairment with a significantly higher frequency than HC of a similar age. Additionally, we found that these patients had a global pattern of cognitive impairment, including executive function, verbal memory and language. Only visuospatial function was more impaired in PD than in HC. CONCLUSIONS: Our data contribute to clarify the pattern of neuropsychological impairment in VP. Therefore, in the clinical evaluation, besides assessing the motor status of the patient, given that these symptoms are frequently found not to be self-reported complaints, the neurologist should evaluate them routinely as a comprehensive assessment of this disease.
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Trastornos Cerebrovasculares/complicaciones , Trastornos del Conocimiento/diagnóstico , Trastornos del Conocimiento/etiología , Trastornos Parkinsonianos/complicaciones , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Neuroimagen , Pruebas Neuropsicológicas , Estudios Prospectivos , Estadísticas no ParamétricasRESUMEN
BACKGROUND: Dystonia is considered as a motor network disorder involving the dysfunction of the posterior parietal cortex, a region involved in preparing and executing reaching movements. OBJECTIVE/HYPOTHESIS: We used transcranial magnetic stimulation to test the hypothesis that cervical dystonic patients may have a disrupted parieto-motor connectivity. METHODS: We enrolled 14 patients with primary cervical dystonia and 14 controls. A paired-pulse transcranial magnetic stimulation protocol was applied over the right posterior parietal cortex and the right primary motor area. Changes in the amplitudes of motor evoked potential were analyzed as an index of parieto-motor effective connectivity. Patients and healthy subjects were also evaluated with a reaching task. Reaction and movement times were measured. RESULTS: In healthy subjects, but not in dystonic patients, there was a facilitation of motor evoked potential amplitudes when the conditioning parietal stimulus preceded the test stimulus applied over the primary motor area by 4 ms. Reaction and movement times were significantly slower in patients than in controls. In dystonic patients, the relative strength of parieto-motor connectivity correlated with movement times. CONCLUSIONS: Parieto-motor cortical connectivity is impaired in cervical dystonic patients. This neurophysiological trait is associated with slower reaching movements.
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Potenciales Evocados Motores , Corteza Motora/fisiopatología , Lóbulo Parietal/fisiopatología , Tortícolis/congénito , Estimulación Magnética Transcraneal/métodos , Adulto , Anciano , Distonía/congénito , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tiempo de Reacción , Tortícolis/diagnóstico , Tortícolis/fisiopatología , Tortícolis/terapiaRESUMEN
Dystonia is generally regarded as a disorder of the basal ganglia and their efferent connections to the thalamus and brainstem, but an important role of cerebellar-thalamo-cortical (CTC) circuits in the pathophysiology of dystonia has been invoked. Here in a sham controlled trial, we tested the effects of two-weeks of cerebellar continuous theta burst stimulation (cTBS) in a sample of cervical dystonia (CD) patients. Clinical evaluations were performed by administering the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) and the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS). We used TMS to measure the inhibitory connectivity between the cerebellum and the contralateral motor cortex (cerebellar brain inhibition [CBI]), and the excitability of the contralateral primary motor cortex assessing intracortical inhibition (SICI), intracortical facilitation (ICF) and cortical silent period (CSP). Paired associative stimulation (PAS) was tested to evaluate the level and the topographical specificity of cortical plasticity, which is abnormally enhanced and non-focal in CD patients. Two weeks of cerebellar stimulation resulted in a small but significant clinical improvement as measured by the TWSTRS of approximately 15%. Cerebellar stimulation modified the CBI circuits and reduced the heterotopic PAS potentiation, leading to a normal pattern of topographic specific induced plasticity. These data provide novel evidence CTC circuits could be a potential target to partially control some dystonic symptoms in patients with cervical dystonia.
