Background: Primary tic disorders, including provisional tic disorder, chronic tic disorders and Tourette syndrome (TS), are common childhood-onset neurodevelopmental conditions. Epidemiological data from Central and Eastern Europe remain limited. This nationwide registry-based study provides the first population-level overview of tic disorders in Poland over a 14-year period. Methods: We analysed anonymised National Health Fund data from 2010-2024, identifying individuals diagnosed with tic disorders (ICD-10 F95), including provisional tic disorder (F95.0), chronic motor or phonic tic disorder (F95.1), and TS (F95.2). Comorbid ADHD (F90) and OCD (F42) were examined. Prevalence was stratified by age, sex, and region. Age at first diagnosis and healthcare utilisation were assessed. Healthcare utilisation was defined as the number of inpatient and outpatient encounters in which tic disorders were recorded as either a primary or comorbid diagnosis. Results: Recorded prevalence increased across all tic disorders. Prevalence was higher in males than females (p < 0.001), with male-to-female ratios ranging from 2:1 for provisional tics to 5-6:1 for TS in children. First diagnoses peaked between 6-12 years, with females diagnosed later than males (p < 0.001). Marked regional variation was observed, with higher prevalence in southern and southeastern regions (p < 0.001). ADHD and OCD were common, particularly in TS, and were associated with increased healthcare utilisation (p < 0.001). While total visits increased, visits per patient declined. Conclusions: Tic disorder prevalence has risen in Poland, with persistent regional disparities, highlighting the need for improved specialist access, earlier recognition, and integrated management of comorbidities.

Background Sleep disturbances, including excessive daytime sleepiness (EDS) and fragmented nocturnal sleep, are common in Parkinson's disease (PD) and significantly reduce quality of life. This pilot study evaluated the efficacy of a novel approach using blue light, delivered via dedicated glasses with integrated LED lights, to improve sleep and non-motor symptoms. Methods Randomised, placebo-controlled, single-blind pilot study with a 2-week light intervention. Participants were assessed at baseline, two weeks, and five weeks. The study was designed to evaluate between- and within-group changes. Participants were randomly allocated to receive blue light therapy (n = 15) or red light placebo (n = 15), delivered via LED-integrated glasses for one hour, twice daily, given for a 2-week period. Primary outcome was improvement in sleep quality, assessed via the Pittsburgh Sleep Quality Index. Secondary outcomes included diary-based sleep outcomes, excessive daytime sleepiness, mood, anxiety, and motor symptoms. Results There was a significant group × time effect with blue light therapy leading to better Pittsburgh Sleep Quality Index scores ( p = 0.021). Between-group analyses showed that at two weeks a trend toward significance was observed ( p = 0.065), while sleep quality significantly improved at five weeks compared to placebo ( p = 0.029) with a large effect size (0.896). Excessive sleepiness improved in the blue light group ( p < 0.001), with a reduction in clinically relevant sleepiness from 50.0% to 6.7% ( p = 0.005). Conclusions Blue light therapy delivered through dedicated glasses appeared to show an improvement in sleep quality and daytime sleepiness in individuals with PD. Blue light therapy offers a promising alternative to traditional light therapy utilising lower light intensities and eliminating the need for light boxes.

BACKGROUND:Parkinson's disease (PD) is a neurodegenerative disorder affecting both sexes, but differences exist between male and female in clinical manifestations, functional impact of symptoms and hormonal influences. Therefore, representativeness of females in PD trials indirectly determines the external validity of the clinical research in this field. OBJECTIVE:To estimate the representativeness of female in infusion therapy trials for advanced PD. METHODS:PubMed and EMBASE databases were searched (1980 to September 2023), along with congress abstracts, to identify controlled clinical trials and large non-controlled studies on infusion therapies in PD enrolling >100 patients. Random-effect meta-analysis was conducted to estimate mean pooled prevalence of females included in the studies. Subgroup analyses were conducted accordingly to study design and intervention. RESULTS:We included 15 studies (six studies on levodopa-carbidopa intestinal gel, six on subcutaneous levodopa, two on subcutaneous apomorphine, and one on levodopa-carbidopa-entacapone intestinal gel). Sex was not a randomisation stratification factor in any of these studies. Only one study explored differences in the outcome estimated according to sex. Overall, the proportion of female included was 38% (95% CI:33%-43%; I2 = 74%), without differences between studies assessing different type of interventions (p = 0.72) or between study design (p = 0.35). In two studies, females represented the majority of included patients. CONCLUSION:Female with advanced PD are underrepresented in infusion therapy trials. Most trials have overlooked sex-based biological differences that can impact clinical and functional outcomes, raising concerns about the generalizability of these findings to real-world contexts.

