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BACKGROUND: Cognition in Parkinson's Disease can be impacted by the wearing-off phenomenon which results from changes in dopaminergic tone throughout the day. Given the well-established role of the cholinergic basal forebrain in cognition, we hypothesized that the Nucleus Basalis of Meynert may support cognitive processes during wearing-off periods. Specifically, we evaluated whether worsening of cognitive symptoms during wearing-off is more likely to occur with structural degeneration of the Nucleus Basalis of Meynert. METHODS: Cognitive wearing-off was evaluated via the Movement Disorders Society Non-Motor Fluctuation Assessment Questionnaire in 33 Parkinson's Disease participants undergoing evaluation for deep brain stimulation. Pre-operative diffusion MRIs were used to measure brain diffusion metrics of the Nucleus Basalis of Meynert and control regions (caudate and putamen). RESULTS: The number of cognitive symptoms which worsened during OFF periods positively correlated with mean diffusivity (ρ = 0.561, p = 0.0007) and generalized fractional anisotropy (ρ=-0.447, p = 0.009) within the Nucleus Basalis of Meynert but not in the caudate or putamen. Meanwhile, stable cognitive symptoms, and ON-state cognitive performance as measured by the DRS-2 did not correlate with Nucleus Basalis of Meynert metrics. Correlations were corrected for age, sex, scanner type, disease duration, education and LEDD. CONCLUSIONS: Our study suggests that reduced structural integrity of the Nucleus Basalis of Meynert is associated with worsening of participant-reported cognitive deficits during OFF periods, but not overall cognitive functioning in the ON-state. These findings support the hypothesis that structural integrity of the cholinergic Nucleus Basalis of Meynert may provide resilience to cognitive worsening during dopamine-related wearing-off.
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Disfunção Cognitiva , Doença de Parkinson , Humanos , Núcleo Basal de Meynert , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/complicações , Autorrelato , Imageamento por Ressonância Magnética , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/complicações , ColinérgicosRESUMO
INTRODUCTION: Freezing of gait (FOG) is a prevalent and debilitating feature of Parkinson's Disease (PD). The subthalamic nucleus (STN) is a center for controlled locomotion and a common DBS target. The objective of this study was to identify STN circuitry associated with FOG response to dopaminergic medication. In this study, we compare BOLD functional connectivity of the subthalamic nucleus (STN) in participants with and without dopa-responsive FOG. METHODS: 55 PD participants either with FOG (n = 38) or without FOG (n = 17) were recruited. Among FOG participants 22 were dopa-responsive and 16 were dopa-unresponsive. STN whole-brain connectivity was performed using CONN toolbox. The relationship between the degree of self-reported FOG dopa-response and STN connectivity was evaluated using partial correlations corrected for age, disease duration, and levodopa equivalent daily dose. RESULTS: Right STN connectivity with the cerebellar locomotor region and the temporal/occipital cortex was greater in the dopa-responsive FOG group (voxel threshold p < 0.01, FWE corrected p < 0.05). Left STN connectivity with the occipital cortex was greater in the dopa-responsive FOG group and connectivity with the postcentral gyrus was greater in the dopa-unresponsive FOG group. Strength of connectivity to these regions correlated with l-dopa induced improvement in UPDRS Item-14 (FOG), but not UPDRS Part-III (overall motor score). DISCUSSION: We demonstrate that dopa-unresponsive FOG is associated with changes in BOLD functional connectivity between the STN and locomotor as well as sensory processing regions. This finding supports the conceptual framework that effective treatment for freezing of gait likely requires the engagement of both locomotor and sensory brain regions.
