Search Results (42)

Background: Paroxysmal dyskinesias (PDs) are rare, episodic movement disorders characterized by sudden and involuntary hyperkinetic motor events. In paediatric populations, their diagnosis is often complicated by clinical overlap with epilepsy and other neurological conditions. Genetic underpinnings have increasingly been recognized as key to understanding phenotypic heterogeneity and guiding treatment. Objectives: This systematic review aims to provide a comprehensive overview of paediatric PD, with a focus on genetic aetiologies, clinical features, subtype classification, and therapeutic approaches, including genotype–treatment correlations. Methods: We systematically reviewed the literature from 2014 to 2025 using PubMed. Inclusion criteria targeted paediatric patients (aged 0–18 years) with documented paroxysmal hyperkinetic movements and genetically confirmed or clinically suggestive PD. Data were extracted regarding demographics, dyskinesia subtypes, age at onset, genetic findings, and treatment efficacy. Gene categories were classified as PD-specific or pleiotropic based on functional and clinical features. Results: We included 112 studies encompassing 605 paediatric patients. The most common subtype was Paroxistic Kinesigenic Dyskinesia (PKD). Male sex was more frequently reported. The mean onset age was 5.99 years. A genetic diagnosis was confirmed in 505 patients (83.5%), involving 38 different genes. Among these, PRRT2 was the most frequently implicated gene, followed by SLC2A1 and ADCY5. Chromosomal abnormalities affecting the 16p11.2 region were identified in ten patients, including deletions and duplications. Among the 504 patients with confirmed monogenic variants, 390 (77.4%) had mutations in PD-specific genes, while 122 (24.2%) carried pleiotropic variants. Antiseizure drugs—particularly sodium channel blockers such as carbamazepine and oxcarbazepine—were the most frequently reported treatment, with complete efficacy documented in 59.7% of the studies describing their use. Conclusions: Paediatric PDs exhibit significant clinical and genetic heterogeneity. While PRRT2 remains the most common genetic aetiology, emerging pleiotropic genes highlight the need for comprehensive diagnostic strategies. Sodium channel blockers are effective in a subset of genetically defined PD, particularly PRRT2-positive cases. Patients with pathogenic variants in other genes, such as ADCY5 and SLC2A1, may benefit from specific therapies that can potentially change their clinical course and prognosis. These findings support genotype-driven management approaches and underscore the importance of genetic testing in paediatric movement disorders. Full article

Rare genetic movement disorders usually manifest early in life with dystonia, parkinsonism, chorea, or a combination thereof. These are often associated with neurodevelopmental delay, intellectual disability, speech problems, retinal abnormalities, seizures, ataxia, spasticity, or systemic features. Due to their vast number and pheno–genotypic heterogeneity, the diagnosis of these disorders can be challenging. However, recognising their core motor phenomenology as well as clinical, laboratory, and neuroradiological clues can expedite appropriate diagnostic workup, molecular diagnosis, and adequate treatment. In this review, we outline diagnostic clues to rare movement disorders (RMDs), focusing on those that present mainly with dystonia, parkinsonism, or paroxysmal dyskinesia due to genetic causes. Additionally, we provide a decision tree approach linking clinical, genetic, and imaging testing. Finally, we highlight selected RMDs that should not be missed, as they possess established treatments that can hinder their progression, prevent irreversible or life-threatening sequelae and, in certain cases, lead to complete symptom remission. Full article

