Should neurologists diagnose and manage functional neurologic disorders? It is complicated

Whereas only neurologists can "rule in" functional neurologic disorders (FNDs)-using physical signs and semiologic features-their role in follow-up care remains debated. We outlined the arguments for and against a neurologist's primary role in both assessing and managing FNDs. Favorable arguments include the following: (1) FND presents neurologically, and thus, only neurologists can ascertain the etiology of new neurologic deficits appearing on follow-up, and (2) neurologic encounters facilitate acceptance of diagnosis and enhance treatment engagement. Counter arguments include the following: (1) FND is a Diagnostic and Statistical Manual of Mental Disorders, 5th Edition codified psychiatric disorder with largely psychiatric treatments, and (2) neurologists can reassess patients if new neurologic symptoms develop without playing a primary follow-up role. Although more research is needed to clarify optimal approaches, neurologic expertise could be leveraged for diagnostic and coordinating roles if the pool of neurologists, psychiatrists, psychotherapists, physical and occupational therapists, and other allied clinicians trained in the interdisciplinary care of FNDs is substantially increased

Pure autonomic failure versus prodromal dysautonomia in Parkinson’s disease: Insights from the bedside

Autonomic failure may include orthostatic hypotension, supine hypertension, bowel and bladder disturbances, impaired thermal regulation, and sexual dysfunction, all of which can be features of Parkinson's disease (PD) and other a‐synucleinopathies. All patients with pure autonomic failure, most patients with multiple system atrophy, and 18% of patients with PD will develop symptomatic orthostatic hypotension. However, the extent of central and peripheral norepinephrine deficiency, parasympathetic nuclei degeneration, and arterial baroreflex failure may be differentially impaired in these disorders. Consequently, clinical features and prognostic implications of autonomic dysfunction in a‐synucleinopathies may be more complex than previously envisioned. The case described in this report highlights the clinical similarities between PD and pure autonomic failure, raising the question of whether pure autonomic failure represents a restricted Lewy body synucleinopathy or an early manifestation of PD

Holmes Tremor‐Like Phenotype in DYT1 Dystonia

Holmes tremor is characterized by a combination of a flexion‐extension resting postural and action tremor, most often due to mesencephalic lesions affecting the nigrostriatal and cerebello‐thalamo‐cortical pathways. On the other hand, dystonic tremor represents a jerky postural and action tremor, which if severe enough may include a resting component and may arise from cerebellar and nigrostriatal dysfunction. Here, we present a patient with a four‐decade history of progressive tremor, initially interpreted as Holmes tremor with a dystonic (pseudospastic) gait, in whom whole exome sequencing (WES) demonstrated a pathogenic TOR1A deletion. This case highlights two important clinical points, (1) the need for proper semiologic interpretation: direct DYT1 testing could have been entertained if tremor was properly categorized as dystonic rather than cerebellar at the outset; and (2) the phenotypic variability of DYT1 dystonia, with tremor as a presenting and disabling feature separate from the body part affected by dystonia (“tremor associated with dystonia”).Fil: Rodríguez Quiroga, Sergio Alejandro. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; ArgentinaFil: González Morón, Dolores. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Espay, Alberto J. University of Cincinnati; Estados UnidosFil: Kauffman, Marcelo Andres. Universidad Austral. Facultad de Ciencias Biomédicas. Instituto de Investigaciones en Medicina Traslacional. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones en Medicina Traslacional; Argentin