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Estimulação Encefálica Profunda , Transtornos Neurológicos da Marcha , Doença de Parkinson , Humanos , Doença de Parkinson/complicações , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/tratamento farmacológico , Transtornos Neurológicos da Marcha/diagnóstico por imagem , Transtornos Neurológicos da Marcha/tratamento farmacológico , Transtornos Neurológicos da Marcha/etiologia , Levodopa/farmacologia , Levodopa/uso terapêutico , Marcha/fisiologiaRESUMO
BACKGROUND: Freezing of gait (FOG) is notoriously difficult to quantify, which has led to the use of multiple markers as outcomes for clinical trials. The instrumented timed up and go (TUG) and the many parameters that can be derived from it are commonly used as objective markers of FOG severity in clinical trials; however, it is unknown if they represent actual FOG severity. OBJECTIVE: To determine the specificity and responsiveness of objective surrogate markers of FOG severity commonly utilized in FOG studies. METHODS: Study design: We compared the specificity and responsiveness of commonly used markers in FOG clinical trials. Markers compared included velocity, step/stride length, step/stride length variability, TUG, and turn duration. Data was collected in four conditions (ON and OFF dopaminergic drugs, with and without a dual task). Unified Parkinson's Disease Rating Scale (UPDRS) was administered in the ON and OFF states. RESULTS: Thirty-three subjects were recruited (17 PD subjects without FOG (PD-control) and 16 subjects with PD and dopa-responsive FOG PD-FOG). The UPDRS motor scores were 24.9 for the PD-control group in the ON state, 24.8 for the FOG group in the ON state, and 42.4 for the FOG group in the OFF state. Significant mean differences between the ON and OFF conditions were observed with all surrogate markers (p < 0.01). However, only dual task turn duration and step variability showed trends toward significance when comparing PD-control and ON-FOG (p = 0.08). Test-retest reliability was high (ICC > 0.90) for all markers except standard deviations. Step length variability was the only marker to show an area under the ROC curve analysis > 0.70 comparing ON-FOG vs. PD-control. CONCLUSIONS: Multiple candidate surrogate markers for FOG severity showed responsiveness to levodopa challenge; however, most were not specific for FOG severity.
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BACKGROUND: Background: Parkinson's disease (PD) patients who develop freezing of gait (FOG) have reduced mobility and independence. While some patients experience improvement in their FOG symptoms with dopaminergic therapies, a subset of patients have little to no response. To date, it is unknown what changes in brain structure underlie dopa-response and whether this can be measured using neuroimaging approaches. OBJECTIVE: We tested the hypothesis that structural integrity of brain regions (subthalamic nucleus and globus pallidus internus, GPi) which link basal ganglia to the mesencephalic locomotor region (MLR), a region involved in automatic gait, would be associated with FOG response to dopaminergic therapy. METHODS: In this observational study, thirty-six participants with PD and definite FOG were recruited to undergo diffusion kurtosis imaging (DKI) and multiple assessments of dopa responsiveness (UPDRS scores, gait times ON versus OFF medication). RESULTS: The right GPi in participants with dopa-unresponsive FOG showed reduced fractional anisotropy, mean kurtosis (MK), and increased radial diffusivity relative to those with dopa-responsive FOG. Furthermore, using probabilistic tractography, we observed reduced MK and increased mean diffusivity along the right GPi-MLR tract in dopa-unresponsive FOG. MK in the right GPi was associated with a subjective dopa-response for FOG (râ=â-0.360, dfâ=â30, pâ=â0.043) but not overall motor dopa-response. CONCLUSION: These results support structural integrity of the GPi as a correlate to dopa-response in FOG. Additionally, this study suggests DKI metrics may be a sensitive biomarker for clinical studies targeting dopaminergic circuitry and improvements in FOG behavior.
