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1.
Front Neurol ; 12: 741859, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34777209

RESUMO

Objective: The head impulse test (HIT) assesses the vestibulo-ocular reflex (VOR) and is used to differentiate vestibular neuritis (abnormal VOR) from stroke (normal VOR) in patients presenting with an acute vestibular syndrome (AVS). The video-oculography-based HIT (vHIT) quantifies VOR function and provides information imperceptible for the clinician during clinical bedside HIT. However, the vHIT-like an electrocardiogram-requires experienced interpretation, which is especially difficult in the emergency setting. This calls for a simple, reliable and rater-independent way of analysis. Methods: We retrospectively collected 171 vHITs performed in patients presenting with AVS to our emergency department. Three neuro-otological experts comprehensively assessed the vHITs including interpretability (artifacts), VOR gain (eye/head velocity ratio), velocity profile (abrupt decline) and corrective saccades (overt/covert). Their consensus rating (abnormal/peripheral vs. normal/central) was compared to a simple algorithm that automatically classified the vHITs based on a single VOR gain cutoff (0.7). Results: Inter-rater agreement between experts was high (Fleiss' kappa = 0.74). Five (2.9 %) vHITs were "uninterpretable" according to experts' consensus, 80 (46.8 %) were rated "normal" and 86 (50.3 %) "abnormal". The algorithm had substantial agreement with the experts' consensus (Cohen's kappa = 0.75). Importantly, it correctly classified all of the normal/central vHITs denoted by the experts (100% specificity) and at the same time it had sufficient sensitivity (75.6%) in detecting abnormal/peripheral vHITs. Conclusion: A simple, automated, gain-based evaluation of the vHIT reliably detects normal/central VOR and may be a feasible and effective tool to screen AVS patients for potentially underlying stroke in the emergency setting.

2.
Eur J Neurol ; 28(9): 2965-2970, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34184370

RESUMO

BACKGROUND AND PURPOSE: Some groups of cardiovascular drugs (beta-blocking drugs, Ca antagonists, antiarrhythmics) are listed as potentially worsening myasthenia. An empirical basis for alternative recommendations for antihypertensive and antiarrhythmic therapy in myasthenia patients has not yet been provided. METHODS: From the World Health Organization pharmacovigilance database, we retrieved total and myasthenia-related counts of adverse drug reactions for various groups of drugs used in cardiovascular disease and drugs with related mechanism of action used in other indications. We calculated the reporting odds ratio as a measure of a disproportional fraction of myasthenia-related events among all events. A 95% confidence interval of reporting odds ratio (ROR) >1 was taken as an indication for a higher risk. Because our approach involves a considerable number of tests, this situation is referred to as a signal that requires additional confirmation. RESULTS: A signal for an increased risk was noted for tizanidine, for alpha-blocking drugs, for beta-blocking drugs, and for Ca antagonists. ROR indicated a lower-than-average risk for salbutamol, angiotensin receptor antagonists, oral anticoagulants, thrombocytic function inhibitors, and heparins. CONCLUSIONS: Angiotensin receptor antagonists, angiotensin-converting enzyme inhibitors, and diuretics seem to be safe in antihypertensive therapy. Surprisingly, and yet requiring confirmation by case reports, alpha receptor-blocking drugs seem to carry a risk of myasthenia worsening. Amiodarone seems to be a safe alternative in antiarrhythmic therapy in patients with myasthenia.


Assuntos
Antagonistas de Receptores de Angiotensina , Hipertensão , Inibidores da Enzima Conversora de Angiotensina , Anti-Hipertensivos/efeitos adversos , Diuréticos , Humanos , Farmacovigilância
3.
BMC Cancer ; 21(1): 386, 2021 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-33836671