Endothelial dysfunction (ED) promotes and maintains atrial fibrillation (AF). Using a CHA2DS2-VASc score in women and men with paroxysmal AF, we aimed to determine which patients’ ED would be more pronounced. We recruited 47 females and 48 males (mean BMI 31 kg/m² and 30 kg/m², respectively) with paroxysmal AF and abnormal body mass and divided them into those with low (F < 3; M < 2) and high (F ≥ 3; M ≥ 2) CHA2DS2-VASC score. The blood samples were taken before AF ablation. Using Elisa tests, we measured tissue plasminogen activator (t-PA), plasminogen activator inhibitor 1 (PAI-1), vascular cell adhesion molecule 1 (sVCAM-1), intercellular adhesion molecule (sICAM-1), von Willebrand factor (vWF), and thrombomodulin (sTM). ED was more pronounced in females, expressed by higher endothelial cell marker concentrations: sVCAM-1 and sTM in low scores and sICAM-1 in high scores, CHA2DS2-VASc. Females were characterized by postmenopausal status, higher risk of thrombosis, lower GFR, and more frequent treatment with antiarrhythmic drugs. In contrast, males have only higher suppression of tumorigenicity 2 (ST2). In conclusion, women with paroxysmal AF exhibited more pronounced ED compared to men, regardless of their CHA2DS2-VASc scores. The soluble pro-inflammatory adhesion molecules and thrombomodulin emerge as the most sensitive biomarkers of ED elevated in females. Full article

Background and Clinical Significance: Sandifer syndrome is an uncommon manifestation of gastroesophageal reflux disease, characterized by paroxysmal episodes of abnormal posturing, particularly involving the neck and upper body, often associated with underlying esophageal discomfort. Case Presentation: In this report, we present a 16-month-old infant who exhibited multiple daily paroxysmal episodes of atypical head posturing, primarily tilted to the right, each lasting less than 10 s, with spontaneous resolution. Notably, these episodes lacked other neurological or systemic symptoms, and the clinical presentation differed from classical descriptions of Sandifer syndrome, which often include more prolonged dystonic posturing or correlation with feeding. The diagnosis was supported by the resolution of symptoms following the administration of a proton pump inhibitor, highlighting the importance of recognizing this condition in infants with unexplained posturing behaviors. Conclusions: This case emphasizes the variability in clinical manifestations of Sandifer syndrome and underscores the need for a high index of suspicion, as timely management of gastroesophageal reflux disease can lead to complete symptom resolution and prevent unnecessary neurological investigations. Full article

Introduction: This edition of the Audiology Research journal is dedicated to Dr. John Epley. For this reason, we would like to present a very unusual case involving the development of a bilateral abnormality of the otolith organs. The otoliths are the structures from which calcium particles detach to induce benign paroxysmal positional vertigo, the disorder for which Dr. Epley is famous for managing. Case report: This case report outlines an unusual presentation of vestibular pathology involving the otoliths. Discussion: We suggest that the atypical presentation may be related to a bilaterally asymmetrical insult to the otoliths. Conclusions: The central insult suffered by this patient resulted in bilateral peripheral otolithic pathology. Full article

Background/Objectives: Functional seizures (FSs) are paroxysmal, time-limited events with motor, sensory, autonomic, or cognitive manifestations related to pathophysiological processes other than abnormal electric discharges in the brain. However, these seizures are often followed by different psychiatric comorbidities. Their impact on the overall quality of life and the cofounding factors, especially the ones that can be treated, were the main investigation aims of this study. Methods: This study comprised 76 patients who were diagnosed with FSs. This study included patients who were diagnosed with FSs via video-EEG telemetry. We used the “Likert scale” from the QOLIE 31 questionnaire to evaluate patients’ subjective perception of their quality of life. We researched the association of various clinical factors with the subjective QoL score. Results: A statistically significant marginal association was shown for seven variables, four of them with a positive association (subjective perception of disease severity, belief in treatments’ positive effects, functional seizure cessation, and not being afraid of next seizure) and three of them with a negative association (age at FS onset, depression symptoms, and current age of life). After Bonferroni correction for multiple testing only symptoms of depression stayed statistically significantly associated with outcome. Multivariable logistic regression following variable selection identified that six variables (age at FS onset, absence of psychiatric testing, perceiving oneself as mentally changed due to the disease, seizure severity, depressive symptoms, and fear of therapy side effects) were statistically significantly negatively associated with the outcome. Conclusions: It seems that patients who have FSs coexisting with depressive symptoms and also those with worse disease perception have less chances to be satisfied with their overall quality of life. Full article

