Fokus auf der Untersuchung des Einflusses biometrischer Faktoren auf das Ergebnis der nTMS Messung sprachrelevanter Areale neurochirurgischer Patienten

Objective: Navigated transcranial magnetic stimulation (nTMS) is a non-invasive mapping tool to locate functional areas of the brain, gaining importance as a preoperative diagnostic device. This is a summary of three studies, Schwarzer et al., Rosenstock et al. and Zdunczyk et al., whose aim it is to increase the accuracy and usability of nTMS in different neurosurgical patient groups. They intend to describe neurophysiological data gained through nTMS as a supportive measure for surgical planning to increase patient safety and improve outcome. Methods: All patients and healthy subjects were examined via bihemispheric nTMS. Schwarzer et al. ascertained a baseline picture naming performance and used repetitive nTMS (rnTMS) to induce speech disruptions to identify individual language areas in patients with language eloquent lesions. Nine biometric factors were analyzed for correlation with elevated error occurrence. Rosenstock et al. concentrated on the primary motor cortex of patients with motor-eloquent glioma and performed correlation analyses to test the association of nTMS-related variables and postoperative motor outcome. Zdunczyk et al. examined patients with degenerative cervical myelopathy (DCM) and healthy volunteers to see differences in neurophysiological nTMS data due to disease severity. Results: Schwarzer et al. showed a significant increase in error occurrence with increased severity of cognitive impairment (p8mm (p=0.014). New postoperative deficits could be seen in patients with pathological excitability of the motor cortex (resting motor threshold ratio 110%, p=0.031). Patients with DCM had a reduced corticospinal excitability estimated by the recruitment curve (p=0.022), and patients with mild symptoms showed an increased activation on non- primary motor areas (p<0.005). Patients with severe symptoms showed a higher cortical inhibition (p<0.05) and a reduced motor area (p<0.05). Conclusion: Most patients are eligible for rnTMS language mapping. A new protocol for language mapping is proposed for secure identification of patients eligible for reliable rnTMS in Schwarzer et al. Rosenstock et al. introduce a new risk stratification model, based on objective functional-anatomical and neurophysiological measures, which enables physicians to counsel patients about the risk of functional deterioration or the potential for recovery and supports surgical planning. Zdunczyk et al. propose a new concept for functional compensation for DCM on the cortical and spinal level: the corticospinal reserve capacity. nTMS is a viable diagnostic tool to characterize this and its parameters serve as valuable prognostic factors.Fragestellung: Navigierte transkranielle Magnetstimulation (nTMS) ist eine nicht-invasive Untersuchungsmethode, um kortikale Funktionsareale zu identifizieren, welche zunehmend an Bedeutung als präoperatives diagnostisches Mittel gewinnt. Dies ist eine Zusammenfassung dreier Studien, Schwarzer et al., Rosenstock et al. und Zdunczyk et al. Die Studien haben als Ziel, die Benutzerfreundlichkeit und Genauigkeit von nTMS für unterschiedliche neurochirurgische Patientengruppen zu verbessern. Neurophysiologische Parameter wurden mittels nTMS erhoben, um die operative Planung zu unterstützen und das individuelle Patientenrisiko korrekt einzuschätzen und zu verbessern. Methodik: Alle Patienten und Probanden wurden bihemisphärisch mittels nTMS untersucht. Schwarzer et al. erhoben vorher die individuelle Fähigkeit zur Objektbenennung (baseline) und nutzten repetitive nTMS (rnTMS), um Sprachunterbrechungen hervorzurufen und somit Kortexareale bei Patienten mit sprachrelevanten Hirnläsionen zu identifizieren. Neun biometrische Patienteneigenschaften wurden in ein Verhältnis mit der Fehleranfälligkeit gesetzt. Rosenstock et al. untersuchten den primär motorischen Kortex bei Gliompatienten und analysierten den Zusammenhang von nTMS-ermittelten Parametern mit dem postoperativen Patientenzustand. Zdunczyk et al. betrachteten Patienten mit degenerativer zervikaler Myelopathie (DCM), sowie gesunde Probanden und ermittelten die unterschiedlichen nTMS-Parameter in Abhängigkeit von der Symptomschwere. Ergebnisse: Die meisten biometrischen Faktoren zeigten keinen statistischen Zusammenhang mit dem Stimulationsergebnis bei Schwarzer et al. Je schwerer der Aphasiegrad und die kognitiven Einschränkungen waren, desto mehr Sprachfehler wurden in der rnTMS Untersuchung gemacht (je p8mm zwischen Tumor und kortikospinalem Trakt keine neuen permanenten postoperativen Defizite auftraten (p=0.014). Neue postoperative Defizite traten bei Patienten mit präoperativ pathologischer Kortexerregbarkeit (Ruhemotorschwellenverhältnis RMT 110%, p=0.031) auf. DCM Patienten wiesen eine reduzierte kortikospinale Erregbarkeit, gekennzeichnet durch ein Abflachen der recruitment curve, auf (p=0.022). Ein vergrößertes motorisch relevantes Kortexareal mit Aktivierung sekundärer Motorareale zeigte sich bei Patienten mit milder Symptomatik (p<0.005), während bei schwer betroffenen Patienten eine erhöhte kortikale Hemmung (CSP, p<0.05) und reduzierte motorische Kortexfläche auffiel (p<0.05). Schlussfolgerung: Schwarzer et al. stellen ein neues Prüfungsprotokoll für die Eignung von Patienten für ein reliables rnTMS Ergebnis vor, wobei die statistische Analyse ergab, dass die meisten Patienten für eine reliable rnTMS Sprachuntersuchung geeignet sind. Rosenstock et al. präsentieren ein neues Risikostratifikationsmodell für Patienten mit motorisch relevanten Gliomen, wodurch der Operateur anhand von funktionell-anatomischen und neurophysiologischen Parametern das individuelle Patientenrisiko für den postoperativen Verlauf einschätzen kann. Zdunczyk et al. beschreiben einen möglichen funktionellen Kompensationsmechanismus bei DCM Patienten auf kortikaler und spinaler Ebene: die kortikospinale Reservekapazität. Die durch nTMS ermittelten Parameter lassen damit objektivierbare prognostische Aussagen zu

