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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) commonly results in a respiratory illness in symptomatic patients; however, those critically ill can develop a leukoencephalopathy. We describe two patients who had novel subacute MRI findings in the context of coronavirus disease 2019 (COVID-19) leukoencephalopathy, which we hypothesize could implicate a potent small-vessel vasculitis, ischemic demyelination and the presence of prolonged ischemia. Recent evidence of the direct neuroinvasiness of SARS-CoV-2 leading to ischemia and vascular damage supports this hypothesis.

Central nervous system lymphoma (CNSL) represents one of the most aggressive forms of extranodal lymphoma. The gold standard for CNSL diagnosis remains the stereotactic biopsy, with a limited role for cytoreductive surgery that has not been supported by historical data. Our study aims to provide a comprehensive overview of neurosurgery’s role in the diagnosis of systemic relapsed and primary CNSL, with an emphasis on the impact on management and survival. This is a single center retrospective cohort study with data collected between August 2012 and August 2020, including patients referred with a potential diagnosis of CNSL to the local Neuro-oncology Multidisciplinary Team (MDT). The concordance between the MDT outcome and histopathological confirmation was assessed using diagnostic statistics. A Cox regression is used for overall survival (OS) risk factor analysis, and Kaplan–Meier statistics are performed for three prognostic models. The diagnosis of lymphoma is confirmed in all cases of relapsed CNSL, and in all but two patients who underwent neurosurgery. For the relapsed CNSL group, the highest positive predictive value (PPV) is found for an MDT outcome when lymphoma had been considered as single or topmost probable diagnosis. Neuro-oncology MDT has an important role in establishing the diagnosis in CNSL, not only to plan tissue diagnosis but also to stratify the surgical candidates. The MDT outcome based on history and imaging has good predictive value for cases where lymphoma is considered the most probable diagnosis, with the best prediction for cases of relapsed CNSL, questioning the need for invasive tissue diagnosis in the latter group.

A 31-year-old former Game Ranger from South Africa presented with subacute onset parieto-occipital headache, photophobia, and vomiting, followed by diplopia, bradykinesia and progressive unsteadiness. There was a history of neonatal eczema, recurrent skin abscesses, osteomyelitis, tuberculosis, hepatitis A, and Rickettsia.On examination he had meningism, papilloedema, bilateral sixth nerve palsies, left lower motor neurone facial weakness and left upper limb pyramidal weakness. He was areflexic with normal sensation. Mild bilateral extrapyramidal signs, postural instability and gait initiation failure were observed. During admission, he developed acute left lumbar polyradiculopathy. Deep set eyes, coarse facial features, bony deformities, and retention of primary teeth were noted on examination.MRI showed bilateral globus pallidus necrosis, basal leptomeningeal enhancement, and multilevel lumbar root thickening and enhancement.CSF culture confirmed Cryptococcus gattii infection and an apical lung opacity seen on chest x-ray was consistent with a cryptococcoma. Twelve months of antifungal therapy was commenced with full symptom resolution.HIV was negative. Immunological tests revealed elevated IgE levels and IL-17 deficiency. A de novo mutation in the STAT3 gene (c.1241G>C; p.Arg414Thr) confirmed the diagnosis of autosomal dominant Hyperimmunoglobulin E (Job’s) syndrome.We discuss Job’s syndrome, the challenges in managing cryptococcal infection and immunological testing in non-HIV patients.