RESUMO

BACKGROUND: Gliomas are often associated with symptoms including seizures. Most patients with high-grade gliomas are treated with radiotherapy or radio-chemotherapy. Since irradiation causes inflammation, it may initially aggravate symptoms. Studies focusing on seizure activity during radiotherapy for gliomas are not available. Such knowledge may improve patient monitoring and anti-epileptic treatment. This study evaluates seizure activity during radiotherapy for high-grade gliomas. METHODS: The primary objective this prospective interventional study is the evaluation of seizure activity during a course of radiotherapy for high-grade gliomas. Progression of seizure activity is defined as increased frequency of seizures by > 50%, increased severity of seizures, or initiation/increase by ≥25% of anti-epileptic medication. Seizure frequency up to 6 weeks following radiotherapy and electroencephalography activity typical for epilepsy will also be evaluated. Patients keep a seizure diary during and up to 6 weeks following radiotherapy. Every day, they will document number (and type) of seizures and anti-epileptic medication. Once a week, the findings of the diary are checked and discussed with a neurologist to initiate or adjust anti-epileptic medication, if necessary. Patients complete a questionnaire regarding their satisfaction with the seizure diary. If the dissatisfaction rate is > 40%, the seizure diary will be considered not suitable for the investigated indication. Thirty-five patients (32 patients plus drop-outs) should be enrolled. With this sample size, a one-sample binomial test with a one-sided significance level of 2.5% has a power of 80% to yield statistical significance, if the rate of patients with progression of seizure activity is 30% (rate under the alternative hypothesis), assuming a 'natural' background progression-rate of 10% without radiotherapy (null hypothesis). DISCUSSION: If an increase in seizure activity during a course of radiotherapy for high-grade glioma occurs, the findings of this study may pave the way for a larger prospective trial and will likely lead to closer patient monitoring and better anti-epileptic treatment. TRIAL REGISTRATION: clinicaltrials.gov ( NCT04552756 ); registered on 16th of September, 2020.


Assuntos
Neoplasias Encefálicas/complicações , Neoplasias Encefálicas/patologia , Irradiação Craniana/efeitos adversos , Glioma/complicações , Glioma/patologia , Convulsões/diagnóstico , Convulsões/etiologia , Anticonvulsivantes/uso terapêutico , Neoplasias Encefálicas/radioterapia , Quimiorradioterapia , Irradiação Craniana/métodos , Gerenciamento Clínico , Suscetibilidade a Doenças , Eletroencefalografia , Feminino , Glioma/radioterapia , Humanos , Masculino , Gradação de Tumores , Estadiamento de Neoplasias , Convulsões/terapia , Avaliação de Sintomas , Resultado do Tratamento
4.
Eur J Neurol ; 28(7): 2349-2356, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33566440

RESUMO

BACKGROUND AND PURPOSE: Many drugs can worsen myasthenia symptoms. The clinician usually relies on cautionary lists compiled according to case reports. We intended to provide a quantitative basis for a risk comparison within the groups of antiepileptic, antidepressant, neuroleptic, and sedative drugs. METHODS: We extracted adverse drug reaction (ADR) counts (total and myasthenia related) for drugs from these groups and calculated the reporting odds ratio (ROR) within the drug groups from the World Health Organization pharmacovigilance database. For a given drug, the ROR was increased above 1 if the proportion of myasthenia-related ADRs for this drug was larger than the same proportion for the rest of drugs in that same group. If the 95% confidence interval of ROR was >1, this was taken as a signal for a higher risk of the given drug as compared to the average of the respective group. RESULTS: Gabapentin, sertraline, citalopram, lithium, and amisulpride had a signal for the ROR to be increased above 1 within their respective groups. Bupropion, desvenlafaxine, duloxetine, escitalopram, and paroxetine had ROR values <1. For all other drugs, 1 was within the ROR confidence interval. CONCLUSIONS: For gabapentin and lithium, the analysis of RORs confirmed case reports and cautionary lists. For a number of antidepressant drugs associated with a higher-than-average risk, no case reports exist substantiating our results. For these drugs, special attention should be paid to this risk. The remarkable difference between citalopram and escitalopram could prompt experimental work to confirm differential influence of the two preparations on neuromuscular transmission.


Assuntos
Antipsicóticos , Anticonvulsivantes , Antidepressivos/efeitos adversos , Bases de Dados Factuais , Humanos , Hipnóticos e Sedativos , Farmacovigilância
5.
Anticancer Res ; 41(1): 379-384, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33419834

RESUMO

BACKGROUND/AIM: In a previous study investigating radiotherapy for newly diagnosed glioblastoma multiforme (GBM), significant or almost significant associations with survival were found for performance status, upfront resection, O6-methylguanine-DNA methyl-transferase (MGMT) promoter methylation and unifocal GBM. This study aimed to create a survival score based on these factors. PATIENTS AND METHODS: Most of the 81 patients included received resection of GBM followed by radiochemotherapy (59.4 Gy/33 or 60 Gy/30 fractions). The previously identified predictors of survival were re-evaluated. Factors significantly associated with survival were used for the score. RESULTS: All factors were significantly associated with survival. For each factor, 0 points (less favorable survival) or 1 point (more favorable survival) were assigned and added for each patient. Three groups were designed, 0-1 (n=10), 2 (n=21) and 3-4 points (n=50); 12-month survival rates were 0%, 38% and 78% (p<0.001). CONCLUSION: A new survival score was created for patients requiring radiotherapy for GBM that can improve treatment personalization.


