Trans-Spinal Theta Burst Magnetic Stimulation in Parkinson's Disease and Gait Disorders.

BACKGROUND: Gait disorders in patients with Parkinson's disease (PD) can become disabling with disease progression without effective treatment. OBJECTIVES: To investigate the efficacy of intermittent θ burst trans-spinal magnetic stimulation (TsMS) in PD patients with gait and balance disorders. METHODS: This was a randomized, parallel, double-blind, controlled trial. Active or sham TsMS was applied at third thoracic vertebra with 100% of the trans-spinal motor threshold, during 5 consecutive days. Participants were evaluated at baseline, immediately after last session, 1 and 4 weeks after last session. Primary outcome was Total Timed Up and Go (TUG) values comparing active versus sham phases 1 week after intervention. The secondary outcome measurements consisted of motor, gait and balance scales, and questionnaires for quality of life and cognition. RESULTS: Thirty-three patients were included, average age 68.5 (6.4) years in active group and 70.3 (6.3) years in sham group. In active group, Total TUG mean baseline was 107.18 (95% CI, 52.1-116.1), and 1 week after stimulation was 93.0 (95% CI, 50.7-135.3); sham group, Total TUG mean baseline was 101.2 (95% CI, 47.1-155.3) and 1 week after stimulation 75.2 (95% CI 34.0-116.4), P = 0.54. Similarly, intervention had no significant effects on secondary outcome measurements. During stimulation period, five patients presented with mild side effects (three in active group and two in sham group). DISCUSSION: TsMS did not significantly improve gait or balance analysis in patients with PD and gait disorders. The protocol was safe and well tolerated. © 2024 International Parkinson and Movement Disorder Society.

Encephalitis associated with anti-mGluR5 antibodies.

A 30-year-old woman had 5 days of visual hallucinations, nystagmus, memory impairment and mutism. On examination, she was disorientated with reduced attention span, gaze-evoked nystagmus, paratonia and abnormal frontal reflexes. Cerebrospinal fluid (CSF) showed 80 cells, protein 0.41 g/L and glucose 3.2 mmol/L (plasma glucose 5.0 mmol/L). MR scan of the brain showed involvement of limbic and extra-limbic regions and brainstem. Commercial cell-based assays were negative, but tissue-based assays showed neuropil staining, and cell-based assays for anti-metabotropic glutamate receptor 5 (mGluR5) antibodies were positive in serum and CSF. Six months later, she was diagnosed with Hodgkin's lymphoma. This case emphasises the broader clinical spectrum of anti-mGluR5 encephalitis, challenging its initial characterisation as Ophelia syndrome. It underscores the significance of interpreting commercial cell-based assays and advocates for tissue-based assay testing followed by cell-based assay testing in serum and CSF for diagnosing rare autoimmune encephalitis.

Long-term tonic spinal cord stimulation in advanced Parkinson's disease: No effect from stimulation under placebo-controlled evaluation.

•Chronic spinal cord stimulation effectiveness was evaluated in four PD patients.•Double blinded cross over evaluation was performed using subthreshold stimulation.•An open label evaluation with regular suprathreshold stimulation was also performed.•No statistically significant effect was produced with either stimulation.•This study highlights the lack of strong clinical evidence supporting SCS for PD.

Controversies and Clinical Applications of Non-Invasive Transspinal Magnetic Stimulation: A Critical Review and Exploratory Trial in Hereditary Spastic Paraplegia.

