搜索结果：Neuropediatrics

Two accelerated magnetic resonance imaging (MRI) protocols for pediatric brain imaging, GOBrain and Deep Resolve Swift Brain, developed by Siemens Healthineers (Erlangen, Germany), were evaluated in a series of clinically relevant pediatric cases at 3 Tesla. Pediatric patients are particularly prone to motion, may be uncooperative, and often require sedation, especially in emergency settings. Consequently, there is a persistent clinical demand for fast brain MRI protocols that provide diagnostically sufficient image quality while minimizing examination time. Contemporary turbo spin-echo (TSE)-based clinical protocols commonly integrate parallel imaging (PI) and simultaneous multi-slice (SMS) techniques to achieve substantial reductions in scan time. Recent advances in three-dimensional volumetric encoding, compressed sensing, and deep learning (DL)-based reconstruction have further mitigated geometry-factor-related noise amplification, enabling higher acceleration factors (GOBrain). In parallel, echo-planar imaging (EPI) has emerged as a promising approach for ultrafast multi-contrast imaging. To overcome the limitations of single-shot EPI, a multi-shot EPI-based brain MRI protocol combined with the DL-based reconstruction method Deep Resolve Swift Brain has been developed. This approach leverages the efficiency of EPI while improving image quality. Using these accelerated protocols, a comprehensive diagnostic multi-contrast brain MRI examination, particularly suited to triage and emergency imaging, can be completed in minutes. This case overview, including therapy-related leukencephalopathy in acute lymphoblastic leukemia (ALL), a brain abscess, traumatic diffuse axonal injury (DAI), a posterior circulation infarction due to vertebral artery dissection, leuokostasis syndrome, and a posterior fossa tumor with obstructive hydrocephalus, demonstrates the potential clinical feasibility of both protocols in pediatric neuroimaging. Both protocols position them as supplementary options alongside established imaging protocols, while dedicated high-resolution protocols might remain necessary for subtle pathological findings, such as focal cortical dysplasia, and for neuronavigation until larger comparative studies are available.

Leigh syndrome (Leigh) is an untreatable mitochondrial disorder characterized by lactic acidosis and basal ganglia and midbrain pathology, leading to psychomotor regression and early death. We previously uncovered impaired neuronal morphogenesis in Leigh cerebral organoids carrying SURF1 gene variants. Leveraging this phenotype, we here develop a deep learning algorithm tailored for cell type-specific drug repurposing screening. In parallel, we perform a survival drug screen in a yeast model of Leigh. The two approaches independently converge on azole compounds, two of which - talarozole and sertaconazole - rescue neuronal morphogenesis in Leigh neurons and lower lactate release and improve growth rate in Leigh midbrain organoids. Mechanistically, these compounds modulate the retinoic acid pathway and membrane-associate lipid metabolism. The findings highlight azoles as promising candidates for Leigh and demonstrate the potential of combining in silico screens with human brain organoids as new approach methodologies (NAMs) to advance the discovery of therapeutics addressing rare neurodevelopmental disorders.

Magnetic resonance imaging (MRI) is the imaging of choice to diagnose brain injury and prognosticate long-term neurodevelopmental outcomes in infants with hypoxic-ischemic encephalopathy (HIE). Independent scoring from Neuroradiology and Neonatology fellows was obtained for 97 brain MRIs for HIE after teaching. Analysis for reliability was compared against a gold standard of an experienced Neuroradiologist. There was good (intraclass correlation coefficient: 0.87) reliability for the Neonatology fellow and excellent (intraclass correlation coefficient: 0.94) reliability for the Neuroradiology fellow compared with the Neuroradiologist. This suggests that the scoring system used has good interobserver reliability between less experienced readers compared with an experienced reader.

Background/Objectives: Telerehabilitation expands access to specialized neuropediatric physiotherapy for families facing barriers related to geography, work, or caregiving. This systematic review aimed to summarize the evidence regarding the effects of telerehabilitation on gross motor function (GMF) in children with cerebral palsy (CP). Methods: An electronic search was conducted in the following databases: PubMed, Web of Science, Embase, and the Cochrane Library; Google Scholar was consulted for additional literature. The search targeted randomized and non-randomized intervention studies evaluating the effects of telerehabilitation on GMF in children with CP at various levels of the Gross Motor Function Classification System (GMFCS), as well as related functional outcomes. The risk of bias in the included studies was assessed using the original Cochrane Collaboration risk of bias tool. The certainty of evidence was graded according to the GRADE framework. Results: Five studies involving 152 children were included, with CP aged 2.5 to 17 years. Telerehabilitation programs varied in duration, frequency, and type of intervention, as well as in caregiver involvement, comparator conditions, and outcome measures. The included studies suggested potential benefits in GMF and related functional outcomes; however, findings were heterogeneous, and superiority over comparison conditions was not consistently demonstrated. Conclusions: Although the reviewed studies suggest that telerehabilitation may be a feasible and potentially beneficial approach for children with CP, the limited number of studies and variability of interventions highlight the need for caution in interpreting these findings. Further high-quality studies with standardized outcome reporting are needed to clarify its contribution to GMF.

