Protein aggregates containing wild-type and mutant NOTCH3 are major drivers of arterial pathology in CADASIL.

Loss of arterial smooth muscle cells (SMCs) and abnormal accumulation of the extracellular domain of the NOTCH3 receptor (Notch3ECD) are the 2 core features of CADASIL, a common cerebral small vessel disease caused by highly stereotyped dominant mutations in NOTCH3. Yet the relationship between NOTCH3 receptor activity, Notch3ECD accumulation, and arterial SMC loss has remained elusive, hampering the development of disease-modifying therapies. Using dedicated histopathological and multiscale imaging modalities, we could detect and quantify previously undetectable CADASIL-driven arterial SMC loss in the CNS of mice expressing the archetypal Arg169Cys mutation. We found that arterial pathology was more severe and Notch3ECD accumulation greater in transgenic mice overexpressing the mutation on a wild-type Notch3 background (TgNotch3R169C) than in knockin Notch3R170C/R170C mice expressing this mutation without a wild-type Notch3 copy. Notably, expression of Notch3-regulated genes was essentially unchanged in TgNotch3R169C arteries. We further showed that wild-type Notch3ECD coaggregated with mutant Notch3ECD and that elimination of 1 copy of wild-type Notch3 in TgNotch3R169C was sufficient to attenuate Notch3ECD accumulation and arterial pathology. These findings suggest that Notch3ECD accumulation, involving mutant and wild-type NOTCH3, is a major driver of arterial SMC loss in CADASIL, paving the way for NOTCH3-lowering therapeutic strategies.

Lifestyle Factors Associated With Frequent Recurrent Headaches in Children and Adolescents: A Canadian Population-Based Study.

BACKGROUND AND OBJECTIVES: Lifestyle behaviors have been postulated to affect headache frequency in youth and are often the primary target of self-management recommendations. Our study aimed to assess the association between various lifestyle factors and frequent recurrent headaches in children and youth. METHODS: Children and adolescents aged 5-17 years were enrolled in a large cross-sectional Canadian population-based health survey, completed on January 31, 2019. Headache frequency was dichotomized into "approximately once/week or less" or ">once/week" (defined as frequent recurrent headaches). The association between frequent headaches and meal schedules, screen exposure, physical activity, chronotype, and frequent substance use/exposure (alcohol, cigarettes, electronic cigarettes, and cannabis) was assessed using both unadjusted logistic regression models and models adjusted for age/sex. Fully adjusted models examined the odds of frequent headaches according to all exposures. Survey design effects were accounted for using bootstrap replicate weighting. RESULTS: There were an estimated nweighted = 4,978,370 eligible participants in the population. The mean age was 10.9 years (95% CI 10.9-11.0); 48.8% were female; 6.1% had frequent headaches. Frequent headaches were associated with older age (odds ratio [OR] = 1.31, 95% CI 1.28-1.34, p < 0.001) and female sex (OR = 2.39, 95% CI 2.08-2.75, p < 0.001). In models adjusted for age/sex, the odds of frequent headaches decreased with meal regularity (adjusted OR [aOR] = 0.90, 95% CI 0.89-0.92, p < 0.001) and increased with later chronotype (aOR = 1.10, 95% CI 1.05-1.15, p < 0.001) and excess screen exposure (≥21 hours vs none in past week: aOR = 2.97, 95% CI 1.53-5.77, p = 0.001); there was no significant association with reported physical activity (aOR = 0.95, 95% CI 0.67-1.34, p = 0.77). In 12- to 17-year-olds, frequent headaches were associated with frequent alcohol use (≥1/wk vs never: aOR = 3.50, 95% CI 2.18-5.62, p < 0.001), binge drinking (≥5 times in past month vs never: aOR = 5.52, 95% CI 2.95-10.32, p < 0.001), smoking cigarettes (daily vs never: aOR = 3.81, 95% CI 1.91-7.62, p < 0.001), using e-cigarettes (daily vs never: aOR = 3.10, 95% CI 2.29-4.20, p < 0.001), and cannabis use (daily vs never: aOR = 3.59, 95% CI 2.0-6.45, p < 0.001). In the entire sample, daily exposure to smoking inside the house was associated with frequent headaches (aOR = 2.00, 95% CI 1.23-3.27, p = 0.005). DISCUSSION: Several lifestyle behaviors were associated with frequent headaches in children and youth, such as meal irregularity, late chronotype, prolonged screen exposure, and frequent substance use/exposure, suggesting that these are potential modifiable risk factors to target in this population.

