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1.
J Neurol Neurosurg Psychiatry ; 87(3): 302-10, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25817520

RESUMO

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.


Assuntos
Melanoma/epidemiologia , Doença de Parkinson/diagnóstico , Doença de Parkinson/epidemiologia , Sintomas Prodrômicos , Estudos de Casos e Controles , Comorbidade , Feminino , Humanos , Masculino , Melanoma/diagnóstico por imagem , Pessoa de Meia-Idade , Doença de Parkinson/diagnóstico por imagem , Prevalência , Estudos Prospectivos , Ultrassonografia Doppler Transcraniana
2.
Mov Disord ; 31(3): 302-9, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26362398

RESUMO

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.


Assuntos
Estimulação Encefálica Profunda , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Doença de Parkinson/terapia , Núcleo Subtalâmico/cirurgia , Adulto , Idoso , Eletrodos Implantados , Feminino , Globo Pálido/cirurgia , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Procedimentos Neurocirúrgicos/métodos , Doença de Parkinson/patologia , Núcleo Subtalâmico/fisiologia
3.
Neurodegener Dis ; 16(3-4): 184-91, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26613522

RESUMO

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.


Assuntos
Esclerose Lateral Amiotrófica/psicologia , Função Executiva , Idoso , Esclerose Lateral Amiotrófica/epidemiologia , Cognição , Progressão da Doença , Escolaridade , Feminino , Seguimentos , Alemanha/epidemiologia , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Fatores de Tempo
4.
Cell Mol Neurobiol ; 35(1): 111-4, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25283186

RESUMO

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.


Assuntos
Metilprednisolona/farmacologia , Rede Nervosa/efeitos dos fármacos , Rede Nervosa/fisiologia , Neurônios/efeitos dos fármacos , Neurônios/fisiologia , Potenciais de Ação/efeitos dos fármacos , Potenciais de Ação/fisiologia , Animais , Células Cultivadas , Camundongos , Rede Nervosa/citologia , Medula Espinal/citologia , Medula Espinal/efeitos dos fármacos , Medula Espinal/fisiologia
5.
J Neural Transm (Vienna) ; 122(6): 789-97, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25217967

RESUMO

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.


Assuntos
Transtorno Depressivo Maior/complicações , Doença de Parkinson/complicações , Doença de Parkinson/diagnóstico , Idoso , Transtorno Depressivo Maior/diagnóstico por imagem , Transtorno Depressivo Maior/fisiopatologia , Olho/fisiopatologia , Feminino , Seguimentos , Humanos , Entrevistas como Assunto , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Atividade Motora , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/fisiopatologia , Projetos Piloto , Sintomas Prodrômicos , Prognóstico , Substância Negra/diagnóstico por imagem , Ultrassonografia
6.
Epilepsy Behav ; 49: 351-3, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25960425

RESUMO

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.


Assuntos
Anticonvulsivantes/uso terapêutico , Estado Epiléptico/tratamento farmacológico , Administração Intravenosa , Adulto , Idoso , Anticonvulsivantes/administração & dosagem , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Estado Epiléptico/classificação , Resultado do Tratamento
7.
Epilepsy Behav ; 45: 176-9, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25819947

RESUMO

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.


Assuntos
Anticonvulsivantes/uso terapêutico , Piridonas/uso terapêutico , Estado Epiléptico/diagnóstico , Estado Epiléptico/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Registros Eletrônicos de Saúde/tendências , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nitrilas , Estudos Retrospectivos , Resultado do Tratamento
8.
Epilepsy Behav ; 31: 334-8, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24262784

RESUMO

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.


Assuntos
Depressão/complicações , Epilepsia/complicações , Transtornos da Memória/diagnóstico , Transtornos da Memória/etiologia , Testes Neuropsicológicos , Aprendizagem Verbal , Adulto , Eletroencefalografia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Fatores de Tempo
9.
J Neurosci Res ; 91(6): 838-47, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23553727

RESUMO

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.


Assuntos
Toxinas Botulínicas Tipo A/administração & dosagem , Corpo Estriado/efeitos dos fármacos , Neurotoxinas/administração & dosagem , Transtornos Parkinsonianos/patologia , Animais , Comportamento Animal/efeitos dos fármacos , Corpo Estriado/patologia , Imuno-Histoquímica , Injeções Intraventriculares , Masculino , Atividade Motora/efeitos dos fármacos , Transtornos Parkinsonianos/fisiopatologia , Ratos , Ratos Wistar
10.
Epilepsy Behav ; 27(1): 135-9, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23416284

RESUMO

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.


Assuntos
Anticonvulsivantes/uso terapêutico , Substituição de Medicamentos/estatística & dados numéricos , Medicamentos Genéricos/uso terapêutico , Epilepsia/psicologia , Preferência do Paciente/estatística & dados numéricos , Adolescente , Adulto , Idoso , Atitude , Áustria/epidemiologia , Estudos Transversais , Epilepsia/tratamento farmacológico , Epilepsia/epidemiologia , Feminino , Alemanha/epidemiologia , Inquéritos Epidemiológicos , Humanos , Masculino , Pessoa de Meia-Idade , Preferência do Paciente/psicologia , Inquéritos e Questionários , Suíça/epidemiologia , Adulto Jovem
11.
J Neurol Neurosurg Psychiatry ; 83(4): 441-7, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22362921

RESUMO

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.