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Transtornos Neurológicos da Marcha , Doença de Parkinson , Di-Hidroxifenilalanina , Dopamina , Marcha , Transtornos Neurológicos da Marcha/diagnóstico por imagem , Transtornos Neurológicos da Marcha/tratamento farmacológico , Transtornos Neurológicos da Marcha/etiologia , Globo Pálido/diagnóstico por imagem , Humanos , Doença de Parkinson/complicações , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/tratamento farmacológicoRESUMO
CASE: A 20-year-old woman presented with recurrent bilateral shoulder instability concurrent with severe, treatment-refractory epilepsy. Imaging revealed glenoid bone loss of 25% to 28% and large Hill-Sachs defects bilaterally. Bone graft augmentation of the glenoid and infill of the Hill-Sachs defects was performed bilaterally. Perioperative neuromuscular paralysis of shoulder girdle muscles with botulinum toxin was performed to facilitate recovery. Both shoulders at 2.5 and 4 years, respectively, demonstrate excellent stability and radiographic union despite continued seizure activity. CONCLUSION: Perioperative neuromuscular paralysis with botulinum toxin may provide early graft protection after the surgical treatment of glenohumeral instability because of seizures.
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Toxinas Botulínicas Tipo A , Instabilidade Articular , Luxação do Ombro , Articulação do Ombro , Toxinas Botulínicas Tipo A/uso terapêutico , Feminino , Humanos , Instabilidade Articular/tratamento farmacológico , Instabilidade Articular/etiologia , Instabilidade Articular/cirurgia , Convulsões/complicações , Convulsões/etiologia , Ombro , Luxação do Ombro/complicações , Luxação do Ombro/cirurgia , Articulação do Ombro/diagnóstico por imagem , Articulação do Ombro/cirurgia , Adulto JovemRESUMO
BACKGROUND: This investigation examined whether aspects of attention and executive functioning differed between Parkinson's Disease (PD) patients with freezing of gait (FOG) based on responsiveness to dopamine. We also explored association of cognition with FOG severity and gait metrics. METHODS: Fifty-four individuals with PD completed the study protocol: 17 without freezing (PDC), 23 with dopa-responsive FOG (RFOG), and 14 with dopa-unresponsive (URFOG). Standardized neuropsychological tests assessed attention (focused and sustained), psychomotor speed, and set-switching (time and errors). FOG severity was measured using the new FOG Questionnaire (nFOG-Q). Metrics from timed up and go (TUG) tasks were obtained while "on" and "off" dopamine, with and without dual cognitive tasks. RESULTS: After controlling for clinical and demographic factors, analysis of covariance revealed a significant between-group difference for set-switching errors; planned contrasts revealed increased set-switching errors in URFOG relative to RFOG and PD control groups. Groups were not different in other cognitive domains. FOG severity was modestly associated with set-switching errors in RFOG but not URFOG. TUG performances while "on" were associated with set-switching errors in PD controls, and with focused attention in RFOG. CONCLUSION: PD patients with dopa-unresponsive FOG are more prone to set-switching errors than those who respond to treatment. Furthermore, executive function appears relevant to FOG severity only in patients who show dopamine response. Together, these findings suggest disruption of a common dopamine-mediated pathway for FOG and ability to monitor rules while alternating cognitive processes. Consideration of dopa-response could be useful in characterizing cohorts and treating FOG in PD.