Remote Inference of Cognitive Scores in ALS Patients Using a Picture Description

Amyotrophic lateral sclerosis is a fatal disease that not only affects movement, speech, and breath but also cognition. Recent studies have focused on the use of language analysis techniques to detect ALS and infer scales for monitoring functional progression. In this paper, we focused on another important aspect, cognitive impairment, which affects 35-50% of the ALS population. In an effort to reach the ALS population, which frequently exhibits mobility limitations, we implemented the digital version of the Edinburgh Cognitive and Behavioral ALS Screen (ECAS) test for the first time. This test which is designed to measure cognitive impairment was remotely performed by 56 participants from the EverythingALS Speech Study. As part of the study, participants (ALS and non-ALS) were asked to describe weekly one picture from a pool of many pictures with complex scenes displayed on their computer at home. We analyze the descriptions performed within +/- 60 days from the day the ECAS test was administered and extract different types of linguistic and acoustic features. We input those features into linear regression models to infer 5 ECAS sub-scores and the total score. Speech samples from the picture description are reliable enough to predict the ECAS subs-scores, achieving statistically significant Spearman correlation values between 0.32 and 0.51 for the model's performance using 10-fold cross-validation.Comment: conference pape

Historical Analyses of Disordered Handwriting

Handwritten texts carry significant information, extending beyond the meaning of their words. Modern neurology, for example, benefits from the interpretation of the graphic features of writing and drawing for the diagnosis and monitoring of diseases and disorders. This article examines how handwriting analysis can be used, and has been used historically, as a methodological tool for the assessment of medical conditions and how this enhances our understanding of historical contexts of writing. We analyze handwritten material, writing tests and letters, from patients in an early 20th-century psychiatric hospital in southern Germany (Irsee/Kaufbeuren). In this institution, early psychiatrists assessed handwriting features, providing us novel insights into the earliest practices of psychiatric handwriting analysis, which can be connected to Berkenkotter’s research on medical admission records. We finally consider the degree to which historical handwriting bears semiotic potential to explain the psychological state and personality of a writer, and how future research in written communication should approach these sources

