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1.
J Neurol Neurosurg Psychiatry ; 87(3): 302-10, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-25817520

RESUMEN

OBJECTIVE: The results of register studies suggest an association between Parkinson's disease (PD) and melanoma. We studied the frequency and profile of early markers of PD in patients with malignant melanoma. METHODS: 100 participants were enrolled in a prospective observational study, of whom 65 had a history of high-risk cutaneous (n=53) or uveal (n=12) melanoma (31 women; age, 61.2±14.9 years) and another 35 served as control participants (19 women; 54.6±20.5 years). Participants underwent assessments of motor function (Unified PD Rating Scale; keyboard tapping test), olfactory function, colour vision, depressive symptoms, the Non-Motor Symptoms Questionnaire, and transcranial brain sonography. Raters were blinded to the diagnosis and clinical data of study participants. RESULTS: Patients with melanoma showed increased frequency of substantia nigra hyperechogenicity and prodromal motor and non-motor features of PD, especially asymmetric motor slowing and apathy. Hyposmia and colour vision disturbance were, however, infrequent. Larger echogenicity of substantia nigra correlated with lower serum iron in patients with melanoma, similar to previously reported findings in PD, and independently from the earlier findings, with lighter skin pigmentation. Substantia nigra hyperechogenicity, combined with motor asymmetry or hyposmia, was present at baseline in all participants with mild or definite parkinsonism diagnosed after 1 year. Parkinsonism was specifically related to melanoma location at the sun-exposed skin of the head or neck. CONCLUSIONS: History of melanoma was associated with increased prevalence of prodromal markers of PD. Their predictive value needs to be established in long-term investigations. The similarity of serum iron characteristics found in patients with melanoma and PD deserves further research.


Asunto(s)
Melanoma/epidemiología , Enfermedad de Parkinson/diagnóstico , Enfermedad de Parkinson/epidemiología , Síntomas Prodrómicos , Estudios de Casos y Controles , Comorbilidad , Femenino , Humanos , Masculino , Melanoma/diagnóstico por imagen , Persona de Mediana Edad , Enfermedad de Parkinson/diagnóstico por imagen , Prevalencia , Estudios Prospectivos , Ultrasonografía Doppler Transcraneal
2.
Mov Disord ; 31(3): 302-9, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-26362398

RESUMEN

BACKGROUND: A combination of preoperative magnetic resonance imaging (MRI) with real-time transcranial ultrasound, known as fusion imaging, may improve postoperative control of deep brain stimulation (DBS) electrode location. Fusion imaging, however, employs a weak magnetic field for tracking the position of the ultrasound transducer and the patient's head. Here we assessed its feasibility, safety, and clinical relevance in patients with DBS. METHODS: Eighteen imaging sessions were conducted in 15 patients (7 women; aged 52.4 ± 14.4 y) with DBS of subthalamic nucleus (n = 6), globus pallidus interna (n = 5), ventro-intermediate (n = 3), or anterior (n = 1) thalamic nucleus and clinically suspected lead displacement. Minimum distance between DBS generator and magnetic field transmitter was kept at 65 cm. The pre-implantation MRI dataset was loaded into the ultrasound system for the fusion imaging examination. The DBS lead position was rated using validated criteria. Generator DBS parameters and neurological state of patients were monitored. RESULTS: Magnetic resonance-ultrasound fusion imaging and volume navigation were feasible in all cases and provided with real-time imaging capabilities of DBS lead and its location within the superimposed magnetic resonance images. Of 35 assessed lead locations, 30 were rated optimal, three suboptimal, and two displaced. In two cases, electrodes were re-implanted after confirming their inappropriate location on computed tomography (CT) scan. No influence of fusion imaging on clinical state of patients, or on DBS implantable pulse generator function, was found. CONCLUSIONS: Magnetic resonance-ultrasound real-time fusion imaging of DBS electrodes is safe with distinct precautions and improves assessment of electrode location. It may lower the need for repeated CT or MRI scans in DBS patients.