Testing the specificity of phenomenological criteria for functional tic-like behaviours in youth with Tourette syndrome.

BACKGROUND AND PURPOSE: The aim was to test the specificity of phenomenological criteria for functional tic-like behaviours (FTLBs). The European Society for the Study of Tourette Syndrome (ESSTS) criteria for the diagnosis of FTLBs include three major criteria: age at symptom onset ≥12 years, rapid evolution of symptoms and specific phenomenology. METHODS: Children and adolescents with primary tic disorders have been included in a Registry in Calgary, Canada, since 2017. Using the Yale Global Tic Severity Scale, the proportion of youth with primary tic disorders who met specific phenomenological criteria for FTLBs at first visit was assessed: (1) having ≥1 specific complex motor tic commonly seen in FTLBs, including complex arm/hand movements, self-injurious behaviour, blocking, copropraxia; (2) having ≥1 specific complex phonic tic commonly seen in FTLBs, including saying words, phrases, disinhibited speech, coprolalia; (3) having a greater number of complex tics than simple tics. Children seen for the first time between 2017 and 2019 and between 2021 and 2023 were analysed separately. RESULTS: Of 156 participants included between 2017 and 2019, high specificity (94.2%) of the age at onset criterion (≥12 years) and of having at least two complex motor behaviours and one complex phonic behaviour at first visit (96.2%) was observed. Some of the complex motor tics had lower specificity. The specificity of the FTLB diagnostic criterion of having more complex tics than simple tics was 89.7%. There was no significant difference in specificity of the criteria for children seen for the first time between 2017 and 2019 and between 2021 and 2023 (n = 149). CONCLUSION: This information supports the use of the ESSTS criteria for FTLBs in clinical practice.

What are the Key Phenomenological Clues to Diagnose Functional Tic-Like Behaviors in the Pandemic Era?

BACKGROUND: Functional tic-like behaviors (FTLBs) can be difficult to distinguish from tics. OBJECTIVES: To describe the phenomenology of FTLBs in youth and assess the movements and vocalizations most suggestive of the diagnosis. METHODS: We compared the phenomenology of tics between youth (<20 yr) with FTLBs and with primary tics from our Registry in Calgary, Canada. RESULTS: Two hundred and thirty-six youths were included: 195 with primary tics (75% males; mean age: 10.8 yr) and 41 with FTLBs (98% females; 16.1 yr). In the bivariate models, FTLBs were most associated with copropraxia (OR = 15.5), saying words (OR = 14.5), coprolalia (OR = 13.1), popping (OR = 11.0), whistling (OR = 9.8), simple head movements (OR = 8.6), and self-injurious behaviors (OR = 6.9). In the multivariable model, FTLBs were still associated with saying words (OR = 13.5) and simple head movements (OR = 6.3). Only 12.2% of youth with FTLBs had throat clearing tics (OR = 0.2). CONCLUSIONS: This study shall help physicians diagnose youth with FTLBs according to the presence/association of specific movements and vocalizations.

Prospective follow-up study of youth and adults with onset of functional tic-like behaviours during the COVID-19 pandemic.

