Despite the introduction of many novel antiseizure medications (ASMs), about one third of people with epilepsy remain resistant to the pharmacotherapy. Currently available ASMs have other limitations, including a significant burden of adverse effects and the fact that their action on seizures is purely symptomatic and has no impact on the underlying disease. To address these shortcomings, intensive research is ongoing to develop newer treatments with improved effectiveness. This article provides a narrative review of epilepsy treatments currently in clinical development, grouped into three categories (i) novel small-molecule chemical entities; (iii) gene-targeted therapies, including antisense oligonucleotides, vector gene therapies and cell-based therapies; (iii) therapeutic devices. As an indication of ongoing trends in epilepsy drug development, many of these investigational treatments are directed at rare syndromes. Some of these treatments also target the underlying etiology, with the potential to modify the trajectory of the disease and to impact favorably on neurodevelopment and epilepsy comorbidities. For some treatments discussed in this review, promising preliminary efficacy data are already available, offering hope for millions of people with epilepsy who do not adequately respond to currently available therapies.

Objective: Smoking is the second most significant cause of early death and disability worldwide. Considering existing clinical and psychological differences between patients with epilepsy and psychogenic nonepileptic seizures (PNES), it was assumed that these 2 groups of patients vary in their rates of smoking. This retrospective study was based on an electronic dataset of patients with seizures. Methods: All patients aged 20 years or older were surveyed at the outpatient epilepsy clinic of Shiraz University of Medical Sciences in Shiraz, Iran, between 2008 and 2020. Age at seizure onset, sex, and the final diagnosis were entered into the database for all patients. Other collected data included tobacco smoking (including cigarette and water-pipe as the 2 common forms of smoking). Results: A total of 1491 patients were examined. In total, 226 patients (15.2%) reported smoking. Smoking rates were 13.3% in patients with idiopathic generalized epilepsy, 14.3% in those with focal epilepsy, and 21.3% in individuals with PNES (P = .01); a diagnosis of PNES was significantly linked to smoking. Female sex, younger age at the seizure onset, and having a college education were significantly inversely associated with smoking. Conclusion: The high prevalence rate of smoking among patients with functional seizures is notable. It would be helpful to do a qualitative study on patients with functional seizures to understand why they are smoking. This can help us to understand the actual reasons behind the high prevalence rate of smoking in this population. Cite this article as: Pooya AAA, Farazdaghi M, Damabi NM, Pooya AA, Akbari N, Rezaei A. Prevalence of smoking in patients with seizures: epilepsy vs. psychogenic nonepileptic seizures. Neuropsychiatr Invest. 2026, 64, 0072, doi: 10.5152/ NI.2026.25072.

BACKGROUND AND OBJECTIVES:More than half of people undergoing epilepsy surgery become seizure-free and may consider withdrawing antiseizure medications (ASMs). Withdrawal practices vary, and the optimal timing remains unclear. We aim to compare seizure relapse risk among individuals initiating ASM withdrawal at different time points after epilepsy surgery. METHODS:We conducted a multicenter observational cohort study of adults who underwent resective epilepsy surgery between 1990 and 2016 at 12 tertiary centers. Participants were seizure-free before medication withdrawal and had at least 1 year of follow-up. Seizure relapse risk was compared among those initiating withdrawal 1, 2, 3, 4, or 5 years postoperatively vs later. We used propensity score matching for each comparison to adjust for treatment selection bias. RESULTS:Of the 964 people included (51% female; median age at surgery 34 years [interquartile range 26-44]), 446 (46%) began ASM withdrawal in the first year after surgery, 255 (26%) in the second, 110 (11%) in the third, 58 (6%) in the fourth, 29 (3%) in the fifth, and 66 (7%) after the fifth year. After matching, those starting withdrawal in the first (hazard ratio [HR] 1.4; p = 0.003) or second (HR 1.18; p < 0.001) year had a higher risk of relapse than those who withdrew later. Starting withdrawal in the third (HR 1.7; p = 0.12), fourth (HR 1.3; p = 0.45), or fifth (HR 0.17; p = 0.82) year after surgery showed no increase in risk compared with later withdrawal. Long-term outcomes, such as seizure freedom and being entirely off ASMs at the final follow-up, were not substantially associated with withdrawal timing. DISCUSSION:Initiating ASM withdrawal within the first 2 postoperative years was linked to a higher initial risk of seizure relapse compared with later withdrawal, although long-term outcomes were similar regardless of withdrawal timing. Waiting more than 2 years did not confer additional benefit in reducing seizure risk. Deciding whether and when to withdraw ASMs is a shared process involving individuals, caregivers, and clinicians, balancing preferences, risk of injury, social factors (e.g., driving, work, and supervision), and clinical judgment. Transparent information on risks and benefits is essential. Our findings offer real-world evidence that may inform future evidence-based withdrawal protocols and follow-up strategies.

