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Aim To investigate the characteristics and severity of dysarthria in children and adults with ataxia telangiectasia. Method All children and adults with ataxia telangiectasia who visited our multidisciplinary outpatient clinic for ataxia telangiectasia were asked to participate in this study, which took place in March 2019. To evaluate dysarthria, we used the Radboud Dysarthria Assessment in adults (older than 18y) and the paediatric Radboud Dysarthria Assessment in children (5–18y), including the observational tasks ‘conversation’ and ‘reading’, and the speech‐related maximum performance tasks ‘repetition rate’, ‘phonation time’, ‘fundamental frequency range’, and ‘phonation volume’. Speech intelligibility was measured using the Intelligibility in Context Scale. Results Twenty‐two individuals (15 children [5–17y], seven adults [19–47y]; 14 males and eight females; mean age 19y, SD 15y 2mo) participated. Dysarthria was present in all participants and characterized by ataxic components in adults and similar uncontrolled movements in children. In most participants, speech was mildly to mildly/severely affected. Almost all participants had an abnormal score for at least one maximum performance task. Interpretation Dysarthria in ataxia telangiectasia is characterized by uncontrolled, ataxic, and involuntary movements, resulting in monotonous, unstable, slow, hypernasal, and chanted speech. What this paper adds Dysarthria in ataxia telangiectasia is characterized by uncontrolled, ataxic, and involuntary movements.Dysarthria in ataxia telangiectasia results in monotonous, unstable, slow, hypernasal, and chanted speech.Dysarthria in ataxia telangiectasia can be assessed using the Radboud Dysarthria Assessment and the paediatric Radboud Dysarthria Assessment., What this paper adds Dysarthria in ataxia telangiectasia is characterized by uncontrolled, ataxic, and involuntary movements.Dysarthria in ataxia telangiectasia results in monotonous, unstable, slow, hypernasal, and chanted speech.Dysarthria in ataxia telangiectasia can be assessed using the Radboud Dysarthria Assessment and the paediatric Radboud Dysarthria Assessment.

Contains fulltext : 244271.pdf (Publisher’s version ) (Open Access) BACKGROUND: Treatment of animal models with ataxia telangiectasia (A-T) with nicotinamide riboside (NR) improved their neurological outcome and survival. OBJECTIVE: The aim of this study is to investigate the effects of NR in patients with A-T. METHODS: In this open-label, proof-of-concept study, 24 patients with A-T were treated with NR during four consecutive months. The effects of NR on ataxia, dysarthria, quality of life, and laboratory parameters were analyzed. RESULTS: During treatment, ataxia scores improved; mean total Scale for the Assessment and Rating of Ataxia and International Cooperative Ataxia Rating Scale scores decreased to 2.4 and 10.1 points, respectively. After NR withdrawal, ataxia scores worsened. In immunodeficient patients, the mean serum IgG concentration increased substantially until the end of the study period with 0.52 g/L. Untargeted metabolomics analysis revealed increased plasma levels of NR metabolites and purine nucleosides during treatment. Adverse effects did not occur. CONCLUSIONS: Treatment with NR is tolerated well and associated with improvement in ataxia and serum immunoglobulin concentrations in patients with A-T. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Objective Patients with classic ataxia–telangiectasia (A–T) generally die in the second or third decade of life. Clinical descriptions of A–T tend to focus on the symptoms at presentation. However, during the course of the disease, other symptoms and complications emerge. As long-term survivors with classic A–T develop a complex multisystem disorder with a largely unknown extent and severity, we aimed to comprehensively assess their full clinical picture. Methods Data from Dutch patients with classic A–T above the age of 30 years were retrospectively collected. In addition, we searched the literature for descriptions of classic A–T patients who survived beyond the age of 30 years. Results In the Dutch cohort, seven classic A–T patients survived beyond 30 years of age. Fourteen additional patients were retrieved by the literature search. Common problems in older patients with classic A–T were linked to ageing. Most patients had pulmonary, endocrine, cardiovascular, and gastro-intestinal problems. All patients had a tetraparesis with contractures. This led to immobilization and frequent hospital admissions. Most patients expressed the wish to no longer undergo intensive medical treatments, and waived follow-up programs. Conclusions Paucity of descriptions in the literature, and withdrawal from medical care complicate the acquisition of follow-up data on the natural history of long-term survivors. Irrespective of these limitations, we have obtained impression of the many problems that these patients face when surviving beyond 30 years of age. Awareness of these problems is needed to guide follow-up, counselling, and (palliative) care; decisions about life-prolonging treatments should be well considered.