We describe a 62-year-old smoker, presenting with a 6-week evolving history of progressive weakness of his legs and right hand, with sphincter disturbance. Past medical history included latent tuberculosis aged 25, which was treated. MRI whole-spine revealed longitudinally extensive transverse myelitis (LETM) spanning C4-T1. CSF examination revealed WCC 43 (93% lymphocytes), protein 844 mg/L, normal paired glucose, unmatched CSF oligoclonal bands, negative viral PCR, AFB, and mycobacterial culture, and cytology in keeping with chronic inflammation. He was treated with intravenous steroids with an oral taper; however, he made no improvement. Aquaporin-4 and anti-MOG antibodies were negative. Anti-Hu antibodies were strongly positive. CT thorax revealed a right hilar mass with mediastinal lymph node enlargement. Whole-body FDG PET-CT was in keeping with a primary lung malignancy. EBUS-guided fine needle aspiration confirmed a histological diagnosis of small-cell lung cancer. Oncology MDT deemed the tumour to be inoperable and he was treated with palliative chemotherapy. To our knowledge, this is the first reported case of paraneoplastic LETM, secondary to small-cell lung cancer, associated with positive anti-Hu antibodies. This case highlights that a paraneoplastic work-up should be considered early in LETM, particularly in older patients and those with risk factors for cancer.

Objectives Conventional magnetic resonance imaging (MRI) is used to diagnose and monitor inflammatory disease in relapsing remitting (RR) multiple sclerosis (MS). In the less common primary progressive (PP) form of MS, in which focal inflammation is less evident, biomarkers are still needed to enable evaluation of novel therapies in clinical trials. Our objective was to characterize the association — across the brain and cervical spinal cord — between clinical disability measures in PPMS and two potential biomarkers (one for myelin, and one for atrophy, both resulting from the same imaging technique). Methods Multi-component driven equilibrium single pulse observation of T1 and T2 (mcDESPOT) MRI of the brain and cervical spinal cord were obtained for 15 PPMS patients and 11 matched controls. Data were analysed to estimate the signal related to myelin water (VFM), as well as volume measurements. MS disability was assessed using the Multiple Sclerosis Functional Composite score, which includes measures of cognitive processing (Paced Auditory Serial Addition Test), manual dexterity (9-Hole Peg Test) and ambulatory function (Timed 25-Foot Walk); and the Expanded Disability Status Scale. Results Brain and spinal cord volumes were different in PPMS compared to controls, particularly ventricular (+ 46%, p = 0.0006) and cervical spinal cord volume (− 16%, p = 0.0001). Brain and spinal cord myelin (VFM) were also reduced in PPMS (brain: − 11%, p = 0.01; spine: − 19%, p = 0.000004). Cognitive processing correlated with brain ventricular volume (p = 0.009). Manual dexterity correlated with brain ventricular volume (p = 0.007), and both brain and spinal cord VFM (p = 0.01 and 0.06, respectively). Ambulation correlated with spinal cord volume (p = 0.04) and spinal cord VFM (p = 0.04). Interpretation In this study we demonstrated that mcDESPOT can be used to measure myelin and atrophy in the brain and spinal cord. Results correlate well with clinical disability scores in PPMS representing cognitive, fine motor and ambulatory disability., Highlights • A biomarker is needed to evaluate therapies for primary progressive MS (PPMS). • We used novel MRI providing both general atrophy and specific myelin measures. • We studied brain and cervical spinal cord in PPMS and healthy controls. • Brain and spinal cord volume and myelin measures were reduced in PPMS vs controls. • MRI measures described cognitive, fine motor and ambulatory disability scores.

Objective: Changing trends in multiple sclerosis (MS) epidemiology may first be apparent in the childhood population affected with first onset acquired demyelinating syndromes (ADSs). We aimed to determine the incidence, clinical, investigative and magnetic resonance imaging (MRI) features of childhood central nervous system ADSs in the British Isles for the first time. Methods: We conducted a population active surveillance study. All paediatricians, and ophthalmologists ( n = 4095) were sent monthly reporting cards (September 2009–September 2010). International Paediatric MS Study Group 2007 definitions and McDonald 2010 MS imaging criteria were used for acute disseminated encephalomyelitis (ADEM), clinically isolated syndrome (CIS) and neuromyelitis optica (NMO). Clinicians completed a standard questionnaire and provided an MRI copy for review. Results: Card return rates were 90%, with information available for 200/222 positive notifications (90%). After exclusion of cases, 125 remained (age range 1.3–15.9), with CIS in 66.4%, ADEM in 32.0% and NMO in 1.6%. The female-to-male ratio in children older than 10 years ( n = 63) was 1.52:1 ( p = 0.045). The incidence of first onset ADS in children aged 1–15 years old was 9.83 per million children per year (95% confidence interval [CI] 8.18–11.71). A trend towards higher incidence rates of ADS in children of South Asian and Black ethnicity was observed compared with White children. Importantly, a number of MRI characteristics distinguished ADEM from CIS cases. Of CIS cases with contrast imaging, 26% fulfilled McDonald 2010 MS diagnostic criteria. Conclusions: We report the highest surveillance incidence rates of childhood ADS. Paediatric MS diagnosis at first ADS presentation has implications for clinical practice and clinical trial design.