Asunto(s)
Estimulación Encefálica Profunda , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Enfermedad de Parkinson/terapia , Núcleo Subtalámico/cirugía , Adulto , Anciano , Electrodos Implantados , Femenino , Globo Pálido/cirugía , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Procedimientos Neuroquirúrgicos/métodos , Enfermedad de Parkinson/patología , Núcleo Subtalámico/fisiología
3.
Neurodegener Dis ; 16(3-4): 184-91, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-26613522

RESUMEN

BACKGROUND/AIMS: A substantial proportion of amyotrophic lateral sclerosis (ALS) patients develop cognitive impairments. Longitudinal investigations of cognition in ALS have shown mixed results. While some authors report that cognitive performance remains stable as the disease progresses, others have found evidence for deterioration in various domains. Our objective was to investigate cognitive performance in ALS longitudinally, using the example of executive functions. METHODS: 93 ALS patients and 73 age-, sex- and education-matched healthy controls underwent up to four neuropsychological evaluations, separated by 3- to 6-month intervals. We examined whether performance declined longitudinally on seven tests assessing various sub-components of executive functioning. Furthermore, we assigned an executive-performance-based 'cognitive status' to each participant for every evaluation, examining whether cognitive deterioration (if present) was modulated by their baseline cognitive status and whether cognitive status changed over time. RESULTS: Regardless of their cognitive status at baseline, ALS patients showed no significant decline in the sub-components of executive functioning. CONCLUSION: Our findings imply that the executive deficits which develop in some ALS patients emerge before motor symptoms and remain stable after an initial decline. The discrepancy between this trajectory and the progressive decline in motor functions may result from a differential vulnerability of motor and non-motor prefrontal neurons to the pathomechanism of ALS.


Asunto(s)
Esclerosis Amiotrófica Lateral/psicología , Función Ejecutiva , Anciano , Esclerosis Amiotrófica Lateral/epidemiología , Cognición , Progresión de la Enfermedad , Escolaridad , Femenino , Estudios de Seguimiento , Alemania/epidemiología , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Factores de Tiempo
4.
Cell Mol Neurobiol ; 35(1): 111-4, 2015 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-25283186

RESUMEN

Glucocorticosteroids (GCS) are widely used for the treatment of neurological diseases, e.g. multiple sclerosis. High levels of GCS are toxic to the central nervous system and can produce adverse effects. The effect of methylprednisolone (MP) on mammalian neuronal networks was studied in vitro. We demonstrate a dose-dependent excitatory effect of MP on cultured neuronal networks, followed by a shut-down of electrical activity using the microelectrode array technique.


Asunto(s)
Metilprednisolona/farmacología , Red Nerviosa/efectos de los fármacos , Red Nerviosa/fisiología , Neuronas/efectos de los fármacos , Neuronas/fisiología , Potenciales de Acción/efectos de los fármacos , Potenciales de Acción/fisiología , Animales , Células Cultivadas , Ratones , Red Nerviosa/citología , Médula Espinal/citología , Médula Espinal/efectos de los fármacos , Médula Espinal/fisiología
5.
J Neural Transm (Vienna) ; 122(6): 789-97, 2015 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-25217967

RESUMEN

Major depressive disorder (MDD) has been associated with an increased risk of subsequent Parkinson's disease (PD) in case-control and cohort studies. However, depression alone is unlikely to be a useful marker of prodromal PD due to its low specificity. In this longitudinal observational study, we assessed whether the presence of other potential markers of prodromal PD predicts the subsequent development of PD in MDD patients. Of 57 patients with severe MDD but no diagnosis of PD who underwent a structured interview, olfactory and motor investigation and transcranial sonography at baseline, 46 (36 women; mean age 54.9 ± 11.7 years) could be followed for up to 11 (median, 10) years. Three patients (2 women; age 64, 65 and 70 years) developed definite PD after 1, 7, and 9 years, respectively. The combined finding of mild asymmetric motor slowing, idiopathic hyposmia, and substantia nigra hyperechogenicity predicted subsequent PD in all patients who could be followed for longer than 1 year. Out of the whole study cohort, only the subjects with subsequent PD presented with the triad of asymmetric motor slowing, idiopathic hyposmia, and substantia nigra hyperechogenicity in combination with at least two out of four reportable risk factors (family history of PD, current non-smoker, non-coffee drinker, constipation) at baseline investigation. Post-hoc analysis revealed that additional rating of eye and eye-lid motor abnormalities might further improve the prediction of PD in larger cohorts. Findings of this pilot-study suggest that MDD patients at risk of subsequent PD can be identified using an inexpensive non-invasive diagnostic battery.