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Tortícolis/terapia , Estimulación Magnética Transcraneal , Adulto , Anciano , Cerebelo/fisiopatología , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Corteza Motora/fisiopatología , Tálamo/fisiopatología , Tortícolis/fisiopatologíaRESUMEN
Primary dystonia is thought to be a disorder of the basal ganglia because the symptoms resemble those of patients who have anatomical lesions in the same regions of the brain (secondary dystonia). However, these two groups of patients respond differently to therapy suggesting differences in pathophysiological mechanisms. Pathophysiological deficits in primary dystonia are well characterized and include reduced inhibition at many levels of the motor system and increased plasticity, while emerging evidence suggests additional cerebellar deficits. We compared electrophysiological features of primary and secondary dystonia, using transcranial magnetic stimulation of motor cortex and eye blink classical conditioning paradigm, to test whether dystonia symptoms share the same underlying mechanism. Eleven patients with hemidystonia caused by basal ganglia or thalamic lesions were tested over both hemispheres, corresponding to affected and non-affected side and compared with 10 patients with primary segmental dystonia with arm involvement and 10 healthy participants of similar age. We measured resting motor threshold, active motor threshold, input/output curve, short interval intracortical inhibition and cortical silent period. Plasticity was probed using an excitatory paired associative stimulation protocol. In secondary dystonia cerebellar-dependent conditioning was measured using delayed eye blink classical conditioning paradigm and results were compared with the data of patients with primary dystonia obtained previously. We found no difference in motor thresholds, input/output curves or cortical silent period between patients with secondary and primary dystonia or healthy controls. In secondary dystonia short interval intracortical inhibition was reduced on the affected side, whereas it was normal on the non-affected side. Patients with secondary dystonia had a normal response to the plasticity protocol on both the affected and non-affected side and normal eye blink classical conditioning that was not different from healthy participants. In contrast, patients with primary dystonia showed increased cortical plasticity and reduced eye blink classical conditioning. Normal motor cortex plasticity in secondary dystonia demonstrates that abnormally enhanced cortical plasticity is not required for clinical expression of dystonia, and normal eye blink conditioning suggests an absence of functional cerebellar involvement in this form of dystonia. Reduced short interval intracortical inhibition on the side of the lesion may result from abnormal basal ganglia output or may be a consequence of maintaining an abnormal dystonic posture. Dystonia appears to be a motor symptom that can reflect different pathophysiological states triggered by a variety of insults.
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Parpadeo/fisiología , Distonía/fisiopatología , Trastornos Distónicos/fisiopatología , Potenciales Evocados Motores/fisiología , Adulto , Anciano , Análisis de Varianza , Lesiones Encefálicas/complicaciones , Estudios de Casos y Controles , Condicionamiento Clásico , Distonía/etiología , Distonía/patología , Trastornos Distónicos/patología , Electromiografía , Femenino , Lateralidad Funcional , Humanos , Masculino , Persona de Mediana Edad , Corteza Motora/fisiopatología , Inhibición Neural/fisiología , Tractos Piramidales/fisiopatología , Estimulación Magnética Transcraneal , Adulto JovenRESUMEN
BACKGROUND: Although functional changes in the activation of the cerebellum in Parkinson's disease (PD) patients have been consistently described, it is still debated whether such altered cerebellar activation is a natural consequence of PD pathophysiology or rather it involves compensatory mechanisms. OBJECTIVE/HYPOTHESIS: We used different forms of cerebellar transcranial magnetic stimulation to evaluate the hypothesis that altered cerebello-cortical interactions can be observed in PD patients and to evaluate the role of dopaminergic treatment. METHODS: We studied the effects of a single cerebellar magnetic pulse over the excitability of the contralateral primary motor cortex tested with motor-evoked potentials (MEPs) (cerebellar-brain inhibition-CBI) in a group of 16 PD patients with (ON) and without dopaminergic treatment (OFF), and in 16 age-matched healthy controls. Moreover, we also tested the effects of cerebellar continuous theta-burst stimulation (cTBS) on MEP amplitude, short intracortical inhibition (SICI) and short intracortical facilitation (SICF) tested in the contralateral M1 in 13 PD patients in ON and OFF and in 16 age-matched healthy controls. RESULTS: CBI was evident in controls but not in PD patients, even when tested in both ON and OFF conditions. Similarly, cerebellar cTBS reduced MEP amplitude and SICI in controls but not in PD patients under any condition. CONCLUSION(S): These results demonstrate that PD patients have deficient short-latency and long-lasting cerebellar-thalamocortical inhibitory interactions that cannot be promptly restored by standard dopaminergic medication.