The International League Against Epilepsy (ILAE) Academy is the world's eminent e-learning campus for epileptology. Its modular teaching content was developed to cover all competencies and learning objectives specified in the ILAE's curriculum for epileptology. The tutorless and self-paced entry Level 1 program for beginners offers an interactive case-based e-learning approach. A blended e-learning format was developed for the proficiency Level 2 with various learning domains and formats. They comprise a series of interactive, self-paced and case-based e-learning modules covering common, but also rare or complex epilepsy conditions, through state-of-the-art diagnosis and rational treatment decisions. Interactive EEG and MRI readers were integrated to support a tutorless online teaching format. An innovative adaptive e-learning format was applied for specific learning domains to reflect not only the proficiency level of the learner but also their self-confidence and perceived and unperceived knowledge of the topic. Our analysis of the completed adaptive e-learning courses revealed that 21% of the learning objectives had been answered incorrectly despite the learner indicating that they know the answer. This so-called "unconscious incompetence" should be regarded as a key motivation for building continuing medical education (CME) programs in epileptology. Level 2 utilizes a blended learning approach requiring 200 CME or equivalent ILAE credit points, earned through a mix of online learning with in-person participation in ILAE schools and congressional teaching activities. Level 3 is the subsequent step in the ILAE's structured learning path towards advanced proficiency and includes skill-based training in epileptology. Registered learners can apply for training visits in internationally renowned epilepsy centers around the world. Limited financial support is made available for selected applicants, e.g., to support candidates from resource limited settings. Designed to bridge the gap in knowledge and access to continuing education in epileptology, this unique structured learning path is open to all healthcare professionals.

Background: As a debilitating and severe repercussion, the clinical and economic impact of Status epilepticus (SE) has not been thoroughly explored in various regions around the world, especially those with limited resources. Therefore, we aimed to identify the predictors of mortality and healthcare costs associated with SE in one tertiary care center with limited resources. Methods: This retrospective single-center cohort study, carried out at Namazi Hospital, Shiraz, Iran, included 130 SE cases from March 21, 2021, to March 20, 2022. Patient data were extracted from medical records, including demographics, clinical presentations, hospital course, treatment modalities, and costs. Multivariable regression models were used to identify factors associated with mortality and hospital stay costs. Results: Patients were aged 1 month to 92 years (mean 20.36 years, median 7), with a male predominance of 59.23 %. Pre-existing epilepsy was found to be associated with lower mortality (p < 0.05), while cardiovascular complications (p < 0.05) and cerebrovascular disease (p < 0.001) were significantly associated with increased mortality risks. In addition, Intensive Care Unit (ICU) admission, necessitated by complex treatment regimens, was linked to significantly higher healthcare costs (p < 0.001). Older age and the use of sedatives were also associated with higher costs, while psychiatric disorders were linked to lower costs. Conclusion: SE imposes a substantial clinical and economic burden in resource-limited settings, as limited availability of ICU beds is common. Thus, screening SE cases based on clinical characteristics (e.g., comorbidities) is paramount. Therefore, targeted strategies are essential for optimizing care and reducing costs.