CHARGE syndrome (CS) and trisomy 13 (T13) and 18 (T18) are heterogeneous diseases with overlapping morphological features. Historically, T13 and T18 were deemed incompatible with life. Recently, numerous studies have reported prolonged survival for some affected patients. Consequently, the question of individual counseling has arisen. This study aimed to analyze the fetal MRI-based phenome of CS, T13, and T18. Fetal MRI-based phenotyping was conducted, and a morphological disease severity score that assessed 16 anatomical regions was proposed. Furthermore, a co-occurrence analysis was generated to visualize the overlapping and differentiating features of CS, T13, and T18. Forty-eight fetuses who underwent fifty-seven fetal MRI scans were analyzed. Disease severity scores ranged from 1-25 (mean 12.7) and highlighted heterogeneous disease manifestations among investigated patients. In the co-occurrence analysis the T13 network showed the highest complexity. Considering recent trends towards a change in management from mostly palliative to therapeutic care for patients with CS, T13, and T18, care providers face challenging decisions regarding management. The proposed preliminary MRI-based phenotyping score and the provided phenome visualization aim to aid physicians in counseling and choosing appropriate management plans. Future studies will be necessary to correlate prenatal imaging findings to outcome data in larger patient collectives. Question What are the phenotypical presentations of CHARGE syndrome, trisomy 13, and trisomy 18 in fetal MRI and can prenatal MRI findings help clinicians in predicting postnatal outcomes? Findings MRI phenomes were visualized in co-occurrence networks, and a preliminary disease severity score was proposed, based on available outcome data, to aid in risk stratification. Clinical relevance Recent trends in management, a shift from mostly palliative to therapeutic care for affected patients, have challenged clinicians. The provided phenome visualization of these heterogeneous diseases and the proposed disease severity score may aid physicians in counseling and selecting appropriate pregnancy management.

This study was undertaken to test whether arterial spin labeling (ASL) performs comparably to 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET), the mainstay functional imaging technique, in pediatric lesional epilepsy, while avoiding radiotracer exposure and additional sedation. We retrospectively included children with epilepsy due to focal cortical dysplasia, low-grade epilepsy-associated tumors, or hippocampal sclerosis who underwent standardized magnetic resonance imaging (MRI; including single-delay ASL) and FDG-PET during presurgical evaluation. Lesions, perilesional perfusion, and metabolic abnormalities were segmented and coregistered. Spatial overlap was quantified using DICE scores to compare functional modalities with each other (perfusion-to-metabolism: DICEP-to-M), with the lesion (metabolism-to-lesion: DICEM-to-L; perfusion-to-lesion: DICEP-to-L), and, in seizure-free children, with the resection cavity (lesion-, metabolism-, perfusion-to-resection cavity: DICEL-/M-/P-to-Post). We also assessed the temporal stability of perilesional ASL abnormalities and the presence of remote ipsilateral/contralateral abnormalities. Equivalence testing used the Wilcoxon signed-rank equivalence test with FDG-PET as reference; Cohen &#x3ba; quantified agreement for remote abnormalities. Fifteen children were included; median ages at FDG-PET and ASL were 7.7 and 7.5&#x2009;years; 53% required sedation. Median perilesional volumes were 11&#x2009;339&#x2009;mm3 (FDG-PET) and 10&#x2009;791&#x2009;mm3 (ASL); both were larger under sedation (p&#x2009;<&#x2009;.001). Perilesional volumes were equivalent (p&#x2009;=&#x2009;.037). Median DICEM-to-L and DICEP-to-L were .3 and .4; equivalence was confirmed (p&#x2009;<&#x2009;.001). Median DICEP-to-M was .7, indicating strong ASL-FDG-PET concordance. In seizure-free children following surgery, DICEM-to-Post and DICEP-to-Post were both .6 and equivalent (p&#x2009;=&#x2009;.01). ASL findings were stable over time (DICE = .27-.75; n&#x2009;=&#x2009;4 with repeat ASL). Remote ipsilateral abnormalities were common (ASL 73%, FDG-PET 67%; &#x3ba;&#x2009;=&#x2009;.53), with poor contralateral agreement (&#x3ba;&#x2009;=&#x2009;.12). ASL yielded perilesional findings equivalent to FDG-PET and showed comparable overlap with the resection cavity in seizure-free children. As a radiation-free technique embedded into routine MRI, ASL reduces logistics and avoids an additional sedation session. These findings support ASL as a practical alternative to FDG-PET for presurgical workup, especially when FDG-PET access is limited.