Asunto(s)
Trastorno Depresivo Mayor/complicaciones , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/diagnóstico , Anciano , Trastorno Depresivo Mayor/diagnóstico por imagen , Trastorno Depresivo Mayor/fisiopatología , Ojo/fisiopatología , Femenino , Estudios de Seguimiento , Humanos , Entrevistas como Asunto , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Actividad Motora , Enfermedad de Parkinson/diagnóstico por imagen , Enfermedad de Parkinson/fisiopatología , Proyectos Piloto , Síntomas Prodrómicos , Pronóstico , Sustancia Negra/diagnóstico por imagen , Ultrasonografía
6.
Epilepsy Behav ; 49: 351-3, 2015 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-25960425

RESUMEN

The preliminary data presented here shall give an impression on how different criteria for the identification of an antiepileptic drug (AED) with a possible or certain treatment effect can have an influence on the results of retrospective case series. We present a data subset from a large retrospective study which, when completed, will cover all treatment episodes of status epilepticus (SE) at the neurological department of the Universitätsmedizin Rostock from January 2010 to June 2013. We compare and contrast the results of four different efficacy criteria for the effectiveness of phenytoin (PHT), valproate (VPA), levetiracetam (LEV), and lacosamide (LCM): criterion 1 = the last AED administered before SE termination; criterion 2 = the last drug introduced into the antiepileptic therapy within 72 h before SE termination and without changes in the comedication; criterion 3 = the last drug introduced into the antiepileptic therapy or increased in dose within 24h before SE termination without changes in the comedication; and criterion 4 = the last drug introduced into the antiepileptic therapy within 72 h before SE termination, even allowing changes in the comedication. Thirty-seven treatment episodes in 32 patients (13 male and 19 female, mean age at first episode: 68 years, SD: 17) could be analyzed. In 31 episodes, at least one AED was given intravenously. Efficacy rates in the whole case series according to all four criteria were not significantly different between the four AEDs, but there was a considerable difference in the efficacy rates of each AED when evaluating them with the different efficacy criteria. Our data show that statistically significant results concerning the efficacy of different AEDs in different subtypes of SE may depend on the outcome criteria. Therefore, efficacy criteria for the effectiveness of AEDs in the treatment of SE should be standardized. This article is part of a Special Issue entitled Status Epilepticus.


Asunto(s)
Anticonvulsivantes/uso terapéutico , Estado Epiléptico/tratamiento farmacológico , Administración Intravenosa , Adulto , Anciano , Anticonvulsivantes/administración & dosificación , Relación Dosis-Respuesta a Droga , Quimioterapia Combinada , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Estado Epiléptico/clasificación , Resultado del Tratamiento
7.
Epilepsy Behav ; 45: 176-9, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25819947

RESUMEN

We provide some evidence concerning the efficacy of perampanel (PER) in refractory status epilepticus (SE). We retroactively identified patients with SE treated in our department by searching for the term "status epilepticus" in the electronic archive of medical records. We present and analyze in this paper the subset of data of the patients treated with PER. We analyzed ten episodes of SE in nine patients. At the first administration, PER was given in a dosage of 6mg to most of our patients (7 of 10). On average, PER was administered as the 6th antiepileptic drug (AED) (range: 2-10). Depending on the criterion for efficacy, PER appears effective for the termination of SE in 2 to 6 (of 10) episodes. Unfortunately, safety data for the administration of PER with loading doses needed for the treatment of SE are lacking. Because of this, PER should be used very carefully in refractory SE and only after first-line treatment options have failed.


Asunto(s)
Anticonvulsivantes/uso terapéutico , Piridonas/uso terapéutico , Estado Epiléptico/diagnóstico , Estado Epiléptico/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Registros Electrónicos de Salud/tendencias , Femenino , Humanos , Masculino , Persona de Mediana Edad , Nitrilos , Estudios Retrospectivos , Resultado del Tratamiento
8.
Epilepsy Behav ; 31: 334-8, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-24262784

RESUMEN

This prospective study was performed to investigate whether verbal memory deficits are present in patients with a first unprovoked seizure irrespective of significant lesions in the brain and whether symptoms of depression were experienced by those patients in the week before the seizure. After having given informed consent, patients who presented with a first unprovoked seizure were investigated with a psychometric battery consisting of a verbal memory test, a figural memory test, a test following the Stroop paradigm, and a self-rating scale for depression in addition to the routine diagnostic work-up with EEG and MRI. The data of 53 patients aged 45years on average (33 males and 20 females) were available. Verbal memory deficits were present in 60% of the patients, and 21% of the patients delivered a self-rating that was suggestive of at least minor depression in the week before the seizure. Neither verbal memory deficits nor symptoms of depression were associated with a significant lesion of the brain. There was a significant negative correlation between immediate recall in the verbal memory test and the score in the self-rating scale for depression. Our data suggest that even at the time of the first unprovoked seizure, there is an epileptic condition of the brain, which facilitates the occurrence of verbal memory deficits and depression in the presence of an epileptogenic focus irrespective of its localization.