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Antiparkinsonianos/uso terapêutico , Dopamina/uso terapêutico , Função Executiva/efeitos dos fármacos , Transtornos Neurológicos da Marcha/psicologia , Doença de Parkinson/tratamento farmacológico , Idoso , Atenção/efeitos dos fármacos , Feminino , Transtornos Neurológicos da Marcha/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Doença de Parkinson/complicações , Doença de Parkinson/psicologia , Índice de Gravidade de Doença , Análise e Desempenho de Tarefas , Estudos de Tempo e Movimento , Resultado do TratamentoRESUMO
INTRODUCTION: Freezing of gait (FOG) is a debilitating feature of Parkinson's disease (PD). Evidence suggests patients with FOG have increased cortical control of gait. The supplementary motor area (SMA) may be a key structure due to its connectivity with locomotor and cognitive networks. The objectives of this study were to determine (1) if SMA connectivity is disrupted in patients with FOG and (2) if "inhibitory" repetitive transcranial magnetic stimulation can decrease maladaptive SMA connectivity. METHODS: Two experiments were performed. In experiment 1 resting-state (T2* BOLD imaging) was compared between 38 PD freezers and 17 PD controls. In experiment 2, twenty PD patients with FOG were randomized to either 10 sessions of real or sham rTMS to the SMA (1 Hz, 110% motor threshold, 1200 pulses/session) combined with daily gait training. RESULTS: (Experiment 1) Freezers had increased connectivity between the left SMA and the vermis of the cerebellum and decreased connectivity between the SMA and the orbitofrontal cortex (pFDR-corr <0.05). (Experiment 2) 10 sessions of active TMS reduced SMA connectivity with the anterior cingulate, angular gyrus and the medial temporal cortex, whereas sham TMS did not reduce SMA connectivity. From a behavioral perspective, both groups showed nFOG-Q improvements (F(4, 25.7) = 3.87, p = 0.014). CONCLUSIONS: The SMA in freezers is hyper-connected to the cerebellum, a key locomotor region which may represent maladaptive compensation. In this preliminary study, 1 Hz rTMS reduced SMA connectivity however, this was not specific to the locomotor regions. Intervention outcomes may be improved with subject specific targeting of SMA.
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Cerebelo/fisiopatologia , Conectoma , Transtornos Neurológicos da Marcha/terapia , Córtex Motor/fisiopatologia , Reabilitação Neurológica , Doença de Parkinson/terapia , Estimulação Magnética Transcraniana , Idoso , Cerebelo/diagnóstico por imagem , Terapia Combinada , Terapia por Exercício , Feminino , Transtornos Neurológicos da Marcha/etiologia , Transtornos Neurológicos da Marcha/fisiopatologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Córtex Motor/diagnóstico por imagem , Doença de Parkinson/complicações , Doença de Parkinson/fisiopatologiaRESUMO
BACKGROUND: Deep brain stimulation (DBS) of the subthalamic nucleus is an established therapeutic option for managing motor symptoms of Parkinson's disease. We conducted a double-blind, sham-controlled, randomised controlled trial to assess subthalamic nucleus DBS, with a novel multiple independent contact current-controlled (MICC) device, in patients with Parkinson's disease. METHODS: This trial took place at 23 implanting centres in the USA. Key inclusion criteria were age between 22 and 75 years, a diagnosis of idiopathic Parkinson's disease with over 5 years of motor symptoms, and stable use of anti-parkinsonian medications for 28 days before consent. Patients who passed screening criteria were implanted with the DBS device bilaterally in the subthalamic nucleus. Patients were randomly assigned in a 3:1 ratio to receive either active therapeutic stimulation settings (active group) or subtherapeutic stimulation settings (control group) for the 3-month blinded period. Randomisation took place with a computer-generated data capture system using a pre-generated randomisation table, stratified by site with random permuted blocks. During the 3-month blinded period, both patients and the assessors were masked to the treatment group while the unmasked programmer was responsible for programming and optimisation of device settings. The primary outcome was the difference in mean change from baseline visit to 3 months post-randomisation between the active and control groups in the mean number of waking hours per day with good symptom control and no troublesome dyskinesias, with no increase in anti-parkinsonian medications. Upon completion of the blinded phase, all patients received active treatment in the open-label period for up to 5 years. Primary and secondary outcomes were analysed by intention to treat. All patients who provided informed consent were included in the safety analysis. The open-label phase is ongoing with no new enrolment, and current findings are based on the prespecified interim analysis of the first 160 randomly assigned patients. The study is registered with ClinicalTrials.gov, NCT01839396. FINDINGS: Between May 17, 2013, and Nov 30, 2017, 313 patients were enrolled across 23 sites. Of these 313 patients, 196 (63%) received the DBS implant and 191 (61%) were randomly assigned. Of the 160 patients included in the interim analysis, 121 (76%) were randomly assigned to the active group and 39 (24%) to the control group. The difference in mean change from the baseline visit (post-implant) to 3 months post-randomisation in increased ON time without troublesome dyskinesias between the active and control groups was 3·03 h (SD 4·52, 95% CI 1·3-4·7; p<0·0001). 26 serious adverse events in 20 (13%) patients occurred during the 3-month blinded period. Of these, 18 events were reported in the active group and 8 in the control group. One death was reported among the 196 patients before randomisation, which was unrelated to the procedure, device, or stimulation. INTERPRETATION: This double-blind, sham-controlled, randomised controlled trial provides class I evidence of the safety and clinical efficacy of subthalamic nucleus DBS with a novel MICC device for the treatment of motor symptoms of Parkinson's disease. Future trials are needed to investigate potential benefits of producing a more defined current field using MICC technology, and its effect on clinical outcomes. FUNDING: Boston Scientific.