BackgroundThe apolipoprotein E (APOE) gene, encompassing three alleles (ε2, ε3, ε4), is a critical player in lipid metabolism and has been extensively studied for its role in neurodegenerative diseases. This study examines APOE genetic variability and its association with PD in an Egyptian cohort.MethodsA total of 891 participants, including 422 PD patients and 469 healthy controls, were included in this study. APOE genotyping was performed using Kompetitive Allele Specific PCR (KASP) to detect the rs429358 and rs7412 SNPs, which define the APOE alleles. APOE alleles were categorized based on the genotypes into ε2, ε3, and ε4 groups. Clinical assessments of PD patients included age at onset, disease severity (MDS-UPDRS), and demographic factors. Statistical analyses compared APOE distributions between PD and control groups and examined associations with clinical variables.ResultsThe ε3 allele was the most prevalent in the cohort (77.3%), aligning with global and African trends. The ε2 allele was observed in 11.4%, and the ε4 allele in 11.3%, with both frequencies being lower than reported African estimates. The ε3/ε3 genotype was predominant in both PD patients (72.51%) and controls (72.07%). The ε4/ε4 genotype was absent in PD cases and rare among controls (0.64%). No significant association was found between APOE genotypes and PD risk, age at onset, or disease severity.ConclusionOur findings do not support a significant role for APOE in PD susceptibility or severity in Egyptians.

BACKGROUND:Essential tremor (ET) is associated with various of non-motor symptoms including hearing impairment and imbalance attributed to the neurodegenerative ET pathology affecting brainstem structures. OBJECTIVE:This study aimed to assess auditory and vestibular brainstem functions in patients with ET in comparison to controls using auditory brainstem responses (ABR) and cervical and ocular vestibular-evoked myogenic potentials (cVEMP and oVEMP), and to correlate their dysfunction to disease characteristics. METHODS:24 patients (48 ears) with ET and 24 healthy controls were recruited and assessed by ABR, cVEMP and oVEMP. Patients were assessed by Fahn-Tolosa-Marin Tremor Rating Scale (FTM-TRS) and functional gait assessment scale. RESULTS:High-rate ABR showed significant increase of waves III and V latencies and I-V interpeak latencies among patients, compared to age and gender matched controls. Low-rate ABR showed less significant differences; right, I-III and I-V interpeak latencies, and average I-III interlatences. ET patients showed prolonged latencies of P1 and N1 waves of cVEMP (P = 0.007 and P = 0.003), average P1-N1 latency and amplitude differences (P < 0.001) and P1 latency of oVEMP (P = 0.009), compared to controls, with more differences in cVEMP than in oVEMP. Age, age of onset, disease duration showed correlations with ABR responses, tremor severity correlated with oVEMP, while functional gait scores correlated with both. CONCLUSION:The study confirmed and localized the dysfunction of the auditory and vestibular brainstem connections in ET and demonstrated a possible correlation with tremor severity and associated gait dysfunction.

BACKGROUND:Functional movement disorder (FMD) is a neuropsychiatric condition characterized by involuntary motor symptoms that are inconsistent with known neurological diseases and linked to dysfunction in brain networks involved in motor control, emotion regulation, attention, and agency. OBJECTIVE:To provide an updated and integrative review of the clinical, neurobiological, and therapeutic dimensions of FMD, incorporating recent evidence across diagnostic and treatment modalities. METHODS:We conducted a comprehensive review of the leading studies on FMD, emphasizing the most common clinical presentations: functional tremor, dystonia, myoclonus, parkinsonism, gait disorder, and tics. Drawing on recent evidence, we examined recovery-associated factors and integrated these insights into a structured diagnostic and therapeutic algorithm. RESULTS:FMD primarily affects women and typically presents with tremor, weakness, or mixed motor symptoms. Phenotypic heterogeneity is common; non-motor symptoms such as pain, fatigue, and psychiatric comorbidities contribute to clinical complexity. Neuroimaging and electrophysiological studies reveal salience, interoception, and motor network disruptions, often involving the amygdala, sensorimotor cortex, and temporoparietal junction. Diagnosis relies on positive clinical signs rather than exclusion. A five-phase diagnostic framework is recommended, including neurological examination, patient-centred communication, and multidisciplinary engagement. Treatment requires an individualized approach combining physiotherapy, cognitive behavioral therapy, neuromodulation, pharmacotherapy, and digital tools. Prognosis varies, but early diagnosis, a strong therapeutic alliance, and patient confidence in recovery improve outcomes. CONCLUSIONS:FMD is a multisystem disorder requiring integrated, personalized, and humanized care. Advances in neurobiology and therapeutic modalities offer promise, but unmet needs remain-particularly the development of diagnostic biomarkers, standardized outcome measures, and scalable treatment models.

