Our staff editors continue to share exciting, interesting, and thought-provoking reading material in the recommended articles series.
This week, we would like to share several latest articles from Prof. Mark Hallett, our Associate Editor.
Title: A Review and Expert Opinion on the Neuropsychiatric Assessment of Motor Functional Neurological Disorders
Authors: David L. Perez, Selma Aybek, Stoyan Popkirov, Kasia Kozlowska, Christopher D. Stephen, Jordan Anderson, Robert Shura, Simon Ducharme, Alan Carson, Mark Hallett, Timothy R. Nicholson, Jon Stone, W. Curt LaFrance Jr., Valerie Voon, (On behalf of the American Neuropsychiatric Association Committee for Research)
Type: Special Articles from The Journal of Neuropsychiatry and Clinical Neurosciences
Functional neurological (conversion) disorder (FND) is a prevalent and disabling condition at the intersection of neurology and psychiatry. Advances have been made in elucidating an emerging pathophysiology for motor FND, as well as in identifying evidenced-based physiotherapy and psychotherapy treatments. Despite these gains, important elements of the initial neuropsychiatric assessment of functional movement disorders (FND-movt) and functional limb weakness/paresis (FND-par) have yet to be established. This is an important gap from both diagnostic and treatment planning perspectives. In this article, the authors performed a narrative review to characterize clinically relevant variables across FND-movt and FND-par cohorts, including time course and symptom evolution, precipitating factors, medical and family histories, psychiatric comorbidities, psychosocial factors, physical examination signs, and adjunctive diagnostic tests. Thereafter, the authors propose a preliminary set of clinical content that should be assessed during early-phase patient encounters, in addition to identifying physical signs informing diagnosis and potential use of adjunctive tests for challenging cases. Although clinical history should not be used to make a FND diagnosis, characteristics such as acute onset, precipitating events (e.g., injury and surgery), and a waxing and waning course (including spontaneous remissions) are commonly reported. Active psychiatric symptoms (e.g., depression and anxiety) and ongoing psychosocial stressors also warrant evaluation. Positive physical examination signs (e.g., Hoover’s sign and tremor entrainment) are key findings, as one of the DSM-5 diagnostic criteria. The neuropsychiatric assessment proposed emphasizes diagnosing FND by using “rule-in” physical signs while also considering psychiatric and psychosocial factors to aid in the development of a patient-centered treatment plan.
Access this article: https://doi.org/10.1176/appi.neuropsych.19120357
Title: Identification of a Brain Network Underlying the Execution of Freely Chosen Movements
Authors: Quentin Welniarz, Emmanuel Roze, Benoît Béranger, Aurélie Méneret, Marie Vidailhet, Stéphane Lehéricy, Pierre Pouget, Mark Hallett, Sabine Meunier, Cécile Galléa
Type: Original Article of Cerebral Cortex
Action selection refers to the decision regarding which action to perform in order to reach a desired goal, that is, the “what” component of intention. Whether the action is freely chosen or externally instructed involves different brain networks during the selection phase, but it is assumed that the way an action is selected should not influence the subsequent execution phase of the same movement. Here, we aim to test this hypothesis by investigating whether the modality of movement selection influences the brain networks involved during the execution phase of the movement. Twenty healthy volunteers performed a delayed response task in an event-related functional magnetic resonance imaging design to compare freely chosen and instructed unimanual or bimanual movements during the execution phase. Using activation analyses, we found that the pre-supplementary motor area (preSMA) and the parietal and cerebellar areas were more activated during the execution phase of freely chosen as compared to instructed movements. Connectivity analysis showed an increase of information flow between the right posterior parietal cortex and the cerebellum for freely chosen compared to instructed movements. We suggest that the parieto-cerebellar network is particularly engaged during freely chosen movement to monitor the congruence between the intentional content of our actions and their outcome.
Access this article: https://doi.org/10.1093/cercor/bhab204
Title: Functional Neurological Disorder After SARS-CoV-2 Vaccines: Two Case Reports and Discussion of Potential Public Health Implications
Authors: Matthew Butler, Jan Coebergh, Farinaz Safavi, Alan Carson, Mark Hallett, Benedict Michael, Thomas A. Pollak, Tom Solomon, Jon Stone, Timothy R. Nicholson; on behalf of the Coronerve Studies Group
Type: Case Reports of The Journal of Neuropsychiatry and Clinical Neurosciences
Access this article: https://doi.org/10.1176/appi.neuropsych.21050116
Title: Nutritional Ketosis in Parkinson’s Disease — a Review of Remaining Questions and Insights
Authors: Alexander Choi, Mark Hallett, Debra Ehrlich
Type: Current Perspectives of Neurotherapeutics
Nutritional ketosis has promise for treating Parkinson's disease. Three previous studies explored the use of a ketogenic diet in cohorts with Parkinson's disease, and, while not conclusive, the data suggest non-motor symptom benefit. Before the ketogenic diet can be considered as a therapeutic option, it is important to establish with greater certainty that there is a reliable symptomatic benefit: which symptoms or groups of symptoms are impacted (if non-motor symptoms, which ones, and by which mechanism), what timescale is needed to obtain benefit, and how large an effect size can be achieved? To accomplish this, further investigation into the disease mechanisms based on pre-clinical data and hints from the clinical outcomes to date is useful to understand target engagement and gauge which mechanism could lead to a testable hypothesis. We review research pertaining to ketogenic diet, exogenous ketones, fasting, clinical studies, and theoretical review papers regarding therapeutic mechanisms from direct ketone body signaling and indirect metabolic effects. Through discussion of these findings and consideration of whether the ketogenic diet can be regarded as therapeutically useful for adjunctive therapy for Parkinson’s disease, we identify remaining questions for the clinician to consider prior to recommending this diet.