Asunto(s)
Depresión/complicaciones , Epilepsia/complicaciones , Trastornos de la Memoria/diagnóstico , Trastornos de la Memoria/etiología , Pruebas Neuropsicológicas , Aprendizaje Verbal , Adulto , Electroencefalografía , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Factores de Tiempo
9.
J Neurosci Res ; 91(6): 838-47, 2013 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-23553727

RESUMEN

Botulinum neurotoxin (BoNT) inhibits the release of acetylcholine from presynaptic vesicles through its proteinase activity cleaving the SNARE complex. Parkinson's disease (PD) is associated with locally increased cholinergic activity in the striatum. Therefore, the present study investigates the effect of unilateral intrastriatal BoNT-A injection in naïve rats on striatal morphology; i.e., the total number of Nissl-stained neurons and the volume of caudate-putamen (CPu) were estimated. Furthermore, stainings for markers of gliosis (glial fibrillary acidic protein) and microglia (Iba1) were performed. In addition, the potential beneficial effects of a unilateral intrastriatal injection of BoNT-A on motor activity in the rat model of hemi-PD were evaluated. Hemi-PD was induced by unilateral injection of 6-hydroxydopamine (6-OHDA) into the right medial forebrain bundle. Six weeks later, rats received an ipsilateral intrastriatal injection of BoNT-A. Behaviorally, motor performance was tested. The total number of CPu neurons and the striatal volume were not significantly different between the BoNT-A-injected right and the intact left hemispheres of naïve rats. In hemi-PD rats, intrastriatal BoNT-A abolished apomorphine-induced rotations, increased amphetamine-induced rotations, and tended to improve left forelimb usage. Forced motor function in the accelerod test was not significantly changed by BoNT-A, and open field activity was also unaltered compared with sham treatment. Thus, intrastriatal BoNT-A affects spontaneous motor activity of hemi-PD rats to a minor degree compared with drug-induced motor function. In the future, tests assessing the cognitive and emotional performance should be performed to ascertain finally the potential therapeutic usefulness of intrastriatal BoNT-A for PD.


Asunto(s)
Toxinas Botulínicas Tipo A/administración & dosificación , Cuerpo Estriado/efectos de los fármacos , Neurotoxinas/administración & dosificación , Trastornos Parkinsonianos/patología , Animales , Conducta Animal/efectos de los fármacos , Cuerpo Estriado/patología , Inmunohistoquímica , Inyecciones Intraventriculares , Masculino , Actividad Motora/efectos de los fármacos , Trastornos Parkinsonianos/fisiopatología , Ratas , Ratas Wistar
10.
Epilepsy Behav ; 27(1): 135-9, 2013 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-23416284

RESUMEN

In this study, we sought to determine the patients' attitudes towards generic substitution of antiepileptic drugs (AEDs) and their experiences with the usage of generic antiepileptic drugs in Germany and other German-speaking countries. A questionnaire was designed for a cross-sectional study. Two thousand copies of the questionnaire were delivered with a magazine edited by a patients' organization. Additionally, the questionnaire was placed on the internet platform of another patients' organization. Thirty-two percent of the patients who already experienced a switch to generic AEDs complained of problems with the switch. Patients who answered the magazine survey worried significantly more about generic substitution of AEDs than patients who answered the internet version. Patients who had never switched were more concerned about generic substitution than those who had already switched. Moreover, patients' beliefs differed between the use of generic drugs in acute medical conditions such as pain and infections and the use of generic AEDs in epilepsy.


Asunto(s)
Anticonvulsivantes/uso terapéutico , Sustitución de Medicamentos/estadística & datos numéricos , Medicamentos Genéricos/uso terapéutico , Epilepsia/psicología , Prioridad del Paciente/estadística & datos numéricos , Adolescente , Adulto , Anciano , Actitud , Austria/epidemiología , Estudios Transversales , Epilepsia/tratamiento farmacológico , Epilepsia/epidemiología , Femenino , Alemania/epidemiología , Encuestas Epidemiológicas , Humanos , Masculino , Persona de Mediana Edad , Prioridad del Paciente/psicología , Encuestas y Cuestionarios , Suiza/epidemiología , Adulto Joven
11.
J Neurol Neurosurg Psychiatry ; 83(4): 441-7, 2012 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-22362921