Magnetic stimulation is a safe, non-invasive diagnostic tool and promising treatment strategy for neurological and psychiatric disorders. Although most studies address transcranial magnetic stimulation, transspinal magnetic stimulation (TsMS) has received recent attention since trials involving invasive spinal cord stimulation showed encouraging results for pain, spasticity, and Parkinson's disease. While the effects of TsMS on spinal roots is well understood, its mechanism of action on the spinal cord is still controversial. Despite unclear mechanisms of action, clinical benefits of TsMS have been reported, including improvements in scales of spasticity, hyperreflexia, and bladder and bowel symptoms, and even supraspinal gait disorders such as freezing and camptocormia. In the present study, a critical review on the application of TsMS in neurology was conducted, along with an exploratory trial involving TsMS in three patients with hereditary spastic paraplegia. The goal was to understand the mechanism of action of TsMS through H-reflex measurement at the unstimulated lumbosacral level. Although limited by studies with a small sample size and a low to moderate effect size, TsMS is safe and tolerable and presents consistent clinical and neurophysiological benefits that support its use in clinical practice.

Deep brain stimulation in Parkinson's disease: state of the art and future perspectives.

For more than 30 years, Deep Brain Stimulation (DBS) has been a therapeutic option for Parkinson's disease (PD) treatment. However, this therapy is still underutilized mainly due to misinformation regarding risks and clinical outcomes. DBS can ameliorate several motor and non-motor symptoms, improving patients' quality of life. Furthermore, most of the improvement after DBS is long-lasting and present even in advanced PD. Adequate patient selection, precise electric leads placement, and correct DBS programming are paramount for good surgical outcomes. Nonetheless, DBS still has many limitations: axial symptoms and signs, such as speech, balance and gait, do not improve to the same extent as appendicular symptoms and can even be worsened as a direct or indirect consequence of surgery and stimulation. In addition, there are still unanswered questions regarding patient's selection, surgical planning and programming techniques, such as the role of surgicogenomics, more precise imaging-based lead placement, new brain targets, advanced programming strategies and hardware features. The net effect of these innovations should not only be to refine the beneficial effect we currently observe on selected symptoms and signs but also to improve treatment resistant facets of PD, such as axial and non-motor features. In this review, we discuss the current state of the art regarding DBS selection, implant, and programming, and explore new advances in the DBS field.

Deep brain stimulation in Parkinson's disease: state of the art and future perspectives / Estimulação cerebral profunda na doença de Parkinson: estado da arte e perspectivas futuras

ABSTRACT For more than 30 years, Deep Brain Stimulation (DBS) has been a therapeutic option for Parkinson's disease (PD) treatment. However, this therapy is still underutilized mainly due to misinformation regarding risks and clinical outcomes. DBS can ameliorate several motor and non-motor symptoms, improving patients' quality of life. Furthermore, most of the improvement after DBS is long-lasting and present even in advanced PD. Adequate patient selection, precise electric leads placement, and correct DBS programming are paramount for good surgical outcomes. Nonetheless, DBS still has many limitations: axial symptoms and signs, such as speech, balance and gait, do not improve to the same extent as appendicular symptoms and can even be worsened as a direct or indirect consequence of surgery and stimulation. In addition, there are still unanswered questions regarding patient's selection, surgical planning and programming techniques, such as the role of surgicogenomics, more precise imaging-based lead placement, new brain targets, advanced programming strategies and hardware features. The net effect of these innovations should not only be to refine the beneficial effect we currently observe on selected symptoms and signs but also to improve treatment resistant facets of PD, such as axial and non-motor features. In this review, we discuss the current state of the art regarding DBS selection, implant, and programming, and explore new advances in the DBS field.