Aim of study. To investigate the treatment strategies of Parkinson's Disease (PD) among movement disorder specialists in tertiary centres in Poland, and how literature warnings (levodopa and dopamine agonist phobia) have influenced their practice. Material and methods. The survey was conducted between 30 November, 2020 and 18 October, 2021, in four Polish tertiary referral centres for PD (two in Gdansk, one in Sosnowiec, and one in Warsaw). Movement disorder specialists collected information on the treatment of 494 consecutive patients diagnosed with PD.The questionnaire included information on the age of the patient, the duration of PD, the Hoehn&Yahr (H&Y) stage, comorbidities, pharmacotherapy, and advanced PDtherapies i.e. deep brain stimulation (DBS), levodopa/carbidopa intestinal gel (LCIG), and continuous subcutaneous apomorphine infusions (CSAI). Results. Levodopa was the most prescribed medication (n = 465/494), followed by dopamine agonists (n = 292/494).The mean dose of levodopa was 810.58 +/- 473.11 mg, and it did not exceed 2,000 mg/d in 98.5% of patients.The mean doses of dopamine agonists used were relatively low (ropinirole 8.64 +/- 3.94 mg, pramipexole base 1.76 +/- 0.65mg). Amantadine (n = 197/494) and MAO-B inhibitors (n = 202/494) were prescribed less frequently. Catechol-o-methyltransferase (COMT) inhibitors (n = 7/494) and anticholinergics (n = 4/494) were rarely used in the studied population. Complex polytherapy with three or more PD medications was the most often used treatment strategy (n = 223/494). Conclusions and clinical implications. Levodopa remains the gold standard in PD treatment in tertiary movement disorder centres in Poland. Dopamine agonists formed the second most frequently prescribed group of medications; however, the observed low dosages of both levodopa and dopamine agonists may suggest a cautious approach by clinicians. Amantadine and MAO-B inhibitors (mainly rasagiline) constituted important elements of PD pharmacotherapy.The high prevalence of complex polytherapy underlines the complexity of PD management, the cautious use of single medication at high doses, and the need for personalised therapeutic strategies.

INTRODUCTION:Functional movement disorders (FMD) are defined by diverse phenotypes of altered movements that lack corresponding pathology in an anatomical region, and are typically characterized by inconsistent findings on neurological examination. STATE OF THE ART:While there are several suggestive clinical features indicating FMD, objective biomarkers are still lacking. We conducted a systematic review of the literature with an emphasis on literature published after February 2019 aiming to summarise current knowledge on biomarkers of FMD. We divided our findings into four main categories: genetic, biofluid, neuroimaging, and electrophysiological biomarkers. For the differential diagnosis of functional tremor, functional tic-like behaviours (FTLB), and functional myoclonus, previous studies support the use of electrophysiological biomarkers. Evidence from neuroimaging research supports the multi-network model of FMD as a condition affecting the attentional, sensorimotor, self-agency/multimodal integration, and limbic/salience circuits. Biomarkers such as neurofilament light chain, inflammatory, and autoimmune factors should still be considered experimental, since results are based on small sample sizes. There is preliminary evidence from a genetic study that in FMD there is a complex interaction between individual predisposing risk genes involved in the serotonergic pathway. CLINICAL IMPLICATIONS:Although the diagnosis of FMD remains challenging, and depends mainly on clinical judgement, research is underway to identify potential biomarkers to improve diagnostic confidence. Previous studies indicate that, in addition to psychological symptoms, biological changes can be detected in patients with FMD. This is evidenced by different patterns of neurotransmission related to stress responses and emotional regulation. FUTURE DIRECTIONS:We believe it is vital to conduct larger trials in diverse populations from different regions of the world in order to find more reliable biomarkers of FMD.

INTRODUCTION:Non-motor symptoms of Parkinson's disease (PD), particularly visual disturbances, often appear before a formal diagnosis and may serve as early signs or prodromal features of the disease. This review aims to evaluate ocular biomarkers associated with prodromal and early-stage PD, highlighting ophthalmic indicators that could support earlier diagnosis and aid in tracking disease progression. MATERIAL AND METHODS:PubMed and Scopus databases were systematically searched for all records available from their inception through May 2024, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement extension for Scoping Reviews (PRISMA-ScR) guidelines. Two distinct PICO (PICO stands for Population, Intervention, Control, Outcome) frameworks were employed to guide the selection criteria: one for people with early Parkinson's disease and another for individuals at risk of prodromal PD. RESULTS:30 studies were included - 4 solely on prodromal cohorts (RBD), 18 on patients with PD and 8 studies with both prodromal and clinical cohorts. Studies of people with RBD have shown abnormalities in pupillary light reflex, eye movements, and color discrimination. People with early PD showed impaired contrast sensitivity, impaired color discrimination, retinal structural changes, including retinal thinning (in the inner nuclear layer and ganglion cell-inner plexiform layer, altered pupillary responses, visual hallucinations, and ocular movement disorders). CONCLUSIONS:Impairment of both color and contrast vision, as well as changes in optical coherence tomography (OCT), correlate with disease severity and cognitive decline. They can serve as an early, safe, noninvasive biomarker of neurodegeneration.

INTRODUCTION:Early onset Parkinson's disease (EOPD) has been defined as PD with onset of motor symptoms after age 21 but before age 50. While diagnostic criteria are clear, data suggest that clinicians are still uncomfortable making the diagnosis, resulting in multiple investigations and delays in diagnosis and initiation of treatment. METHODS:Following the Delphi process, the 15 members of the steering committee of the EOPD study group of the International Parkinson Disease and Movement Disorder Society (MDS) designed and completed a 10 binary or multiple-choice questions survey then met to establish recommendations regarding which investigations are needed for the diagnosis of EOPD. RESULTS:The average age of the 15 respondents (5 females) was 49 years, with 18.2 years average experience in the management of EOPD (range 9-30 years). All geographic sections of the MDS were represented to account for variability of practice. The committee discussed the role of brain MRI, Dopamine transporter (DaT) SPECT scan, laboratory investigation, and genetic testing when suspecting EOPD. CONCLUSION:If EOPD is suspected on history and examination without any additional findings concerning for secondary or genetic parkinsonism, we recommend limiting investigations to brain MRI and laboratory investigation for Wilson's disease. This may expedite diagnosis and starting the appropriate treatment. Genetic testing is not necessary for diagnosis but can be useful to identify new genetic etiologies which could plausibly be used for trial inclusion.