Despite advances in the treatment of patients with human immunodeficiency virus (HIV), HIV-associated neurocognitive disorder occurs in 15–50% of HIV-infected individuals, and may become more apparent as ageing advances. In the present study we investigated regional cerebral blood flow (rCBF) and regional cerebral metabolic rate of glucose uptake (rCMRglc) in medically and psychiatrically stable HIV-1-infected participants in two age-groups. Positron emission tomography (PET) and magnetic resonance imaging (MRI)-based arterial spin labeling (ASL) were used to measure rCMRglc and rCBF, respectively, in 35 HIV-infected participants and 37 HIV-negative matched controls. All participants were currently asymptomatic with undetectable HIV-1 viral loads, without medical or psychiatric comorbidity, alcohol or substance misuse, stable on medication for at least 6 months before enrolment in the study. We found significant age effects on both ASL and PET with reduced rCBF and rCMRglc in related frontal brain regions, and consistent, although small, reductions in rCBF and rCMRglc in the anterior cingulate cortex (ACC) in HIV, a finding of potential clinical significance. There was no significant interaction between HIV status and the ageing process, and no significant HIV-related changes elsewhere in the brain on PET or ASL. This is the first paper to combine evidence from ASL and PET method in HIV participants. These finding provide evidence of crossvalidity between the two techniques, both in ageing and a clinical condition (HIV). Hum Brain Mapp 34:2484–2493, 2013. © 2012 Wiley Periodicals, Inc.

Introduction Over the past decade the developments made in treating people with human immune deficiency virus (HIV) have greatly improved quality of life and life expectancy. However, the nature of asymptomatic HIV-associated minor neurocognitive disorder (HAND) remains unclear. In this study we explored the occurrence of neuropsychological and neuroimaging changes in medically and psychiatrically stable HIV-1 infected patients on highly active antiretroviral treatment (HAART) from two separate age groups. Methods Participants included 20 HIV-1 infected younger (aged 20–40) and 20 HIV-1 older patients (aged 50–75). Comparisons were made with 20 age- and education-matched younger and 22 matched older healthy seronegative males. Participants were stable on treatment and asymptomatic at study onset with undetectable HIV-1 viral loads, and free of medical or psychiatric co-morbidity, alcohol or substance misuse. A detailed neuropsychological assessment was used and volumetric-magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) performed to assess grey and white-matter integrity. Results We found significant effects of ageing on memory, grey and white matter measures. Comparison of the HIV-positive and HIV-negative groups did not show significant differences on the neuropsychological tests after Bonferroni correction, and there were no significant age by HIV status interactions. However, we did find reduced grey matter volume on MRI in our HIV-positive participants within the medial and superior frontal gyri. We also found significant ageing effects in fronto-temporal grey and white matter, independent of the effect of HIV. Conclusions The results from this study suggest that HIV-1 disease by itself does not significantly impair cognitive function when patients are otherwise asymptomatic. Nevertheless, the imaging techniques were sensitive enough to detect subtle grey matter changes not normally evident until much later in the disease. If confirmed in a longitudinal study this frontal grey matter change could represent an important biomarker for trials in HIV disease.

