A Novel KCNQ2 Variant in a Patient with a Combined Tremor Syndrome.

Background: Tremor disorders have various genetic causes. Case report: A 60-year-old female with a family history of tremor presented a combined tremor syndrome, transient episodes of loss of contact and speech disturbances, as well as distal painful symptoms. Genetic screening revealed a novel heterozygous missense variant in the KCNQ2 gene. Discussion: The KCNQ2 protein regulates action potential firing, and mutations in its gene are associated with epilepsy and neuropathic pain. The identified variant, although of uncertain significance, may disrupt KCNQ2 function and also play a role in tremor pathogenesis. This case highlights the importance of genetic screening in combined tremor disorders.

The Effects of Hand Tremors on the Shooting Performance of Air Pistol Shooters with Different Skill Levels.

Physiologic hand tremors are a critical factor affecting the aim of air pistol shooters. However, the extent of the effect of hand tremors on shooting performance is unclear. In this study, we aim to explore the relationship between hand tremors and shooting performance scores as well as investigate potential links between muscle activation and hand tremors. In this study, 17 male air pistol shooters from China's national team and the Air Pistol Sports Center were divided into two groups: the elite group and the sub-elite group. Each participant completed 40 shots during the experiment, with shooters' hand tremors recorded using three-axis digital accelerometers affixed to their right hands. Muscle activation was recorded using surface electromyography on the right anterior deltoid, posterior deltoid, biceps brachii (short head), triceps brachii (long head), flexor carpi radialis, and extensor carpi radialis. Our analysis revealed weak correlations between shooting scores and hand tremor amplitude in multiple directions (middle-lateral, ML: r2 = -0.22, p < 0.001; vertical, VT: r2 = -0.25, p < 0.001), as well as between shooting scores and hand tremor complexity (ML: r2 = -0.26, p < 0.001; VT: r2 = -0.28, p < 0.001), across all participants. Notably, weak correlations between shooting scores and hand tremor amplitude (ML: r2 = -0.27, p < 0.001; VT: r2 = -0.33, p < 0.001) and complexity (ML: r2 = -0.31, p < 0.001) were observed in the elite group but not in the sub-elite group. Moderate correlation were found between the biceps brachii (short head) RMS and hand tremor amplitude in the VT and ML directions (ML: r2 = 0.49, p = 0.010; VT: r2 = 0.44, p = 0.025) in all shooters, with a moderate correlation in the ML direction in elite shooters (ML: r2 = 0.49, p = 0.034). Our results suggest that hand tremors in air pistol shooters are associated with the skill of the shooters, and muscle activation of the biceps brachii (long head) might be a factor affecting hand tremors. By balancing the agonist and antagonist muscles of the shoulder joint, shooters might potentially reduce hand tremors and improve their shooting scores.

Potential Prodromal Digital Postural Sway Markers for Fragile X-Associated Tremor/Ataxia Syndrome (FXTAS) Detected via Dual-Tasking and Sensory Manipulation.

FXTAS is a neurodegenerative disorder occurring in some Fragile X Messenger Ribonucleoprotein 1 (FMR1) gene premutation carriers (PMCs) and is characterized by cerebellar ataxia, tremor, and cognitive deficits that negatively impact balance and gait and increase fall risk. Dual-tasking (DT) cognitive-motor paradigms and challenging balance conditions may have the capacity to reveal markers of FXTAS onset. Our objectives were to determine the impact of dual-tasking and sensory and stance manipulation on balance in FXTAS and potentially detect subtle postural sway deficits in FMR1 PMCs who are asymptomatic for signs of FXTAS on clinical exam. Participants with FXTAS, PMCs without FXTAS, and controls underwent balance testing using an inertial sensor system. Stance, vision, surface stability, and cognitive demand were manipulated in 30 s trials. FXTAS participants had significantly greater total sway area, jerk, and RMS sway than controls under almost all balance conditions but were most impaired in those requiring vestibular control. PMCs without FXTAS had significantly greater RMS sway compared with controls in the feet apart, firm, single task conditions both with eyes open and closed (EC) and the feet together, firm, EC, DT condition. Postural sway deficits in the RMS postural sway variability domain in asymptomatic PMCs might represent prodromal signs of FXTAS. This information may be useful in providing sensitive biomarkers of FXTAS onset and as quantitative balance measures in future interventional trials and longitudinal natural history studies.