Ataxia-telangiectasia (A-T) is an autosomal recessive disorder linked to mutations in the ATM gene, and is characterized by neurodegeneration with an early onset cerebellar syndrome, hyperkinetic movement disorders, neuropathy, and oculocutaneous telangiectasia. Immunodeficiency, pulmonary disease, growth failure, diabetes mellitus, increased malignancy risk and hypersensitivity to ionizing radiation complicate the clinical picture. Serum alpha-fetoprotein levels are increased in patients with A-T and can therefore serve as a diagnostic marker for the disease. In resource-limited settings, diagnosis and management of patients with a rare and complex disorder such as A-T may be extremely challenging. This expert opinion-based guideline aims to give an overview of diagnosis and management of A-T in resource-limited settings, by prioritizing different options based on medical necessity, availability, and costs.

Contains fulltext : 174098.pdf (Publisher’s version ) (Open Access) Ataxia-telangiectasia (AT) is a neurodegenerative disorder characterized by ataxia, telangiectasia, and immunodeficiency. An increased risk of malignancies and respiratory diseases dramatically reduce life expectancy. To better counsel families, develop individual follow-up programs, and select patients for therapeutic trials, more knowledge is needed on factors influencing survival. This retrospective cohort study of 61 AT patients shows that classical AT patients had a shorter survival than variant patients (HR 5.9, 95%CI 2.0-17.7), especially once a malignancy was diagnosed (HR 2.5, 95%CI 1.1-5.5, compared to classical AT patients without malignancy). Patients with the hyper IgM phenotype with hypogammaglobulinemia (AT-HIGM) and patients with an IgG2 deficiency showed decreased survival compared to patients with normal IgG (HR 9.2, 95%CI 3.2-26.5) and patients with normal IgG2 levels (HR 7.8, 95%CI 1.7-36.2), respectively. If high risk treatment trials will become available for AT, those patients with factors indicating the poorest prognosis might be considered for inclusion first.

Contains fulltext : 174099.pdf (Publisher’s version ) (Closed access) Ataxia-telangiectasia is a rare, neurodegenerative, and multisystem disease, characterized by cerebellar ataxia, oculocutaneous telangiectasia, immunodeficiency, progressive respiratory failure, and an increased risk of malignancies. It demands specialized care tailored to the individual patient's needs. Besides the classic ataxia-telangiectasia phenotype, a variant phenotype exists with partly overlapping but some distinctive disease characteristics. This guideline summarizes frequently encountered medical problems in the disease course of patients with classic and variant ataxia-telangiectasia, in the domains of neurology, immunology and infectious diseases, pulmonology, anaesthetic and perioperative risk, oncology, endocrinology, and nutrition. Furthermore, it provides a practical guide with evidence- and expert-based recommendations for the follow-up and treatment of all these different clinical topics.

