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1.
Neuromodulation ; 26(2): 320-332, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35219571

RESUMO

BACKGROUND: Deep brain stimulation (DBS) programming of multicontact DBS leads relies on a very time-consuming manual screening procedure, and strategies to speed up this process are needed. Beta activity in subthalamic nucleus (STN) local field potentials (LFP) has been suggested as a promising marker to index optimal stimulation contacts in patients with Parkinson disease. OBJECTIVE: In this study, we investigate the advantage of algorithmic selection and combination of multiple resting and movement state features from STN LFPs and imaging markers to predict three relevant clinical DBS parameters (clinical efficacy, therapeutic window, side-effect threshold). MATERIALS AND METHODS: STN LFPs were recorded at rest and during voluntary movements from multicontact DBS leads in 27 hemispheres. Resting- and movement-state features from multiple frequency bands (alpha, low beta, high beta, gamma, fast gamma, high frequency oscillations [HFO]) were used to predict the clinical outcome parameters. Subanalyses included an anatomical stimulation sweet spot as an additional feature. RESULTS: Both resting- and movement-state features contributed to the prediction, with resting (fast) gamma activity, resting/movement-modulated beta activity, and movement-modulated HFO being most predictive. With the proposed algorithm, the best stimulation contact for the three clinical outcome parameters can be identified with a probability of almost 90% after considering half of the DBS lead contacts, and it outperforms the use of beta activity as single marker. The combination of electrophysiological and imaging markers can further improve the prediction. CONCLUSION: LFP-guided DBS programming based on algorithmic selection and combination of multiple electrophysiological and imaging markers can be an efficient approach to improve the clinical routine and outcome of DBS patients.


Assuntos
Estimulação Encefálica Profunda , Doença de Parkinson , Núcleo Subtalâmico , Humanos , Estimulação Encefálica Profunda/métodos , Movimento/fisiologia , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/terapia , Núcleo Subtalâmico/diagnóstico por imagem , Núcleo Subtalâmico/fisiologia , Resultado do Tratamento , Biomarcadores
2.
Neuromodulation ; 24(2): 392-399, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33389771

RESUMO

BACKGROUND: Different deep brain stimulation (DBS) targets have been suggested as treatment for patients with pharmacologically refractory Holmes tremor (HT). We report the clinical and quality of life (QoL) long-term (up to nine years) outcome in four patients with HT treated with DBS (in thalamic ventral intermediate nucleus-VIM or in dentato-rubro-thalamic tract-DRTT). MATERIALS AND METHODS: The patients underwent routine clinical evaluations before and after DBS (typically annually). Tremor severity and activities of daily living (ADL) were quantified by the Fahn-Tolosa-Marin Tremor-Rating-Scale (FTMTRS). QoL was assessed using the RAND SF-36-item Health Survey (RAND SF-36). In addition, we computed, in all four patients, the VTA based on the best stimulation settings using heuristic approaches included in the open source toolbox LEAD-DBS. RESULTS: In all patients, tremor and ADL improved significantly at one-year post-DBS follow-up (34-61% improvement in FTMTRS total score compared to baseline). In three out of four patients, the improvement of tremor was sustained no longer than two to three years and only in one patient was sustained up to nine years. In this patient, the largest intersection between VTA and DBS target has been observed. Scores for ADL deteriorated over the course of time, reaching worse levels compared to baseline already during the three-year post-DBS follow-up, in three out of four patients. Physical and mental health component scores of RAND SF-36 had very different outcome between patients and follow-ups and were not associated with tremor-related outcomes. CONCLUSIONS: The benefits of DBS in HT might not be always long lasting. Although QoL slightly improved, this change seemed to be independent of the motor outcome following DBS. The estimation of DBS target and VTA proximity could be a useful tool for DBS clinicians in order to facilitate the DBS programming process and optimize DBS treatment.


Assuntos
Estimulação Encefálica Profunda , Tremor Essencial , Atividades Cotidianas , Tremor Essencial/terapia , Humanos , Neuroimagem , Qualidade de Vida , Resultado do Tratamento , Tremor/diagnóstico por imagem , Tremor/terapia
3.
Case Rep Neurol ; 16(1): 55-62, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38444718