[Tremor-dominant form of Parkinson's disease]. / Tremor-dominantnaya forma bolezni Parkinsona.

The article is of a review nature and is devoted to tremor, one of the maladaptive and difficult-to-treat symptoms of Parkinson's disease (PD). Along with the classic rest tremor, patients with PD may experience tremor of other modalities: postural tremor, kinetic tremor, which reflects a multimodal mechanism of tremor formation involving multiple neurotransmitter systems. The unpredictable response to therapeutic options, the ambiguous response to levodopa, also reflects the role of multiple underlying pathophysiological processes. Among the drug methods of tremor correction, preference is given to dopamine receptor agonists - due to the spectrum of their pharmaceutical action, high efficiency in relation to all leading motor and a number of non-motor manifestations. The evidence for advanced neurosurgical, non-invasive modalities is mixed, and there are insufficient comparative studies to assess their efficacy in patients with tremor-dominant forms of PD.

Type selective ablation of postnatal slow and fast fatigue-resistant motor neurons in mice induces late onset kinetic and postural tremor following fiber-type transition and myopathy.

Animals on Earth need to hold postures and execute a series of movements under gravity and atmospheric pressure. VAChT-Cre is a transgenic Cre driver mouse line that expresses Cre recombinase selectively in motor neurons of S-type (slow-twitch fatigue-resistant) and FR-type (fast-twitch fatigue-resistant). Sequential motor unit recruitment is a fundamental principle for fine and smooth locomotion; smaller-diameter motor neurons (S-type, FR-type) first contract low-intensity oxidative type I and type IIa muscle fibers, and thereafter larger-diameter motor neurons (FInt-type, FF-type) are recruited to contract high-intensity glycolytic type IIx and type IIb muscle fibers. To selectively eliminate S- and FR-type motor neurons, VAChT-Cre mice were crossbred with NSE-DTA mice in which the cytotoxic diphtheria toxin A fragment (DTA) was expressed in Cre-expressing neurons. The VAChT-Cre;NSE-DTA mice were born normally but progressively manifested various characteristics, including body weight loss, kyphosis, kinetic and postural tremor, and muscular atrophy. The progressive kinetic and postural tremor was remarkable from around 20 weeks of age and aggravated. Muscular atrophy was apparent in slow muscles, but not in fast muscles. The increase in motor unit number estimation was detected by electromyography, reflecting compensatory re-innervation by remaining FInt- and FF-type motor neurons to the orphaned slow muscle fibers. The muscle fibers gradually manifested fast/slow hybrid phenotypes, and the remaining FInt-and FF-type motor neurons gradually disappeared. These results suggest selective ablation of S- and FR-type motor neurons induces progressive muscle fiber-type transition, exhaustion of remaining FInt- and FF-type motor neurons, and late-onset kinetic and postural tremor in mice.

Resist-as-Needed ADL Training With SPINDLE for Patients With Tremor.

Individuals with neurological disorders often exhibit altered manual dexterity and muscle weakness in their upper limbs. These motor impairments with tremor lead to severe difficulties in performing Activities of Daily Living (ADL). There is a critical need for ADL-focused robotic training that improves individual's strength when engaging with dexterous ADL tasks. This research introduces a new approach to training ADLs by employing a novel robotic rehabilitation system, Spherical Parallel INstrument for Daily Living Emulation (SPINDLE), which incorporates Virtual Reality (VR) to simulate ADL tasks. The study results present the feasibility of training individuals with movements similar to ADLs while interacting with the SPINDLE. A new game-based robotic training paradigm is suggested to perform ADL tasks at various intensity levels of resistance as needed. The proposed system can facilitate the training of various ADLs requiring 3-dimensional rotational movements by providing optimal resistance and visual feedback. We envision this system can be utilized as a table-top home device by restoring the impaired motor function of individuals with tremor and muscle weakness, guiding to improved ADL performance and quality of life.

A machine-learning method isolating changes in wrist kinematics that identify age-related changes in arm movement.