The Effects of Speech Impairment on Quality of Life over Time in Patients with Amyotrophic Lateral Sclerosis

Limited research exists on how speech impairments affect quality of life (QOL) factors over time in patients with amyotrophic lateral sclerosis (ALS). A review of the literature, including the history, disease course, and prevalence of ALS, is presented. Physical and psychosocial functioning, especially the decline of bulbar functioning’s potential impact on QOL factors and communication style, are outlined. This study is a follow-up study on a study by Duff, who found a significant difference in QOL relative to level of bulbar functioning in a cross-sectional design. The current study used a longitudinal design to look at bulbar functioning, specifically levels of speech, and how that affects certain aspects of QOL over time. This study used archival data, collected from a multidisciplinary clinic at three time points, and evaluated the following measures: ALS Functional Rating Scale–Revised (ALSFRS–R) and the ALS–Specific Quality of Life Measurement–Revised (ALSSQOL–R). ALSSQOL–R domains of Negative Emotion, Interaction with People and the Environment, Intimacy, and Bulbar Function were analyzed by repeated measures tests, and correlated to speech impairment over time. Results indicated that as speech became significantly more impaired, no significant differences were observed on the Negative Emotion, Interaction with People and the Environment, and Intimacy subscales. However, as the ability to speak declines over time, participants’ Bulbar Functioning subscale scores decreased. These findings suggest that increased bulbar symptoms are perceived as more problematic over time point. However, results also indicated that at the third time point (most recent clinic visit) the relationship between actual speech impairment and perceived bulbar functioning weakens

Occasional essay: upper motor neuron syndrome in amyotrophic lateral sclerosis

The diagnosis of amyotrophic lateral sclerosis (ALS) requires recognition of both lower (LMN) and upper motor neuron (UMN) dysfunction.1 However, classical UMN signs are frequently difficult to identify in ALS.2 LMN involvement is sensitively detected by electromyography (EMG)3 but, as yet, there are no generally accepted markers for monitoring UMN abnormalities,4 the neurobiology of ALS itself, and disease spread through the brain and spinal cord,.5 Full clinical assessment is therefore necessary to exclude other diagnoses and to monitor disease progression. In part, this difficulty regarding detection of UMN involvement in ALS derives from the definition of ‘the UMN syndrome’. Abnormalities of motor control in ALS require reformulation within an expanded concept of the UMN, together with the neuropathological, neuro-imaging and neurophysiological abnormalities in ALS. We review these issues here

Safety and feasibility of Lin- cells administration to ALS patients : a novel view on humoral factors and miRNA profiles

Therapeutic options for amyotrophic lateral sclerosis (ALS) are still limited. Great hopes, however, are placed in growth factors that show neuroprotective abilities (e.g., nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and vascular endothelial growth factor (VEGF)) and in the immune modulating features, in particular, the anti-inflammatory effects. In our study we aimed to investigate whether a bone marrow-derived lineage-negative (Lin-) cells population, after autologous application into cerebrospinal fluid (CSF), is able to produce noticeable concentrations of trophic factors and inflammatory-related proteins and thus influence the clinical course of ALS. To our knowledge, the evaluation of Lin- cells transplantation for ALS treatment has not been previously reported. Early hematopoietic Lin- cells were isolated from twelve ALS patients&rsquo; bone marrow, and later, the suspension of cells was administered into the subarachnoid space by lumbar puncture. Concentrations of selected proteins in the CSF and plasma were quantified by multiplex fluorescent bead-based immunoassays at different timepoints post-transplantation. We also chose microRNAs (miRNAs) related to muscle biology (miRNA-1, miRNA-133a, and miRNA-206) and angiogenesis and inflammation (miRNA-155 and miRNA-378) and tested, for the first time, their expression profiles in the CSF and plasma of ALS patients after Lin- cells transplantation. The injection of bone marrow cells resulted in decreased concentration of selected inflammatory proteins (C3) after Lin- cells injection, particularly in patients who had a better clinical outcome. Moreover, several analyzed miRNAs have changed expression levels in the CSF and plasma of ALS patients subsequent to Lin- cells administration. Interestingly, the expression of miR-206 increased in ALS patients, while miR-378 decreased both in the CSF and plasma one month after the cells&rsquo; injection. We propose that autologous lineage-negative early hematopoietic cells injected intrathecally may be a safe and feasible source of material for transplantations to the central nervous system (CNS) environment aimed at anti-inflammatory support provision for ALS adjuvant treatment strategies. Further research is needed to evaluate whether the observed effects could significantly influence the ALS progression