BACKGROUND AND PURPOSE: Very little is known about the long-term prognosis of patients with functional tic-like behaviours (FTLBs). We sought to characterize the trajectory of symptom severity over a 12-month period. METHODS: Patients with FTLBs were included in our prospective longitudinal child and adult clinical tic disorder registries at the University of Calgary. Patients were prospectively evaluated 6 and 12 months after their first clinical visit. Tic inventories and severity were measured with the Yale Global Tic Severity Scale (YGTSS). RESULTS: Eighty-three youths and adults with FTLBs were evaluated prospectively until April 2023. Mean YGTSS total tic severity scores were high at baseline, with a mean score of 29.8 points (95% confidence interval [CI] = 27.6-32.1). Fifty-eight participants were reevaluated at 6 months, and 32 participants were reevaluated at 12 months. The YGTSS total tic severity score decreased significantly from the first clinical visit to 6 months (raw mean difference = 8.9 points, 95% CI = 5.1-12.7, p < 0.0001), and from 6 to 12 months (raw mean difference = 6.4 points, 95% CI = 0.8-12.0, p = 0.01). Multivariable linear regression demonstrated that tic severity at initial presentation and the presence of other functional neurological symptoms were associated with higher YGTSS total tic scores at 6 months, whereas younger age at baseline, receiving cognitive behavioural therapy for anxiety and/or depression, and prescription of selective serotonin reuptake inhibitors were associated with lower YGTSS total tic scores at 6 months. CONCLUSIONS: We observed a meaningful improvement in tic severity scores in youth and adults with FTLBs over a period of 6-12 months.

Tourette syndrome and other tic disorders of childhood.

Tics are repetitive, patterned, and nonrhythmic movements or vocalizations/audible sounds that are misplaced in context. Phenomenology and characteristics of tics (e.g., premonitory urge, suppressibility) differentiate them from compulsions, stereotypies, functional tic-like behaviors, and other types of hyperkinetic movement disorders. With a prevalence of approximately 1% in school-aged boys, Tourette syndrome (TS) is considered a common childhood-onset neurodevelopmental disorder, defined by the combination of at least two motor tics and at least one phonic tic lasting more than 1 year. TS is a highly heritable disorder, with a wide spectrum of severity. In some individuals, tics can cause pain, distress, functional impairment, or stigmatization. About 90% of individuals with TS have at least one mental health comorbidity (attention-deficit/hyperactivity disorder, obsessive-compulsive disorder, anxiety/depressive disorders). These comorbidities significantly impact patients' quality of life and must therefore be screened and managed accordingly in this population. Treatment of tics is based on behavioral therapies targeting tics (habit reversal training included in the comprehensive behavioral intervention for tics, and exposure and response prevention for tics), in association with medication if needed (e.g., alpha-2-agonists, second-generation antipsychotics). Deep brain stimulation is considered an experimental option in the most severe, treatment-resistant patients. In adulthood, less than 25% of individuals still have moderate or severe tics.

Association Between Peer Victimization, Gender Diversity, Mental Health, and Recurrent Headaches in Adolescents: A Canadian Population-Based Study.

BACKGROUND AND OBJECTIVES: It is unknown whether bullying and gender diversity are associated with increased headache frequency in adolescents. Our study aimed to assess the association between peer victimization, gender diversity, and frequent recurrent headaches in adolescents, while controlling for age, sex, socioeconomic status, and potential confounders (mood and anxiety disorders, suicidality). METHODS: This was a cross-sectional observational study of adolescents aged 12-17 years using data from a Canadian population-based health survey. Headache frequency was dichotomized into "≤once/wk" or ">once/wk" (i.e., frequent recurrent headaches). Logistic regression was used to quantify the association between frequent peer victimization (overt or relational), gender diversity (female sex at birth + male gender, male sex at birth + female gender, or gender diverse), mood/anxiety disorder, suicidality, and the odds of frequent recurrent headaches. The fully adjusted multivariable logistic regression model included all exposures and was controlled for age, sex, and socioeconomic status. Bootstrap replicate weighting was used to account for survey design effects. RESULTS: There were an estimated 2,268,840 eligible participants (weighted sample size) (mean age = 14.4 years, 48.8% female, 0.5% gender diverse), and 11.2% reported frequent recurrent headaches. Frequent recurrent headaches were associated with older age (odds ratio [OR] = 1.26 per year of age, 95% CI 1.20-1.31), female sex (OR = 2.89, 95% CI 2.47-3.37), and being gender diverse (OR = 3.30, 95% CI 1.64-6.63, adjusted for age/sex). Youth with frequent headaches had higher odds of experiencing both overt and relational bullying compared with peers (OR = 2.69, 95% CI 2.31-3.14, and OR = 3.03, 95% CI 2.58-3.54, adjusted for age/sex). In the fully adjusted model, frequent headaches were no longer associated with gender diversity (OR = 1.53, 95% CI 0.63-3.69) but were still associated with frequent overt and relational peer victimization (OR = 1.82, 95% CI 1.41-2.34, and OR = 1.54, 95% CI 1.17-2.03, respectively), suicidality (OR = 1.83, 95% CI 1.44-2.32), and having a mood or anxiety disorder (OR = 1.50, 95% CI 1.01-2.21, and OR = 1.74, 95% CI 1.24-2.45, respectively). In a model adjusted for age, sex, and mood/anxiety disorders, the risk of suicidality increased incrementally with headache frequency. DISCUSSION: Peer victimization and suicidality may be associated with higher headache frequency in adolescents with headaches, independently of mood and anxiety symptoms. Gender-diverse adolescents may have a higher risk of experiencing frequent headaches when compared with cisgender peers, and this may be explained by associated psychosocial factors (anxiety, depression, suicidality, and peer victimization).