Normal aging often results in an increase in physiological tremors and slowing of the movement of the hands, which can impair daily activities and quality of life. This study, using lightweight wearable non-invasive sensors, aimed to detect and identify age-related changes in wrist kinematics and response latency. Eighteen young (ages 18-20) and nine older (ages 49-57) adults performed two standard tasks with wearable inertial measurement units on their wrists. Frequency analysis revealed 5 kinematic variables distinguishing older from younger adults in a postural task, with best discrimination occurring in the 9-13 Hz range, agreeing with previously identified frequency range of age-related tremors, and achieving excellent classifier performance (0.86 AUROC score and 89% accuracy). In a second pronation-supination task, analysis of angular velocity in the roll axis identified a 71 ms delay in initiating arm movement in the older adults. This study demonstrates that an analysis of simple kinematic variables sampled at 100 Hz frequency with commercially available sensors is reliable, sensitive, and accurate at detecting age-related increases in physiological tremor and motor slowing. It remains to be seen if such sensitive methods may be accurate in distinguishing physiological tremors from tremors that occur in neurological diseases, such as Parkinson's Disease.

Interdisciplinary insights into tremor in dystonia: Navigating clinical controversies, definitional challenges, and pathophysiological complexities.

This review delves into the historical evolution and ongoing controversy surrounding the relationship between tremor and dystonia. The Dystonia Consensus Panel and the International Parkinson's and Movement Disorders Society's Tremor Taskforce have attempted to define these entities, but the complexity arises when patients have a combination of both dystonia and tremor. The term "dystonic tremor" has sparked diverse interpretations, with debates over its clinical features and the need for more objectively defined characteristics. Logistic regression analyses in a large cohort of dystonia patients identified determinants such as body region affected by dystonia, dystonia severity, age, and recruitment site, with unexpected associations emphasizing the subjectivity in detecting and classifying tremor. The study further discovered diverse prevalence of "dystonic tremor" based on different definitions, revealing substantial variability among investigators. The recently convened Dystonia-Tremor panel aimed to address these challenges by proposing a more uniform nomenclature, emphasizing precise and descriptive terms. Despite the complexity, instrumented measures, such as electromyography, temporal discrimination threshold, blink reflex, and trajectory shape analysis, seem to be useful in distinguishing between tremor and dystonia. The pathophysiology debate centers around the involvement of the cerebello-thalamo-cortical and basal ganglia-thalamo-cortical circuits. Evidence supports the role of both circuits in driving the pathophysiology of dystonic tremor, challenging the notion of a clear dichotomy. The review concludes by emphasizing the need for a nuanced understanding, highlighting the intricate interplay between tremor and dystonia, and the potential of instrumental measures in advancing diagnostic accuracy.

Exploring obstructive sleep apnea and sleep architecture in Parkinson's disease motor subtypes.

INTRODUCTION: Parkinson's disease (PD) can be divided into motor subtypes: postural instability/gait difficulty (PIGD), tremor dominant, and indeterminate. This study aimed to assess differences in sleep structure and obstructive sleep apnea (OSA) between the PIGD and non-PIGD subtypes. METHODS: PD participants with or without OSA (defined as apnea-hypopnea index (AHI) ≥ 15 events/hour on overnight polysomnography) were included. Patients were separated into two groups: PIGD and non-PIGD. Linear regression was used to explore differences in sleep, AHI, and other respiratory parameters between groups (adjusted for variables determined a priori). Logistic regression adjusted for the same variables was used to determine if the proportion of patients with OSA differed across groups. Subset analyses were performed: subset 1 excluding patients on psychoactive medication; subset 2 excluding patients taking levodopa or dopaminergic agonists (DAs) at nighttime and subset 3 excluding patients on either of the abovementioned drugs. RESULTS: 146 participants were studied. The non-PIGD group had less N3 sleep compared to the PIGD group (12.4% vs 16.9% p = 0.06), reaching significance in subsets 1 and 3. The AHI was significantly lower in the PIGD group (p = 0.047), including when medication effects were removed (p < 0.05). OSA was more frequent in the non-PIGD group, but only significantly in subset 3 (adjusted OR 0.3, p = 0.04). CONCLUSION: OSA may be more severe in non-PIGD subtypes, and more frequent, in a subset free of psychoactive medication, and of levodopa and DAs, possibly owing to motor complications and dyskinesia. Future studies are required to confirm this.

Reliability and validity of the Roche PD Mobile Application for remote monitoring of early Parkinson's disease.