Background and Objectives: This study reviews the current literature on ocular movements, specifically focusing on nystagmus associated with peripheral vestibular disorders, to enhance diagnostic accuracy. The evaluation of ocular movements, particularly nystagmus, provides essential insights into the function and dysfunction of the vestibular system, helping clinicians distinguish between peripheral and central causes of vertigo and imbalance. Materials and Methods: A comprehensive search of PubMed was conducted using key terms such as “ocular movements”, “nystagmus”, “vestibular nystagmus”, and “peripheral vestibular disorders”. Results: The search yielded 2739 titles, and after a rigorous selection process, 52 articles were reviewed in full. Discussion: The review highlights different classifications and types of nystagmus, including physiological and pathological forms, and their diagnostic relevance in vestibular disorders such as benign paroxysmal positional vertigo (BPPV), vestibular neuritis, and Meniere’s disease. Diagnostic techniques like video/electro-oculography are emphasized for their role in assessing vestibular function and identifying abnormalities. The study underscores the importance of detailed ocular examination in the diagnosis of peripheral vestibular disorders and proposes an algorithm to aid this process. Conclusions: While not a systematic review, this study highlights the importance of detailed ocular examination in diagnosing peripheral vestibular disorders and presents an algorithm to facilitate this process. It also emphasizes the need for continued research and advancements in vestibular medicine to further understand ocular movements and their clinical significance, ultimately contributing to improved patient outcomes. Full article

Mitochondrial fission and fusion are vital dynamic processes for mitochondrial quality control and for the maintenance of cellular respiration; they also play an important role in the formation and maintenance of cells with high energy demand including cardiomyocytes and neurons. The DNM1L (dynamin-1 like) gene encodes for the DRP1 protein, an evolutionary conserved member of the dynamin family that is responsible for the fission of mitochondria; it is ubiquitous but highly expressed in the developing neonatal heart. De novo heterozygous pathogenic variants in the DNM1L gene have been previously reported to be associated with neonatal or infantile-onset encephalopathy characterized by hypotonia, developmental delay and refractory epilepsy. However, cardiac involvement has been previously reported only in one case. Next-Generation Sequencing (NGS) was used to genetically assess a baby girl characterized by developmental delay with spastic–dystonic, tetraparesis and hypertrophic cardiomyopathy of the left ventricle. Histochemical analysis and spectrophotometric determination of electron transport chain were performed to characterize the muscle biopsy; moreover, the morphology of mitochondria and peroxisomes was evaluated in cultured fibroblasts as well. Herein, we expand the phenotype of DNM1L-related disorder, describing the case of a girl with a heterozygous mutation in DNM1L and affected by progressive infantile encephalopathy, with cardiomyopathy and fatal paroxysmal vomiting correlated with bulbar transitory abnormal T2 hyperintensities and diffusion-weighted imaging (DWI) restriction areas, but without epilepsy. In patients with DNM1L mutations, careful evaluation for cardiac involvement is recommended. Full article

In patients with atrial fibrillation (AF) recurrences after pulmonary vein isolation (PVI), concomitant treatment using anti arrhythmic drugs (AADs) can lead to clinical success. However, patients with atrioventricular (AV) block may not be good candidates for concomitant AAD therapy due to the risk of further worsening of conduction abnormalities. Cardioneuroablation (CNA), as an adjunct to PVI, may offer a solution to this problem. We present a case of a 74-year-old male with paroxysmal AF and first degree AV block in whom CNA following PVI led to PR normalization. The presented case describes an example of CNA utilization in patients with AF undergoing PVI who have concomitant problems with AV conduction and shows that CNA can be sometimes useful in older patients with functional AV block. Full article