Developmental stuttering, physical concomitants associated with stuttering, and Tourette syndrome: A scoping review.

BACKGROUND AND PURPOSE: Developmental stuttering and Tourette syndrome (TS) are common neurodevelopmental disorders. Although disfluencies may co-occur in TS, their type and frequency do not always represent pure stuttering. Conversely, core symptoms of stuttering may be accompanied by physical concomitants (PCs) that can be confused for tics. This scoping review aimed to explore the similarities and differences between stuttering and tics in terms of epidemiology, comorbidities, phenomenology, evolution, physiopathology, and treatment. We also described the nature of PCs in stuttering and disfluencies in TS. METHODS: A literature search on Medline, Embase and PsycInfo was executed in March 2022. From 426 studies screened, 122 were included in the review (a majority being narrative reviews and case reports). RESULTS: TS and stuttering have several epidemiological, phenomenological, comorbidity, and management similarities suggesting shared risk factors and physiopathology (involving the basal ganglia and their connections with speech and motor control cortical regions). PCs in stuttering commonly involve the face (eyelids, jaw/mouth/lip movements) and sometimes the head, trunk and limbs. PCs can be present from early stages of stuttering and vary over time and within individuals. The function of PCs is unknown. Some individuals with TS have a distinct disfluency pattern, composed of a majority of typical disfluencies (mostly between-word disfluencies), and a mix of cluttering-like behaviors, complex phonic tics (e.g. speech-blocking tics, echolalia, palilalia), and rarely, atypical disfluencies. CONCLUSION: Future investigations are warranted to better understand the complex relationships between tics and stuttering and address the management of disfluencies in TS and PCs in stuttering.

Scoping Review on ADCY5-Related Movement Disorders.

Background: Adenylyl cyclase 5 (ADCY5)-related movement disorder (ADCY5-RMD) is a rare, childhood-onset disease resulting from pathogenic variants in the ADCY5 gene. The clinical features, diagnostic options, natural history, and treatments for this disease are poorly characterized and have never been established through a structured approach. Objective: This scoping review attempts to summarize all available clinical literature on ADCY5-RMD. Methods: Eighty-seven articles were selected for inclusion in this scoping review. The majority of articles identified were case reports or case series. Results: These articles demonstrate that patients with ADCY5-RMD suffer from permanent and/ or paroxysmal hyperkinetic movements. The paroxysmal episodes can be worsened by environmental triggers, in particular the sleep-wake transition phase in the early morning. Occurrence of nocturnal paroxysmal dyskinesias and perioral twitches are highly suggestive of the diagnosis when present. In the majority of patients intellectual capacity is preserved. ADCY5-RMD is considered a non-progressive disorder, with inter-individual variations in evolution with aging. Somatic mosaicism, mode of inheritance and the location of the mutation within the protein can influence phenotype. Conclusions: The current evidence for therapeutic options for ADCY5-RMD is limited: caffeine, benzodiazepines and deep brain stimulation have been consistently reported to be useful in case reports and case series.

Have We Forgotten What Tics Are? A Re-Exploration of Tic Phenomenology in Youth with Primary Tics.