While prolonged impaired consciousness is often attributed to encephalopathy or meningitis, its occurrence and associated factors in patients with febrile status epilepticus without these conditions remain unclear. This study investigated the duration and determinants of impaired consciousness following febrile status epilepticus lasting&#xa0;&#x2265;&#xa0;30&#xa0;min in children treated with antiseizure medications. This retrospective multicenter study used data from the Febrile Acute Convulsion and Encephalopathy registry, a prospective multicenter consecutive case registry for acute encephalopathy and febrile convulsive status epilepticus in Japan. Children aged 6-60&#xa0;months with febrile status epilepticus lasting&#xa0;&#x2265;&#xa0;30&#xa0;min who received antiseizure medication were analyzed. Clinical data and early laboratory results were compared between prolonged (&#x2265;4&#xa0;h) and non-prolonged (<4&#xa0;h) impaired consciousness groups. Among 227 children with febrile status epilepticus lasting&#xa0;&#x2265;&#xa0;30&#xa0;min, the median time to recovery of consciousness was 176&#xa0;min, and 79 (34.8%) had prolonged impaired consciousness (&#x2265;4&#xa0;h). The two groups did not differ in age, sex, seizure duration, body temperature, history of febrile seizures, or number of antiseizure medications. Phenobarbital use was more frequent in the prolonged group. Laboratory abnormalities, including lower pH, lower base excess, higher creatinine, higher glucose, and higher ammonia were associated with prolonged impairment. Low pH was the only independent factor. In children with febrile status epilepticus&#xa0;&#x2265;&#xa0;30&#xa0;min, prolonged unconsciousness (&#x2265;4&#xa0;h) was associated with phenobarbital use and laboratory abnormalities, with acidosis as the sole independent predictor. Early recognition of delayed recovery may support timely clinical decision making and optimize emergency care.

Congenital melanocytic nevus syndrome is a disorder characterized by postzygotic, mosaic NRAS Proto-Oncogene, GTPase mutations. Clinical manifestations include melanotic skin lesions and, optionally, central nervous system melanosis typically noted during early infancy. Affected individuals have an increased risk of developing malignant melanomas at an early age. We report a child with neurocutaneous melanosis due to this syndrome, who had innumerable nevi at birth and diffuse leptomeningeal thickening. He developed increased intracranial pressure at 4&#xa0;weeks of age. The nucleoside analogue azacitidine and the Mitogen-Activated Protein Kinase, Kinase inhibitor trametinib were started at 6&#xa0;weeks of age resulting in rapid reduction of leptomeningeal thickening. At 53&#xa0;months of age, the patient still takes trametinib and has met all developmental milestones. There has been no evidence of melanoma, and he exhibits minimal residual leptomeningeal changes. To our best knowledge, this is the first child with this syndrome who has undergone successful therapy to reduce leptomeningeal thickening.