Purpose: To evaluate the accuracy of H-1-MR spectroscopy (H-1-MRS) as an intervention limiting diagnostic tool for glioblastoma multiforme. GBM is the most common and aggressive primary brain tumor, with mean survival under a year. Onco logical practice currently requires histopathological diagnosis before radiotherapy. Materials and Methods: Eighty-nine patients had clinical computed tomography (CT) and MR imaging and 1.5T SV SE H-1-MRS with PRESS localization for neuroradiological diagnosis and tumor classification with spectroscopic and automated pattern recognition analysis (TE 30 ms, TR 2000 ms, spectral width 2500 Hz and 2048 data points, 128-256 signal averages were acquired, depending on voxel size (8 cm(3) to 4 cm(3)). Eighteen patients from a cohort of 89 underwent stereotactic biopsy. Results: The 18 stereotactic biopsies revealed 14 GBM, 2 grade II astrocytomas, 1 lymphoma, and 1 anaplastic astrocytoma. All 14 biopsied GBMs were diagnosed as GBM by a protocol combining an individual radiologist and an automated spectral pattern recognition program. Conclusion: In patients undergoing stereotactic biopsy combined neuroradiological and spectroscopic evaluation diagnoses GBM with accuracy that could replace the need for biopsy. We do not advocate the replacement of biopsy in all patients: instead our data suggest a specific intervention limiting role for the use of H-1-MRS in brain tumor diagnosis.

Background Sickle cell anemia is one of the commonest causes of stroke in children. It is usually, but not always, associated with intracranial vasculopathy. We have assessed the value of ultrasound screening for extracranial internal carotid artery disease. Design and Methods Using Doppler ultrasound scanning, we assessed peak systolic blood velocity, tortuosity and stenosis in the extracranial internal carotid arteries of 236 children with sickle cell anemia. Seventeen of the children had previously had a stroke. All measurements were performed as part of routine clinical care. Results The median extracranial internal carotid artery velocity was 148cm/s (5th centile 84, 95th centile 236). Higher velocities were significantly correlated with younger age, higher white blood cell counts and higher rates of hemolysis. Fourteen (5.9%) had tortuous extracranial internal carotid arteries and 13 (5.4%) had stenosis or occlusion. None of the children with tortuous vessels but 8 of those with stenosis had previously had a stroke; the presence of stenosis was strongly associated with overt clinical stroke (OR 35.9, 95% C.I. 9.77–132, P

Background: Primary CNS malignant rhabdoid tumors are very rare in adults and much less is known about their biological behavior than in children. Recently, two adult cases of SMARCB1 (also known as INI1)-deficient tumor with rhabdoid cells have been described, suggesting an emerging group of primary meningeal SMARCB1-deficient tumors. We have recently encountered a case of INI1-deficient tumor with similar histology and immunophenotype to the above cases, but with a superficial cerebral, yet apparent intra-axial origin. Case Description: A 22-year-old woman presented with approximately one year history of focal sensorimotor right upper limb seizures and recently developed a slowly progressive weakness in her right hand. An MRI of the brain demonstrated an avidly enhancing lesion centered on the left perirolandic region with no definite dural involvement. The patient underwent a complete surgical excision. Histology revealed a tumor with monotonous epithelioid and spindle-shaped cells in a mucoid/myxoid background. There was focal mitotic activity and a few necrotic areas, in addition to many rhabdoid cells. The immunohistochemistry was negative for INI1 and there was strong positivity with CD34, while focal smooth muscle actin (SMA) and epithelial membrane antigen (EMA) immunoreactivity were also noted. Conclusions: As an addition to the two cases of adult SMARCB1-deficient tumors recently described, we present a further adult case with a similar immunohistochemical profile but with an apparent intra-axial origin, questioning the necessary meningeal origin of this type of tumor. The prognosis of this adult INI1/SMARCB1-deficient tumor is to be determined, but may be better than the pediatric atypical/teratoid tumor (AT/RT).