Background: The first systematic description of tics in a large sample was in 1978. Objectives: To assess the phenomenology of tics in youth and investigate how age and sex influence tic phenomenology. Methods: Children and adolescents with primary tic disorders have been prospectively included in our Registry in Calgary, Canada, since 2017. We examined tic frequency and distribution using the Yale Global Tic Severity Scale, differences between sexes, and changes in tic severity with age and with mental health comorbidities. Results: A total of 203 children and adolescents with primary tic disorders were included (76.4% males; mean age = 10.7 years, 95% CI = 10.3-11.1). At first assessment, the most common simple motor tics were eye blinking (57%), head jerks/movements (51%), eye movements (48%) and mouth movements (46%); 86% had at least one simple facial tic. The most frequent complex motor tics were tic-related compulsive behaviors (19%). Throat clearing was the most common simple phonic tic (42%); 5% only had coprolalia. Females had higher frequency and intensity of motor tics than males (P = 0.032 and P = 0.006, respectively), associated with greater tic-related impairment (P = 0.045). Age was positively correlated with the Total Tic Severity Score (coefficient 0.54, P = 0.005), along with the number, frequency and intensity of motor tics but not with their complexity. Psychiatric comorbidities were associated with greater tic severity. Conclusions: Our study suggests that age and sex affect clinical presentation in youth with tics. The phenomenology of tics in our sample was similar to the 1978 description of tics, and contrasts with functional tic-like behaviors.

"Unvoluntary" Movement Disorders: Distinguishing between Tics, Akathisia, Restless Legs, and Stereotypies.

Tics, stereotypies, akathisia, and restless legs fall at different places on the spectrum of discrete, unwanted and potentially disabling motor routines. Unlike tremor, chorea, myoclonus, or dystonia, this subgroup of abnormal movements is characterized by the subject's variable ability to inhibit or release undesired motor patterns on demand. Though it may be sometimes clinically challenging, it is crucial to distinguish these "unvoluntary" motor behaviors because secondary causes and management approaches differ substantially. To this end, physicians must consider the degree of repetitiveness of the movements, the existence of volitional control, and the association with sensory symptoms, or cognitive-ideational antecedent. This review aims to summarize the current existing knowledge on phenomenology, diagnosis, and treatment of tics, stereotypies, akathisia, and restless leg syndrome.

European Society for the Study of Tourette Syndrome 2022 criteria for clinical diagnosis of functional tic-like behaviours: International consensus from experts in tic disorders.

BACKGROUND AND PURPOSE: In 2020, health professionals witnessed a dramatic increase in referrals of young people with rapid onset of severe tic-like behaviours. We assembled a working group to develop criteria for the clinical diagnosis of functional tic-like behaviours (FTLBs) to help neurologists, pediatricians, psychiatrists, and psychologists recognize and diagnose this condition. METHODS: We used a formal consensus development process, using a multiround, web-based Delphi survey. The survey was based on an in-person discussion at the European Society for the Study of Tourette Syndrome (ESSTS) meeting in Lausanne in June 2022. Members of an invited group with extensive clinical experience working with patients with Tourette syndrome and FTLBs discussed potential clinical criteria for diagnosis of FTLBs. An initial set of criteria were developed based on common clinical experiences and review of the literature on FTLBs and revised through iterative discussions, resulting in the survey items for voting. RESULTS: In total, 24 members of the working group were invited to participate in the Delphi process. We propose that there are three major criteria and two minor criteria to support the clinical diagnosis of FTLBs. A clinically definite diagnosis of FTLBs can be confirmed by the presence of all three major criteria. A clinically probable diagnosis of FTLBs can be confirmed by the presence of two major criteria and one minor criterion. CONCLUSIONS: Distinguishing FTLBs from primary tics is important due to the distinct treatment paths required for these two conditions. A limitation of the ESSTS 2022 criteria is that they lack prospective testing of their sensitivity and specificity.

Diagnosis and Outcomes of Late-Onset Wilson's Disease: A National Registry-Based Study.