Access this article: https://doi.org/10.1007/s13311-021-01067-w
Title: Predictive modeling of spread in adult-onset isolated dystonia: Key properties and effect of tremor inclusion
Authors: Meng Wang, Tolulope Sajobi, Francesca Morgante, Charles Adler, Pinky Agarwal, Tobias Bäumer, Alfredo Berardelli, Brian D. Berman, Joel Blumin, Max Borsche, Allison Brashear, Andres Deik, Kevin Duque, Alberto J. Espay, Gina Ferrazzano, Jeanne Feuerstein, Susan Fox, Samuel Frank, Mark Hallett, Joseph Jankovic, Mark S. LeDoux, Julie Leegwater-Kim, Abhimanyu Mahajan, Irene A. Malaty, William Ondo, Alexander Pantelyat, Sarah Pirio-Richardson, Emmanuel Roze, Rachel Saunders-Pullman, Oksana Suchowersky, Daniel Truong, Marie Vidailhet, Aparna Wagle Shukla, Joel S. Perlmutter, Hyder A. Jinnah, Davide Martino
Type: Original Article of European Journal of Neurology
Background and purpose
Several clinical and demographic factors relate to anatomic spread of adult-onset isolated dystonia, but a predictive model is still lacking. The aims of this study were: (i) to develop and validate a predictive model of anatomic spread of adult-onset isolated dystonia; and (ii) to evaluate whether presence of tremor associated with dystonia influences model predictions of spread.
Adult-onset isolated dystonia participants with focal onset from the Dystonia Coalition Natural History Project database were included. We developed two prediction models, one with dystonia as sole disease manifestation (“dystonia-only”) and one accepting dystonia OR tremor in any body part as disease manifestations (“dystonia OR tremor”). Demographic and clinical predictors were selected based on previous evidence, clinical plausibility of association with spread, or both. We used logistic regressions and evaluated model discrimination and calibration. Internal validation was carried out based on bootstrapping.
Both predictive models showed an area under the curve of 0.65 (95% confidence intervals 0.62–0.70 and 0.62–0.69, respectively) and good calibration after internal validation. In both models, onset of dystonia in body regions other than the neck, older age, depression and history of neck trauma were predictors of spread.
This predictive modeling of spread in adult-onset isolated dystonia based on accessible predictors (demographic and clinical) can be easily implemented to inform individuals’ risk of spread. Because tremor did not influence prediction of spread, our results support the argument that tremor is a part of the dystonia syndrome, and not an independent or coincidental disorder.
Access this article: https://doi.org/10.1111/ene.15031
Title: Corticolimbic Modulation via Intermittent Theta Burst Stimulation as a Novel Treatment for Functional Movement Disorder: A Proof-of-Concept Study
Authors: Primavera A. Spagnolo, Jacob Parker, Silvina Horovitz, Mark Hallett
Type: Article of Brain Sciences
Neuroimaging studies suggest that corticolimbic dysfunctions, including increased amygdala reactivity to emotional stimuli and heightened fronto-amygdala coupling, play a central role in the pathophysiology of functional movement disorders (FMD). Transcranial magnetic stimulation (TMS) has the potential to probe and modulate brain networks implicated in neuropsychiatric disorders, including FMD. Therefore, the objective of this proof-of-concept study was to investigate the safety, tolerability and preliminary efficacy of fronto-amygdala neuromodulation via targeted left prefrontal intermittent theta burst stimulation (iTBS) on brain and behavioral manifestations of FMD. Six subjects with a clinically defined diagnosis of FMD received three open-label iTBS sessions per day for two consecutive study visits. Safety and tolerability were assessed throughout the trial. Amygdala reactivity to emotionally valenced stimuli presented during an fMRI task and fronto-amygdala connectivity at rest were evaluated at baseline and after each stimulation visit, together with subjective levels of arousal and valence in response to affective stimuli. The FMD symptom severity was assessed at baseline, during treatment and 24 h after the last iTBS session. Multiple doses of iTBS were well-tolerated by all participants. Intermittent TBS significantly decreased fronto-amygdala connectivity and influenced amygdala reactivity to emotional stimuli. These neurocircuitry changes were associated to a marked reduction in FMD symptom severity. Corticolimbic modulation via iTBS represents a promising treatment for FMD that warrants additional research.
Access this article: https://doi.org/10.3390/brainsci11060791