Background/Objectives: In a patient suspected of having epilepsy, routine EEG primarily contributes to the recording of interictal epileptiform discharges (IEDs). Similarly, magnetic resonance imaging (MRI) has become the gold standard imaging technique for identifying epileptogenic structural brain abnormalities. Various EEG and MRI tools to improve epilepsy diagnosis will be presented. Methods: When the initial EEG fails to record IEDs, various EEG measures that can improve EEG performance are presented; a comprehensive epilepsy-targeted MRI protocol to identify, localize, and characterize an epileptogenic lesion will also be described. Results: Studies show that the initial routine EEG fails to record IEDs in approximately 47–50% of epileptic patients. To improve the yield of EEG, subsequent EEG recording should include sleep deprivation, sleep recording, prolonged hyperventilation, optimized light stimulation, addition of an inferior temporal electrode chain, extended EEG duration, and continuous video-EEG monitoring, all measures known to activate IEDs. Furthermore, MRI is interpreted as “normal” in many epilepsy patients, even when performed according to an epilepsy-specific protocol and evaluated by a specialized MRI reader. In such case, the use of the Harmonized Epilepsy Structural Sequence Imaging (HARNESS-MRI) protocol and other imaging tools will improve the detection of potential epileptic lesions, as described in this study. Conclusions: In a patient with a clinical diagnosis of epilepsy but a normal EEG and brain MRI, several options can improve the performance of subsequent EEG and MRI examinations, the subjects of this review.

BACKGROUND:Deep brain stimulation (DBS) has proven efficacy in advanced Parkinson's disease (PD) and is the current standard of care for these patients. However, its cost-effectiveness in low- and middle-income settings has not been assessed before. OBJECTIVES:This study aims to assess the cost-effectiveness of DBS compared with best medical therapy (BMT) in advanced PD from a societal perspective in Egypt. METHODS:We developed a Markov model with a 15-year time horizon and annual cycles to compare DBS with BMT. The cohort was aged 55-years-old at model entry and transitioned between three states: DBS, BMT, or death. Effectiveness was measured by improvement in the Unified Parkinson's Disease Rating Scale (UPDRS) and reduction in drug doses. The main outcome was quality-adjusted life years (QALYs) mapped from the UPDRS scores. The model included medical, informal care, and indirect costs. Both costs and utilities were discounted at an annual rate of 3.5%. RESULTS:DBS had yielded an increase of 1.4 QALYs per patient at an additional cost of 1,159,150 Egyptian pounds (EGP)/patient ($25,566). This results in an incremental cost-effectiveness ratio (ICER) of 830,726 EGP/QALY ($18,322/QALY). Patients with DBS have lower costs for medications, hospitalizations, informal care, and productivity loss. The main cost driver in the DBS arm is the device and implantation procedure costs, which accounted for 70% of total costs. The model was most sensitive to informal care costs. CONCLUSIONS:DBS markedly improves the quality of life for advanced patients with PD and reduces informal care and indirect costs. However, at its current price, the ICER exceeds the Egyptian cost-effectiveness threshold.