Technology in Parkinson's disease: challenges and opportunities

"The miniaturization, sophistication, proliferation, and accessibility of technologies are enabling the capture of more and previously inaccessible phenomena in Parkinson's disease (PD). However, more information has not translated into a greater understanding of disease complexity to satisfy diagnostic and therapeutic needs. Challenges include noncompatible technology platforms, the need for wide-scale and long-term deployment of sensor technology (among vulnerable elderly patients in particular), and the gap between the “big data” acquired with sensitive measurement technologies and their limited clinical application. Major opportunities could be realized if new technologies are developed as part of open-source and/or open-hardware platforms that enable multichannel data capture sensitive to the broad range of motor and nonmotor problems that characterize PD and are adaptable into self-adjusting, individualized treatment delivery systems. The International Parkinson and Movement Disorders Society Task Force on Technology is entrusted to convene engineers, clinicians, researchers, and patients to promote the development of integrated measurement and closed-loop therapeutic systems with high patient adherence that also serve to (1) encourage the adoption of clinico-pathophysiologic phenotyping and early detection of critical disease milestones, (2) enhance the tailoring of symptomatic therapy, (3) improve subgroup targeting of patients for future testing of disease-modifying treatments, and (4) identify objective biomarkers to improve the longitudinal tracking of impairments in clinical care and research. This article summarizes the work carried out by the task force toward identifying challenges and opportunities in the development of technologies with potential for improving the clinical management and the quality of life of individuals with PD."info:eu-repo/semantics/acceptedVersio

Rapidly progressive atypical parkinsonism associated with frontotemporal lobar degeneration and motor neuron disease

Objective To report the rare but distinct clinical and neuropathological phenotype of non-familial, rapidly progressive parkinsonism and dementia associated with frontotemporal lobar degeneration with motor neuron disease (FTLD-MND). Methods Subjects included two 70-year-old women presenting with rapidly progressive severe postural instability, axial-predominant parkinsonism, oculomotor dysfunction and frontal-predominant dementia with language impairment and pseudobulbar palsy. One had diffuse weakness without signs of lower motor neuron disease. Post-mortem evaluations included immunohistochemistry with antiphospho-TAR DNA-binding protein 43 (TDP-43) and genetic analysis of the TARDBP and PGRN genes. Results Subjects died within 14 months from symptom onset. TDP-43-positive neuronal intracytoplasmic inclusions were prominent in the primary motor cortex, granule cell layer of the hippocampus, and several cranial and spinal cord nuclei. TDP-43 globular glial inclusions (GGI) were identified in one case. There were no mutations in PGRN or TARDBP genes. Conclusions FTLD-MND due to TDP-43-proteinopathy should be considered in patients with rapidly progressive parkinsonism and dementia phenotype, especially when aphasia and/or weakness are also present

Cautionary optimism: caffeine and Parkinson’s disease risk

Most Parkinson’s disease (PD) patients present without known family history and without a diagnosed prodromal phase, underscoring the difficulty of employing primary (neuroprevention) and secondary (neuroprotection) preventions. In cases of monogenic forms, however, potential gene-carrying family members of a proband could engage in neuroprevention, such as exercise or diet modifications, to attenuate the risk of, or delay, disease development. However, a historical lack of recognized disease-modifying interventions has limited clinicians’ ability to recommend reliable preventive measures in caring for at-risk populations. We briefly analyze the first retrospective study to examine caffeine consumption and PD risk in a LRRK2 R1628P cohort

Movement Disorders in Prionopathies: A Systematic Review

Background: Movement disorders are frequent features of prionopathies. However, their prevalence and onset remain poorly described. Methods: We performed a systematic review of case reports and case series of pathologically- and genetically confirmed prionopathies. Timing of symptom and movement disorder onset were documented. Continuous variables were compared between two groups using the Wilcoxon rank sum test and between multiple groups using Kruskal–Wallis test. Categorical variables were compared using Fisher’s exact test. Results: A total of 324 cases were included in this analysis. Movement disorders were a common feature at the onset of symptoms in most prionopathies. Gait ataxia was present in more than half of cases in all types of prionopathies. The prevalence of limb ataxia (20%) and myoclonus (24%) was lower in Gerstmann–Sträussler–Scheinker disease compared to other prionopathies (p ≤ 0.004). Myoclonus was common but often a later feature in sporadic Creutzfeldt–Jakob disease (2 months before death). Chorea was uncommon but disproportionately prevalent in variant Creutzfeldt–Jakob disease (30% of cases; p < 0.001). In genetic Creutzfeldt–Jakob disease, E200K PRNP carriers exhibited gait and limb ataxia more often when compared to other mutation carriers. Discussion: Movement disorders are differentially present in the course of the various prionopathies. The movement phenomenology and appearance are associated with the type of prion disease and the PRNP genotype and likely reflect the underlying pattern of neurodegeneration. Reliance on myoclonus as a diagnostic feature of sporadic Creutzfeldt–Jakob disease may delay its recognition given its relatively late appearance in the disease course