Assuntos
Glioblastoma/mortalidade , Glioblastoma/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Terapia Combinada , Gerenciamento Clínico , Feminino , Glioblastoma/diagnóstico , Glioblastoma/etiologia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Prognóstico , Radioterapia , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
6.
J Neurol ; 268(1): 249-264, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32772173

RESUMO

Intravenous thrombolysis (IVT) is rarely performed in dizzy patients with acute vestibular syndrome (AVS) or acute imbalance (AIS) even if posterior circulation stroke (PCS) is suspected. Decision-making may be affected by uncertainties in discriminating central from peripheral vestibulopathy or concerns of IVT-related harm, particularly intracerebral hemorrhage (ICH), but related studies are missing. Using an in-house register of dizzy patients coming to the emergency room, we identified 29 AVS/AIS patients who presented within 4.5 h after onset, revealed clinical signs indicative of PCS (central oculomotor signs, mild focal abnormalities), and had non-contrast computed tomography (NCCT). Patients treated with IVT (n = 15) were compared to NoIVT patients (n = 14) with regard to clinical and imaging (including perfusion computed tomography, CTP) parameters, occurrence of ICH and short-term clinical outcome (NIHSS improvement; ability to walk independently). IVT and NoIVT patients did not differ in baseline characteristics, central oculomotor signs, or clinical outcome. IVT patients more often exhibited disabling vestibular symptoms (severe dizziness/vertigo, inability to stand unsupported) and focal abnormalities than NoIVT patients. There was no ICH in either group. CTP was performed in 0% of NoIVT versus 80% of IVT patients, seven of twelve revealing posterior circulation hypoperfusion. Comparison of initial hypoperfusion (CTP) and final stroke (NCCT) revealed IVT-related benefit (smaller lesion) in three of seven IVT patients. In AVS/AIS patients with suspected PCS, disabling vestibular symptoms, focal neurological deficits, and hypoperfusion on CTP seem to direct decision-making pro IVT. In our small cohort, there were no significant IVT-related clinical benefits, no IVT-related ICHs, and salvage of brain tissue in some patients.


Assuntos
Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Isquemia Encefálica/complicações , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/tratamento farmacológico , Fibrinolíticos/uso terapêutico , Humanos , Estudos Retrospectivos , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/tratamento farmacológico , Terapia Trombolítica , Resultado do Tratamento , Vertigem/tratamento farmacológico , Vertigem/etiologia
7.
Eur J Neurol ; 28(5): 1737-1744, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33382146

RESUMO

BACKGROUND AND PURPOSE: The bedside head impulse test (bHIT) is used to differentiate vestibular neuritis (VN) from posterior circulation stroke (PCS) in patients presenting with acute vestibular syndrome (AVS). If assessed by neuro-otological experts, diagnostic accuracy is high. We report on its diagnostic accuracy when applied by nonexperts during routine clinical practice in the emergency department (ED), its impact on patient management, and the potential diagnostic yield of the video-oculography-supported head impulse test (vHIT). METHODS: Medical chart review of 38 AVS patients presenting to our university medical center's ED, assessed by neurology residents. We collected bHIT results (abnormal/peripheral or normal/central) and whether patients were admitted to the stroke unit or general neurological ward. Final diagnosis (VN, n = 24; PCS, n = 14) was determined by clinical course, magnetic resonance imaging, and vHIT. RESULTS: The bHIT's accuracy was only 58%. Its sensitivity for VN was high (88%), but due to many false-abnormal bHITs in PCS (36%), the specificity was low (64%). The vHIT yielded excellent specificity (100%) and moderate sensitivity (67%). The decision on the patient's further care was almost arbitrary and independent from the bHIT: 58% of VN and 57% of PCS patients were admitted to the stroke unit. CONCLUSIONS: The bHIT, applied by nonexperts during routine practice in the ED, has low accuracy, is too often mistaken as abnormal/peripheral, and is not consistently used for patients' in-hospital triage. As false-abnormal bHITs can lead to misdiagnosis/mistreatment of stroke patients, we recommend that bHIT applied by nonexperts should be reassessed by a neuro-otological expert or preferably quantitative vHIT in the ED.