A 40-year-old male presented as a wake-up stroke with right hemiparesis and aphasia consistent with a left MCA territory infarct. Rapid deterioration within 24 hours resulted in intubation thought to be secondary to malignant MCA syndrome. Within 48 hours, he had acquired new, multi-territory infarcts leading to tetraparesis. Initial ‘routine’ young stroke work-up was unyielding. MRI/MRA suggested vasculitis and CSF analysis revealed raised protein, lymphocytosis, and low glucose ratio with negative gram stain, culture and virology. HIV test was negative. Broad-spectrum antibiotics were commenced with anti-TB cover, pending results. Steroids were administered given diagnostic uncertainty whilst empirical treatment with cyclophosphamide was considered. Interval MRI at one-week post treatment showed significant improvement in vasculitis prompting testing for syphilis. Revisiting the history, the patient was in a same sex relationship and had a prodrome of increasing headaches, anorexia, insomnia, personality change and a palmar rash diagnosed as contact dermatitis, eight weeks prior to admission. Neurosyphilis was confirmed: serum RPR 1:32, TPPA>1:1280, positive EIA; CSF RPR 1:8 and TPPA>1:1280. He was treated with an extended course of antibiotics with slow improvement. We review the challenges in reaching a diagnosis and the latest BASHH guidelines – in this increasingly prevalent disease.

Aims: To describe the clinical and radiological features of orbital apex syndromes caused by presumed tuberculosis (TB). Methods: A review of the discharge summaries of all patients seen in the Medical Eye Unit (MEU), St Thomas’ Hospital between 1975 and 2006 identified seven patients with a diagnosis of orbital apex syndrome or optic neuropathy attributable to TB. Case notes and radiology were reviewed retrospectively for each patient. Results: All of the patients were born outside the UK and were HIV-negative. Four presented during 2005–6. Six of the seven patients presented with a visual acuity (VA) of less than counting fingers (CF), but all achieved a VA of 6/9 or better after a median 3 weeks of treatment with antituberculous treatment and systemic corticosteroids. All patients had constitutional symptoms. Chest x ray and CSF were normal in each case, but MRI was abnormal in six. Conclusions: We report a recent cluster of tuberculous orbital apex syndromes, in the context of an increasing incidence of TB in the UK. The condition is difficult to diagnose, but the combination of high-dose corticosteroids and anti-TB medication was rapidly effective and achieved a good outcome in all cases.