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Estimulação Encefálica Profunda/métodos , Doença de Parkinson/terapia , Núcleo Subtalâmico/metabolismo , Adulto , Idoso , Método Duplo-Cego , Discinesias/terapia , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
BACKGROUND: Transcranial direct current stimulation (tDCS) is a promising brain modulation technique for several disease conditions. With this technique, some portion of the current penetrates through the scalp to the cortex and modulates cortical excitability, but a recent human cadaver study questions the amount. This insufficient intracerebral penetration of currents may partially explain the inconsistent and mixed results in tDCS studies to date. Experimental validation of a transcranial alternating current stimulation-generated electric field (EF) in vivo has been performed on the cortical (using electrocorticography, ECoG, electrodes), subcortical (using stereo electroencephalography, SEEG, electrodes) and deeper thalamic/subthalamic levels (using DBS electrodes). However, tDCS-generated EF measurements have never been attempted. OBJECTIVE: We aimed to demonstrate that tDCS generates biologically relevant EF as deep as the subthalamic level in vivo. METHODS: Patients with movement disorders who have implanted deep brain stimulation (DBS) electrodes serve as a natural experimental model for thalamic/subthalamic recordings of tDCS-generated EF. We measured voltage changes from DBS electrodes and body resistance from tDCS electrodes in three subjects while applying direct current to the scalp at 2â¯mA and 4â¯mA over two tDCS montages. RESULTS: Voltage changes at the level of deep nuclei changed proportionally with the level of applied current and varied with different tDCS montages. CONCLUSIONS: Our findings suggest that scalp-applied tDCS generates biologically relevant EF. Incorporation of these experimental results may improve finite element analysis (FEA)-based models.
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Ondas Encefálicas , Campos Eletromagnéticos , Tálamo/fisiologia , Estimulação Transcraniana por Corrente Contínua , Adulto , Feminino , Humanos , MasculinoRESUMO
Amantadine, which was originally developed as an antiviral medication, functions as a dopamine agonist in the central nervous system and consequently is utilized in the treatment of Parkinson disease, drug-induced extrapyramidal reactions, and neuroleptic malignant syndrome. For reasons that are not entirely understood, abrupt changes in amantadine dosage can produce a severe withdrawal syndrome. Existing medical literature describes case reports of amantadine withdrawal leading to delirium, which at times has progressed to neuroleptic malignant syndrome. Amantadine withdrawal may be under-recognized by mental health clinicians, which has the potential to lead to protracted hospital courses and suboptimal outcomes. The goal of this case series is to highlight the role of amantadine withdrawal in the cases of 3 medically complex patients with altered mental status. In the first case, the cognitive side effects of electroconvulsive therapy masked acute amantadine withdrawal in a 64-year-old man with Parkinson disease. In the second case, a 75-year-old depressed patient developed a catatonic delirium when amantadine was discontinued. Finally, a refractory case of neuroleptic malignant syndrome in a 57-year-old patient with schizoaffective disorder rapidly resolved with the reintroduction of outpatient amantadine. These cases highlight several learning objectives regarding amantadine withdrawal syndrome: First, it may be concealed by co-occurring causes of delirium in medically complex patients. Second, its symptoms are likely to be related to a cortical and limbic dopamine shortage, which may be reversed with electroconvulsive therapy or reintroduction of amantadine. Third, its clinical presentation may occur on a spectrum and may include features suggestive of delirium, catatonia, or neuroleptic malignant syndrome.