DesignA cross-sectional study.SettingNational-level physiotherapy care for Parkinson's Disease across European countries.ParticipantsOne physiotherapist from each of the 26 European countries was invited to provide national-level information based on availability of physiotherapy for Parkinson's Disease, based on a questionnaire.Main measuresNational-level information was collected on accessibility and conditions of physiotherapy specialized in Parkinson's Disease across European countries.ResultsData from 24 countries were collected. Parkinson's Disease-specific physiotherapy was offered in 20 countries. The number of hours of physiotherapy per year available for people with Parkinson's Disease varied widely across countries, from none to an unlimited number of sessions. Treatment was typically provided free of charge through public or government-financed national health systems, with treatment frequency informed by national insurance. Only eight countries reported formal Parkinson's Disease training programs for physiotherapy, which were available only as a separate, external program not integrated with the standard physiotherapy curriculum at a university.ConclusionsPhysiotherapy for people with Parkinson's Disease in European countries varies significantly across countries that completed the questionnaire, with differences in the number of hours and treatment settings. It is crucial to standardize training and care for people with Parkinson's Disease and prioritize the development and implementation of policies to facilitate access to evidence-based physiotherapy services.

Placebo, nocebo, and lessebo effects are very frequent in patients with both neurological and psychiatric disorders. Interestingly, the neural mechanisms underlying placebo effects have been found to be the same as or similar to mechanisms targeted by active pharmaceutical interventions for many of these disorders. In the case of functional neurological disorders (FNDs), there are shared neural substrates between the central nervous system “placebo network” and the dysfunctional networks implicated in the pathophysiology. These networks are primarily involved in emotion regulation, stress responses, and the sense of self-agency. Therefore, placebo effects have also been discussed as therapeutic interventions in FNDs. Such an approach, however, has a variety of ethical implications evolving around informed consent, autonomy, nonmaleficence, beneficence, and justice. In this paper, we discuss the use of placebo, nocebo, and lessebo in FNDs as well as related ethical issues. Overall, the use of placebo in FNDs is currently still considered controversial both for diagnostic as well as therapeutic purposes. Although it is a safe and almost unique intervention, its use violates the core principles of medical ethics and doctor–patient interactions involving autonomy or openness in the therapeutic relationship.

BACKGROUND:Leucine-rich repeat kinase 2 (LRRK2) p.L1795F variant was proposed as a genetic risk factor for Parkinson's disease (PD). However, its prevalence, phenotype, and origin remain unknown. OBJECTIVE:The aim was to evaluate the frequency and phenotype of p.L1795F in early-onset PD (EOPD) and familial PD compared to healthy controls (HC) in Central Europe. METHODS:Whole-exome sequencing was used to screen 219 EOPD and familial PD patients of Central Europeans compared to HC. Sanger sequencing assessed segregation. Detailed clinical phenotype was evaluated for all positive carriers. RESULTS:p.L1795F was identified in 1.37% (3/219) and 3.23% of familial cases (3/93), with no carriers among HCs (0/303). Segregation analysis confirmed association with PD. Carriers were traced to the eastern Slovak-Hungarian region. It also appears to be associated with a more aggressive phenotype. CONCLUSION:Our data indicate that p.L1795F contributes to PD in Central Europe. Further exploration in larger cohorts is warranted to establish its contribution to global PD risk.

Background:Given the growing evidence for an environmental contribution to the etiology of Parkinson's disease (PD), searching for local and regional differences in PD prevalence in multiple areas across the world may further clarify the role of environmental toxins. Objective:To provide local and regional prevalence estimates of PD in Poland. Methods:We analyzed the prevalence of PD and its trend over the last decade (2010 to 2019) based on data from the National Health Fund in Poland. We specifically examined sex differences in PD prevalence, as well as differences across Polish regions. Results:During the above period, the prevalence of PD in Poland increased from 226 per 100,000 to 269 per 100,000 inhabitants. Unexpectedly, we found that PD was 1.2-times more common in women than men. The increase in prevalence over the past decade was different between both sexes: an increase from 250 to 283 per 100,000 for women (13.3% increase), and from 200 to 254 per 100,000 for men (27.1% increase). In addition, we observed differences in prevalence across different Polish regions, with some regions having up to 51% lower prevalence rates than others. Conclusions:The prevalence of PD in Poland is in line with previously reported prevalence rates across Europe. However, unlike the situation in most of the world, PD was more prevalent in women than men. We discuss several possible explanations as well as potential measures that might help to reduce the growth of PD.