RESUMO

Introduction: Identifying the underlying etiology of nonfamilial adult-onset progressive cerebellar ataxia is often challenging because neurologists must consider almost all nongenetic and genetic causes of ataxia. Case Presentation: A 39-year-old woman was hospitalized for progressive ataxia with pyramidal and cognitive dysfunction after a right arm shaking and coordination problem deteriorated progressively over 1.5 years. The patient's medical history included amenorrhea, cataracts, developmental delays, consanguinity of the parents, motor coordination issues, and diarrhea and vomiting in infancy. An important finding that enabled us to solve the diagnostic conundrum was the elevated carbohydrate-deficient transferrin levels in the lack of alcohol-related symptoms, which also occur in untreated carbohydrate metabolism disorders, sometimes with ataxia as a leading symptom. The decreased erythrocyte galactose-1-phosphate uridyltransferase (GALT) enzyme activity and the elevated erythrocyte galactose-1-phosphate (Gal-1P) concentration led to the final diagnosis of galactosemia, a rare metabolic disorder. The patient's condition stayed stable with strict adherence to lactose-free and galactose-restricted diets, regular physiotherapy, and speech therapy, despite attempts to control the crippling tremor. Conclusion: This case highlights the importance of considering rare diseases based on unexplained clinical and laboratory findings. Newborn screening does not change the long-term complications of early-treated classical galactosemia. A small percentage of these patients develop ataxia tremor syndrome.

4.
Mov Disord Clin Pract ; 10(3): 434-439, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36949800

RESUMO

Background: Directional deep brain stimulation (DBS) allows for steering of the stimulation field, but extensive and time-consuming testing of all segmented contacts is necessary to identify the possible benefit of steering. It is therefore important to determine under which circumstances directional current steering is advantageous. Methods: Fifty two Parkinson's disease patients implanted in the STN with a directional DBS system underwent a standardized monopolar programming session 5 to 9 months after implantation. Individual contacts were tested for a potential advantage of directional stimulation. Results were used to build a prediction model for the selection of ring levels that would benefit from directional stimulation. Results: On average, there was no significant difference in therapeutic window between ring-level contact and best directional contact. However, according to our standardized protocol, 35% of the contacts and 66% of patients had a larger therapeutic window under directional stimulation compared to ring-mode. The segmented contacts warranting directional current steering could be predicted with a sensitivity of 79% and a specificity of 57%. Conclusion: To reduce time required for DBS programming, we recommend additional directional contact testing initially only on ring-level contacts with a therapeutic window of less than 2.0 mA.

5.
Mov Disord Clin Pract ; 8(3): 469-473, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33816681

RESUMO

BACKGROUND: Impulse control disorders (ICDs) are a frequent side effect of dopamine replacement therapy (DRT) in Parkinson's disease (PD). Reckless generosity might expand the spectrum of known ICDs. CASES: Over 18 months, we encountered three PD patients exhibiting reckless generosity under DRT, leading to disastrous financial and social consequences. LITERATURE REVIEW: Except for another case series describing reckless generosity in three PD patients, only one study has examined generosity in PD patients; with findings suggesting that PD patients with ICDs are less sensitive to the aversive aspects of the lack of reciprocation in social settings. Studies with healthy individuals suggest that increased availability of dopamine might reduce social discounting and promote egalitarian behavior, and thereby increase generous behavior towards strangers. Genetic studies show that polymorphisms in dopamine D4 receptors influence generous behavior. CONCLUSIONS: Reckless generosity in PD patients with DRT might be underreported and should therefore be carefully be screened for by clinicians. A potential mechanism underlying this ICD-related behavior might be a sensitization of the mesolimbic and mesocortical dopaminergic system, leading to reduced social discounting and maladaptive reward-learning. Further research is needed to investigate the prevalence and underlying mechanisms of reckless generosity in PD patients.

6.
NPJ Parkinsons Dis ; 7(1): 77, 2021 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-34489472

RESUMO

Although deep brain stimulation (DBS) of the globus pallidus internus (GPi) and the subthalamic nucleus (STN) has become an established treatment for Parkinson's disease (PD), a recent meta-analysis of outcomes is lacking. To address this gap, we performed a meta-analysis of bilateral STN- and GPi-DBS studies published from 1990-08/2019. Studies with ≥10 subjects reporting Unified Parkinson's Disease Rating Scale (UPDRS) III motor scores at baseline and 6-12 months follow-up were included. Several outcome variables were analyzed and adverse events (AE) were summarized. 39 STN studies (2035 subjects) and 5 GPi studies (292 subjects) were eligible. UPDRS-II score after surgery in the stimulation-ON/medication-OFF state compared to preoperative medication-OFF state improved by 47% with STN-DBS and 18.5% with GPi-DBS. UPDRS-III score improved by 50.5% with STN-DBS and 29.8% with GPi-DBS. STN-DBS improved dyskinesia by 64%, daily OFF time by 69.1%, and quality of life measured by PDQ-39 by 22.2%, while Levodopa Equivalent Daily Dose (LEDD) was reduced by 50.0%. For GPi-DBS information regarding dyskinesia, OFF time, PDQ-39 and LEDD was insufficient for further analysis. Correlation analysis showed that preoperative L-dopa responsiveness was highly predictive of the STN-DBS motor outcome across all studies. Most common surgery-related AE were infection (5.1%) and intracranial hemorrhage (3.1%). Despite a series of technological advances, outcomes of modern surgery are still comparable with those of the early days of DBS. Recent changes in target selection with a preference of GPi in elderly patients with cognitive deficits and more psychiatric comorbidities require more published data for validation.