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Amantadina/efeitos adversos , Catatonia/complicações , Delírio/etiologia , Dopaminérgicos/efeitos adversos , Síndrome Maligna Neuroléptica/tratamento farmacológico , Síndrome de Abstinência a Substâncias/complicações , Idoso , Amantadina/uso terapêutico , Delírio/diagnóstico , Dopaminérgicos/uso terapêutico , Eletroconvulsoterapia/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos Psicóticos/tratamento farmacológico , Síndrome de Abstinência a Substâncias/tratamento farmacológicoRESUMO
A 59-year-old Caucasian man with a past history of Parkinson's disease (PD) status post-bilateral subthalamic nucleus (STN) deep brain stimulation (DBS), who also had treatment-resistant (TR) obsessive-compulsive disorder (OCD), and treatment-resistant depression (TRD), presented for further evaluation and management of his TR OCD. After an unsuccessful attempt to treat his OCD by reprogramming his existing STN DBS, he was offered bilateral ventral capsule/ventral striatum (VC/VS) DBS surgery. In addition to the expected improvement in OCD symptoms, he experienced significant improvement in both PD-related apathy and depression along with resolution of suicidal ideation. Furthermore, the patient's festinating gait dramatically improved. This case demonstrates that DBS of both the STN and VC/VS appears to have an initial signal of safety and tolerability. This is the first instance where both the STN and the VC/VS DBS targets have been implanted in an individual and the first case where a patient with PD has received additional DBS in mood-regulatory circuitry.
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Estimulação Encefálica Profunda/métodos , Transtornos Neurológicos da Marcha/etiologia , Transtornos Neurológicos da Marcha/terapia , Doença de Parkinson/complicações , Recompensa , Apatia , Transtorno Depressivo Maior/complicações , Transtorno Depressivo Maior/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Transtorno Obsessivo-Compulsivo/complicações , Transtorno Obsessivo-Compulsivo/terapia , Escalas de Graduação Psiquiátrica , Núcleo Subtalâmico/fisiologiaRESUMO
BACKGROUND: Freezing of gait (FoG) is a common and debilitating condition in Parkinson's disease (PD) associated with executive dysfunction. A subtype of FoG does not respond to dopaminergic therapy and may be related to noradrenergic deficiency. This pilot study explores the effects of atomoxetine on gait in PD patients with dopa-unresponsive FoG using a novel paradigm for objective gait assessment. FINDINGS: Ten patients with PD and dopa-unresponsive FoG were enrolled in this eight-week open label pilot study. Assessments included an exploratory gait analysis protocol that quantified spatiotemporal parameters during straight-away walking and turning, while performing a dual task. Clinical, and subjective assessments of gait, quality of life, and safety were also administered. The primary outcome was a validated subjective assessment for FoG (FOG-Q). Atomoxetine was well tolerated, however, no significant change was observed in the primary outcome. The gait analysis protocol correlated well with clinical scales, but not with subjective assessments. DBS patients were more likely to increase gait velocity (p = 0.033), and improved in other clinical assessments. CONCLUSIONS: Objective gait analysis protocols assessing gait while dual tasking are feasible and useful for this patient population, and may be superior correlates of FoG severity than subjective measures. These findings can inform future trials in this population.