BACKGROUND:The decision to choose invasive treatments for Parkinson's disease (PD) is complex and needs careful consideration.OBJECTIVES:Although the recommendations of the European Academy of Neurology/Movement Disorder Society European Section guideline for invasive therapies of PD are useful, the different clinical profiles of people with PD who seek advice for possible invasive therapy need further attention.METHODS AND RESULTS:Here we describe 8 clinical standard situations of people with PD unsatisfied with their current oral treatment where invasive therapies may be considered. These are PD patients presenting with the following symptoms: (1) severe motor fluctuations, (2) beginning of levodopa-responsive fluctuations, severe tremor at (3) young or (4) advanced age, (5) impulse control disorders and related behavioral disorders, (6) hallucinations and psychosis, (7) minimal cognitive impairment or mild dementia, and (8) patients in need of palliative care. For some of these conditions, evidence at lower level or simple clinical considerations exist.CONCLUSIONS:There are no one-fits-all answers, but physician and patient should discuss each option carefully considering symptom profile, psychosocial context, availability of therapy alternatives, and many other factors. The current paper outlines our proposed approach to these circumstances.

Pregnancy in women with early-onset Parkinson’s disease (PD) is likely to have a higher frequency given the trend toward increasing maternal age, thus resulting in a greater overlap time between childbearing age and PD risk. Deep brain stimulation (DBS) therapy is nowadays offered to PD patients at earlier stage of the disease, when women can still be pre-menopausal. However, few data are available about DBS safety during pregnancy. From a review of the available literature, only one article was published on this topic so far. Therefore, we have developed a clinical consensus on the safety of DBS during pregnancy in PD patients.

Objective Access to care for people with Parkinson’s disease (PD), particularly to device-aided therapies (DAT), is not equally distributed. The objective was to analyze accessibility to DAT (deep brain stimulation, intraduodenal levodopa pump therapy, and apomorphine pump therapy) in Poland.Methods We analyzed the distribution of DAT use in Poland by determining the number of persons with PD receiving one of the three DATs during 2015–2021.Results In 2021, the number of persons receiving DAT in Poland was 0.56% of the total PD population, increasing from 0.21% in 2015. Overall, deep brain stimulation was the preferred DAT in Poland, but strong regional differences in the use of the other DATs were observed. Accessibility to DAT was negatively associated with average annual income (p < 0.001).Conclusion Access to DAT for persons with PD in Poland is still limited, and strong regional differences in accessibility were observed, although its general increase over the last decade is encouraging.

BackgroundPost-stroke movement disorders (PSMD) encompass a wide array of presentations, which vary in mode of onset, phenomenology, response to treatment, and natural history. There are no evidence-based guidelines on the diagnosis and treatment of PSMD.ObjectivesTo survey current opinions and practices on the diagnosis and treatment of PSMD.MethodsA survey was developed by the PSMD Study Group, commissioned by the International Parkinson's and Movement Disorders Society (MDS). The survey, distributed to all members, yielded a total of 529 responses, 395 (74.7%) of which came from clinicians with experience with PSMD.ResultsParkinsonism (68%), hemiballismus/hemichorea (61%), tremor (58%), and dystonia (54%) were by far the most commonly endorsed presentation of PSMD, although this varied by region. Basal ganglia stroke (76% of responders), symptoms contralateral to stroke (75%), and a temporal relationship (59%) were considered important factors for the diagnosis of PSMD. Oral medication use depended on the phenomenology of the PSMD. Almost 50% of respondents considered deep brain stimulation and ablative surgeries as options for treatment. The lack of guidelines for the diagnosis and treatment was considered the most important gap to address.ConclusionsRegionally varying opinions and practices on PSMD highlight gaps in (and mistranslation of) epidemiologic and therapeutic knowledge. Multicenter registries and prospective community-based studies are needed for the creation of evidence-based guidelines to inform the diagnosis and treatment of patients with PSMD.