7.
Neuroimage Clin ; 28: 102486, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33395977

RESUMO

Deep Brain Stimulation of the posterior subthalamic area is an emergent target for the treatment of Essential Tremor. Due to the heterogeneous and complex anatomy of the posterior subthalamic area, it remains unclear which specific structures mediate tremor suppression and different side effects. The objective of the current work was to yield a better understanding of what anatomical structures mediate the different clinical effects observed during directional deep brain stimulation of that area. We analysed a consecutive series of 12 essential tremor patients. Imaging analysis and systematic clinical testing performed 4-6 months postoperatively yielded location, clinical efficacy and corresponding therapeutic windows for 160 directional contacts. Overlap ratios between individual activation volumes and neighbouring thalamic and subthalamic nuclei as well as individual fiber tracts were calculated. Further, we generated stimulation heatmaps to assess the area of activity and structures stimulated during tremor suppression and occurrence of side effects. Stimulation of the dentato-rubro-thalamic tract and the zona incerta was most consistently correlated with tremor suppression. Both individual and group analysis demonstrated a similar pattern of activation for tremor suppression and different sorts of side-effects. Unlike current clinical concepts, induction of spasms and paresthesia were not correlated with stimulation of the corticospinal tract and the medial lemniscus. Furthermore, we noticed a significant difference in the therapeutic window between the best and worst directional contacts. The best directional contacts did not provide significantly larger therapeutic windows than omnidirectional stimulation at the same level. Deep brain stimulation of the posterior subthalamic area effectively suppresses all aspects of ET but can be associated with concomitant side effects limiting the therapeutic window. Activation patterns for tremor suppression and side effects were similar and predominantly involved the dentato-rubro-thalamic tract and the zona incerta. We found no different activation patterns between different types of side effects and no clear correlation between structure and function. Future studies with use of more sophisticated modelling of activation volumes taking into account fiber heterogeneity and orientation may eventually better delineate these different clusters, which may allow for a refined targeting and programming within this area.


Assuntos
Estimulação Encefálica Profunda , Tremor Essencial , Núcleo Subtalâmico , Tremor Essencial/terapia , Humanos , Relação Estrutura-Atividade , Tálamo
8.
Neurobiol Dis ; 35(2): 296-301, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19481150

RESUMO

Butyrylcholinesterase (BChE) genotypes and protein (BuChE) activity, especially in combination with Apolipoprotein E4 (ApoE4), have been investigated as risk factors for developing Alzheimer disease (AD) and may be associated with the rate of progression of cognitive decline. Despite similar pathologic (e.g. amyloid deposition) and neurochemical (e.g. cholinergic deficits) aspects between AD and Lewy body diseases (LBD), scarce data is obtainable about BChE genotypes and BuChE activity in LBD. We measured BuChE activity levels in serum and cerebrospinal fluid (CSF) of 114 LBD subjects (59 of them were demented) and 31 elderly controls. We found higher CSF BuChE activity in males compared to females, and a negative correlation of serum BuChE activity with age and cognitive function. Demented LBD patients, non-demented LBD patients and controls did not differ significantly with regard to serum and CSF BuChE activity. Furthermore, BChE K variant and ApoE4 allele frequencies were determined. The BChE K variant was significantly associated with lower serum activity; the same trend was observable in CSF. The subgroups did not differ significantly with regard to BChE K/ApoE4 occurrence. These data confirm and extend previous results on the relationship between BChE gene and BuChE activity, and argue rather against a major impact of BuChE on LBD-associated pathologies.


Assuntos
Butirilcolinesterase/genética , Butirilcolinesterase/metabolismo , Frequência do Gene , Doença por Corpos de Lewy/enzimologia , Doença por Corpos de Lewy/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Envelhecimento , Apolipoproteína E4/genética , Cognição/fisiologia , Transtornos Cognitivos/enzimologia , Transtornos Cognitivos/genética , Enzimas/sangue , Enzimas/líquido cefalorraquidiano , Enzimas/genética , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Sequência de DNA , Caracteres Sexuais
9.
J Neural Transm (Vienna) ; 116(5): 599-605, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19340392