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Cerebelo/fisiopatología , Corteza Motora/fisiopatología , Enfermedad de Parkinson/fisiopatología , Tálamo/fisiopatología , Estimulación Magnética Transcraneal , Adulto , Anciano , Antiparkinsonianos/farmacología , Antiparkinsonianos/uso terapéutico , Cerebelo/efectos de los fármacos , Electromiografía , Potenciales Evocados Motores/efectos de los fármacos , Potenciales Evocados Motores/fisiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Corteza Motora/efectos de los fármacos , Vías Nerviosas/efectos de los fármacos , Vías Nerviosas/fisiopatología , Enfermedad de Parkinson/tratamiento farmacológico , Tálamo/efectos de los fármacosRESUMEN
OBJECTIVE: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a small vessel disease of the brain caused by mutations in the NOTCH3 gene. CADASIL progresses, in some cases, to subcortical dementia with a particular cognitive impairment. Different diseases in the dementia spectrum share a central cholinergic and sensorimotor plasticity alteration. We aimed to study different intracortical circuits and sensorimotor plasticity in CADASIL patients using transcranial magnetic stimulation protocols, and to determine whether these characteristics correlated with the results of clinical neuropsychological evaluation. METHODS: Ten CADASIL patients and 10 healthy subjects were included in the study. All subjects underwent a transcranial magnetic stimulation study examining different intracortical circuits. Sensorimotor plasticity was also assessed using a paired associative stimulation and extensive neuropsychological tests. RESULTS: CADASIL patients showed a lack of intracortical facilitation, short latency afferent inhibition and sensorimotor plasticity when compared with control subjects. CADASIL patients also showed an altered neuropsychological profile. Correlation between sensorimotor plasticity and neuropsychological alterations was observed in CADASIL patients. CONCLUSIONS: These results suggest that acetylcholine and glutamate could be involved in the dementia process in CADASIL and that abnormal sensorimotor plasticity correlates with the neuropsychological profile in CADASIL patients.
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CADASIL/fisiopatología , CADASIL/psicología , Corteza Cerebral/fisiopatología , Plasticidad Neuronal/fisiología , Pruebas Neuropsicológicas/estadística & datos numéricos , Adulto , Anciano , Estudios de Casos y Controles , Electromiografía/métodos , Electromiografía/psicología , Potenciales Evocados Motores/fisiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Vías Nerviosas/fisiopatología , Estimulación Magnética Transcraneal/métodos , Estimulación Magnética Transcraneal/psicologíaRESUMEN
The fragile X syndrome is a mutation-driven developmental disorder caused by a repetition over 200 times of the CGG trinucleotide situated in the 5'-untranslated region of the fragile X mental retardation 1 gene (FMR1). The interval between 55 and 199 CGG repeats, which is over the normal range but below full mutation, is named fragile X premutation. Recent studies have focused on the asymptomatic state of fragile X premutation carriers and their potentially relevant preclinical features. However, the underlying neurological mechanisms leading to altered functions in fragile X premutation carriers are still poorly understood. In this study, we wanted to test the hypothesis that asymptomatic women who carry the fragile X premutation present GABAergic and cerebellar abnormalities compared with healthy women without the premutation. We performed noninvasive brain stimulation protocols on both asymptomatic fragile X premutation carriers and controls comprising of measures of GABAA- and GABAB-mediated intracortical inhibition, afferent inhibition, and cerebello-motor functional interactions. Premutation carriers presented an absence of cerebellar inhibition over primary motor cortex as well as a reduced GABAA-mediated intracortical and afferent inhibition compared with healthy nonpremutated controls. These alterations are most probably dependent on a dysfunctional GABAergic mechanism associated with the fragile X premutation condition as previously found in CGG-repeat animal models. Furthermore, the lack of cerebello-motor inhibition could be related to the cerebellar structural abnormalities previously found in carriers of the premutation.