The most widely applied diagnostic criteria for Tourette syndrome (TS) and other persistent motor and vocal tic disorders (PMVTD) are those included in the Diagnostic and Statistical Manual (DSM) of Mental Disorders of the American Psychiatric Association.1 These criteria have remained substantially unchanged for the past 30 years since the DSM-IV was published in 1994.2 DSM-IV and DSM-5-text revised (TR) criteria for primary tic disorders (Table 1) have set clear diagnostic standards for tic disorders. However, an increasingly shared view among experienced clinicians is that these criteria neither reflect the critical thinking behind the diagnosis of tic disorders nor the neurobiology of these conditions. Moreover, the current criteria may fail to separate neurobiological different conditions also manifesting with tics and tic-like behaviors. The broad inclusivity of the current criteria has been a longstanding problem that became more pressing with the sharp rise in functional tic-like behaviors (FTLBs) during the coronavirus disease 2019 pandemic.3-5 According to the DSM-5-TR,1 many individuals affected by FTLBs meet the criteria for and can formally be diagnosed with TS. There are serious risks related to this misdiagnosis, including unnecessary investigations, delayed treatment, and unwarranted, possibly harmful interventions. Additionally, some individuals with TS may subsequently develop concurrent FTLBs,6 which complicates management if not accurately recognized. Inaccurate diagnostic criteria can compromise the validity and reproducibility of research findings. Finally, misdiagnosis enhances stigma, leading to social isolation, discrimination, psychological distress, and erosion of trust in healthcare systems.7 In response to the growing number of adolescents and young adults seeking care for disabling FTLBs, an international working group collaborating with the European Society for the Study of Tourette Syndrome (ESSTS) has developed, through Delphi methodology, consensus-based criteria for a clinical diagnosis of FTLBs.8 These constitute a helpful tool for health professionals to diagnose and treat this condition with confidence.9-11 FTLBs display typical features of functional neurological symptoms12, 13 and have been demonstrated not to respond to the typical pharmacological therapy for primary tic disorders.14 Moreover, both conditions may benefit from treatment of psychiatric comorbidities and cognitive behavioral therapy.15 Given the clinical and pathophysiological differences between tics and FTLBs and the potential ambiguity of the current diagnostic criteria for primary tic disorders, we believe it is time to reconsider these criteria. In proposing this revision of diagnostic criteria for primary tic disorders, we have taken into account the key features distinguishing primary tic disorders from a pure FTLB disorder, with the aim of minimizing risk of misdiagnosis and inappropriate management. The DSM criteria for the diagnosis of tic disorders have changed from the different versions of the manual.16 The DSM is a product of the American Psychiatric Association's Committee on Nomenclature on Statistics and, historically, had a role in classifying psychiatric conditions into a clinical and medical framework. Both the original version and subsequent revisions reflected the social understanding of diseases at the time, and the evolving understanding shaped the classification.17 As a result, the modifications of the criteria for tic disorders over time were not informed by new evidence of the biological underpinnings of tic disorders. The most recent DSM-5-TR criteria rest on four pillars: (1) presence of vocal (phonic) and/or motor tics; (2) age at onset; (3) duration of tics; and (4) exclusion of secondary etiologies for tics. The criteria then differentiate TS from other persistent tic disorders based on the co-occurrence of motor and phonic tics. A strength of the DSM-5-TR classification is having included tic disorders in the category of "neurodevelopmental disorders," also comprising intellectual disability, communication disorders, autism spectrum disorder, and attention-deficit/hyperactivity disorder (ADHD), in line with the current, biology-driven conceptualization of tic disorders. Although specifically referring to tic disorders, the DSM-5-TR criteria do not consider impairment, whereas not all tics are functionally impairing and, therefore, the threshold for tics representing a disorder can be arbitrary. Overall, relevant limitations of the DSM-5-TR criteria should be highlighted, pertaining to four main themes. Because of these limitations, we believe these criteria do not accurately reflect the natural history of primary tic disorders and may fail to differentiate primary tic disorders from FTLBs accurately. The upper age limit of tic disorders onset has been controversial for decades. Although the DSM-III,18 without clear biological justification, first set the upper limit at age 15, the DSM-III-TR19 changed it to age 21. Eventually, again without a neurobiological rationale, this was modified to age 18 in the DSM-IV without subsequent modifications. The onset of TS is between age 4 and 8, whereas that of PMVTD is ~2 years later.20-24 Freeman et al.25 reported that 93% of 3500 TS participants exhibited tics before 10 years of age. Unlike previous versions, the 11th revision of the International Classification of Diseases (ICD-11) by the World Health Organisation26 does not include any specific age limit in the "essential" diagnostic criteria. However, among "course features," age of onset "commonly…between the ages of 4 and 6" is specified. Considering this natural history data, the current upper limit of 18 years for age at onset of primary tic disorders appears not well justified. Keeping this upper limit unchanged or eliminating altogether the age at onset criteria (as implied in the ICD-11 criteria) may dangerously increase the risk of misdiagnosis between primary tic disorders and FTLBs. The latter is typically present after the age of 12, as demonstrated by recent literature9 and stated in the ESSTS 2022 diagnostic criteria.8 To use age at onset as a supportive diagnostic criterion that reflects the actual time course of primary tic disorders, the upper limit of age at onset should be anticipated to be 10 to 12 years of age. Introducing this as a supportive, rather than mandatory, criterion would prevent a potential, and not uncommon, recall bias in self-reporting age at onset from erroneously ruling out the diagnosis of primary tic disorder. In TS and other PMVTD, initial tics are, in the majority of cases, simple tics involving the face, head, and/or neck regions.27, 28 During the following years of the developmental period, more complex tics or tics affecting other body regions may arise.28 Tics typically peak in severity between age 10 and 1420, 21 and decrease in severity over the course of mid-to-late adolescence,21, 29 although tics remit in adulthood in 10% to 20% of individuals.20 An increase in female proportion of the TS population with increasing age has also been observed, and potential differences in clinical course of TS between sexes were reported, which need further investigation.30 Conversely, the natural history of FTLBs differs substantially from that of primary tic disorders. Indeed, FTLBs often emerge abruptly in adolescents