BACKGROUND: Wilson's disease (WD) is usually diagnosed in children and young adults; limited data exist on late-onset forms. OBJECTIVE: The aim was to characterize the clinical and paraclinical presentations, therapeutic management, and outcomes in patients with late-onset WD. METHODS: Patients diagnosed with WD after age 40 years were identified from the French Wilson's Disease Registry (FWDR). Clinical, laboratory, and imaging findings and treatment were reported at diagnosis and last follow-up. RESULTS: Forty-five patients were identified (median age: 49, range: 40-64) and placed in three groups according to their clinical presentation: neurological (n = 20, median diagnostic delay: 20 months), hepatic (n = 13, diagnostic delay: 12 months), and family screening (n = 12), all confirmed genetically. Six neurological patients had an atypical presentation (1 torticollis, 2 writer's cramps, 2 functional movement disorders, and 1 isolated dysarthria), without T2/fluid-attenuated inversion recovery brain magnetic resonance imaging (MRI) hyperintensities; 5 of 6 had no Kayser-Fleischer ring (KFR); 5 of 6 had liver involvement. In the neurological group, 84% of patients improved clinically, and 1 developed copper deficiency. In the hepatic group, 77% had cirrhosis; 6 patients required liver transplantation. In the screened group, 43% had mild liver involvement; 3 were not treated and remained stable; 24-h urinary copper excretion was normal in 33% of patients at diagnosis. CONCLUSIONS: In the FWDR, late-onset forms of WD affect 8% of patients, mostly with neurological presentations. Thirty percent of the neurological forms were atypical (isolated long-lasting symptoms, inconspicuous brain MRI, no KFR). With personalized treatment, prognosis was good. This study emphasized that WD should be suspected at any age and even in cases of atypical presentation. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

The Prevalence of Idiopathic or Inherited Isolated Dystonia: A Systematic Review and Meta-Analysis.

Background: A systematic review of epidemiological studies of primary dystonia from 1985 and 2010 found an overall prevalence of 16.43 per 100,000 (95% CI = 12.09-22.32). Methods: We performed a systematic review of studies from 2010 and 2022 to determine if there are important differences in epidemiology between these time periods. Results: Nineteen studies were included. Incidence of cervical dystonia, blepharospasm, and oromandibular dystonia were each reported in one study; one study reported incidence for all adult onset idiopathic focal dystonias combined. Using data from 11 studies, we performed random effects meta-analyses of the prevalence of cervical dystonia (9.95 per 100,000; 95% CI = 3.51-28.17), blepharospasm (2.82 per 100,000; 95% CI = 1.12-7.12), laryngeal dystonia (0.40 per 100,000; 95% CI = 0.09-1.83), upper limb dystonia (1.27 per 100,000; 95% CI = 0.36-4.52), oromandibular dystonia (0.57 per 100,000; 95% CI = 0.15-2.15), and idiopathic or inherited isolated dystonia all subtypes combined (30.85 per 100,000; 95% CI = 5.06-187.74). All studies reported more cases of dystonia in females. There was no significant difference in prevalence by subgroup analysis based on time of study publication (1985-2010 vs. 2010-2022). Subgroup analysis of differences in prevalence by dystonia subtype by continent using all studies published (1985-2022) revealed significant regional differences in the prevalence of cervical and laryngeal dystonia. Conclusion: The incidence and prevalence of idiopathic or inherited isolated dystonia in the last decade was not significantly different from earlier reports. Population-based studies across multiple geographic areas are needed to obtain a clearer understanding of the epidemiology of this condition.

The recent surge of functional movement disorders: social distress or greater awareness?

PURPOSE OF REVIEW: To analyze the interrelated factors that have led to the striking increase in functional movement disorders in recent years, with a focus on functional tic-like behaviours (FTLB). RECENT FINDINGS: The sudden onset of FTLB has been widely observed in several countries since the beginning of the SARS-CoV-2 pandemic, whereas it was previously very rarely reported. Pandemic-related FTLB typically occur in young females, share complex, disabling and tic-lookalike patterns, and are usually triggered by the exposure to videos portraying tic-like behaviours on social media. Both pandemic-related FTLB and prepandemic FTLB are associated with high levels of depression and anxiety. FTLB related to the pandemic highlight the role of social media in the psychopathological behaviours of our time. SUMMARY: We suggest FTLB are due to a combination of predisposing factors (high genetic and epigenetic risk for anxiety and depression, negative past experiences) and precipitating factors (pandemic and its impact on mental health, exposure to certain social media content). These factors of vulnerability may increase the risk of developing behavioural and emotional problems in youth, such as FTLB. Early diagnosis and appropriate treatment of psychiatric comorbidities seem to be predictors of positive prognosis.