暂无摘要（点击查看详情）

暂无摘要（点击查看详情）

The onset of epileptic manifestations frequently occurs during childhood and often leads to initial management in pediatric emergency departments. The diagnostic approach is challenging, as epileptic seizures must be distinguished from non-epileptic paroxysmal events and acute symptomatic seizures. Although several national and international recommendations exist, real-world data on the management of first seizures in pediatric emergency settings remain limited. The primary objective of this study was to analyze patient characteristics and management of children presenting to a pediatric emergency department with a first non-febrile convulsive seizure. The secondary objective was to develop a practical management algorithm tailored to pediatric emergency settings. We conducted a retrospective, single-center observational study in a tertiary pediatric hospital in Reims, France. All patients under 18 years of age presenting to the pediatric emergency department with a first non-febrile convulsive seizure between January 1, 2015, and June 30, 2021, were included. Data from 167 children were analyzed and categorized into three groups: epileptic seizure (99, 59.3%), non-epileptic paroxysmal event (64, 38.3%), and acute symptomatic seizure (4, 2.4%). Clinical examination was normal in the majority of cases and did not reliably discriminate between groups. Semiological features such as eye deviation, eye rolling, generalized or focal hypertonia, and postictal confusion were significantly associated with epileptic seizures, whereas stressful or vasovagal situations were more frequent in non-epileptic events. All patients in the epileptic group underwent neuropediatric consultation, and 55 (55.5%) were discharged with antiepileptic treatment. Laboratory investigations were performed in 52 (52.5%) patients, with abnormalities identified in only 4% of cases. Electroencephalography (EEG) was performed in 96 (96.7%) patients and showed abnormalities in 64 (69.8%). In non-epileptic events, the EEG was normal in all cases where it was performed. Brain imaging was selectively performed and identified structural abnormalities in 21 (26.6%) patients who underwent MRI. In children presenting with a first non-febrile convulsive event, epileptic seizures accounted for a substantial proportion of cases, while non-epileptic events remained frequent. Clinical history and witness description were the most informative elements for diagnosis, whereas routine laboratory testing had limited utility. EEG and neuroimaging were valuable in selected cases. The proposed management algorithm provides a pragmatic, emergency-oriented framework to support clinical decision-making and help standardize the evaluation of these patients.

Neonatal ventriculitis is a complication of meningitis and is associated with high morbidity and mortality. Despite clinical importance, evidence regarding intraventricular antibiotic therapy has not been systematically collated. To evaluate the existing literature on intraventricular antibiotic administration for neonatal ventriculitis, focusing on indications, antibiotic type, dosage, administration intervals, adverse effects, and patient outcomes. A systematic search of Ovid MEDLINE, PubMed, EMBASE, CENTRAL, and Scopus was conducted up to October 2025. Conference abstracts, letters, reviews, expert opinions, and studies including patients older than 28 days were excluded. Risk of bias was assessed using the Joanna Briggs Institute (JBI) appraisal tools for case reports and case series. The review was prospectively registered on PROSPERO (CRD420251018399). The inclusion criteria were met by 19 studies involving 43 neonates. Ventriculitis followed persistent or inadequately treated meningitis in 21 cases (48.8%). Most neonates (97.7%) received concurrent systemic antibiotics, mostly intravenously. Dosing regimens and administration intervals varied considerably, except for vancomycin, which was consistently administered at 10&#x2009;mg daily. Overall survival was 79.1%. Clinical and laboratory improvement was reported in 30.2% of cases, while hydrocephalus occurred in 37.2%. Estimated in-hospital mortality was 9.3%, with hydrocephalus the leading cause of death. Intraventricular antibiotic therapy for neonatal ventriculitis has been described in small case series and case reports and may be associated with clinical and laboratory improvement. However, the low level of evidence precludes conclusions of effectiveness. Prospective studies are required to define its role alongside systemic therapy.

The ictal-interictal continuum (IIC) challenges the traditional dichotomous classification of electroencephalographic activity into ictal and interictal states and represents a major zone of diagnostic and therapeutic uncertainty in status epilepticus (SE). IIC is defined by rhythmic and periodic electroencephalographic (EEG) patterns that do not fulfill formal seizure criteria and occupies a gray zone in which the interpretation of what is ictal, treatment responsiveness, and risk of neuronal injury remains controversial. In this narrative review, we explored the boundaries between SE and the IIC, focusing on key controversies and paradoxes that emerge across electroclinical scenarios and neuroimaging findings. More specifically, we examine the time-locked electroclinical correlates and antiseizure medication responsiveness as markers of ictality, ongoing controversies in EEG-based definitions, and the role of peri-ictal neuroimaging abnormalities as complementary markers of metabolic burden. This review aims to summarize these topics and discuss key gaps for future research in the management of IIC.