BACKGROUND:Overcoming existing access barriers is crucial for better-specialized health care of patients with Parkinson's disease (PD). OBJECTIVE:The aim of the study was to compare the access and visit quality/acceptability between in-office and virtual telemedicine visits. METHODS:This was an international, randomized, case-control, prospective, observational study. Patients were randomly assigned either to the control group (in-person/in-office visits at baseline, 3, 6, 9, and 12 months) or to the study group (in-office visits at baseline, 6, and 12 months, and telemedicine visits at 3 and 9 months). Telemedicine visits were conducted using videoconferencing apps that were readily accessible to the patient/caregivers. Outcomes were feasibility, usability, and the noninferiority of telemedicine compared to in-office visits in PD patients regarding clinical progression and initiation of pharmacological/nonpharmacological treatments over 1-year follow-up. RESULTS:We included 209 PD patients from 6 countries (Nigeria, Spain, Saudi Arabia, South Korea, Egypt, and Uruguay), mean age 64.9 ± 12.2 years, 59% males, median Hoehn & Yahr stage 2 (1-4). Overall, disease progression (MDS-Unified PD rating scale), quality of life (PD-Quality of life 39-items) scores, and therapeutic changes were similar in both groups. After 1 year, 124 patients 48.3%, (control group) and 52.1% (study group) completed the visits (P = 0.52), with a similar high rate of patient's satisfaction with the visits (P = 0.57). CONCLUSIONS:This study represents real-world telemedicine practice in different world regions using a telemedicine approach complementary to in-person visits. Based on these results, feasibility, clinical management, PD disease progression, and patient's quality of life are similar when using telemedicine versus in-office visits. Future research should explore ways to integrate different healthcare technologies for long-term PD management.

Gut microbiome alterations are increasingly linked to Parkinson's disease (PD), yet regional signatures remain underexplored. We performed shotgun metagenomic sequencing of stool samples from Egyptian PD patients and healthy controls. PD patients exhibited depletion of short-chain fatty acid-producing taxa, and enrichment of pathobionts. Our findings suggested a pro-inflammatory gut shift in PD and emphasized the need for geographically diverse microbiome studies. While limited in sample size (n = 7 PD patients and n = 6 controls), this pilot addressed a critical gap in African PD microbiome research.

INTRODUCTION:Adolescents with chronic conditions such as epilepsy and diabetes frequently grapple with significant psychological distress, including depression and anxiety. The neglect of these mental health concerns can have severe repercussions, including substance abuse. This study aimed to compare the prevalence of substance use, depression, and anxiety among Adolescents with Epilepsy (AWE) and Diabetic Patients (DP). METHODS:This cross-sectional study included AWE and DP aged 14-18 years referred to Shiraz Namazi Hospital during 2023-2024. Participants were diagnosed by pediatric neurologists and pediatric endocrinologists, respectively, adhering to established diagnostic criteria. Urine toxicology screens were conducted to detect substance use. Additionally, self-reported questionnaires, the Adolescent Substance Abuse Questionnaire (ASQ-AV) and the Depression, Anxiety, and Stress Scale-21 (DASS-21), were administered to assess addiction susceptibility and negative emotions, respectively. Data analysis was performed using SPSS version 26. RESULTS:The study included 143 adolescents, comprising 72 (50.3 %) with epilepsy and 71 (49.7 %) with diabetes. No statistically significant differences were observed between the AWE and DP groups in terms of demographic characteristics (gender, age, and disease duration), the prevalence of depression (76.4 % vs. 73.2 %), anxiety (68.1 % vs. 69.0 %), or substance use (7 % vs. 1.4 %). However, a significantly higher addiction propensity score was found in the AWE group compared to the DP group (p = 0.018). CONCLUSION:The prevalence of anxiety and depression was significant in both AWE and DP groups. Furthermore, the propensity for addiction was significantly higher in AWE, highlighting the need for implementing strategies to prevent the development of addiction in these patients.