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Cerebelo/fisiopatología , Síndrome del Cromosoma X Frágil/fisiopatología , Corteza Motora/fisiopatología , Inhibición Neural , Ácido gamma-Aminobutírico/metabolismo , Adulto , Vías Aferentes/fisiopatología , Enfermedades Asintomáticas , Estudios de Casos y Controles , Potenciales Evocados Motores , Femenino , Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil/genética , Síndrome del Cromosoma X Frágil/diagnóstico , Síndrome del Cromosoma X Frágil/genética , Neuronas GABAérgicas/metabolismo , Neuronas GABAérgicas/fisiología , Humanos , Persona de Mediana Edad , Mutación , Estimulación Magnética TranscranealRESUMEN
BACKGROUND: Bradykinesia in Parkinson's disease is associated with a difficulty in selecting and executing motor actions, likely due to alterations in the functional connectivity of cortico-cortical circuits. OBJECTIVE/HYPOTHESIS: Our aims were to analyse the functional interplay between the posterior parietal cortex and the ipsilateral primary motor area in Parkinson's disease using bifocal transcranial magnetic stimulation, to evaluate its modulation by dopaminergic treatment and its relationship to a simple choice reaction task. METHODS: We studied 12 Parkinson's disease patients with and without dopaminergic treatment and 12 healthy controls. A paired-pulse transcranial magnetic stimulation protocol was applied over the right posterior parietal cortex and the right primary motor area using different conditioning stimulus intensities and interstimulus intervals. Reaction and movement times were studied by a simple choice reaction task. RESULTS: In controls, we observed a significant facilitation of motor evoked potential amplitudes at 4 ms interstimulus interval when conditioning stimulus intensity was set to 90% of resting motor threshold. This functional interaction was not observed in Parkinson's disease patients without dopaminergic treatment and was not restored with treatment. Moreover, correlation analyses revealed that Parkinson's disease patients with less impaired parieto-motor interaction were faster in executing reaching movements in a choice reaction time task, suggesting that the functional parieto-motor impairment described here could be related to bradykinesia observed in Parkinson's disease patients. CONCLUSIONS: Parieto-motor functional connectivity is impaired in Parkinson's disease. The reduced efficacy of this connection could be related to presence of bradykinesia previously observed in Parkinson's disease.
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Corteza Motora/fisiopatología , Lóbulo Parietal/fisiopatología , Enfermedad de Parkinson/fisiopatología , Adulto , Anciano , Conducta de Elección/fisiología , Potenciales Evocados Motores/fisiología , Femenino , Humanos , Hipocinesia/fisiopatología , Masculino , Persona de Mediana Edad , Movimiento/fisiología , Vías Nerviosas/fisiopatología , Tiempo de Reacción/fisiología , Estimulación Magnética TranscranealRESUMEN
Botulinum toxin (BT) acts peripherally by inhibiting acetylcholine release from the presynaptic neuromuscular terminals and by weakening muscle contraction. Therefore, its clinical benefit is primarily due to its peripheral action. As a result, local injection of BT has become a successful and safe tool in the treatment of several neurological and non-neurological disorders. Studies in animals have also shown that the toxin can be retrogradely transported and even transcytosed to neurons in the central nervous system (CNS). Further human studies have suggested that BT could alter the functional organisation of the CNS indirectly through peripheral mechanisms. BT can interfere with and modify spinal, brainstem and cortical circuits, including cortical excitability and plasticity/organisation by altering spindle afferent inflow directed to spinal motoneurons or to the various cortical areas. It is well demonstrated that the distant CNS effects of BT treatment parallel the peripheral effect, although there is limited evidence as to the cause of this. Therefore, further studies focussed on central changes after BT treatment is needed for a better understanding of these non-peripheral effects of BT.