Prognosis of rapid onset functional tic-like behaviors: Prospective follow-up over 6 months.

BACKGROUND AND PURPOSE: The prognosis of rapid onset functional tic-like behaviors (FTLBs) is unknown. This prospective cohort study describes the course and treatment of rapid onset FTLBs in adolescents (n = 20) and adults (n = 9) previously reported in two case series. METHODS: Yale Global Tic Severity Scale (YGTSS) scores were compared between first clinical presentation and 6-month follow-up assessment. All treatments used for FTLBs and any psychiatric comorbidities were recorded. RESULTS: In adolescents with FTLBs, motor tics, vocal tics, total tics, impairment, and global scores on the YGTSS significantly improved at 6 months, with a mean decrease in the YGTSS global score of 31.9 points, 95% confidence interval (CI) 15.4, 48.4, p = .0005. In adults with FTLBs, only impairment and global scores significantly improved, with a mean decrease in the YGTSS global score of 19.6 points, 95% CI -3.2, 42.3, p = .04. Selective serotonin reuptake inhibitors (SSRIs) and cognitive behavioral therapy (CBT) for anxiety and depression were the most used treatment in both age groups. CONCLUSIONS: This prospective study suggests that adolescents have a better prognosis than adults with FTLBs. Management of comorbidities with SSRIs and CBT seems effective.

Primary CNS lymphoma of the corpus callosum: presentation and neurocognitive outcomes.

INTRODUCTION: The corpus callosum (CC) is frequently involved in primary central nervous system lymphomas (PCNSLs). In this cohort study, we described the neurocognition of patients with PCNSL-CC and its posttherapeutic evolution. METHODS: Immunocompetent patients with PCNSL-CC were identified retrospectively at the Pitié-Salpêtrière Hospital. We described their clinical presentation. Neuropsychological test scores (MMSE; digit spans; Free and Cued Selective Reminding Test; Image Oral Naming Test; Frontal Assessment Battery; Trail Making Test; Stroop and verbal fluency tests; Rey's Complex Figure test) and factors impacting them were analyzed. RESULTS: Twenty-seven patients were included (median age: 67 years, median Karnofsky Performance Status: 70); cognitive impairment and balance disorders were present in 74% and 59%, respectively. At diagnosis, neuropsychological test results were abnormal for global cognitive efficiency (63% of patients), memory (33-80% depending on the test) and executive functions (44-100%). Results for visuospatial and language tests were normal. All patients received high-dose methotrexate-based polychemotherapy, followed in one patient by whole-brain radiotherapy; 67% of patients achieved complete response (CR). With a median follow-up of 48 months (range 6-156), patients in CR had persistent abnormal test results for global cognitive efficiency in 17%, executive function in 18-60%, depending on the test, and memory in 40-60%. Splenium location and age ≥ 60 years were significantly associated with worse episodic memory scores throughout the follow-up. CONCLUSIONS: PCNSL-CC is associated with frequent cognitive dysfunctions, especially memory impairment, which may recover only partially despite CR and warrant specific rehabilitation. Older age (≥ 60) and splenium location are associated with worse neurocognitive outcomes.

IgG4-related pachymeningitis and mastoiditis, associated with cerebral venous thrombosis: A case report.

IgG4-related disease (IgG4-RD) is a multisystem fibroinflammatory condition; this can be a challenging diagnosis that requires clinico-pathologic correlation. We report a young woman, presenting with cranial nerve palsy. The work-up revealed pachymeningitis, cerebral venous thrombosis (CVT), and a destructive lesion in the mastoid. We diagnosed IgG4-RD through mastoidectomy. Thus, a biopsy of asymptomatic, infrequently affected organs, like the mastoid, can meet all histopathological criteria. In neuro-meningeal presentations, CVT may be secondary to the local inflammatory environment of pachymeningitis. Since our patient had a deep vein thrombosis one year prior, we discuss a possible higher risk of thrombosis in IgG4-RD patients.