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The Dream Center Neurology Clinic (DCNC) is a free specialty clinic associated with the Medical University of South Carolina that provides health care for uninsured patients with neurologic disorders. Routine neurologic care is often neglected by free primary care clinics, leaving indigent and uninsured patients to suffer from treatable neurologic ailments. The DCNC was established by supplementing existing resources from a free primary care facility called the Dream Center. Our strategy of building a high-need specialty service into a preexisting primary care infrastructure may provide a blueprint for neurologists who are eager to address the neurologic needs of the underserved in their local communities. According to local charge estimates, the DCNC has provided roughly $120,000 worth of outpatient neurologic care over the past year. The clinic runs through the collaborative effort of medical students as well as academic and private health care providers. Donated services such as EEG, diagnostic lab work, botulinum toxin, supplies, and imaging are also critical to clinic operations. In addition to providing the uninsured with services that are normally inaccessible to them, the DCNC provides a unique educational opportunity for medical students, residents, and all volunteers who are eager to help and learn.
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OBJECTIVES: Anterocollis as a rare subtype of cervical dystonia is difficult to treat and thus less appreciated than other subtypes of cervical dystonia. This review aimed at summarising and discussing recent advances in the management of anterocollis. METHODS: Literature review. RESULTS: Pure anterocollis is a rare condition but 1-24% of the cases of complex cervical dystonia present with an anterocollis component. Applying the collum-caput concept, anterocollis may be subdivided into conceptual anterocollis, anterocaput, and forward sagittal shift, which is useful to direct selection of dystonic muscles for treatment. Additionally, identification of dystonic muscles in conceptual anterocollis, anterocaput, or forward sagittal shift is achieved by electromyography, computed tomography, magnetic resonance imaging, or FDG-positron emission tomography. Treatment of choice is botulinum toxin A. In case of treatment failure, more rarely affected muscles need to be identified and injected. Deep muscles, as are frequently involved in conceptual anterocollis, anterocaput, and forward sagittal shift, should be injected only under guidance of electromyography, endoscopy, or imaging. The more accurately affected muscles are identified, the better the outcome. CONCLUSIONS: Anterocollis as a subtype of cervical dystonia, responds poorly to botulinum toxin but management of this condition can be improved by application of identifying and guiding technologies.
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Movimentos da Cabeça/fisiologia , Músculos do Pescoço/fisiopatologia , Equilíbrio Postural/fisiologia , Torcicolo , Toxinas Botulínicas/uso terapêutico , Estimulação Encefálica Profunda , Humanos , Neurotoxinas/uso terapêutico , Torcicolo/classificação , Torcicolo/fisiopatologia , Torcicolo/terapia , Resultado do TratamentoRESUMO
Anterocollis/anterocaput is a subtype of cervical dystonia and the most infrequent of its abnormal head-positions. Anterocollis can be differentiated from anterocaput by the abnormal angle between thoracic and cervical spine or between skull-base and vertebrum-1 in anterocaput. Anterocollis/anterocaput is classified as primary (idiopathic) or secondary (due to identifiable neurological disease) and as pure or complex. Complex anterocollis is most frequently associated with other types of focal dystonia, such as torticollis or laterocollis. Patients complain about impaired head-movement and report to release the fixed head-position occasionally by a "geste antagonistique". Neurological exam shows tonic (contractures with anteflexion) or tremulous head-movements and neck-posturing. The diagnosis is based on the clinical presentation, needle-electromyography to identify affected muscles and rule out other conditions, X-ray of the cervical/thoracic spine, and cerebral MRI. Treatment of choice is botulinum toxin. If botulinum toxin is ineffective, drug-treatment can be tried. If botulinum toxin and drug treatment fail, deep brain-stimulation of the internal pallidal globes should be considered.