RESUMO Há mais de 30 anos, a Estimulação Cerebral Profunda (ECP) é uma opção de tratamento para pessoas com doença de Parkinson (DP). Apesar disso, a ECP ainda é subutilizada, em grande parte por desinformação acerca dos riscos e dos benefícios desse tratamento. A ECP melhora os sintomas motores e não motores da DP, melhorando, assim, a qualidade de vida dos pacientes. Grande parte dos benefícios gerados pela ECP têm longa duração, estando presentes até mesmo em fases avançadas da doença. A seleção adequada dos pacientes, o preciso posicionamento dos eletrodos cerebrais, e a programação correta da ECP são fundamentais para que haja benefício após a cirurgia. Todavia, existem ainda muitas limitações em relação ao tratamento com ECP. Sintomas axiais, como fala e marcha, não melhoram tanto quanto os sintomas apendiculares, e podem até mesmo piorar após a cirurgia. Existem muitas dúvidas relacionadas à seleção de pacientes, especialmente nos aspectos de imagem e genética. Em relação à questão cirúrgica, novas técnicas de imagem podem auxiliar o posicionamento correto dos eletrodos cerebrais. Novas estratégias de programação e avanços de hardware podem melhorar desfechos que ainda são limitados. A fim de melhorar sintomas resistentes à ECP, como cognição e marcha, novos alvos cerebrais estão sendo explorados. Na presente revisão, discutimos o atual estado da arte relacionado à ECP, abordando seleção de pacientes, implante cirúrgico de eletrodos, e programação do dispositivo, além de explorarmos novos avanços em desenvolvimento.

Use of non-invasive stimulation in movement disorders: a critical review.

BACKGROUND: Noninvasive stimulation has been widely used in the past 30 years to study and treat a large number of neurological diseases, including movement disorders. OBJECTIVE: In this critical review, we illustrate the rationale for use of these techniques in movement disorders and summarize the best medical evidence based on the main clinical trials performed to date. METHODS: A nationally representative group of experts performed a comprehensive review of the literature in order to analyze the key clinical decision-making factors driving transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) in movement disorders. Classes of evidence and recommendations were described for each disease. RESULTS: Despite unavoidable heterogeneities and low effect size, TMS is likely to be effective for treating motor symptoms and depression in Parkinson's disease (PD). The efficacy in other movement disorders is unclear. TMS is possibly effective for focal hand dystonia, essential tremor and cerebellar ataxia. Additionally, it is likely to be ineffective in reducing tics in Tourette syndrome. Lastly, tDCS is likely to be effective in improving gait in PD. CONCLUSIONS: There is encouraging evidence for the use of noninvasive stimulation on a subset of symptoms in selected movement disorders, although the means to optimize protocols for improving positive outcomes in routine clinical practice remain undetermined. Similarly, the best stimulation paradigms and responder profile need to be investigated in large clinical trials with established therapeutic and assessment paradigms that could also allow genuine long-term benefits to be determined.

Neurological consultations and diagnoses in a large, dedicated COVID-19 university hospital.

BACKGROUND: More than one-third of COVID-19 patients present neurological symptoms ranging from anosmia to stroke and encephalopathy. Furthermore, pre-existing neurological conditions may require special treatment and may be associated with worse outcomes. Notwithstanding, the role of neurologists in COVID-19 is probably underrecognized. OBJECTIVE: The aim of this study was to report the reasons for requesting neurological consultations by internists and intensivists in a COVID-19-dedicated hospital. METHODS: This retrospective study was carried out at Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Brazil, a 900-bed COVID-19 dedicated center (including 300 intensive care unit beds). COVID-19 diagnosis was confirmed by SARS-CoV-2-RT-PCR in nasal swabs. All inpatient neurology consultations between March 23rd and May 23rd, 2020 were analyzed. Neurologists performed the neurological exam, assessed all available data to diagnose the neurological condition, and requested additional tests deemed necessary. Difficult diagnoses were established in consensus meetings. After diagnosis, neurologists were involved in the treatment. RESULTS: Neurological consultations were requested for 89 out of 1,208 (7.4%) inpatient COVID admissions during that period. Main neurological diagnoses included: encephalopathy (44.4%), stroke (16.7%), previous neurological diseases (9.0%), seizures (9.0%), neuromuscular disorders (5.6%), other acute brain lesions (3.4%), and other mild nonspecific symptoms (11.2%). CONCLUSIONS: Most neurological consultations in a COVID-19-dedicated hospital were requested for severe conditions that could have an impact on the outcome. First-line doctors should be able to recognize neurological symptoms; neurologists are important members of the medical team in COVID-19 hospital care.