Background: Primary Stabbing Headache (PSH) is characterized by brief, focal, and paroxysmal pain (“stab”), occurring sporadically or in clusters. Data on pediatric cases are poor. Methods: We performed a comprehensive literature review by searching PubMed, Cochrane, and Embase in order to collect pediatric case reports and case series of PSH. Results: A total of 12 out of 162 articles assessed for eligibility were finally included. The prevalence of PSH and probable PSH varies from 2.5 to 10% among children with primary headaches and it is higher among children aged less than 6 years old. The mean age of onset is between 7 and 11 years of age. Attack duration greatly varies, ranging from a few seconds to several minutes. The intensity of pain is usually from moderate to severe. Associated symptoms are infrequent but may be observed (mainly photophobia, vertigo, nausea, and vomiting). Neuroradiological findings are usually unremarkable; EEG may show sporadic epileptiform abnormalities (up to 30% of cases). Preventive therapy is anecdotal, including treatment with indomethacin, trazodone, valproate, and amitriptyline. Conclusion: PSH is a common but still underdiagnosed entity among children with primary headaches; further and larger cohort studies are needed to better assess, in particular, prognosis and response to therapy. Full article

In the context of childhood epilepsy, the concept of continuous spike–waves during slow sleep (CSWS) includes several childhood-onset heterogeneous conditions that share electroencephalograms (EEGs) characterized by a high frequency of paroxysmal abnormalities during sleep, which have negative effects on the cognitive development and behavior of the child. These negative effects may have the characteristics of a clear regression or of a slowdown in development. Seizures are very often present, but not constantly. The above makes it clear why CSWS have been included in epileptic encephalopathies, in which, by definition, frequent EEG paroxysmal abnormalities have an unfavorable impact on cognitive functions, including socio-communicative skills, causing autistic features, even regardless of the presence of clinically overt seizures. Although several decades have passed since the original descriptions of the electroclinical condition of CSWS, there are still many areas that are little-known and deserve to be further studied, including the EEG diagnostic criteria, the most effective electrophysiological parameter for monitoring the role of the thalamus in CSWS pathogenesis, its long-term evolution, the nosographic location of Landau–Kleffner syndrome, standardized neuropsychological and behavioral assessments, and pharmacological and non-pharmacological therapies. Full article

Objective: Several studies have investigated the efficacy of VEMP (vestibular evoked myogenic potential) in patients with vestibular disorders and BPPV (benign paroxysmal positional vertigo). However, previous data were inconclusive. The aim of this study was to investigate the difference in latency, amplitude P1-N1, asymmetry ratio (AR), and cervical/ocular-VEMP values between BPPV patients and healthy controls. Methods: 125 healthy subjects and 42 BPPV patients were prospectively enrolled in the study. In both groups, c/oVEMP tests with 500 Hz tone-burst stimuli were performed. Latencies P1, N1 peaks, and corrected amplitudes (CA) were measured, and AR was calculated. Results: in the BPPV group, 14.29% of patients lacked oVEMPs that recovered after therapy. N1 latencies were significantly elongated, and 50% of patients had pathological AR; this value normalized at follow-up sessions. In addition, there was a reduction in CA in the pathologic ear compared to healthy ears (p = 0.04) and compared to healthy controls (p = 0.01). For cVEMP, a significant reduction in latency-P1 was observed in BPPV patients compared to controls; no significant differences were observed for P1, N1, and CA values between the two ears. The cVEMPs were absent in 14.29% of BPPV patients (AR > 35) that recovered after therapy. Conclusion: We identified several abnormal c/oVemp values in BPPV patients compared with healthy controls, with most changes in values occurring in oVEMPs, suggesting that utricular dysfunction may be more common than saccular. In addition, patients with oVEMP alteration showed later clinical recovery, suggesting a possible prognostic role of the test. Full article