or young adults, with maximum disability often reached within the initial weeks, presenting from the outset with vocalizations and complex movements involving multiple body regions, predominantly limbs and torso.8-10 Despite being routinely considered in clinical practice and contributing significantly to the diagnostic process, these basic clinical features of tics are not included in current diagnostic criteria. We propose that early predominance of the cranial and cervical regions and early predominance of simple over complex tics should be included as supportive criteria of primary tic disorders. The current DSM-5-TR criteria specify a minimum 1-year disease duration to define a persistent tic disorder, whereas symptoms of less than 12 months' duration constitute a diagnosis of "Provisional Tic Disorder". Although the 1-year cut off aligns with the definition of "chronic disease" of the National Center for Chronic Disease Prevention and Health Promotion of the Center for Disease Control and Prevention (https://www.cdc.gov/chronicdisease/about/index.htm) and we consider this criterion acceptable, we acknowledge that it remains arbitrary. In fact, limited evidence suggests that most children with provisional tics may continue to exhibit tics for more than a year.31 However, at the present time, we lack prospective data suggesting the existence of an earlier cut point that would identify persistent tics as efficiently as the 12-months one. It has long been suggested that the differentiation between motor and phonic tics is arbitrary.32-34 Phonic tics are motor tics that involve the oral, nasal, pharyngeal, laryngeal, and respiratory musculature, resulting in the production of an audible sound. Both are often preceded by a premonitory urge, are highly suggestible, are usually suppressible, and may be exacerbated by stress or emotions. Of note, the term vocal tics is used interchangeably with phonic tics, but more accurately conveys tics that make sound because of the involvement of the vocal cords. In most cases, phonic tics do not involve the vocal cords, but the passage of air through the upper respiratory tract eventually produces their sound (ie, throat clearing or sniffing). Although commonalities and differences in the neurobiological basis of motor and phonic tics warrant further investigation, there is no evidence from registry-based and observational studies to support a different prognosis of a tic disorder based on the predominance of motor rather than phonic tics. Overall, although they communicate broad clinical categories of tic presentations, there is insufficient evidence to support a net separation between persistent motor tic disorder and persistent vocal (phonic) tic disorder. In addition, this separation may not be helpful in distinguishing between primary tic disorders and pure FTLBs, which too can present with different motor and vocal phenomena that wax and wane over time. Even the complexity of vocalizations is not helpful, as coprolalia is commonly noted among FTLBs.35 Among the important modifications to the DSM, echolalia, suppressibility of tics, fluctuation of symptoms, and impact on daily life activities were all initially proposed as criteria, but subsequently dropped in later editions of the DSM.19 However, the bedrock of the distinction between TS and other PMVTD has always been that motor and phonic tics must co-exist (although not necessarily concurrently or consistently) to diagnose TS. In particular, the DSM-5-TR criteria for TS specify that individuals must experience a combination of a minimum number of tics (ie, at least one phonic and two motor). However, patients with any form of primary persistent tic disorder, including TS, normally experience a much broader and fluid repertoire of tics, which can change widely over time. In keeping with this, the current ICD-11 criteria do not specify the number of required tics. Growing evidence suggests that, rather than distinct clinical entities, TS and PMVTD represent different degrees of severity or impairment of the same underlying condition.36 TS and PMVTD have clinically indistinguishable features, including onset in early childhood, response to the same treatments, waxing and waning clinical course, frequent improvement with age, family history, and comorbidity profile. Although our understanding of the genetic factors contributing to tic disorders is still limited, genome-wide association studies support that TS and PMVTD have a shared genetic profile and represent a continuous spectrum of condition, further reinforcing the diagnostic amalgamation of these two conditions.37 Although patients with TS have greater tic severity and slightly younger age at onset, both TS and PMVTD patients exhibit a high prevalence of psychiatric co-occurring conditions, including obsessive-compulsive disorder (OCD), ADHD, anxiety, and mood disorders.36 As in TS, co-occurring OCD and ADHD in PMVTD predict a higher incidence of maladaptive behaviors.38 This diagnostic differentiation appears, therefore, poorly substantiated. The similarity in comorbidity profile across all primary persistent tic disorders is, on the other hand, in contrast with the difference in frequency of comorbid neurodevelopmental and psychiatric disorders between primary tic disorders and pure FTLBs, with the latter showing greater prevalence of depression, anxiety disorders and, possibly, autism spectrum disorder.9 A unifying corollary to the above considerations is that the categorization of the "primary persistent tic disorder" into different diagnoses or clinical entities is not supported by evidence and has been challenged by the recently increased experience of FTLBs. Keeping the separation among TS, persistent motor tic disorder, and persistent phonic/vocal tic disorder could also perpetuate a stigmatizing divide between TS and non-TS tic disorders that is neither clinically nor neurobiologically justified. We, therefore, propose that the community of clinicians, scientists, and persons with lived experience should join forces to reappraise existing diagnostic criteria and establish a single diagnostic entity identified as primary persistent tic disorder (or other conceptually similar terminology). The key proposed changes are summarized in Table 1. Whether a neutral term will one day be preferred to the use of the TS eponym will require a more detailed risk–benefit analysis, inclusive of impact on stigma and care, patient perspective, as well as research in underdeveloped regions, and is, therefore, beyond the scope of this viewpoint. The lack of in vivo biomarkers and neuropathologic criteria for primary persistent tic disorder currently limit clinicians and scientists to an exclusively clinical definition. Therefore, any proposed revision of clinical criteria will need to be contrasted with newly identified markers when available. We believe that this proposal of revision to the current diagnostic criteria simplifies and provides more clarity to the nosology of primary tic disorders, while offering a diagnostic framework that can limit misdiagnosis and inappropriate management decisions that may occur in routine clinical practice, particularly with respect to pure FTLBs. 