Neurological consultations and diagnoses in a large, dedicated COVID-19 university hospital / Consultas neurológicas e diagnósticos em um grande hospital universitário dedicado a COVID-19

ABSTRACT Background: More than one-third of COVID-19 patients present neurological symptoms ranging from anosmia to stroke and encephalopathy. Furthermore, pre-existing neurological conditions may require special treatment and may be associated with worse outcomes. Notwithstanding, the role of neurologists in COVID-19 is probably underrecognized. Objective: The aim of this study was to report the reasons for requesting neurological consultations by internists and intensivists in a COVID-19-dedicated hospital. Methods: This retrospective study was carried out at Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Brazil, a 900-bed COVID-19 dedicated center (including 300 intensive care unit beds). COVID-19 diagnosis was confirmed by SARS-CoV-2-RT-PCR in nasal swabs. All inpatient neurology consultations between March 23rd and May 23rd, 2020 were analyzed. Neurologists performed the neurological exam, assessed all available data to diagnose the neurological condition, and requested additional tests deemed necessary. Difficult diagnoses were established in consensus meetings. After diagnosis, neurologists were involved in the treatment. Results: Neurological consultations were requested for 89 out of 1,208 (7.4%) inpatient COVID admissions during that period. Main neurological diagnoses included: encephalopathy (44.4%), stroke (16.7%), previous neurological diseases (9.0%), seizures (9.0%), neuromuscular disorders (5.6%), other acute brain lesions (3.4%), and other mild nonspecific symptoms (11.2%). Conclusions: Most neurological consultations in a COVID-19-dedicated hospital were requested for severe conditions that could have an impact on the outcome. First-line doctors should be able to recognize neurological symptoms; neurologists are important members of the medical team in COVID-19 hospital care.

RESUMO Introdução: Mais de um terço dos pacientes com COVID-19 apresentam sintomas neurológicos que variam de anosmia a AVC e encefalopatia. Além disso, doenças neurológicas prévias podem exigir tratamento especial e estar associadas a piores desfechos. Não obstante, o papel dos neurologistas na COVID-19 é provavelmente pouco reconhecido. Objetivo: O objetivo deste estudo foi relatar os motivos para solicitar consultas neurológicas por clínicos e intensivistas em um hospital dedicado à COVID-19. Métodos: Estudo retrospectivo realizado no Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Brasil, um centro dedicado à COVID-19 com 900 leitos (incluindo 300 leitos para unidades de terapia intensiva). O diagnóstico de COVID-19 foi confirmado por SARS-CoV-2-RT-PCR em swabs nasais. Todas as interconsultas de neurologia hospitalar entre 23 de março e 23 de maio de 2020 foram analisadas. Os neurologistas realizaram o exame neurológico, avaliaram todos os dados disponíveis para diagnosticar a patologia neurológica e solicitaram exames adicionais conforme necessidade. Diagnósticos difíceis foram estabelecidos em reuniões de consenso. Após o diagnóstico, os neurologistas participaram da condução dos casos. Resultados: Foram solicitadas consultas neurológicas para 89 de 1.208 (7,4%) em pacientes internados por COVID-19 durante o período. Os principais diagnósticos neurológicos incluíram: encefalopatia (44,4%), acidente vascular cerebral (16,7%), doenças neurológicas prévias (9,0%), crises epilépticas (9,0%), transtornos neuromusculares (5,6%), outras lesões encefálicas agudas (3,4%) e outros sintomas leves inespecíficos (11,2%). Conclusões: A maioria das consultas neurológicas em um hospital dedicado à COVID-19 foi solicitada para condições graves que poderiam afetar o desfecho clínico. Os médicos na linha de frente devem ser capazes de reconhecer sintomas neurológicos. Os neurologistas são membros importantes da equipe médica no atendimento hospitalar à COVID-19.