Assuntos
Acidente Vascular Cerebral , Neuronite Vestibular , Serviço Hospitalar de Emergência , Teste do Impulso da Cabeça , Humanos , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/diagnóstico , Vertigem/diagnóstico , Vertigem/etiologia , Neuronite Vestibular/diagnóstico
9.
J Neurol ; 267(Suppl 1): 126-135, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32462345

RESUMO

The usefulness of brain imaging studies in dizzy patients presenting to the emergency department (ED) is controversial. We aimed to assess the 'real-world' probability of ischemic stroke and other acute brain lesions (ABLs) in these patients to create an algorithm that helps decision-making on whether which and when brain imaging is needed. By reviewing medical records, we identified 610 patients presenting with dizziness, vertigo or imbalance to our university hospital's ED and receiving neurological workup. We collected timing/triggers of symptoms, ABCD2 score, focal neurological abnormalities, HINTS (head impulse, nystagmus, test-of-skew) and other central oculomotor signs. ABLs were extracted from CT/MRI reports. Uni-/multivariate logistic regression analyses investigated associations between clinical parameters and ABLs. Finally, the likelihood of ABLs was assessed for different clinically defined subgroups ('dizziness syndromes'). Early CT (day 1) was performed in 539 (88%) and delayed MR imaging (median: day 4) in 299 (49%) patients. ABLs (89% ischemic stroke) were revealed in 75 (24%) of 318 patients with adequate imaging (MRI or lesion-positive CT). The risk for ABLs increased with the presence of central oculomotor signs (odds ratio 2.8, 95% confidence interval 1.5-5.2) or focal abnormalities (OR 3.3, 95% CI 1.8-6.2). The likelihood of ABLs differed between dizziness syndromes, e.g., HINTS-negative acute vestibular syndrome: 0%, acute imbalance syndrome with ABCD2-score ≥ 4: 50%. We propose a clinical pathway, according to which patients with HINTS-negative acute vestibular syndrome should not receive brain imaging, whereas imaging is suggested in dizzy patients with acute imbalance, central oculomotor signs or focal abnormalities.


Assuntos
Nistagmo Patológico , Acidente Vascular Cerebral , Encéfalo/diagnóstico por imagem , Tontura/diagnóstico por imagem , Tontura/epidemiologia , Tontura/etiologia , Serviço Hospitalar de Emergência , Humanos , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/epidemiologia , Vertigem/diagnóstico por imagem , Vertigem/epidemiologia
10.
J Med Life ; 12(4): 342-353, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-32025252

RESUMO

The restoration of voluntary muscle activity in posttraumatic paraplegia in both animal experiments and other clinical applications requires reproducibility of a technically-demanding microsurgical procedure, limited by physicians' understanding of Brunelli's spinal cord grafting paradigm. The insufficient clinical investigation of the long-term benefits of the CNS-PNS graft application warrants additional inquiry. The objective of this study is to explore the potential benefits of the first replicated, graft-induced neuroregeneration of denervated skeletal muscle regarding long-term clinical outcomes and to investigate the effect of Cerebrolysin on neuromodulation. A randomized study evaluating 30 rats, approved by the National Animal Ethics Advisory Committee was performed. The medication was administered postoperatively. For 14 days, 12 rats received Cerebrolysin (serum), 11 received NaCl 0.9% (shams), and 7 were controls. For microsurgery, the lateral corticospinal tract T10 was grafted to the denervated internal obliquus abdominal muscle. On day 90, intraoperative proof of reinnervation was observed. On day 100, 15 rats were euthanized for fixation, organ removal, and extensive histology-morphology examination, and the Wei-Lachin statistical procedure was employed. After an open revision of 16 rats, 8 were CMAP positive. After intravenous Vecuronium application, two (Cerebrolysin, NaCl) out of two rats showed an incomplete compound muscle action potential (CMAP) loss due to glutamatergic and cholinergic co-transmission, while two others showed a complete loss of amplitude. Cerebrolysin medication initiated larger restored muscle fiber diameters and less scarring. FB+ neurons were not observed in the brain but were observed in the Rexed laminae. Brunelli's concept was successfully replicated, demonstrating the first graft induced existence of cholinergic and glutamatergic neurotransmission in denervated grafted muscles. Statistics of the histometric count of muscle fibers revealed larger fiber diameters after Cerebrolysin. Brunelli's CNS-PNS experimental concept is suitable to analyze graft-neuroplasticity focused on the voluntary restoration of denervated skeletal muscles in spinal cord injury. Neuroprotection by Cerebrolysin is demonstrated.