Long-term unsupervised mobility assessment in movement disorders

Mobile health technologies (wearable, portable, body-fixed sensors, or domestic-integrated devices) that quantify mobility in unsupervised, daily living environments are emerging as complementary clinical assessments. Data collected in these ecologically valid, patient-relevant settings can overcome limitations of conventional clinical assessments, as they capture fluctuating and rare events. These data could support clinical decision making and could also serve as outcomes in clinical trials. However, studies that directly compared assessments made in unsupervised and supervised (eg, in the laboratory or hospital) settings point to large disparities, even in the same parameters of mobility. These differences appear to be affected by psychological, physiological, cognitive, environmental, and technical factors, and by the types of mobilities and diagnoses assessed. To facilitate the successful adaptation of the unsupervised assessment of mobility into clinical practice and clinical trials, clinicians and researchers should consider these disparities and the multiple factors that contribute to them

Neither a novel tau proteinopathy nor an expansion of a phenotype: Reappraising clinicopathology-based nosology

The gold standard for classification of neurodegenerative diseases is postmortem histopathol-ogy; however, the diagnostic odyssey of this case challenges such a clinicopathologic model. We evaluated a 60-year-old woman with a 7-year history of a progressive dystonia–ataxia syndrome with supranuclear gaze palsy, suspected to represent Niemann–Pick disease Type C. Postmortem evaluation unexpectedly demonstrated neurodegeneration with 4-repeat tau deposition in a distribution diagnostic of progressive supranuclear palsy (PSP). Whole-exome sequencing revealed a new het-erozygous variant in TGM6, associated with spinocerebellar ataxia type 35 (SCA35). This novel TGM6 variant reduced transglutaminase activity in vitro, suggesting it was pathogenic. This case could be interpreted as expanding: (1) the PSP phenotype to include a spinocerebellar variant; (2) SCA35 as a tau proteinopathy; or (3) TGM6 as a novel genetic variant underlying a SCA35 phenotype with PSP pathology. None of these interpretations seem adequate. We instead hypothesize that impairment in the crosslinking of tau by the TGM6-encoded transglutaminase enzyme may compromise tau functionally and structurally, leading to its aggregation in a pattern currently classified as PSP. The lessons from this case study encourage a reassessment of our clinicopathology-based nosology.Fil: Marsili, Luca. University of Cincinnati; Estados UnidosFil: Sharma, Jennifer. University of Cincinnati; Estados UnidosFil: Espay, Alberto J.. University of Cincinnati; Estados UnidosFil: Migazzi, Alice. Universita degli Studi di Trento; ItaliaFil: Abdelghany, Elhusseini. University of Cincinnati; Estados UnidosFil: Hill, Emily J.. University of Cincinnati; Estados UnidosFil: Duque, Kevin R.. University of Cincinnati; Estados UnidosFil: Hagen, Matthew C.. University of Cincinnati; Estados UnidosFil: Stephen, Christopher D.. Harvard Medical School; Estados UnidosFil: Kovacs, Gabor G.. University of Toronto; CanadáFil: Lang, Anthony E.. University of Toronto; CanadáFil: Hadjivassiliou, Marios. University Of Sheffield (university Of Sheffield);Fil: Basso, Manuela. Universita degli Studi di Trento; ItaliaFil: Kauffman, Marcelo Andres. Universidad Austral. Facultad de Ciencias Biomédicas. Instituto de Investigaciones en Medicina Traslacional. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones en Medicina Traslacional; ArgentinaFil: Sturchio, Andrea. University of Cincinnati; Estados Unido