RESUMO

In Lewy body disease, inflammation is discussed to be involved in the pathophysiological cascade. Osteopontin (OPN) is a multifunctional molecule, which is increased in inflammatory states. Here, we analyzed the allele frequency of two SNPs of the OPN gene, serum, and CSF OPN levels in Lewy body disease patients and controls. In accordance with our previous findings, we detected increased serum (P = 0.006) and CSF OPN levels (P = 0.0003) in the Lewy body disease cohort, compared to non-Lewy body disease subjects. The genotypic variation of SNP-66 was associated with the occurrence of Lewy body disease (odds ratio: 2.64, 95% CI 1.07-6.54, unadjusted P = 0.036). SNP+1239 was not related to Lewy body disease prevalence (odds ratio 1.61, 95% CI 0.66-3.91, P = 0.29). Genotype prevalence and OPN levels were not significantly related. These findings suggest that OPN is associated with the occurrence of Lewy body disease and SNP-66 may be a susceptibility factor.


Assuntos
Predisposição Genética para Doença/genética , Doença por Corpos de Lewy/genética , Doença por Corpos de Lewy/metabolismo , Osteopontina/genética , Polimorfismo de Nucleotídeo Único/genética , Idoso , Idoso de 80 Anos ou mais , Análise Mutacional de DNA , Feminino , Frequência do Gene/genética , Marcadores Genéticos/genética , Testes Genéticos , Variação Genética/genética , Genótipo , Humanos , Doença por Corpos de Lewy/epidemiologia , Masculino , Pessoa de Meia-Idade , Osteopontina/sangue , Osteopontina/líquido cefalorraquidiano , Prevalência
10.
Neuropsychiatr Dis Treat ; 13: 1861-1865, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28761348

RESUMO

Depression is the most important nonmotor symptom in blepharospasm (BL). As facial expression influences emotional perception, summarized as the facial feedback hypothesis, we investigated if patients report fewer depressive symptoms if injections of botulinum neurotoxin (BoNT) include the "grief muscles" of the glabellar region, compared to treatment of orbicularis oculi muscles alone. Ninety BL patients were included, half of whom had BoNT treatment including the frown lines. While treatment pattern did not predict depressive symptoms overall, subgroup analysis revealed that in male BL patients, BoNT injections into the frown lines were associated with remarkably less depressive symptoms. We hypothesize that in BL patients presenting with dystonia of the eyebrow region, BoNT therapy should include frown line application whenever justified, to optimize nonmotor effects of BoNT denervation.

11.
PLoS One ; 10(7): e0132227, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26168044

RESUMO

BACKGROUND: Alzheimer's disease (AD) is diagnosed based upon medical history, neuropsychiatric examination, cerebrospinal fluid analysis, extensive laboratory analyses and cerebral imaging. Diagnosis is time consuming and labour intensive. Parkinson's disease (PD) is mainly diagnosed on clinical grounds. OBJECTIVE: The primary aim of this study was to differentiate patients suffering from AD, PD and healthy controls by investigating exhaled air with the electronic nose technique. After demonstrating a difference between the three groups the secondary aim was the identification of specific substances responsible for the difference(s) using ion mobility spectroscopy. Thirdly we analysed whether amyloid beta (Aß) in exhaled breath was causative for the observed differences between patients suffering from AD and healthy controls. METHODS: We employed novel pulmonary diagnostic tools (electronic nose device/ion-mobility spectrometry) for the identification of patients with neurodegenerative diseases. Specifically, we analysed breath pattern differences in exhaled air of patients with AD, those with PD and healthy controls using the electronic nose device (eNose). Using ion mobility spectrometry (IMS), we identified the compounds responsible for the observed differences in breath patterns. We applied ELISA technique to measure Aß in exhaled breath condensates. RESULTS: The eNose was able to differentiate between AD, PD and HC correctly. Using IMS, we identified markers that could be used to differentiate healthy controls from patients with AD and PD with an accuracy of 94%. In addition, patients suffering from PD were identified with sensitivity and specificity of 100%. Altogether, 3 AD patients out of 53 participants were misclassified. Although we found Aß in exhaled breath condensate from both AD and healthy controls, no significant differences between groups were detected. CONCLUSION: These data may open a new field in the diagnosis of neurodegenerative disease such as Alzheimer's disease and Parkinson's disease. Further research is required to evaluate the significance of these pulmonary findings with respect to the pathophysiology of neurodegenerative disorders.


Assuntos
Doença de Alzheimer/diagnóstico , Testes Respiratórios , Doença de Parkinson/diagnóstico , Idoso , Peptídeos beta-Amiloides/análise , Animais , Biomarcadores/análise , Western Blotting , Testes Respiratórios/métodos , Estudos de Casos e Controles , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Pulmão/química , Masculino , Camundongos , Camundongos Endogâmicos C3H , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Pessoa de Meia-Idade , Fragmentos de Peptídeos/análise , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Análise Espectral/métodos
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