ObjectiveTo describe and classify the neurologic trajectories in patients with mild neurologic forms of ataxia telangiectasia (A-T) from the Dutch A-T cohort, combined with patients reported in the literature.MethodsClinical, genetic, and laboratory data of 14 patients with mild neurologic phenotypes of A-T from the Dutch cohort were analyzed and combined with corresponding data from the literature. A mild neurologic phenotype was defined by a later onset, nonataxia presenting or dominant feature, or slower progression compared to the classic A-T phenotype. Neurologic trajectories were classified based on age at onset, presenting feature, and follow-up data.ResultsOne hundred five patients were included in the study. Neurologic trajectories were categorized into 6 groups: patients with childhood-onset extrapyramidal (EP) features with cerebellar symptoms developing later (group 1; 18 patients), childhood-onset cerebellar symptoms, with EP features developing later (group 2; 35 patients), childhood- to adolescence-onset dystonia, without cerebellar symptoms (group 3; 23 patients), childhood- to adolescence-onset isolated cerebellar symptoms (group 4; 22 patients), childhood- to adult-onset prominent muscle weakness (group 5; 2 patients), and patients with adult-onset EP features, with anterior horn cell disease arising subsequently (group 6; 5 patients).ConclusionsThis systematic study of the different motor abnormalities and their course over time in patients with mild phenotypes of A-T, enabled us to recognize 6 essentially different phenotypic patterns. Awareness of these different trajectories of motor abnormalities in milder forms of A-T will contribute to a reduction of diagnostic delay in this severe multisystem disorder.

BackgroundAtaxia telangiectasia (A-T) is a neurodegenerative disorder. While patients with classic A-T generally die in their 20s, some patients with variant A-T, who have residual ataxia-telangiectasia mutated (ATM) kinase activity, have a milder phenotype. We noticed two commonly occurring ATM mutations that appeared to be associated with prolonged survival and decided to study patients carrying one of these mutations.MethodsData were retrospectively collected from the Dutch, Italian, German and French A-T cohorts. To supplement these data, we searched the literature for patients with identical genotypes.ResultsThis study included 35 patients who were homozygous or compound heterozygous for the ATM c.3576G>A; p.(Ser1135_Lys1192del58) mutation and 24 patients who were compound heterozygous for the ATM c.8147T>C; p.(Val2716Ala) mutation. Compared with 51 patients with classic A-T from the Dutch cohort, patients with ATM c.3576G>A had a longer survival and were less likely to develop cancer, respiratory disease or immunodeficiency. This was also true for patients with ATM c.8147T>C, who additionally became wheelchair users later in life and had fewer telangiectasias. The oldest patient with A-T reported so far was a 78-year-old patient who was compound heterozygous for ATM c.8147T>C. ATM kinase activity was demonstrated in cells from all patients tested with the ATM c.8147T>C mutant protein and only at a low level in some patients with ATM c.3576G>A.ConclusionCompared with classic A-T, the presence of ATM c.3576G>A results in a milder classic phenotype. Patients with ATM c.8147T>C have a variant phenotype with prolonged survival, which in exceptional cases may approach a near-normal lifespan.

Ataxia telangiectasia (A-T) is a neurodegenerative disorder. While patients with classic A-T generally die in their 20s, some patients with variant A-T, who have residual ataxia-telangiectasia mutated (ATM) kinase activity, have a milder phenotype. We noticed two commonly occurringData were retrospectively collected from the Dutch, Italian, German and French A-T cohorts. To supplement these data, we searched the literature for patients with identical genotypes.This study included 35 patients who were homozygous or compound heterozygous for theCompared with classic A-T, the presence of

Neuroschistosomiasis is a severe complication of an infection with Schistosoma; this infection can lead to myelitis transversa. Acute myelitis transversa is a rare disorder of the spinal cord, which can present with muscular weakness, sensory disturbance and intestinal or bladder dysfunction.A 17-year-old refugee from Eritrea, who had been in the Netherlands for 3 weeks, suffered from back pain and progressive weakness of both legs for one week. Both the clinical presentation and the MRI images were consistent with myelitis transversa. Schistosomamansoni eggs were found in the faeces, and antibodies to Schistosoma eggs and worms were found in both liquor and serum, leading to a diagnosis of neuroschistosomiasis. The patient recovered completely following treatment with praziquantel and prednisone.Schistosomiasis is a commonly occurring parasitic disease in sub-Saharan Africa, which can lead to myelitis transversa if it spreads to the spinal cord. Early detection and treatment are necessary to prevent lasting damage. A good geographical case history is essential for this process.