Digital health technologies enable remote and therefore frequent measurement of motor signs, potentially providing reliable and valid estimates of motor sign severity and progression in Parkinson's disease (PD). The Roche PD Mobile Application v2 was developed to measure bradykinesia, bradyphrenia and speech, tremor, gait and balance. It comprises 10 smartphone active tests (with ½ tests administered daily), as well as daily passive monitoring via a smartphone and smartwatch. It was studied in 316 early-stage PD participants who performed daily active tests at home then carried a smartphone and wore a smartwatch throughout the day for passive monitoring (study NCT03100149). Here, we report baseline data. Adherence was excellent (96.29%). All pre-specified sensor features exhibited good-to-excellent test-retest reliability (median intraclass correlation coefficient = 0.9), and correlated with corresponding Movement Disorder Society-Unified Parkinson's Disease Rating Scale items (rho: 0.12-0.71). These findings demonstrate the preliminary reliability and validity of remote at-home quantification of motor sign severity with the Roche PD Mobile Application v2 in individuals with early PD.

Phenotype of heterozygous variants of dehydrodolichol diphosphate synthase.

AIM: To further identify and broaden the phenotypic characteristics and genotype spectrum of the dehydrodolichol diphosphate synthase (DHDDS) gene. METHOD: Pathogenic variants of DHDDS were identified by whole-exome sequencing; clinical data of 10 patients (six males, four females; age range 2-14y; mean age 5y 9mo, SD 3y 3mo) were collected and analysed. RESULTS: All patients had seizures, and myoclonic seizures could be seen in eight patients, with myoclonic status epilepticus in three. The interictal electroencephalogram (EEG) in four patients at seizure onset showed generalized slow waves, slow wave mixed spikes, and spike and waves. Tremor, ataxia, and hypertonia was observed in six, five, and three patients respectively. The results of short-latency somatosensory evoked potential in two patients were normal, and the symptom of tremor was captured on EEG without time-locked discharges in one patient, suggesting that the tremor in both patients was a motor impairment rather than myoclonic seizures. Global developmental delay occurred in all patients, among whom nine showed severe intellectual disability and one moderate. Five DHDDS variants were identified, three of which have not been reported previously. INTERPRETATION: Myoclonic seizure is the most common seizure type in heterozygous DHDDS variants, while myoclonic status epilepticus can also occur. The pattern of interictal EEG discharges is characterized by slow waves rather than spike and waves, and generalized discharges was prominent.

Correlation between head tremble and the severity of Parkinson's disease.

INTRODUCTION: Parkinson's (PD) is a common degenerative disease of the central nervous system. It affects more than 6 million individuals worldwide. The typical clinical manifestations include static tremor, slow movement, and unstable posture. However, the correlation between head tremor and the severity of PD remains unclear. METHODS: In the current study, 18 patients and 18 healthy subjects were recruited to undergo a phonation test. Noldus facereader 7.0 software was used to analyze the range of head trembling between the two groups. RESULTS: The data revealed that patients with PD had significant differences in the x-, y-, and z-axis of head movement with respect to the specific pronunciation syllables compared with the normal group. Moreover, the head movement of the patients with PD was positively correlated with the severity of the disease in the single, double, and multiple syllable tests. In the phonetic test, the head displacement of patients with PD was significantly greater than that of healthy individuals, and the displacement range was positively correlated with the severity of the disease. CONCLUSION: These pieces of evidence suggested that the measurement of head displacement assists the early diagnosis and severity of the disease.

Subthalamic-Cortical Network Reorganization during Parkinson's Tremor.

Tremor, a common and often primary symptom of Parkinson's disease, has been modeled with distinct onset and maintenance dynamics. To identify the neurophysiologic correlates of each state, we acquired intraoperative cortical and subthalamic nucleus recordings from 10 patients (9 male, 1 female) performing a naturalistic visual-motor task. From this task, we isolated short epochs of tremor onset and sustained tremor. Comparing these epochs, we found that the subthalamic nucleus was central to tremor onset, as it drove both motor cortical activity and tremor output. Once tremor became sustained, control of tremor shifted to cortex. At the same time, changes in directed functional connectivity across sensorimotor cortex further distinguished the sustained tremor state.SIGNIFICANCE STATEMENT Tremor is a common symptom of Parkinson's disease (PD). While tremor pathophysiology is thought to involve both basal ganglia and cerebello-thalamic-cortical circuits, it is unknown how these structures functionally interact to produce tremor. In this article, we analyzed intracranial recordings from the subthalamic nucleus and sensorimotor cortex in patients with PD undergoing deep brain stimulation surgery. Using an intraoperative task, we examined tremor in two separate dynamic contexts: when tremor first emerged, and when tremor was sustained. We believe that these findings reconcile several models of Parkinson's tremor, while describing the short-timescale dynamics of subcortical-cortical interactions during tremor for the first time. These findings may describe a framework for developing proactive and responsive neurostimulation models for specifically treating tremor.