RESUMEN

OBJECTIVE: Characteristic features of Parkinson's disease (PD) are asymmetric parkinsonian motor signs, hyposmia and substantia nigra (SN) hyperechogenicity on transcranial ultrasound. However, each of these features has limited diagnostic value as they may be present, albeit less frequently, in other parkinsonian disorders. Here, the diagnostic sensitivity and specificity of combined assessment of these three features are evaluated. METHODS: 632 patients with parkinsonism (PD, vascular parkinsonism, atypical parkinsonian syndromes, essential tremor and major depressive disorder with motor slowing) were assessed on the Unified Parkinson's disease Rating Scale for motor asymmetry (right-left score difference ≥2), the 12 item Sniffin' Sticks test (SS-12) and transcranial ultrasound. The derivation (validation) cohort consisted of 517 (115) subjects (193 (35) women; age 65.4±9.6 (62.3±10.3) years) of whom 385 (68) had PD and 132 (47) non-PD parkinsonism; another 21 (6) subjects were not included due to missing transcranial insonability. Of the validation cohort, all patients had a disease duration ≤2 years and observers were blind to diagnoses. RESULTS: The optimum cut-off values for discrimination of PD were SS-12 score <8 (hyposmia) and SN echogenic size ≥0.24 cm(2) (SN hyperechogenicity). Sensitivity, specificity and positive predictive values for the diagnosis of PD were as follows, for the derivation cohort: motor asymmetry 88%, 54% and 85%; hyposmia 75%, 70% and 88%; SN hyperechogenicity 90%, 63% and 88%; two features present 96%, 72% and 91%; three features present 57%, 94% and 97%; and for the validation cohort: two features present 91%, 77% and 85%; three features present 49%, 98% and 97%. CONCLUSION: The combined assessment of motor asymmetry, hyposmia and SN hyperechogenicity improves diagnostic specificity and allows early diagnosis of PD.


Asunto(s)
Trastornos del Movimiento/epidemiología , Trastornos del Olfato/epidemiología , Enfermedad de Parkinson/diagnóstico , Enfermedad de Parkinson/epidemiología , Edad de Inicio , Anciano , Algoritmos , Estudios de Cohortes , Comorbilidad , Diagnóstico Diferencial , Femenino , Humanos , Masculino , Persona de Mediana Edad , Trastornos del Movimiento/diagnóstico , Trastornos del Olfato/diagnóstico , Enfermedad de Parkinson/diagnóstico por imagen , Estudios Retrospectivos , Sustancia Negra/diagnóstico por imagen , Ultrasonografía Doppler Transcraneal
12.
J Neural Transm (Vienna) ; 119(1): 53-7, 2012 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-21626410

RESUMEN

In Parkinson's disease (PD), substantia nigra hyperechogenicity (SN-h) has been related to both, local iron accumulation and microglia activation. We analysed its relationship in PD patients with serum iron (n = 31) and C-reactive protein (CRP; n = 193). SN-h correlated with lower CRP and iron levels. Also, patients with a first-degree relative with PD had lower iron levels. Microglia activation, if reflected by SN-h, may be therefore unrelated to serum CRP. Findings support the idea that SN-h indicates inherited alteration of iron metabolism.


Asunto(s)
Proteína C-Reactiva/metabolismo , Hierro/sangre , Enfermedad de Parkinson , Sustancia Negra/diagnóstico por imagen , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/sangre , Enfermedad de Parkinson/diagnóstico por imagen , Enfermedad de Parkinson/patología , Estadísticas no Paramétricas , Ultrasonografía Doppler Transcraneal
13.
J Ultrasound Med ; 31(2): 191-6, 2012 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-22298861

RESUMEN

OBJECTIVES: Transcranial sonography of the substantia nigra for diagnosing premotor stages of Parkinson disease has been attracting increasing interest. Standard reference values defining an abnormal increased echogenic size (hyperechogenicity) of the substantia nigra have been established in several populations using high-end stationary ultrasound systems. It is unknown whether a portable ultrasound system can be appropriately used and how the Filipino population would compare with the well-studied white population. METHODS: We prospectively studied substantia nigra echogenic sizes and third ventricle widths in 71 healthy adult German participants and 30 age- and sex-matched Filipino participants using both a well-established stationary ultrasound system (in the German cohort) and a recently distributed portable ultrasound system (in both ethnic cohorts). RESULTS: Mean substantia nigra echogenic sizes, cutoff values defining abnormal hyperechogenicity, and intra-rater reliability were similar with both systems and in both ethnic cohorts studied. The Filipino and German participants did not differ with respect to the frequency of insufficient insonation conditions (each 3%) and substantia nigra hyperechogenicity (10% versus 9%; P = .80). However, third ventricle widths were smaller in the Filipino than the German participants (mean ± SD, 1.6 ± 1.1 versus 2.4 ± 1.0 mm; P = .004). CONCLUSIONS: The frequency of substantia nigra hyperechogenicity appears to be homogeneous in white and Asian populations. Screening for this feature may well be performed with a present-day portable ultrasound system.