Assuntos
Sistema Nervoso Central/fisiologia , Músculo Esquelético/inervação , Regeneração Nervosa/fisiologia , Sistema Nervoso Periférico/fisiologia , Potenciais de Ação/efeitos dos fármacos , Aminoácidos/farmacologia , Animais , Sistema Nervoso Central/efeitos dos fármacos , Feminino , Músculo Esquelético/efeitos dos fármacos , Regeneração Nervosa/efeitos dos fármacos , Sistema Nervoso Periférico/efeitos dos fármacos , Ratos Sprague-Dawley , Reprodutibilidade dos Testes
11.
Front Neurol ; 8: 51, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28265260

RESUMO

OBJECTIVE: Our aim was to identify the role of the investigators' knowledge of the patient's history of vestibular symptoms (PVH) in the clinical evaluation of the bedside head-impulse test (bHIT). We hypothesized that this knowledge will reduce uncertainty and improve bHIT accuracy when compared to quantitative analysis of the vestibulo-ocular reflex by video head-impulse test (vHIT). METHODS: We looked for changes in the clinical assessment of the bHIT in 594 consecutive patients before and after taking PVH. bHIT was performed by 12 clinical neurologists with various clinical experience in neuro-otological diseases (novices to long-standing experts). vHIT was analyzed by four experts being blinded for the patients' clinical presentation and history of symptoms. The confidence of bHIT and vHIT was rated (0-100%). RESULTS: One hundred fifty-four (15%) of 1,030 bHIT of all eligible patients (n = 515) were rated pathological. Thirty-five (22.7%) of them were rated bilateral vestibulopathies. Sensitivity of bHIT reached 56.3%, its specificity 92.4%; the positive predictive value (PPV) was 41.5% and the negative predictive value 95.7%. These data did not differ between bHIT before and after PVH. bHIT after PVH (post-bHIT) differed from pre-bHIT in 44.3%, usually with regard to the level of confidence but also in polarity (5%). The accuracy of changes in bHIT depended on the direction of change: a "normal" post-bHIT was correct in 92.3% while only 39.8% of pathological post-bHIT were pathological on vHIT. However, sensitivity of a pathological post-bHIT depended on the clinical experience in taking PVH and bHIT: the PPV was 20.5% in novices as compared to 69.6% in experts. CONCLUSION: The study shows that PVH changes the certainty and/or polarity of the clinical evaluation of bHIT. Unlike expected, the increase in confidence in post-bHIT is associated with a consistently high specificity but no increase in sensitivity. Accuracy of changes in post-bHIT depends on the investigators' clinical experience: it increases only in experts but not novices. Since novices show only a poor PPV and moderate sensitivity of bHIT, pathological bHITs should be controlled by vHIT, even in patients with a positive PVH. By contrast, confirmed normal post-bHIT is usually correct.

12.
Eur Arch Psychiatry Clin Neurosci ; 267(3): 225-235, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26816222

RESUMO

Despite many reports on visual processing deficits in psychotic disorders, studies are needed on the integration of visual and non-visual components of eye movement control to improve the understanding of sensorimotor information processing in these disorders. Non-visual inputs to eye movement control include prediction of future target velocity from extrapolation of past visual target movement and anticipation of future target movements. It is unclear whether non-visual input is impaired in patients with schizophrenia. We recorded smooth pursuit eye movements in 21 patients with schizophrenia spectrum disorder, 22 patients with bipolar disorder, and 24 controls. In a foveo-fugal ramp task, the target was either continuously visible or was blanked during movement. We determined peak gain (measuring overall performance), initial eye acceleration (measuring visually driven pursuit), deceleration after target extinction (measuring prediction), eye velocity drifts before onset of target visibility (measuring anticipation), and residual gain during blanking intervals (measuring anticipation and prediction). In both patient groups, initial eye acceleration was decreased and the ability to adjust eye acceleration to increasing target acceleration was impaired. In contrast, neither deceleration nor eye drift velocity was reduced in patients, implying unimpaired non-visual contributions to pursuit drive. Disturbances of eye movement control in psychotic disorders appear to be a consequence of deficits in sensorimotor transformation rather than a pure failure in adding cognitive contributions to pursuit drive in higher-order cortical circuits. More generally, this deficit might reflect a fundamental imbalance between processing external input and acting according to internal preferences.