The abnormal neural control of atria has been considered one of the mechanisms of paroxysmal atrial fibrillation (PAF) pathogenesis. The baroreceptor reflex has an important role in cardiovascular regulation and may serve as an index of autonomic function. This study aimed to analyze the baroreceptor reflex’s role in heart rate regulation during upright tilt (HUT) in patients with lone PAF. The study included 68 patients with lone PAF and 34 healthy individuals who underwent baroreflex assessment. Parameters such as baroreflex sensitivity (BRS), number of systolic blood pressure (BP) ramps, and the baroreflex effectiveness index (BEI) were evaluated. The study found that PAF patients had comparable resting BPs and heart rates (HRs) to healthy individuals. However, unlike healthy individuals, PAF patients showed a sustained increase in BP with an upright posture followed by the delayed activation of the baroreceptor function with a blunted HR response and lower BEI values. This indicates a pronounced baroreflex impairment in PAF patients, even at rest. Our data suggest that together with BRS, BEI could be used as a marker of autonomic dysfunction in PAF patients, making it important to further investigate its relationship with AF recurrence after ablation and its involvement in cardiovascular autonomic remodeling. Full article

Background: Self-limited epilepsy with autonomic seizures (SeLEAS), formerly known as Panayiotopoulos syndrome (PS), is a common multifocal autonomic childhood epileptic syndrome. SeLEAS affects 6% of children in between the ages of 1 and 15 years who have had one or more afebrile seizures in their lifetime. Case: A 5-year-old girl was admitted to the paediatric emergency room (ER) of our hospital due to a reported episode of vomiting during her sleep, followed by central cyanosis perorally of sort duration (<5′), a right turn of her head, and gaze fixation with right eye deviation. She was dismissed after a one-day hospitalization free of symptoms. A month later, the patient was admitted to the paediatric ER of a tertiary health unit due to a similar episode. The patient underwent EEG, which revealed pathologic paroxysmal abnormalities of high-amplitude sharp waves and spike-wave complexes in temporal-occipital areas of the left hemisphere, followed by enhancement of focal abnormalities in temporal-occipital areas of the left hemisphere during sleep. The patient was diagnosed with SeLEAS and started levetiracetam. Conclusions: SeLEAS can be easily misdiagnosed as many physicians may not be very familiar with this disease, and, on the other hand, the autonomic manifestations can be easily disregarded as seizures. The physician must always be alert and search beneath the symptoms to find the cause rather than only treat them. Full article

Abnormal depolarization of neuronal membranes called paroxysmal depolarization shift (PDS) represents a cellular correlate of interictal spikes. The mechanisms underlying the generation of PDSs or PDS clusters remain obscure. This study aimed to investigate the role of ionotropic glutamate receptors (iGluRs) in the generation of PDS and dependence of the PDS pattern on neuronal membrane potential. We have shown that significant depolarization or hyperpolarization (by more than ±50 mV) of a single neuron does not change the number of individual PDSs in the cluster, indicating the involvement of an external stimulus in PDS induction. Based on this data, we have suggested reliable protocols for stimulating single PDS or PDS clusters. Furthermore, we have found that AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptors are necessary for PDS generation since AMPAR antagonist NBQX completely suppresses bicuculline-induced paroxysmal activity. In turn, antagonists of NMDA (N-methyl-D-aspartate) and kainate receptors (D-AP5 and UBP310, respectively) caused a decrease in the amplitude of the first action potential in PDSs and in the amplitude of the oscillations of intracellular Ca²⁺ concentration occurring alongside the PDS cluster generation. The effects of the NMDAR (NMDA receptor) and KAR (kainate receptor) antagonists indicate that these receptors are involved only in the modulation of paroxysmal activity. We have also shown that agonists of some G_i-coupled receptors, such as A₁ adenosine (A₁Rs) or cannabinoid receptors (CBRs) (N₆-cyclohexyladenosine and WIN 55,212-2, respectively), completely suppressed PDS generation, while the A₁R agonist even prevented it. We hypothesized that the dynamics of extracellular glutamate concentration govern paroxysmal activity. Fine-tuning of neuronal activity via action on G_i-coupled receptors or iGluRs paves the way for the development of new approaches for epilepsy pharmacotherapy. Full article