Asunto(s)
Enfermedad de Parkinson/diagnóstico por imagen , Enfermedad de Parkinson/etnología , Sistemas de Atención de Punto , Sustancia Negra/diagnóstico por imagen , Ultrasonografía Doppler Transcraneal/instrumentación , Adulto , Anciano , Distribución de Chi-Cuadrado , Femenino , Alemania , Humanos , Masculino , Persona de Mediana Edad , Filipinas , Estudios Prospectivos , Estadísticas no Paramétricas , Encuestas y Cuestionarios
14.
Neurodegener Dis ; 9(2): 99-103, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-21912095

RESUMEN

BACKGROUND/AIMS: In distinct movement disorders, transcranial sonography detects alterations of deep brain structures with higher sensitivity than other neuroimaging methods. Lenticular nucleus hyperechogenicity on transcranial sonography, thought to be caused by increased local copper content, has been reported as a characteristic finding in primary spontaneous dystonia. Here, we wanted to find out whether deep brain structures are altered in task-specific dystonia. METHODS: The frequency of sonographic brainstem and basal ganglia changes was studied in an investigator-blinded setting in 15 musicians with focal task-specific hand dystonia, 15 musicians without dystonia, and 15 age- and sex-matched nonmusicians without dystonia. RESULTS: Lenticular nucleus hyperechogenicity was found in 12 musicians with task-specific dystonia, but only in 3 nondystonic musicians (Fisher's exact test, p = 0.001) and 2 nonmusicians (p < 0.001). The degree of lenticular nucleus hyperechogenicity in affected musicians correlated with age, but not with duration of music practice or duration of dystonia. In 2 of 3 affected musicians with normal echogenic lenticular nucleus, substantia nigra hyperechogenicity was found. CONCLUSIONS: Our findings support the idea of a pathogenetic link between primary spontaneous and task-specific dystonia. Sonographic basal ganglia alteration might indicate a risk factor that in combination with extensive fine motor training promotes the manifestation of task-specific dystonia.


Asunto(s)
Cuerpo Estriado/diagnóstico por imagen , Cuerpo Estriado/patología , Distonía/diagnóstico por imagen , Distonía/patología , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Música , Ultrasonografía Doppler Transcraneal
15.
Neurobiol Dis ; 41(2): 291-8, 2011 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-20955797

RESUMEN

Central pathophysiological pathways of basal ganglia dysfunction imply a disturbed interaction of dopaminergic and cholinergic circuits. In Parkinson's disease (PD) imbalanced cholinergic hyperactivity prevails in the striatum. Interruption of acetylcholine (ACh) release in the striatum by locally injected botulinum neurotoxin A (BoNT-A) has been studied in the rat 6-hydroxydopamine (6-OHDA) model of PD (hemi-PD). The hemi-PD was induced by injection of 6-OHDA into the right medial forebrain bundle. Motor dysfunction provoked by apomorphine-induced contralateral rotation was completely reversed for more than 3 months by ipsilateral intrastriatal application of 1-2 ng BoNT-A. Interestingly, BoNT-A injected alone into the right striatum of naïve rats caused a slight transient ipsilateral apomorphine-induced rotation, which lasted only for about one month. Immunohistochemically, large axonal swellings appeared within the striatum injected with BoNT-A, which we tentatively named BoNT-A-induced varicosities. They contained either choline acetyltransferase or tyrosine hydroxylase. These findings suggest a selective inhibition of evoked release of ACh by locally applied BoNT-A. Intrastriatal application of BoNT-A may antagonize localized relative functional disinhibited hypercholinergic activity in neurodegenerative diseases such as PD avoiding side effects of systemic anti-cholinergic treatment.


Asunto(s)
Axones/patología , Toxinas Botulínicas Tipo A/uso terapéutico , Cuerpo Estriado/efectos de los fármacos , Regeneración Nerviosa/efectos de los fármacos , Oxidopamina/toxicidad , Trastornos Parkinsonianos/tratamiento farmacológico , Trastornos Parkinsonianos/patología , Rotación/efectos adversos , Animales , Axones/fisiología , Cuerpo Estriado/patología , Cuerpo Estriado/fisiopatología , Modelos Animales de Enfermedad , Discinesias/tratamiento farmacológico , Discinesias/patología , Discinesias/fisiopatología , Conos de Crecimiento/efectos de los fármacos , Conos de Crecimiento/patología , Conos de Crecimiento/ultraestructura , Masculino , Regeneración Nerviosa/fisiología , Neurotoxinas/uso terapéutico , Trastornos Parkinsonianos/etiología , Ratas , Ratas Wistar
16.
Mult Scler ; 17(6): 759-62, 2011 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-21427132

RESUMEN

To describe and treat a relapse of relapsing-remitting multiple sclerosis occurring during escalating therapeutic plasma exchange for a previous relapse. A 47-year-old woman with relapsing-remitting multiple sclerosis received plasma exchange as escalating therapy for a severe prolonged steroid-refractory relapse. During plasma exchange the patient developed another relapse with new neurological symptoms. The newly occurring relapse responded convincingly to pulsed high-dose steroids. During escalating relapse treatment with plasma exchange a new relapse can occur and, where appropriate, treatment with pulsed steroids can be useful, even if the previous relapse was unresponsive to glucocorticoids.