Mechanisms of Genome Instability in the Fragile X-Related Disorders.

The Fragile X-related disorders (FXDs), which include the intellectual disability fragile X syndrome (FXS), are disorders caused by expansion of a CGG-repeat tract in the 5' UTR of the X-linked FMR1 gene. These disorders are named for FRAXA, the folate-sensitive fragile site that localizes with the CGG-repeat in individuals with FXS. Two pathological FMR1 allele size classes are distinguished. Premutation (PM) alleles have 54-200 repeats and confer the risk of fragile X-associated tremor/ataxia syndrome (FXTAS) and fragile X-associated primary ovarian insufficiency (FXPOI). PM alleles are prone to both somatic and germline expansion, with female PM carriers being at risk of having a child with >200+ repeats. Inheritance of such full mutation (FM) alleles causes FXS. Contractions of PM and FM alleles can also occur. As a result, many carriers are mosaic for different sized alleles, with the clinical presentation depending on the proportions of these alleles in affected tissues. Furthermore, it has become apparent that the chromosomal fragility of FXS individuals reflects an underlying problem that can lead to chromosomal numerical and structural abnormalities. Thus, large numbers of CGG-repeats in the FMR1 gene predisposes individuals to multiple forms of genome instability. This review will discuss our current understanding of these processes.

Does Subthalamic Deep Brain Stimulation Impact Asymmetry and Dyscoordination of Gait in Parkinson's Disease?

Background. Subthalamic deep brain stimulation (STN-DBS) is an effective treatment for selected Parkinson's disease (PD) patients. Gait characteristics are often altered after surgery, but quantitative therapeutic effects are poorly described. Objective. The goal of this study was to systematically investigate modifications in asymmetry and dyscoordination of gait 6 months postoperatively in patients with PD and compare the outcomes with preoperative baseline and to asymptomatic controls without PD. Methods. A convenience sample of thirty-two patients with PD (19 with postural instability and gait disorder (PIGD) type and 13 with tremor dominant disease) and 51 asymptomatic controls participated. Parkinson patients were tested prior to the surgery in both OFF and ON medication states, and 6-months postoperatively in the ON stimulation condition. Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) I to IV and medication were compared to preoperative conditions. Asymmetry ratios, phase coordination index, and walking speed were assessed. Results. MDS-UPDRS I to IV at 6 months improved significantly, and levodopa equivalent daily dosages significantly decreased. STN-DBS increased step time asymmetry (hedges' g effect sizes [95% confidence interval] between pre- and post-surgery: .27 [-.13, .73]) and phase coordination index (.29 [-.08, .67]). These effects were higher in the PIGD subgroup than the tremor dominant (step time asymmetry: .38 [-.06, .90] vs .09 [-.83, 1.0] and phase coordination index: .39 [-.04, .84] vs .13 [-.76, .96]). Conclusions. This study provides objective evidence of how STN-DBS increases asymmetry and dyscoordination of gait in patients with PD and suggests motor subtypes-associated differences in the treatment response.

A novel non-human primate model of Pelizaeus-Merzbacher disease.

Pelizaeus-Merzbacher disease (PMD) is a severe hypomyelinating disorder of the central nervous system (CNS) linked to mutations in the proteolipid protein-1 (PLP1) gene. Although there are multiple animal models of PMD, few of them fully mimic the human disease. Here, we report three spontaneous cases of male neonatal rhesus macaques with the clinical symptoms of hypomyelinating disease, including intention tremors, progressively worsening motor dysfunction, and nystagmus. These animals demonstrated a paucity of CNS myelination accompanied by reactive astrogliosis, and a lack of PLP1 expression throughout white matter. Genetic analysis revealed that these animals were related to one another and that their parents carried a rare, hemizygous missense variant in exon 5 of the PLP1 gene. These animals therefore represent the first reported non-human primate model of PMD, providing a novel and valuable opportunity for preclinical studies that aim to promote myelination in pediatric hypomyelinating diseases.