Tuberous sclerosis complex (TSC) is a rare autosomal dominant multi-systemic disease, leading to excessive cell proliferation and the formation of hamartomas affecting various organs. International and French national guidelines emphasize the need for regular follow-up by different specialists with regular clinical evaluation, and biological and imaging investigations. This study aims to assess patient follow-up, its cost, and its adherence to the French National follow-up recommendations since the establishment of the day-hospital program tailored for pediatric patients with TSC. Clinical and follow-up data were collected among 81 patients, aged from 3 to 18 years old, from the epilepsy reference center of Necker Hospital in Paris, with a confirmed diagnosis of TSC, retrospectively from January 1st, 2021 to January 1st, 2024. Patients had an average of 9.4 days of pathology-related follow-up events, and an average of 1.1 teleconsultation over 3 years. Patients attended 1.6 day hospital stays over the duration of follow-up. The mean annual cost per patient for consultations and hospitalizations was &#x20ac;1344. The level of disability significantly increases the cost of follow-up. However, home-hospital distance has no significant impact on overall follow-up costs, the number of teleconsultations, or day-hospital visits. While paraclinical imaging and neurological follow-up were consistent with national recommendations, compliance with TSC national guidelines for specialist consultations was more challenging to implement. Our findings suggest that a mixed day hospital model, centered on neuropediatrics and incorporating additional examinations and consultations, would facilitate compliance with follow-up recommendations. Reducing patient travel and optimizing costs should be considered key objectives for improving long-term care.

Aicardi-Gouti&#xe8;res syndrome (AGS) is a prototypical type I interferon-driven neuroimmunological disorder in which immune-mediated inflammation causes progressive brain injury. Targeted immunosuppression with Janus kinase (JAK) inhibitors has shown clinical benefit, yet neurological outcomes remain difficult to quantify, and the interferon (IFN) score poorly reflects neuroaxonal damage. We investigated whether plasma neurofilament light chain (pNfL) and glial fibrillary acidic protein (pGFAP) serve as sensitive biomarkers of neurological involvement and response to immunosuppressive therapy. Plasma samples from 55 patients with genetically confirmed AGS and 55 age- and sex-matched healthy controls were analyzed using single molecule array assays. pNfL and pGFAP levels were assessed in relation to age, clinical disease severity, IFN score, and treatment with JAK inhibitors. Longitudinal samples before and during therapy were available from 11 patients. Treatment-na&#xef;ve AGS patients exhibited significantly elevated pNfL and pGFAP levels compared with controls, and biomarker concentrations correlated with clinical disease severity. pNfL and pGFAP were strongly correlated with each other but showed only weak to moderate associations with the IFN score. Longitudinal within-patient analyses demonstrated significant declines in pNfL and pGFAP following initiation of JAK inhibitor therapy, whereas the IFN score remained unchanged. pNfL and pGFAP are sensitive indicators of neuroaxonal and astroglial injury in AGS, capturing neurological disease burden and treatment-associated changes more accurately than the IFN score. These findings support their use as objective biomarkers for monitoring immune-mediated brain injury and therapeutic response, and warrant validation in larger longitudinal studies.

The diagnostic odyssey in rare diseases often involves the misinterpretation of genetic data, particularly when multidisciplinary approaches are lacking. This study illustrates the critical process of interpreting variants from next-generation sequencing (NGS) through a real-life case of a child misdiagnosed with Marfan Syndrome (MFS). The misdiagnosis was maintained for over seven years despite repeated clinical evaluations by different specialists. An initial clinical suspicion of MFS due to joint hypermobility at 3 years of age became a definitive diagnosis after an external laboratory reported a heterozygous variant in the MYH11 gene at age 5, despite the patient never fulfilling the established clinical diagnostic criteria for the disease. To provide an accurate diagnosis and end the family's diagnostic odyssey, a complete clinical and genetic reinterpretation was performed when the patient was 7 years old. The proband and 9 asymptomatic relatives were recruited for a functional study of the MYH11 c.5544_5548del, p.(D1848Efs*60) variant. The functional analysis demonstrated that the variant operates through a loss-of-function mechanism, leading to nonsense-mediated mRNA decay. While gain-of-function variants in MYH11 are associated with thoracic aortic aneurysms and dissections, loss-of-function variants are linked to autosomal recessive Megacystis-Microcolon-Intestinal Hypoperistalsis Syndrome (MMIHS). As a heterozygous carrier of a loss-of-function variant, the patient is asymptomatic for MMIHS and definitively does not have MFS. Currently, the 11-year-old child is progressing favorably without any notable pathology. This case exposes the entire diagnostic odyssey suffered by the patient's family and highlights three fundamental systemic errors: the critical delay in genetic counseling, the over-interpretation of NGS data by external laboratories lacking phenotypic context, and the health system's inefficiency in integrating clinical geneticists. Overcoming these barriers is essential for the true implementation of personalized precision medicine.