Assuntos
Transtornos dos Movimentos/epidemiologia , Transtornos do Olfato/epidemiologia , Doença de Parkinson/diagnóstico , Doença de Parkinson/epidemiologia , Idade de Início , Idoso , Algoritmos , Estudos de Coortes , Comorbidade , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos dos Movimentos/diagnóstico , Transtornos do Olfato/diagnóstico , Doença de Parkinson/diagnóstico por imagem , Estudos Retrospectivos , Substância Negra/diagnóstico por imagem , Ultrassonografia Doppler Transcraniana
12.
J Neural Transm (Vienna) ; 119(1): 53-7, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21626410

RESUMO

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.


Assuntos
Proteína C-Reativa/metabolismo , Ferro/sangue , Doença de Parkinson , Substância Negra/diagnóstico por imagem , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/sangue , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/patologia , Estatísticas não Paramétricas , Ultrassonografia Doppler Transcraniana
13.
J Ultrasound Med ; 31(2): 191-6, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22298861

RESUMO

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.


Assuntos
Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/etnologia , Sistemas Automatizados de Assistência Junto ao Leito , Substância Negra/diagnóstico por imagem , Ultrassonografia Doppler Transcraniana/instrumentação , Adulto , Idoso , Distribuição de Qui-Quadrado , Feminino , Alemanha , Humanos , Masculino , Pessoa de Meia-Idade , Filipinas , Estudos Prospectivos , Estatísticas não Paramétricas , Inquéritos e Questionários
14.
Neurodegener Dis ; 9(2): 99-103, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-21912095

RESUMO

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.


Assuntos
Corpo Estriado/diagnóstico por imagem , Corpo Estriado/patologia , Distonia/diagnóstico por imagem , Distonia/patologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Música , Ultrassonografia Doppler Transcraniana
15.
Neurobiol Dis ; 41(2): 291-8, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20955797

RESUMO

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.


Assuntos
Axônios/patologia , Toxinas Botulínicas Tipo A/uso terapêutico , Corpo Estriado/efeitos dos fármacos , Regeneração Nervosa/efeitos dos fármacos , Oxidopamina/toxicidade , Transtornos Parkinsonianos/tratamento farmacológico , Transtornos Parkinsonianos/patologia , Rotação/efeitos adversos , Animais , Axônios/fisiologia , Corpo Estriado/patologia , Corpo Estriado/fisiopatologia , Modelos Animais de Doenças , Discinesias/tratamento farmacológico , Discinesias/patologia , Discinesias/fisiopatologia , Cones de Crescimento/efeitos dos fármacos , Cones de Crescimento/patologia , Cones de Crescimento/ultraestrutura , Masculino , Regeneração Nervosa/fisiologia , Neurotoxinas/uso terapêutico , Transtornos Parkinsonianos/etiologia , Ratos , Ratos Wistar
16.
Mult Scler ; 17(6): 759-62, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21427132

RESUMO

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.


Assuntos
Esclerose Múltipla Recidivante-Remitente/terapia , Troca Plasmática/efeitos adversos , Feminino , Glucocorticoides/administração & dosagem , Humanos , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Esclerose Múltipla Recidivante-Remitente/diagnóstico , Pulsoterapia , Índice de Gravidade de Doença , Resultado do Tratamento
17.
Amyotroph Lateral Scler ; 12(6): 393-7, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21554031

RESUMO

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.


Assuntos
Esclerose Lateral Amiotrófica/fisiopatologia , Movimento/fisiologia , Adulto , Idoso , Esclerose Lateral Amiotrófica/patologia , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Estimulação Magnética Transcraniana
18.
Pain Med ; 12(11): 1607-14, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21692970

RESUMO

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.


Assuntos
Dor nas Costas/tratamento farmacológico , Toxinas Botulínicas Tipo A , Injeções , Síndromes da Dor Miofascial/tratamento farmacológico , Fármacos Neuromusculares , Pontos-Gatilho , Adulto , Toxinas Botulínicas Tipo A/administração & dosagem , Toxinas Botulínicas Tipo A/uso terapêutico , Vértebras Cervicais , Método Duplo-Cego , Humanos , Masculino , Pessoa de Meia-Idade , Músculos , Fármacos Neuromusculares/administração & dosagem , Fármacos Neuromusculares/uso terapêutico , Medição da Dor , Placebos , Estudos Prospectivos , Ombro , Resultado do Tratamento
19.
Neurology ; 94(20): e2109-e2120, 2020 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-32332130

RESUMO

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.


Assuntos
Toxinas Botulínicas Tipo A/efeitos adversos , Distúrbios Distônicos/tratamento farmacológico , Espasticidade Muscular/tratamento farmacológico , Animais , Blefarospasmo/induzido quimicamente , Blefarospasmo/tratamento farmacológico , Toxinas Botulínicas Tipo A/uso terapêutico , Distúrbios Distônicos/induzido quimicamente , Feminino , Seguimentos , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Fármacos Neuromusculares/efeitos adversos , Fármacos Neuromusculares/uso terapêutico , Fatores de Risco , Torcicolo/induzido quimicamente , Torcicolo/tratamento farmacológico
20.
Stroke ; 40(5): 1903-6, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19286597

RESUMO

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.


Assuntos
Encéfalo/patologia , Transtornos de Deglutição/etiologia , Transtornos de Deglutição/patologia , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/patologia , Doença Aguda , Adulto , Idoso , Idoso de 80 Anos ou mais , Infarto Cerebral/complicações , Infarto Cerebral/patologia , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Fibras Ópticas , Paralisia/etiologia , Estudos Prospectivos , Acidente Vascular Cerebral/psicologia , Resultado do Tratamento
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