Sarcomeric deficits underlie MYBPC1-associated myopathy with myogenic tremor.

Myosin binding protein-C slow (sMyBP-C) comprises a subfamily of cytoskeletal proteins encoded by MYBPC1 that is expressed in skeletal muscles where it contributes to myosin thick filament stabilization and actomyosin cross-bridge regulation. Recently, our group described the causal association of dominant missense pathogenic variants in MYBPC1 with an early-onset myopathy characterized by generalized muscle weakness, hypotonia, dysmorphia, skeletal deformities, and myogenic tremor, occurring in the absence of neuropathy. To mechanistically interrogate the etiologies of this MYBPC1-associated myopathy in vivo, we generated a knock-in mouse model carrying the E248K pathogenic variant. Using a battery of phenotypic, behavioral, and physiological measurements spanning neonatal to young adult life, we found that heterozygous E248K mice faithfully recapitulated the onset and progression of generalized myopathy, tremor occurrence, and skeletal deformities seen in human carriers. Moreover, using a combination of biochemical, ultrastructural, and contractile assessments at the level of the tissue, cell, and myofilaments, we show that the loss-of-function phenotype observed in mutant muscles is primarily driven by disordered and misaligned sarcomeres containing fragmented and out-of-register internal membranes that result in reduced force production and tremor initiation. Collectively, our findings provide mechanistic insights underscoring the E248K-disease pathogenesis and offer a relevant preclinical model for therapeutic discovery.

Molecular Pathogenesis and Peripheral Monitoring of Adult Fragile X-Associated Syndromes.

Abnormal trinucleotide expansions cause rare disorders that compromise quality of life and, in some cases, lifespan. In particular, the expansions of the CGG-repeats stretch at the 5'-UTR of the Fragile X Mental Retardation 1 (FMR1) gene have pleiotropic effects that lead to a variety of Fragile X-associated syndromes: the neurodevelopmental Fragile X syndrome (FXS) in children, the late-onset neurodegenerative disorder Fragile X-associated tremor-ataxia syndrome (FXTAS) that mainly affects adult men, the Fragile X-associated primary ovarian insufficiency (FXPOI) in adult women, and a variety of psychiatric and affective disorders that are under the term of Fragile X-associated neuropsychiatric disorders (FXAND). In this review, we will describe the pathological mechanisms of the adult "gain-of-function" syndromes that are mainly caused by the toxic actions of CGG RNA and FMRpolyG peptide. There have been intensive attempts to identify reliable peripheral biomarkers to assess disease progression and onset of specific pathological traits. Mitochondrial dysfunction, altered miRNA expression, endocrine system failure, and impairment of the GABAergic transmission are some of the affectations that are susceptible to be tracked using peripheral blood for monitoring of the motor, cognitive, psychiatric and reproductive impairment of the CGG-expansion carriers. We provided some illustrative examples from our own cohort. Understanding the association between molecular pathogenesis and biomarkers dynamics will improve effective prognosis and clinical management of CGG-expansion carriers.

Oral Health Disorders in Parkinson's Disease: More than Meets the Eye.

Despite clinical evidence of poor oral health and hygiene in Parkinson's disease (PD) patients, the mouth is often overlooked by both patients and the medical community, who generally focus on motor or psychiatric disorders considered more burdensome. Yet, oral health is in a two-way relationship with overall health-a weakened status triggering a decline in the quality of life. Here, we aim at giving a comprehensive overview of oral health disorders in PD, while identifying their etiologies and consequences. The physical (abnormal posture, muscle tone, tremor, and dyskinesia), behavioral (cognitive and neuropsychiatric disorders), and iatrogenic patterns associated with PD have an overall detrimental effect on patients' oral health, putting them at risk for other disorders (infections, aspiration, pain, malnutrition), reducing their quality of life and increasing their isolation (anxiety, depression, communication issues). Interdisciplinary cooperation for prevention, management and follow-up strategies need to be implemented at an early stage to maintain and improve patients' overall comfort and condition. Recommendations for practice, including (non-)pharmacological management strategies are discussed, with an emphasis on the neurologists' role. Of interest, the oral cavity may become a valuable tool for diagnosis and prognosis in the near future (biomarkers). This overlooked but critical issue requires further attention and interdisciplinary research.