NDUFAF6 encodes a mitochondrial complex I assembly factor essential for the proper biogenesis and stability of the nicotinamide adenine dinucleotide (NAD) + hydrogen (H) (NADH)-ubiquinone oxidoreductase complex. Pathogenic variants in NDUFAF6 have been increasingly recognized as a cause of mitochondrial disease, particularly Leigh syndrome, a severe neurodegenerative disorder characterized by bilateral symmetrical lesions in the central nervous system. To date, fewer than 50 patients with NDUFAF6-related mitochondrial disease have been reported, displaying a broad phenotypic spectrum ranging from early-onset neurodevelopmental regression to milder, more chronic presentations. The molecular mechanisms underlying these phenotypes are linked to impaired complex I assembly and reduced enzymatic activity, highlighting the critical role of NDUFAF6 in mitochondrial function. Here we present a cohort of 27 patients (14 males and 13 females) from 18 families harbouring biallelic variants in the NDUFAF6 gene. The patient's mean age was 9.15 &#xb1; 8.30 years (range: 4 weeks to 25 years); 12 patients (37%) had died by the time the data were collected for this article. The clinical presentation showed wide phenotypic variability, from mild to severe psychomotor regression (74%) most commonly before the age of 5 years, hypotonia (22%), movement disorders (30%), and hypertonia (15%). Bilateral striatal necrosis lesions were the most characteristic features on cranial MRI (67%) although white matter abnormalities were also noted (15%), occasionally accompanied by cystic formations, suggestive of early neurodevelopmental anomalies. Genomic sequencing was applied, leading to the identification of 19 distinct variants in the NDUFAF6 gene, including nine novel variants not previously reported and either absent or extremely rare in public population databases. Functional studies confirmed the pathogenicity of these variants, demonstrating a deleterious effect on NDUFAF6 protein expression and a consequent impairment in complex I assembly and stability. To date, this represents the largest reported cohort of patients with NDUFAF6-associated mitochondrial disease. Our findings provide a comprehensive overview of clinical characteristics-including age of symptom onset, phenotypic variability, and patient outcomes-aiming to improve prognostic information and facilitate genetic counselling in clinical practice.

The large decrease in body weight with glucagon-like peptide-1 (GLP-1) medicines raises concern about a loss of lean body mass (LBM) and skeletal muscle. In this work, we present four pre-clinical studies and a proof-of-concept clinical trial that address this issue. We report that in obese mice, GLP-1 medicines predominantly reduce body fat alongside a small but significant decrease in LBM. Among lean tissues, loss of liver mass exceeds change in muscle mass. While absolute muscle mass and strength decrease, relative muscle mass and strength improve, resulting in better running performance. Interestingly, while atrophy is similar during immobilization, GLP-1 medicines have a distinct effect on the muscle proteome compared to calorie restriction. Patients with obesity on GLP-1 medicines improve their body composition without negatively affecting strength. Overall, in middle-aged mice and men, GLP-1 medicines slightly decrease absolute muscle values but positively impact body composition and mobility. The clinical trial is registered on clinicaltrials.gov (NCT05606471).

Postinfectious autoimmune processes are hypothesized to be causally implicated in tic disorders, including Tourette syndrome and chronic tic disorder. However, this hypothesis remains controversial. In this nationwide cohort study, we aimed to clarify the mechanisms underlying the association between proneness to infections and tic disorders. Using Swedish national registers, we identified 3,886,533 individuals (probands) born between 1970 and 2008 with available data on both biological parents. Probands were linked to six clusters of relatives: parents, full siblings, maternal half-siblings, paternal half-siblings, aunts/uncles, and cousins. Cox proportional hazards regression models were used to estimate the risk of tic disorders in probands exposed to infections and their relatives, compared with unexposed probands and their relatives. We also examined dose-response associations using logistic regression models. Probands exposed to infections had an increased risk of tic disorders (hazard ratio [HR], 1.46; 95% confidence interval [CI], 1.40-1.52), as did their relatives. The observed risks increased with the degree of genetic relatedness, from HR (95% CI) of 1.15 (1.12-1.19) in cousins to 1.31 (1.25-1.37) in first-degree relatives. There was a dose-response association between the number of infections in the probands and the odds for tic disorders in the probands and their relatives. Results remained consistent after adjustment for infections in relatives, tic disorders in probands, and autoimmune diseases in probands and relatives. Our results suggest an important role of shared genetic factors in the association between infections and tic disorders, potentially pointing to pleiotropic mechanisms.