Assuntos
Transtorno Bipolar/fisiopatologia , Percepção de Movimento/fisiologia , Acompanhamento Ocular Uniforme/fisiologia , Esquizofrenia/fisiopatologia , Adolescente , Adulto , Análise de Variância , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estimulação Luminosa , Escalas de Graduação Psiquiátrica , Tempo de Reação/fisiologia , Adulto Jovem
13.
J Neurol Neurosurg Psychiatry ; 87(9): 1005-15, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27113605

RESUMO

OBJECTIVE: Antibodies to cell surface central nervous system proteins help to diagnose conditions which often respond to immunotherapies. The assessment of antibody assays needs to reflect their clinical utility. We report the results of a multicentre study of aquaporin (AQP) 4 antibody (AQP4-Ab) assays in neuromyelitis optica spectrum disorders (NMOSD). METHODS: Coded samples from patients with neuromyelitis optica (NMO) or NMOSD (101) and controls (92) were tested at 15 European diagnostic centres using 21 assays including live (n=3) or fixed cell-based assays (n=10), flow cytometry (n=4), immunohistochemistry (n=3) and ELISA (n=1). RESULTS: Results of tests on 92 controls identified 12assays as highly specific (0-1 false-positive results). 32 samples from 50 (64%) NMO sera and 34 from 51 (67%) NMOSD sera were positive on at least two of the 12 highly specific assays, leaving 35 patients with seronegative NMO/spectrum disorder (SD). On the basis of a combination of clinical phenotype and the highly specific assays, 66 AQP4-Ab seropositive samples were used to establish the sensitivities (51.5-100%) of all 21 assays. The specificities (85.8-100%) were based on 92 control samples and 35 seronegative NMO/SD patient samples. CONCLUSIONS: The cell-based assays were most sensitive and specific overall, but immunohistochemistry or flow cytometry could be equally accurate in specialist centres. Since patients with AQP4-Ab negative NMO/SD require different management, the use of both appropriate control samples and defined seronegative NMOSD samples is essential to evaluate these assays in a clinically meaningful way. The process described here can be applied to the evaluation of other antibody assays in the newly evolving field of autoimmune neurology.


Assuntos
Aquaporina 4/sangue , Autoanticorpos/sangue , Neuromielite Óptica/sangue , Aquaporina 4/imunologia , Autoanticorpos/imunologia , Ensaio de Imunoadsorção Enzimática/métodos , Humanos , Imuno-Histoquímica/métodos , Neuromielite Óptica/imunologia , Sensibilidade e Especificidade
15.
PLoS One ; 8(4): e60358, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23593200

RESUMO

We study the impact of coil orientation on the motor threshold (MT) and present an optimal coil orientation for stimulation of the foot. The result can be compared to results of models that predict this orientation from electrodynamic properties of the media in the skull and from orientations of cells, respectively. We used a robotized TMS system for precise coil placement and recorded motor-evoked potentials with surface electrodes on the abductor hallucis muscle of the right foot in 8 healthy control subjects. First, we performed a hot-spot search in standard (lateral) orientation and then rotated the coil in steps of 10° or 20°. At each step we estimated the MT. For navigated stimulation and for correlation with the underlying anatomy a structural MRI scan was obtained. Optimal coil orientation was 33.1 ± 18.3° anteriorly in relation to the standard lateral orientation. In this orientation the threshold was 54 ± 18% in units of maximum stimulator output. There was a significant difference of 8.0 ± 5.9% between the MTs at optimal and at standard orientation. The optimal coil orientations were significantly correlated with the direction perpendicular to the postcentral gyrus ([Formula: see text]). Robotized TMS facilitates sufficiently precise coil positioning and orientation to study even small variations of the MT with coil orientation. The deviations from standard orientation are more closely matched by models based on field propagation in media than by models based on orientations of pyramidal cells.