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Torcicolo/terapia , Toxinas Botulínicas Tipo A/uso terapêutico , Estimulação Encefálica Profunda , Humanos , Fármacos Neuromusculares/uso terapêutico , Procedimentos Neurocirúrgicos , Torcicolo/classificação , Torcicolo/epidemiologia , Torcicolo/patologia , Resultado do TratamentoRESUMO
The underlying etiology of parkinsonian anterocollis has been the subject of recent debate. The purpose of this study is to test the hypothesis that anterocollis in parkinsonian syndromes is associated with dystonia of the deep cervical flexors (longus colli and capitis). Eight patients with anterocollis, six in the setting of parkinsonism and two primary cervical dystonia control subjects with anterocollis underwent prospective structured clinical evaluations (interview, examination and rating scales), systematic electromyography of the cervical extensor musculature and (18)F-FDG PET/CT studies of cervical muscles to examine evidence of hypermetabolism or overactivity of deep cervical flexors. Subjects with parkinsonian anterocollis were found to have hypermetabolism of the extensor and sub-occipital muscles but not in the cervical flexors (superficial or deep). EMG abnormalities were observed in all evaluated patients, but only one patient was definitely myopathic. Meanwhile, both dystonia controls exhibited hypermetabolism of cervical flexors (including the longus colli). In conclusion, we were able to demonstrate hypermetabolism of superficial and deep cervical flexors with muscle (18)F-FDG PET/CT in dystonic anterocollis patients, but not in parkinsonian anterocollis patients. The hypermetabolic changes seen in parkinsonian anterocollis patients in posterior muscles may be compensatory. Alternative explanations for anterocollis include myopathy of the cervical extensors, or unbalanced rigidity of the cervical flexors, but this remains to be proven.
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Fluordesoxiglucose F18 , Músculos do Pescoço/diagnóstico por imagem , Transtornos Parkinsonianos , Torcicolo/congênito , Adulto , Idoso , Idoso de 80 Anos ou mais , Distonia/congênito , Eletromiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos Parkinsonianos/complicações , Transtornos Parkinsonianos/diagnóstico por imagem , Transtornos Parkinsonianos/patologia , Tomografia por Emissão de Pósitrons , Tomógrafos Computadorizados , Torcicolo/complicações , Torcicolo/diagnóstico por imagem , Torcicolo/patologiaRESUMO
Freezing of gait (FOG) is a debilitating feature of Parkinson's disease (PD) and other forms of parkinsonism. The anatomical or pathophysiological correlates are poorly understood largely due to the lack of a well-established animal model. Here we studied whether FOG is reproduced in the non-human primate (NHP) model of PD. 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated monkeys (Genus Macaca, n=29) were examined for the development of FOG, and the leg movements were recorded with accelerometry. The relationships between developing FOG and the animals' characteristics, the MPTP treatments, and the modeled outcomes were determined. In parkinsonian monkeys FOG developed frequently (48%) manifesting similar characteristics to those seen in PD patients. In addition, FOG episodes in the monkey were accompanied by leg trembling with the typical duration (2-10s) and frequency (~7 Hz). The development of NHP FOG was significantly associated with the severity of parkinsonism, as shown by high motor disability scores (≥ 20) and levodopa-induced dyskinesia scores (p=0.01 and p=0.04, respectively). Differences in demographics and MPTP treatments (doses, treatment duration, etc.) had no influence on NHP FOG occurrence, with the exception of gender that showed FOG predominance in males (p=0.03). The unique features of FOG in PD can be replicated in severely parkinsonian macaques, and this represents the first description of a FOG animal model.
Assuntos
Modelos Animais de Doenças , Transtornos Neurológicos da Marcha/etiologia , Coxeadura Animal/etiologia , Transtornos Parkinsonianos/complicações , Animais , Feminino , Transtornos Neurológicos da Marcha/fisiopatologia , Coxeadura Animal/fisiopatologia , Macaca , Masculino , Transtornos Parkinsonianos/fisiopatologiaRESUMO
Postural deformities in parkinsonian syndromes are well recognized, but poorly understood and largely refractory to available therapies. In recent times a number of hypotheses have been proposed to explain the underlying etiology of anterocollis and camptocormia, but currently there is no consensus. As these conditions are more precisely characterized we begin to uncover that this is a heterogeneous and evolving phenomenon. These conditions bring to light the inadequacies of our current tools to study biomechanics of posture, neuromuscular disorders, and dystonic muscular contractions. The development of objective, accurate tools to directly study and measure the severity of these postural disorders will allow for further understanding of the pathophysiology, the development of novel therapeutics, and adequate clinical trial design.