A systematic review and narrative analysis of digital speech biomarkers in Motor Neuron Disease

Motor Neuron Disease (MND) is a progressive and largely fatal neurodegeneritve disorder with a lifetime risk of approximately 1 in 300. At diagnosis, up to 25% of people with MND (pwMND) exhibit bulbar dysfunction. Currently, pwMND are assessed using clinical examination and diagnostic tools including the ALS Functional Rating Scale Revised (ALS-FRS(R)), a clinician-administered questionnaire with a single item on speech intelligibility. Here we report on the use of digital technologies to assess speech features as a marker of disease diagnosis and progression in pwMND. Google Scholar, PubMed, Medline and EMBASE were systematically searched. 40 studies were evaluated including 3670 participants; 1878 with a diagnosis of MND. 24 studies used microphones, 5 used smartphones, 6 used apps, 2 used tape recorders and 1 used the Multi-Dimensional Voice Programme (MDVP) to record speech samples. Data extraction and analysis methods varied but included traditional statistical analysis, CSpeech, MATLAB and machine learning (ML) algorithms. Speech features assessed also varied and included jitter, shimmer, fundamental frequency, intelligible speaking rate, pause duration and syllable repetition. Findings from this systematic review indicate that digital speech biomarkers can distinguish pwMND from healthy controls and can help identify bulbar involvement in pwMND. Preliminary evidence suggests digitally assessed acoustic features can identify more nuanced changes in those affected by voice dysfunction. No one digital speech biomarker alone is consistently able to diagnose or prognosticate MND. Further longitudinal studies involving larger samples are required to validate the use of these technologies as diagnostic tools or prognostic biomarkers

Studies on the impact of assistive communication devices on the quality of life of patients with amyotrophic lateral sclerosis