Assuntos
Potencial Evocado Motor/fisiologia , Pé/fisiologia , Estimulação Magnética Transcraniana/instrumentação , Estimulação Magnética Transcraniana/métodos , Humanos , Imageamento por Ressonância Magnética
16.
Parkinsonism Relat Disord ; 19(4): 422-5, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23332219

RESUMO

BACKGROUND: Neurological and psychiatric disorders show clinical overlap suggesting a shared pathophysiological background. We evaluated myoclonus-dystonia, a monogenic movement disorder as a disease model for inherited psychopathology. METHOD: We investigated 12 SGCE mutation carriers using standardized neurological and psychiatric examinations to assign DSM-IV diagnoses. Furthermore, we analyzed all studies in the Medline database which included psychiatric information on SGCE mutation-positive patients. RESULTS: Of our twelve SGCE mutation carriers, 10 were older than 16 years. Two of them (20%) reported psychiatric diagnoses before our examination, which resulted in at least one psychiatric diagnosis in seven (70%) patients, most frequently anxiety (60%), depression (30%) or both. Substance abuse was observed in 20%, whereas obsessive-compulsive disorders were absent. One mutation carrier showed Axis 2 features. In the literature analysis, the ten studies using standardized tools covering DSM-IV criteria reported prevalences similar to those in our sample. This was three times the frequency of psychiatric disorders detected in 13 studies using clinical history or patient report only. CONCLUSION: About two thirds of SGCE mutation carriers develop psychiatric comorbidity and >80% are previously undiagnosed.


Assuntos
Distúrbios Distônicos/epidemiologia , Distúrbios Distônicos/psicologia , Transtornos Mentais/epidemiologia , Adolescente , Adulto , Idoso , Criança , Comorbidade , Distúrbios Distônicos/genética , Feminino , Heterozigoto , Humanos , Masculino , Transtornos Mentais/genética , Pessoa de Meia-Idade , Mutação , Testes Neuropsicológicos , Sarcoglicanas/genética
17.
Brain Stimul ; 6(3): 315-21, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-22749687

RESUMO

BACKGROUND: Transcranial Magnetic Stimulation (TMS) is based on a changing magnetic field inducing an electric field in the brain. Conventionally, the TMS coil is mounted to a static holder and the subject is asked to avoid head motion. Additionally, head resting frames have been used. In contrast, our robotized TMS system employs active motion compensation (MC) to maintain the correct coil position. OBJECTIVE/HYPOTHESIS: We study the effect of patient motion on TMS. In particular, we compare different coil positioning techniques with respect to the induced electric field. METHODS: We recorded head motion for six subjects in three scenarios: (a) avoiding head motion, (b) using a head rest, and (c) moving the head freely. Subsequently, the motion traces were replayed using a second robot to move a sensor to measure the electric field in the target region. These head movements were combined with 2 types of coil positioning: (1) using a coil holder and (2) using robotized TMS with MC. RESULTS: After 30 min the induced electric field was reduced by 32.0% and 19.7% for scenarios (1a) and (1b), respectively. For scenarios (2a)-(2c) it was reduced by only 4.9%, 1.4% and 2.0%, respectively, which is a significant improvement (P < 0.05). Furthermore, the orientation of the induced field changed by 5.5°, 7.6°, 0.4°, 0.2°, 0.2° for scenarios (1a)-(2c). CONCLUSION: While none of the scenarios required rigid head fixation, using a simple holder to position a coil during TMS can lead to substantial deviations in the induced electric field. In contrast, robotic motion compensation results in clinically acceptable positioning throughout treatment.


Assuntos
Biofísica , Mapeamento Encefálico , Encéfalo/fisiologia , Mãos/inervação , Movimento (Física) , Estimulação Magnética Transcraniana , Análise de Variância , Movimentos da Cabeça , Humanos
18.
Eur Arch Psychiatry Clin Neurosci ; 263(3): 223-31, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22639244