OBJECTIVE:Approximately, one-third of patients with epilepsy (PWE) have drug-resistant epilepsy (DRE). This condition significantly impacts quality of life, leads to various negative socioeconomic consequences, and increases the risk of sudden unexpected death in epilepsy (SUDEP). Surgical treatment is considered the most effective option for patients with lesional DRE. However, real-world data suggest that this treatment method remains significantly underutilized. We aimed to assess the awareness and attitudes of PWE in Serbia toward epilepsy surgery (ES). METHODS:This multicenter study included 247 consecutive patients referred to epileptologists at various centers in Serbia between May 2023 and September 2024. Participants voluntarily completed a self-reported questionnaire. The questionnaire had 27 questions, covering socioepidemiological data (six questions), patients' epilepsy and any previous surgery (11 questions), awareness of different modalities of epilepsy treatment and sources of information about them (2 questions), while the last six questions were in the form of hypothetical scenarios, in which patients had to choose whether to accept or refuse ES when faced with different estimated efficacy and risk of ES. RESULTS:Less than half of the participants were familiar with ES. Only 16.6% of the patients expressed willingness to undergo the procedure when presented as a safe and effective therapeutic option. Patients who had not achieved seizure control and those with a history of ictal injuries and hospitalization due to seizures were more motivated to consider ES. The most common reasons for accepting surgery were the potential for freedom from ASMs and improved seizure control. In contrast, the most frequent reasons for rejecting it were a perception of adequate seizure control with ASMs and fear of surgery complications. SIGNIFICANCE:Patients in Serbia are not adequately informed about the surgical treatment options for epilepsy. A multidisciplinary approach, combined with greater media involvement, is essential to raise awareness about this effective treatment option for those with DRE. PLAIN LANGUAGE SUMMARY:This study was conducted in order to understand how much people with epilepsy in Serbia know about epilepsy surgery (ES) and what their attitude is toward it. Fewer than half of the participants were aware of ES, and only a small percentage were willing to consider it, even when it was presented as a safe and effective option. Those who struggled more with their seizures or had experienced serious injuries seemed more open to the idea of surgery. This shows that a significant upgrade in patient education and availability of different sources of information concerning ES is needed in Serbia.

Background A prospective observational study recruited patients with acute stroke. Patients were assessed for the presence of post-stroke movement disorders PSMDs during the first week of stroke. This study aimed to identify the frequency, clinical characteristics, and neuroimaging of early PSMDs (within the first week) and followed for 1 year. Results A total of 600 patients were recruited; 21 patients (3.5%) with PSMDs were detected. Thirteen (2.2%) patients presented with intention tremor/ataxia and eight (1.3%) presented with other movement disorders (most commonly, chorea and tremor). One patient presented with periodic left upper limb shaking with right subcortical watershed infarction, and one patient developed palatal myoclonus with right middle cerebral artery infarction. Patients with PSMDs had significantly lower stroke severity (NIHSS) and were more likely to have lacunar strokes (p < 0.001 and < 0.006, respectively) than patients without PSMDs. Early PSMDs were more associated with posterior circulation strokes (84.25%). Conclusions Early PSMDs are commonly hyperkinetic, more associated with small vessel disease, and less severe and posterior circulation strokes, implying their clinical importance for the proper management of stroke patients.

BackgroundVascular parkinsonism (VaP) is a subtype of parkinsonism which needs better characterization of its risks and determinants.ObjectiveThe aim of this report is to present an understanding of genetic risks of vascular parkinsonism.MethodsFive participants diagnosed with VaP were recruited and Whole Exome Sequencing (WES) was performed to analyze deleterious variants in relevant genes associated with vascular and parkinsonian diseases.ResultsWe identified several candidate risk variants for VaP in our patients, particularly in LRRK2, PLA2G6, TGM6, BSN, UBR4, CD36 and NOTCH3, that are different from the classical Parkinson’s disease -associated variants.ConclusionIn this case series we highlighted the complexity of genetic contributions to VaP through predicted deleterious variants in genes associated with parkinsonism, cerebrovascular disease as well as collagen-related genes.

OBJECTIVE:The glymphatic system is a critical brain waste-clearance mechanism that facilitates the removal of metabolic byproducts and maintains neural homeostasis. Its dysfunction has been implicated in various neurological disorders; however, its role in functional (psychogenic nonepileptic) seizures (FS/PNES), a functional neurological condition, remains unexplored. This study aimed to indirectly evaluate glymphatic system function using the along the perivascular space (ALPS) index derived from diffusion tensor imaging (DTI) in patients with FS/PNES compared to healthy controls (HCs). METHODS:Twenty-one patients with PNES and 21 HCs underwent DTI scans. Glymphatic system function was assessed using the DTI-ALPS method. The DTI-ALPS index was calculated and analyzed for differences between the groups. Correlations with clinical and cognitive measures, including the Addenbrooke's Cognitive Examination (ACE-III), were investigated. RESULTS:Patients with FS/PNES demonstrated significantly lower DTI-ALPS indices compared to those in HCs in the left hemisphere (1.306 ± 0.171 vs. 1.502 ± 0.224, p = 0.005) and the bilateral hemispheric average (1.262 ± 0.174 vs. 1.415 ± 0.195, p = 0.014). No significant correlations were found between the DTI-ALPS index and clinical, demographic, or cognitive assessments. SIGNIFICANCE:This study identified alterations in the DTI-ALPS index in patients with FS/PNES, particularly in the left hemisphere. This finding indirectly suggests disrupted perivascular fluid dynamics in FS/PNES and highlights the need for further research to elucidate the neurobiological underpinnings of FS/PNES with particular attention to the potential role of the glymphatic system in functional neurological disorders. PLAIN LANGUAGE SUMMARY:The brain has a cleanup system called the glymphatic system, which removes waste to keep it functioning well. In this study, we examined whether this system works differently in people with functional seizures-seizures not caused by epilepsy. We compared brain scans from individuals with functional seizures and healthy controls. The results showed reduced activity in the glymphatic system, especially on the brain's left side, in those with functional seizures. This suggests that their brains may not clear waste as efficiently. Although this finding may point to brain differences in functional seizures, further research is needed to understand the connection.