Tese de doutoramento, Ciências Biomédicas (Neurociências), Universidade de Lisboa, Faculdade de Medicina, 2016Amyotrophic Lateral Sclerosis (ALS) is a progressive neuromuscular disease with rapid and generalized degeneration of motor neurons. Patients with ALS experiment a relentless decline in functions that affect performance of most activities of daily living (ADL), such as speaking, eating, walking or writing. For this reason, dependence on caregivers grows as the disease progresses. Management of the respiratory system is one of the main concerns of medical support, since respiratory failure is the most common cause of death in ALS. Due to increasing muscle weakness, most patients experience dramatic decrease of speech intelligibility and difficulties in using upper limbs (UL) for writing. There is growing evidence that mild cognitive impairment is common in ALS, but most patients are self-conscious of their difficulties in communicating and, in very severe stages, locked-in syndrome can occur. When no other resources than speech and writing are used to assist communication, patients are deprived of expressing needs or feelings, making decisions and keeping social relationships. Further, caregivers feel increased dependence due to difficulties in communication with others and get frustrated about difficulties in understanding partners’ needs. Support for communication is then very important to improve quality of life of both patients and caregivers; however, this has been poorly investigated in ALS. Assistive communication devices (ACD) can support patients by providing a diversity of tools for communication, as they progressively lose speech. ALS, in common with other degenerative conditions, introduces an additional challenge for the field of ACD: as the disease progresses, technologies must adapt to different conditions of the user. In early stages, patients may need speech synthesis in a mobile device, if dysarthria is one of the initial symptoms, or keyboard modifications, as weakness in UL increases. When upper limbs’ dysfunction is high, different input technologies may be adapted to capture voluntary control (for example, eye-tracking devices). Despite the enormous advances in the field of Assistive Technologies, in the last decade, difficulties in clinical support for the use of assistive communication devices (ACD) persist. Among the main reasons for these difficulties are lack of assessment tools to evaluate communication needs and determine proper input devices and to indicate changes over disease progression, and absence of clinical evidence that ACD has relevant impact on the quality of life of affected patients. For this set of reasons, support with communication tools is delayed to stages where patients are severely disabled. Often in these stages, patients face additional clinical complications and increased dependence on their caregivers’ decisions, which increase the difficulty in adaptation to new communication tools. This thesis addresses the role of assistive technologies in the quality of life of early-affected patients with ALS. Also, it includes the study of assessment tools that can improve longitudinal evaluation of communication needs of patients with ALS. We longitudinally evaluated a group of 30 patients with bulbar-onset ALS and 17 caregivers, during 2 to 29 months. Patients were assessed during their regular clinical appointments, in the Hospital de Santa Maria-Centro Hospitalar Lisboa_Norte. Evaluation of patients was based on validated instruments for assessing the Quality of Life (QoL) of patients and caregivers, and on methodologies for recording communication and measuring its performance (including speech, handwriting and typing). We tested the impact of early support with ACD on the QoL of patients with ALS, using a randomized, prospective, longitudinal design. Patients were able to learn and improve their skills to use communication tools based on electronic assistive devices. We found a positive impact of ACD in psychological and wellbeing domains of quality of life in patients, as well as in the support and psychological domains in caregivers. We also studied performance of communication (words per minute) using UL. Performance in handwriting may decline faster than performance in typing, supporting the idea that the use of touchscreen-based ACD supports communication for longer than handwriting. From longitudinal recordings of speech and typing activity we could observe that ACD can support tools to detect early markers of bulbar and UL dysfunction in ALS. Methodologies that were used in this research for recording and assessing function in communication can be replicated in the home environment and form part of the original contributions of this research. Implementation of remote monitoring tools in daily use of ACD, based on these methodologies, is discussed. Considering those patients who receive late support for the use of ACD, lack of time or daily support to learn how to control complex input devices may hinder its use. We developed a novel device to explore the detection and control of various residual movements, based on sensors of accelerometry, electromyography and force, as input signals for communication. The aim of this input device was to develop a tool to explore new communication channels in patients with generalized muscle weakness. This research contributed with novel tools from the Engineering field to the study of assistive communication in patients with ALS. Methodologies that were developed in this work can be further applied to the study of the impact of ACD in other neurodegenerative diseases that affect speech and motor control of UL

Language contributions to health related quality of life in Amyotrophic Lateral Sclerosis

Concurrent with the well-documented motor speech production impairments in amyotrophic lateral sclerosis (ALS), individuals with ALS exhibit language problems including confrontation and generative naming difficulties, single word auditory and reading comprehension problems, and decreased self-regulation based on fewer self-corrected utterances, among other language disruptions. Health related quality of life (HRQoL) measures specific to ALS often contain items related to its characteristic speech production problems that are thought to influence overall quality of life. However, the language problems in ALS are rarely if ever considered within the context of HRQoL. The current study aimed to identify the relationship between language problems (i.e., quality of communication) and HRQoL among individuals with ALS. Twenty-eight participants with ALS completed a general HRQoL (i.e., SF-36) and a quality of communication measure (i.e., ASHA QCL). Scores on these measures were compared with standardized language test scores and discourse measures including verbal fluency, the Boston Naming Test (BNT), and discourse measures obtained from a picture description task. Participants also completed a cognitive status and depression screening using the Montreal Cognitive Assessment (MoCA) and the Geriatric Depression Scale (GDS), respectively. The severity of ALS was measured using the ALS Functional Rating Scale. Results indicated that verbal fluency (animals), discourse output, and speech intelligibility are associated with quality of communication. Regression analyses revealed important predictors of quality of communication including the BNT, MoCA, GDS, and speech intelligibility. The only significant predictor for general HRQol (i.e., SF-36) was the GDS. Results suggest that poor performance on standardized language tests may not be indicative of poor quality of communication, however, findings show that poor efficiency on discourse tasks does affect quality of communication. Results also show that depression in individuals with ALS is associated with poor HRQoL. Overall physical functioning does not significantly contribute to quality of communication or overall HRQoL. An important implication of the findings is that clinicians should focus on optimizing communication in those individuals with ALS who have poor speech intelligibility in order to optimize discourse output, which, in turn, will enhance the quality of communication in individuals with ALS