Asunto(s)
Esclerosis Múltiple Recurrente-Remitente/terapia , Intercambio Plasmático/efectos adversos , Femenino , Glucocorticoides/administración & dosificación , Humanos , Imagen por Resonancia Magnética , Persona de Mediana Edad , Esclerosis Múltiple Recurrente-Remitente/diagnóstico , Quimioterapia por Pulso , Índice de Severidad de la Enfermedad , Resultado del Tratamiento
17.
Amyotroph Lateral Scler ; 12(6): 393-7, 2011 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-21554031

RESUMEN

Amyotrophic lateral sclerosis (ALS) is a progressive motor syndrome with clinical evidence of upper and lower motor neuron dysfunction. Mirror movements (MM) in ALS have been reported and attributed to a disturbed transcallosal inhibition (TI). Hence, occurrence of MM in ALS might be explained by involvement of transcallosal projecting fibre tracts into the degenerative process of the motor system. Twenty-six consecutive ALS patients were studied by clinical investigation of MM and by transcranial magnetic stimulation testing of TI using evaluation of the ipsilateral silent period. MM were observed in 39% of ALS patients. There was a significant correlation between the revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) and occurrence of MM (correlation coefficient -0.315; p = 0.044). In conclusion, all MM patients had pathological TI at least in one hemisphere, which indicates involvement of transcallosally projecting output neurons in ALS patients, which in turn may be an early feature of the disease process with the potential of a diagnostic biomarker.


Asunto(s)
Esclerosis Amiotrófica Lateral/fisiopatología , Movimiento/fisiología , Adulto , Anciano , Esclerosis Amiotrófica Lateral/patología , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Estimulación Magnética Transcraneal
18.
Pain Med ; 12(11): 1607-14, 2011 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-21692970

RESUMEN

OBJECTIVE: This was a prospective, randomized, double-blind, placebo-controlled, 12-week, multicenter study to evaluate the efficacy and tolerability of fixed location injections of botulinum type A toxin (BoNT-A, Dysport) in predetermined injection sites in patients with myofascial pain syndrome of the upper back. DESIGN: Patients with moderate-to-severe myofascial pain syndrome affecting cervical and/or shoulder muscles (10 trigger points, disease duration 6-24 months) and moderate-to-severe pain intensity were randomized to BoNT-A (N = 81) or saline (N = 72). INTERVENTION: Patients received treatment into 10 predetermined fixed injection sites in the head, neck, and shoulder (40 units of BoNT-A per site or saline, a total of 400 units of BoNT-A). OUTCOME MEASURES: The primary efficacy outcome was the proportion of patients with mild or no pain at week 5 (responders). Secondary outcomes included changes in pain intensity and the number of pain-free days per week. RESULTS: At week 5, 49% (37/76) of BoNT-A patients and 38% (27/72) of placebo patients had responded to treatment (P = 0.1873). Duration of daily pain was reduced in the BoNT-A group compared with the placebo group from week 5, with statistically significant differences at weeks 9 and 10 (P = 0.04 for both). Treatment was well tolerated. CONCLUSION: Fixed-location treatment with BoNT-A of patients with upper back myofascial pain syndrome did not lead to a significant improvement of the main target parameter in week 5 after treatment. Only in week 8 were significant differences found. Several secondary parameters, such as physicians' global assessment and patients' global assessment, significantly favored BoNT-A over placebo at weeks 8 and 12.