RESUMO

Alterations in sensorimotor processing and predictive mechanisms have both been proposed as the primary cause of eye tracking deficits in schizophrenia. 20 schizophrenia patients and 20 healthy controls were assessed on blocks of predictably moving visual targets at constant speeds of 10, 15 or 30°/s. To assess internal drive to the eye movement system based on predictions about the ongoing target movement, targets were blanked off for either 666 or 1,000 ms during the ongoing pursuit movement in additional conditions. Main parameters of interest were eye deceleration after extinction of the visual target and residual eye velocity during blanking intervals. Eye deceleration after target extinction, reflecting persistence of predictive signals, was slower in patients than in controls, implying greater rather than diminished utilization of predictive mechanisms for pursuit in schizophrenia. Further, residual gain was not impaired in patients indicating a basic integrity of internal predictive models. Pursuit velocity gain in patients was reduced in all conditions with visible targets replicating previous findings about a sensorimotor transformation deficit in schizophrenia. A pattern of slower eye deceleration and unimpaired residual gain during blanking intervals implies greater adherence to top-down predictive models for pursuit tracking in schizophrenia. This suggests that predictive modeling is relatively intact in schizophrenia and that the primary cause of abnormal visual pursuit is impaired sensorimotor transformation of the retinal error signal needed for the maintenance of accurate visually driven pursuit. This implies that disruption in extrastriate and sensorimotor systems rather than frontostriatal predictive mechanisms may underlie this widely reported endophenotypes for schizophrenia.


Assuntos
Transtornos da Motilidade Ocular/etiologia , Acompanhamento Ocular Uniforme/fisiologia , Esquizofrenia/complicações , Adolescente , Adulto , Análise de Variância , Piscadela/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Percepção de Movimento/fisiologia , Desempenho Psicomotor , Tempo de Reação , Adulto Jovem
19.
J Neurosci Methods ; 211(2): 185-90, 2012 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-23000723

RESUMO

The quantification of stimulation intensity in transcranial magnetic stimulation (TMS) as a function of depth is of interest in order to adjust stimulator output when non-motor regions are stimulated. Currently, a linear increase of stimulator output to correct for depth has been suggested. This is contrary to the physical properties of the electric field that is induced by the stimulation coil as measured in vitro. For two stimulation coils, we determined the characteristics of their field in air. We then measured motor thresholds for the abductor hallucis muscle of 10 healthy subjects. Coil position, distance from the scalp, and orientation were controlled with a head tracking robotic system that corrected for head movements. In both coils an approximately exponential increase, rather than a linear increase, of the threshold with the scalp-coil distance was measured. The slope of the increase was slightly smaller than expected from the field characteristic, but overall in good agreement. With respect to the depth of the TMS target, different results were obtained from the threshold ratios of the coils and from the slopes of the threshold increase with distance. For the adjustment of stimulator output to scalp-to-cortex distances exponential functions with parameters motivated by physical properties of the coils should be used. Estimation of the target depth from the thresholds, with different coils, is not reliable. Our results resolve a conflict between physiological data and physical properties of TMS coils. They provide a more reliable base for depth dependent corrections for TMS stimulator output.


Assuntos
Estimulação Magnética Transcraniana/métodos , Adulto , Campos Eletromagnéticos , Potencial Evocado Motor/fisiologia , Humanos , Adulto Jovem
20.
Neuropharmacology ; 63(5): 898-904, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22771976

RESUMO

Evidence exists that modulation of neuronal activity in nucleus accumbens shell region may re-establish normal function in various neuropsychiatric conditions such as drug-withdrawal, obsessive-compulsive disorder, depression and chronic pain. Here, we study the effects of acute repetitive transcranial magnetic stimulation on monoamine outflow in the nucleus accumbens shell in awake and freely moving rats using in vivo microdialysis. To scale the biochemical results to the induced electric field in the rat brain, we obtained a realistic simulation of the stimulation scenario using a finite element model. Applying 20 Hz repetitive transcranial magnetic stimulation in 6 trains of 50 stimuli with 280 µs pulse width at a magnetic field strength of 130% of the individual motor threshold, dopamine as well as serotonin outflow in the nucleus accumbens shell significantly increased compared to sham stimulation. Since the electric field decays rapidly with depth in the rat brain, we can conclude that the modulation in neurotransmitter outflow from the nucleus accumbens shell is presumably a remote effect of cortical stimulation.


Assuntos
Monoaminas Biogênicas/metabolismo , Dopamina/metabolismo , Neurônios/metabolismo , Núcleo Accumbens/metabolismo , Serotonina/metabolismo , Estimulação Magnética Transcraniana , Ácido 3,4-Di-Hidroxifenilacético/metabolismo , Animais , Gânglios da Base/metabolismo , Comportamento Animal , Cromatografia Líquida de Alta Pressão , Técnicas Eletroquímicas , Ácido Homovanílico/metabolismo , Ácido Hidroxi-Indolacético/metabolismo , Masculino , Microdiálise , Atividade Motora , Ratos , Ratos Wistar , Fatores de Tempo
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