Background: Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a central nervous system inflammatory disease.Objective: To describe the disease course of CLIPPERS.Design: A nationwide study was implemented to collect clinical, magnetic resonance imaging, cerebrospinal fluid, and brain biopsy specimen characteristics of patients with CLIPPERS.

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Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a treatable brainstem encephalitis recently described by Pittock et al. [1]. We report a case with clinical, radiological, and pathological signs of CLIPPERS but with final diagnosis of type B primary central nervous system lymphoma (PCNSL).In March 2010, a 33-year-old man with unremarkable personal history was first seen in the internal medicine unit for isolated vomiting with weight loss of 5 kg. The clinical and paraclinical examinations were unremarkable. In June, he was admitted to our unit for subacute gait ataxia, dysphagia, and binocular diplopia. Clinical examination revealed bilateral sixth nerve palsy and gait ataxia with pyramidal signs. Brain magnetic resonance imaging (MRI) showed hyperintense lesions on T2-weighted and fluidattenuated inversion recovery (FLAIR) sequences within the pons, medulla, and upper cervical cord, with enhancement after gadolinium administration. Cerebrospinal fluid (CSF) analysis showed elevated levels of proteins (1.10 g/l) with normal electrophoretic pattern and without abnormal cell count (2/mm 3 ). Extensive laboratory investigations were normal. Whole-body fluorodeoxyglucose positron emission tomography (FDG-PET), and labial salivary gland biopsies were negative, including aquaporin-4 water channel and onconeural antibodies. Biopsy of pons revealed perivascular lymphocyte infiltrates without any findings of sarcoidosis, lymphoma, glioma, or lymphomatoid granulomatosis (Fig. 1d). CLIPPERS syndrome was suspected, and the patient was treated for five consecutive days with 1,000 mg intravenous methylprednisolone followed by oral prednisone 60 mg (1 mg/kg/day) every day, with dramatic recovery except for persistence of moderate gait ataxia. In August 2010, a second brain MRI showed a reduction in the number and size of brainstem lesions. Localized proton magnetic resonance spectroscopy (MRS) examination showed a slight decrease of N-acetyl-aspartate/creatine (NAA/Cr) ratio (1:52) and an increase in choline/creatine (Cho/Cr) ratio (1:58) in the brain and medulla (Fig. 1a). The dose of steroids was reduced by 10 mg/week until 30 mg/ day was reached. In September 2010, he complained of numbness in all four limbs with worsening gait ataxia. A third brain MRI showed enlargement of the pontine lesions with necrosis. The MRS showed a slightly elevated Cho/ NAA ratio, as well as strong resonance of lipids and lactates (Fig. 1b). The patient was then treated with 1,000 mg intravenous methylprednisolone for 5 days; this was followed by double-filtration plasmapheresis. Because no further clinical improvement was observed, monthly intravenous cyclophosphamide was added. In October, the fourth brain MRI revealed radiological progression of brainstem lesions with the appearance of gadoliniumenhanced lesions localized close to the left lateral ventricle.

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Sleep disorders are among the most common comorbidities in children with Autism Spectrum Disorder (ASD), and subjectively defined sleep disturbances have been related to ASD symptom severity. However, no study has investigated the differential impact of objectively measured sleep and circadian rhythm disturbances on behavioral difficulties in this population. Fifty-two children with ASD aged 3–10 years underwent assessments of sleep and circadian rest–activity rhythms objectively with actigraphy and subjectively with the Children’s Sleep Habits Questionnaire. Behavioral difficulties were assessed using the ABC-C. Group comparison analyses were used to compare sleep and circadian rhythm parameters of children with higher and lower behavioral difficulties and dominance analysis to rank predictors and address multicollinearity. Children with high irritability had a shorter continuous sleep period compared to those with lower irritability (−60 min, p = 0.04), as well as those with high stereotypic behaviors compared to children with less stereotypies (−75 min, p = 0.006). Objective circadian and sleep disturbances accounted together for, respectively, 17%, 18% and 36% of the variance in social withdrawal, irritability and stereotypic behaviors. The identification of both sleep and circadian rhythm disturbances as explanatory factors for behavioral difficulties warrants their inclusion in the existing behavioral management strategies for children with ASD.