1. Research project: A. Conception, B. Organization, C. Execution; 2. Statistical Analysis: A. Design, B. Execution, C. Review and Critique; 3. Manuscript Preparation: A. Writing of the First Draft, B. Review and Critique. M.S.: 1A, 1C, 3A; J.F.: 3B C.G.: 3B D.L.G.: 3B A.H.: 3B T.H.: 3B D.I.: 3B I.M.: 3B J.M.M.: 3B A.M.E.: 3B K.R.M.V.: 3B M.O.: 3B M.P.: 3B H.S.: 3B K.Ś.: 3B N.S.: 3B K.T.: 3B Y.W.: 3B T.P.: 1B, 3B D.M.: 1A, 1C, 3B M.S. is employed by King's College Hospital National Health Service (NHS) Trust. J.F. received honoraria from The New England Journal of Medicine: Clinical Neurology Update and American Academy of Neurology Course Presenter; and received grants from TAA Young Investigator Award. C.G. is employed by the University of Toronto; has received honoraria from the Movement Disorders Society; and has received grants from VolkswagenStiftung. D.G. provided consultancies to PTC Therapeutics and Emalex Biosciences; is employed by the Cincinnati Children's Hospital Medical Center; received honoraria from Illumina, PTC Therapeutics; received royalties from Elsevier, Wolters Kluwer; and received grants to the Institution of the United States (US) National Institute of Mental Health, US Department of Defense, Clinical Trials site investigator PTC Therapeutics, and Emalex Biosciences. A.H. provided consultancies to Noema Pharma; belongs to the advisory board of Association Française pour le syndrome Gilles de la Tourette; and is employed by Assistance Publique des Hôpitaux de Paris. T.H. is employed by GSTT and Kings College London, Faculty of Life Sciences and Medicine, Department of Women and Children's Health, London United Kingdom. D.I. belongs to the advisory board of Tourette Association of America; is employed by Vanderbilt University Medical Center; received honoraria from Tourette Association of America; received grants from National Institute of Neurological Disorders and Stroke (NINDS) (K23NS131592), Teva Branded Pharmaceutical Products, and R&D. I.M. provided consultancies to AbbVie; is employed by the University of Florida; received honoraria from the Tourette Association of America, Parkinson Foundation, Medscape, Efficient CME, and Cleveland Clinic; received royalties from Robert Rose publishers; received grants from the Parkinson Foundation, Tourette Association, Dystonia Coalition, AbbVie, Boston Scientific, Eli Lilly, Neuroderm, and Revance. J.M.M. is employed by Wake Forest University Health Sciences; received honoraria from the Movement Disorders Society, American Academy of Neurology; received grants from the Tourette Association of America, American Board of Psychiatry and Neurology, and NINDS NeuroNEXT. A.M.E. is employed by Horizon Health Network, New Brunswick, Canada. K.M.V. provided consultancies to Abide Therapeutics, adjupharm, Alexion, AMP Alternative Medical Products, Becanex, Boehringer Ingelheim International, Bionorica Ethics, CannaMedical Pharma, Canopy Grouth, Columbia Care, CTC Communications, Demecan, Enua pharma, DHMS Direct Health Medical Services, Ethypharm, Eurox Group, Global Praxis Group, Hormosan Pharma, Lundbeck, Marry Jane, MCI Germany, Neuraxpharm, Noema Pharma, Sanity Group, Stadapharm, Synendos Therapeutics AG, Syqe, Tilray, and Zambon; belongs to the advisory boards of Alexion, Branchenverband Cannabiswirtschaft e.V., CannaMedical Pharma, Bionorica Ethics, Canopy Growth, Columbia Care, Ethypharm, Hormosan Pharma, IMC Germany, Leafly Deutschland, Neuraxpharm, Sanity Group, Stadapharm, Synendos Therapeutics AG, Syqe Medical, Therapix Biosciences, and Tilray; received honoraria from Agaplesion Frankfurter Diakonie Kliniken gemeinnützige, Almirall, Aphria Deutschland, Arbeitsgemeinschaft Cannabis als Medizin, Astra Zeneca, Bedrocan, Bundesverband pharmazeutischer Cannabinoidunternehmen, Camurus, canymed, CEREBRO SPAIN BIDCO S.L, Cogitando, Deutsche Gesellschaft für Psychiatrie und Psychotherapie, Psychosomatik und Nervenheilkunde, Diplomado Internacional de Endocannabinología (Programa Universitario de Investigación en Salud—PUIS, UNAM), Dresden International University, Emalex, EpiCampusNord, Eurox Deutschland, Ever pharma, Four20 Pharma, Georgia Medical Cannabis Project, Grow Group PLC, Hessische Landesstelle für Suchtfragen e.V., Landschaftsverband Westfalen-Lippe, LIO Pharmaceuticals, Medizinischer Dienst Westfalen Lippe, Meinhardt Congress, PR Berater, Salus—Fachklinikum Bernburg, Spectrum Therapeutics, streamedup!, Swiss Alpinopharm, SynopticCon, targoEvent, Takeda, Tilray, VFnK—Verein zur Förderung neurologisch Kranker e.V., von Mende Marketing, Wayland Group, and WeCann; received royalties from Deutsches Ärzteblatt, Der Neurologie und Psychiater, Elsevier, Medizinisch Wissenschaftliche Verlagsgesellschaft Berlin, and Kohlhammer; and received grants from German Research Foundation, German Federal Ministry of Education and Research, Tourette Gesellschaft Deutschland e.V., Else-Kröner-Fresenius-Stiftung, and Almirall. M.S.O. is employed by Medical Advisor, Parkinson's Foundation; received honoraria from The Movement Disorders Society, American Academy of Neurology, Vanderbilt University, WebMD/Medscape; received royalties from Books4Patients; received grants from National Institutes of Health (NIH), The Michael J. Fox Foundation, and Tourette Association of America. M.P. provided consultancies to GuidePoint Global and Orphalan; belonged to the advisory board of Teva; employed by Baylor College of Medicine; received honoraria from The Movement Disorders Society; and received grants from Clinical trial support from NIH, PTC Therapeutics, Alexion, and Neurocrine Biosciences. H.S. provided consultancies to Novo Nordisk; received honoraria from The Movement Disorder Society and American Academy of Neurology; and received grants from Clinical trial support from Novo Nordisk, Blue Rock, Neuroderm, Prevail, Bukwang, Genentech, Biogen, MeiraGTX, Sun Pharma, NIH, and Insightec. K.S. is employed by the 5th Regional Hospital, Sosnowiec, Poland; received honoraria from AbbVie and Orphalan; and received grants supported by the Brain Disease Foundation. N.S. is employed by the University of Calgary; and received grants supported by an American Academy of Neurology Fellowship grant, American Brain Foundation, and Tourette Association as well as Polish Ministry of Health, and travel grant from the International Movement Disorders Society. Y.W. is employed by King's College Hospital NHS Trust. K.T. provided consultancies to Emalex; is employed by Boston Children's Hospital; and received grants from Toretta-Lee Family. T.P. is employed by the University of Calgary; and received grants from The Canadian Institutes of Health Research and the Azrieli Accelerator. D.M. provided consultancies to Roche; belonged to the advisory board of Merz Pharmaceuticals; is employed by the University of Calgary; received honoraria from Dystonia Medical Research Foundation Canada, Movement Disorders Society, Canadian Movement Disorders Society; received royalties from Springer-Verlag, Oxford University Press; and received grants from Neuroscience, Rehabilitation, and Vision Strategic Clinical Network of the Alberta Health Services, Owerko Foundation, Dystonia Medical Research Foundation (DMRF) USA, DMRF Canada, and National Spasmodic Torticollis Association Sacramento Chapter in Memory of Howard Thiel, Parkinson Canada, The Canadian Institutes of Health Research, and Michael P. Smith Family. The data that support the findings of this study are available from the corresponding author upon reasonable request.