Asunto(s)
Dolor de Espalda/tratamiento farmacológico , Toxinas Botulínicas Tipo A , Inyecciones , Síndromes del Dolor Miofascial/tratamiento farmacológico , Fármacos Neuromusculares , Puntos Disparadores , Adulto , Toxinas Botulínicas Tipo A/administración & dosificación , Toxinas Botulínicas Tipo A/uso terapéutico , Vértebras Cervicales , Método Doble Ciego , Humanos , Masculino , Persona de Mediana Edad , Músculos , Fármacos Neuromusculares/administración & dosificación , Fármacos Neuromusculares/uso terapéutico , Dimensión del Dolor , Placebos , Estudios Prospectivos , Hombro , Resultado del Tratamiento
19.
Neurology ; 94(20): e2109-e2120, 2020 05 19.
Artículo en Inglés | MEDLINE | ID: mdl-32332130

RESUMEN

OBJECTIVE: To investigate the risk factors of neutralizing antibody (NAB)-induced complete secondary treatment failure (cSTF) during long-term botulinum neurotoxin (BoNT) treatment in various neurologic indications. METHODS: This monocenter retrospective cohort study analyzed the data of 471 patients started on BoNT therapy between 1995 and 2015. Blood samples of 173 patients were investigated for NABs using the mouse hemidiaphragm test (93 with suspected therapy failure, 80 prospective study participants). The frequency of NAB-cSTF was assessed for various indications: hemifacial spasm, blepharospasm, cervical dystonia, other dystonia, and spasticity. A priori defined potential risk factors for NAB-cSTF were evaluated, and a stepwise binary logistic regression analysis was performed to identify independent risk factors. RESULTS: Treatment duration was 9.8 ± 6.2 years (range, 0.5-30 years; adherence, 70.6%) and number of treatment cycles 31.2 ± 22.5 (3-112). Twenty-eight of 471 patients (5.9%) had NAB-cSTF at earliest after 3 and at latest after 103 treatment cycles. None of the 49 patients treated exclusively with incobotulinumtoxinA over 8.4 ± 4.2 (1-14) years developed NAB-cSTF. Independent risk factors for NAB-cSTF were high BoNT dose per treatment, switching between onabotulinumtoxinA and other BoNT formulations (except for switching to incobotulinumtoxinA), and treatment of neck muscles. CONCLUSIONS: We present a follow-up study with the longest duration to date on the incidence of NAB-cSTF in patients treated with various BoNT formulations, including incobotulinumtoxinA. Whereas the overall risk of NAB-cSTF is low across indications and BoNT formulations, our findings underpin the recommendations to use the lowest possible dose particularly in cervical dystonia, and to avoid unnecessary switching between different formulations.


Asunto(s)
Toxinas Botulínicas Tipo A/efectos adversos , Trastornos Distónicos/tratamiento farmacológico , Espasticidad Muscular/tratamiento farmacológico , Animales , Blefaroespasmo/inducido químicamente , Blefaroespasmo/tratamiento farmacológico , Toxinas Botulínicas Tipo A/uso terapéutico , Trastornos Distónicos/inducido químicamente , Femenino , Estudios de Seguimiento , Humanos , Masculino , Ratones , Persona de Mediana Edad , Fármacos Neuromusculares/efectos adversos , Fármacos Neuromusculares/uso terapéutico , Factores de Riesgo , Tortícolis/inducido químicamente , Tortícolis/tratamiento farmacológico
20.
Stroke ; 40(5): 1903-6, 2009 May.
Artículo en Inglés | MEDLINE | ID: mdl-19286597

RESUMEN

BACKGROUND AND PURPOSE: The relationship of brain lesion location and swallowing disturbance pattern has been poorly studied in acute stroke patients. METHODS: Sixty patients with first-ever acute ischemic stroke at clearly assessed location and clinical signs of dysphagia were studied. Swallowing-related parameters rated clinically and fiberendoscopically were attention deficit, buccofacial apraxia, orofacial paresis, gag reflex, delay of pharyngeal swallow, pharyngeal contraction, larynx elevation, function of upper esophageal sphincter (UES), and aspiration severity. RESULTS: Attention deficit was independently predicted only by parietotemporal infarction, buccofacial apraxia by left-sided parietotemporal infarction, orofacial paresis by infarction encompassing upper motor neuron of cranial nerves, and impaired UES opening by lateral medullary infarction. Other swallowing parameters were not related to lesion topology. On posthoc analysis, pneumonia within 21 days after stroke was predicted only by insular lesion. CONCLUSIONS: Distinct acute brain lesion locations result in characteristic swallowing disturbance patterns. Dysphagic patients with insular stroke appear to have even higher risk of pneumonia suggesting a further associated factor promoting infection in these subjects.


Asunto(s)
Encéfalo/patología , Trastornos de Deglución/etiología , Trastornos de Deglución/patología , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/patología , Enfermedad Aguda , Adulto , Anciano , Anciano de 80 o más Años , Infarto Cerebral/complicaciones , Infarto Cerebral/patología , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Fibras Ópticas , Parálisis/etiología , Estudios Prospectivos , Accidente Cerebrovascular/psicología , Resultado del Tratamiento
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