BACKGROUND:Parkinson's Disease (PD) is frequently associated with a spectrum of sleep-related disorders, including insomnia, Excessive Daytime Sleepiness (EDS), REM sleep Behaviour Disorder (RBD), Restless Legs Syndrome (RLS), and Sleep-related Breathing Disorders (SBDs). These disorders significantly impact PD patients' Quality of Life (QoL) and present unique diagnostic and therapeutic challenges. METHODS:This review has explored the intricate relationship between PD and sleep-related disorders, emphasizing their distinctive features and underlying neurobiological mechanisms. It aimed to consolidate current knowledge to optimize clinical management and improve patient care. The profound impact of these disorders on QoL has been evaluated, along with precise diagnostic methodologies. Additionally, various therapeutic strategies, including pharmacological treatments, nonpharmacological interventions, and device-aided therapies, have been examined. RESULTS:Sleep-related disorders are prevalent among PD patients. Specifically, RBD exhibits a prevalence of 40-50%, often preceding the onset of motor symptoms, indicating its potential as an early marker of PD. Despite their significant impact on QoL, these non-motor symptoms are frequently under-recognized and inadequately managed in clinical practice. Pharmacological treatments, along with nonpharmacological interventions, like cognitive-behavioral therapy for insomnia and lifestyle modifications, have shown varied efficacy. Device-aided therapies have also demonstrated the potential to improve sleep-related disorders and overall non-motor symptom burden. CONCLUSION:Effective management of sleep-related disorders in PD calls for personalized, comprehensive, and multimodal therapeutic approaches. This requires the collaborative efforts of neurologists, sleep specialists, psychiatrists, and other healthcare professionals. Future research should focus on the intricate relationship between PD and sleep disorders, aiming to develop innovative treatments and significantly improve patient outcomes.

There is no definite biomarker for confirming the diagnosis of essential tremor (ET) or differentiating it from other diseases, particularly Parkinson's disease. The present study aimed to investigate the serum levels of the alpha-synuclein protein (alpha-syn) and its autoantibodies in patients with ET compared with healthy controls and its relation to motor and non-motor symptoms in patients with ET. Serum alpha-syn and its autoantibodies were measured in 32 patients with ET and 32 age- and sex-matched controls. Both groups were assessed using the non-motor symptoms scale, MoCA, Beck Depression Inventory, Hamilton Anxiety Rating Scale, and the Short Form 36 Health Survey Questionnaire. Tremor was assessed using the Fahn-Tolosa-Marin Tremor Rating Scale. The serum alpha-syn concentration in patients with ET was significantly lower than that in healthy controls (P<0.001), with a positive predictive value of 0.81 and a negative predictive value of 0.75, while the serum anti-a-syn autoantibody concentration was not significantly different between the two groups. There were no correlations between serum alpha-syn or its autoantibodies and patients' clinical characteristics. Furthermore, patients with ET had worse cognitive impairment, depression, anxiety, non-motor symptoms and quality of life. The serum alpha-syn concentration was lower in patients with ET than in controls, with favorable predictive values, suggesting that it could serve as a biomarker for ET diagnosis.