Pathogenic variants in LRRK2 are one of the most common genetic risk factors for Parkinson’s disease (PD). Recently, the lesser-known p.L1795F variant was proposed as a strong genetic risk factor for PD, however, further families are currently lacking in literature. A multicentre young onset and familial PD cohort (n = 220) from 9 movement disorder centres across Central Europe within the CEGEMOD consortium was screened for rare LRRK2 variants using whole exome sequencing data. We identified 4 PD cases with heterozygous p.L1795F variant. All 4 cases were characterised by akinetic-rigid PD phenotype with early onset of severe motor fluctuations, 2 receiving LCIG therapy and 2 implanted with STN DBS; all 4 cases showed unsatisfactory effect of advanced therapies on motor fluctuations. Our data also suggest that p.L1795F may represent the most common currently known pathogenic LRRK2 variant in Central Europe compared to the more studied p.G2019S, being present in 1.81% of PD cases within the Central European cohort and 3.23% of familial PD cases. Together with the ongoing clinical trials for LRRK2 inhibitors, this finding emphasises the urgent need for more ethnic diversity in PD genetic research.

Background: The circadian system and its dysfunction in persons with Parkinson's disease (PwP) has a clear impact on both motor and non-motor symptoms. Examples include circadian patterns in motor disability, with worsening of symptoms throughout the day, but also the existence of similar patterns in non-motor symptoms. Objective: In this narrative review, we discuss the role of the circadian system, we address the role of dopamine in this system, and we summarise the evidence that supports the use of circadian system treatments for motor and non-motor symptoms in PwP. Methods: A systematic search in PubMed and Web of Science database was performed and the final search was performed in November 2021. We included articles whose primary aim was to investigate the effect of melatonin, melatonin agonists, and light therapy in PwP.Results: In total 25 articles were retrieved. Of these, 12 were related to bright light therapy and 13 to melatonin or/and melatonin agonists. Most, but not all, studies showed that melatonin and melatonin agonists and light therapy induced improvements in measures of sleep, depression, motor function, and some also cognitive function and other non-motor symptoms. For some of these outcomes, including daytime sleepiness, depressive symptoms, and some motor symptoms, there is level 2 B evidence for the use of circadian treatments in PwP.Conclusions: Treatment with bright light therapy, exogenous melatonin and melatonin agonists seems to have not only positive effects on sleep quality and depression but also on motor function in PwP. Drawbacks in earlier work include the relatively small number of participants and the heterogeneity of outcome measures. Further large and well-designed trials are needed to address these shortcomings and to confirm or refute the possible merits of the circadian system as a treatment target in PwP.

Background The decision to choose invasive treatments for Parkinson's disease (PD) is complex and needs careful consideration. Objektives Although the recommendations of the EAN/MDS‐ES guideline for invasive therapies of PD are useful, the different clinical profiles of people with PD who seek advice for possible invasive therapy need further attention. Methods and Results Here we describe eight clinical standard situations of people with PD unsatisfied with their current oral treatment where invasive therapies may be considered. These are PD patients presenting with (1) severe motor fluctuations, (2) beginning of levodopa‐responsive fluctuations, severe tremor at (3) young or (4) advanced age, (5) impulse control disorders and related behavioural disorders, (6) hallucinations and psychosis, (7) minimal cognitive impairment or mild dementia and (8) patients in palliative care need. For some of these conditions evidence at lower level or simple clinical considerations exist. Conclusions There are no one‐fits‐all answers, but physician and patient should discuss each option carefully considering symptom profile, psychosocial context, availability of therapy alternatives, and many other factors. The current paper outlines our proposed approach to these circumstances. This article is protected by copyright. All rights reserved.