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Toxinas Botulínicas/farmacología , Fenómenos Fisiológicos del Sistema Nervioso/efectos de los fármacos , Fármacos Neuromusculares/farmacología , Animales , Tronco Encefálico/efectos de los fármacos , Tronco Encefálico/fisiología , Corteza Cerebral/efectos de los fármacos , Corteza Cerebral/fisiología , Humanos , Inyecciones Intramusculares , Ratones , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/fisiología , Ratas , Médula Espinal/efectos de los fármacos , Médula Espinal/fisiologíaRESUMEN
Sensory symptoms are common nonmotor manifestations of Parkinson's disease. It has been hypothesized that abnormal central processing of sensory signals occurs in Parkinson's disease and is related to dopaminergic treatment. The objective of this study was to investigate the alterations in sensory perception induced by transcranial magnetic stimulation of the primary somatosensory cortex in patients with Parkinson's disease and the modulatory effects of dopaminergic treatment. Fourteen patients with Parkinson's disease with and without dopaminergic treatment and 13 control subjects were included. Twenty milliseconds after peripheral electrical tactile stimuli in the contralateral thumb, paired-pulse transcranial magnetic stimulation over the right primary somatosensory cortex was delivered. We evaluated the perception of peripheral electrical tactile stimuli at 2 conditioning stimulus intensities, set at 70% and 90% of the right resting motor threshold, using different interstimulus intervals. At 70% of the resting motor threshold, paired-pulse transcranial magnetic stimulation over the right primary somatosensory cortex induced an increase in positive responses at short interstimulus intervals (1-7 ms) in controls but not in patients with dopaminergic treatment. At 90% of the resting motor threshold, controls and patients showed similar transcranial magnetic stimulation effects. Changes in peripheral electrical tactile stimuli perception after paired-pulse transcranial magnetic stimulation over the primary somatosensory cortex are altered in patients with Parkinson's disease with dopaminergic treatment compared with controls. These findings suggest that primary somatosensory cortex excitability could be involved in changes in somatosensory integration in Parkinson's disease with dopaminergic treatment.
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Enfermedad de Parkinson/patología , Corteza Somatosensorial/fisiología , Percepción del Tacto/fisiología , Estimulación Magnética Transcraneal , Adulto , Vías Aferentes , Anciano , Dopaminérgicos/farmacología , Dopaminérgicos/uso terapéutico , Electromiografía , Femenino , Dedos/inervación , Humanos , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/terapia , Umbral Sensorial/fisiología , Estadísticas no Paramétricas , TactoRESUMEN
Approximately 10% of patients diagnosed clinically with early Parkinson's disease (PD) have normal dopaminergic functional imaging (Scans Without Evidence of Dopaminergic Deficit [SWEDDs]). An important subgroup of SWEDDs are those with asymmetric rest tremor resembling parkinsonian tremor. Clinical and pathophysiological features which could help to distinguish SWEDDs from PD have not been explored. We therefore studied clinical details including non-motor symptoms in 25 tremulous SWEDDs patients in comparison to 25 tremor-dominant PD patients. Blinded video rating was used to compare examination findings. Electrophysiological tremor parameters and also response to a cortical plasticity protocol using paired associative stimulation (PAS) was studied in 9 patients with SWEDDs, 9 with tremor-dominant PD (with abnormal dopamine transporter single photon emission computed tomography findings), 8 with segmental dystonia, and 8 with essential tremor (ET). Despite clinical overlap, lack of true bradykinesia, presence of dystonia, and head tremor favored a diagnosis of SWEDDs, whereas re-emergent tremor, true fatiguing or decrement, good response to dopaminergic drugs, and presence of non-motor symptoms favored PD. A single tremor parameter could not differentiate between groups, but the combination of re-emergent tremor and highest tremor amplitude at rest was characteristic of PD tremor. SWEDDs and segmental dystonia patients exhibited an abnormal exaggerated response to the PAS protocol, in contrast to a subnormal response in PD and a normal response in ET. We conclude that despite clinical overlap, there are features that can help to distinguish between PD and SWEDDs which may be useful in clinical practice. The underlying pathophysiology of SWEDDs differs from PD but has similarities with primary dystonia.