A 61-year-old man presented with a 9 month history of progressive coordination, speech and memory problems as well as a 20 lb weight loss. He had fatigue, daytime somnolence and anxiety. Past personal and family medical histories were non-contributory. Examination demonstrated poor recall [Mini Mental State Examination (MMSE) 27/30, losing three points for memory]. He had an unsteady gait, could not tandem walk, had a fine upper limb postural tremor and had mild limb apraxia. The remainder of his neurological exam was normal. Investigations for a cerebellar syndrome were initiated. Full blood count, electrolytes, liver enzymes, B12, folate, thyroid-stimulating hormone (TSH), free T4, autoantibodies (mitochondrial, anti-gastric parietal cell, liver kidney microsomal, anti-smooth muscle, antinuclear antibody, anti-neutrophil cytoplasmic antibody), immunoglobulins, serum protein electrophoresis, copper, caeruloplasmin, manganese, neuronal antibodies (anti Ri, Yo, Hu), voltage-gated K channel antibodies, TSH receptor binding antibody and thyroid peroxisome antibodies were normal or negative. Cerebrospinal fluid (CSF) glucose and protein were normal, and there were no cells. The diagnosis of multiple system atrophy-cerebellar phenotype was considered. One year into the illness, dopamine transporter imaging (DAT) using 123I-Ioflupane single-photon emission computed tomography (SPECT) showed equivocally abnormal appearance qualitatively. After standard processing protocols, which involves attenuation correction during reconstruction, quantification of specific to non-specific ratios showed reduced caudate and putamen uptake bilaterally (see Fig. 1 for qualitative appearance and ratios), the right putamen having the lowest ratio. Subsequent brain magnetic resonance imaging (MRI) revealed T2 hyperintensity and corresponding restricted diffusion of the basal ganglia and thalami bilaterally as well as the cingulate gyri, right middle frontal gyrus and left parietal cortex, suggestive of sporadic Creutzfeldt–Jakob disease (CJD) (Fig. 2). Electroencephalogram (EEG) was normal. Within weeks, startle myoclonus developed, and he died shortly thereafter. Autopsy confirmed the diagnosis of sporadic CJD. A single published case of DAT in CJD also revealed reduced pre-synaptic putaminal uptake [1], and together with our case, suggests dopaminergic pathway dysfunction in CJD. These in vivo findings are in agreement with a recent pathologic study of the nigrostriatal pathway in sporadic CJD in which Vital et al. [2] found both preand post-synaptic cell loss in the nigrostriatal system. The loss of dopaminergic neurons in the substantia nigra correlated with the loss of neurons in the caudate and putamen. Interestingly, the patient previously reported by Ragno et al. [1] had an extrapyramidal syndrome while our patient had a cerebellar syndrome yet also had abnormal DAT imaging. In our patient, the DAT imaging appearance was not felt to be typical of idiopathic Parkinson’s disease. C. Hinnell M. Samuel (&) Department of Neurology, King’s College Hospital, 9th Floor, Ruskin Wing, Denmark Hill, London SE5 9RS, UK e-mail: m.samuel@nhs.net

Glioblastoma multiforme with an oligodendroglial component (GBMO) has been recognized in the World Health Organization classification-however, the diagnostic criteria, molecular biology, and clinical outcome of primary GBMO remain unclear. Our aim was to investigate whether primary GBMO is a distinct clinicopathological subgroup of GBM and to determine the relative frequency of prognostic markers such as loss of heterozygosity (LOH) on 1p and/or 19q, O(6)-methylguanine-DNA methyltransferase (MGMT) promoter methylation, and isocitrate dehydrogenase 1 (IDH1) mutation.We examined 288 cases of primary GBM and assessed the molecular markers in 57 GBMO and 50 cases of other primary GBM, correlating the data with clinical parameters and outcome.GBMO comprised 21.5% of our GBM specimens and showed significantly longer survival compared with our other GBM (12 mo vs 5.8 mo, P = .006); there was also a strong correlation with younger age at diagnosis (56.4 y vs 60.6 y, P = .005). Singular LOH of 19q (P = .04) conferred a 1.9-fold increased hazard of shorter survival. There was no difference in the frequencies of 1p or 19q deletion, MGMT promoter methylation, or IDH1 mutation (P = .8, P = 1.0, P = 1.0, respectively).Primary GBMO is a subgroup of GBM associated with longer survival and a younger age group but shows no difference in the frequency of LOH of 1p/19q, MGMT, and IDH1 mutation compared with other primary GBM.

Despite advances in the treatment of patients with human immunodeficiency virus (HIV), HIV‐associated neurocognitive disorder occurs in 15–50% of HIV‐infected individuals, and may become more apparent as ageing advances. In the present study we investigated regional cerebral blood flow (rCBF) and regional cerebral metabolic rate of glucose uptake (rCMRglc) in medically and psychiatrically stable HIV‐1‐infected participants in two age‐groups. Positron emission tomography (PET) and magnetic resonance imaging (MRI)‐based arterial spin labeling (ASL) were used to measure rCMRglc and rCBF, respectively, in 35 HIV‐infected participants and 37 HIV‐negative matched controls. All participants were currently asymptomatic with undetectable HIV‐1 viral loads, without medical or psychiatric comorbidity, alcohol or substance misuse, stable on medication for at least 6 months before enrolment in the study. We found significant age effects on both ASL and PET with reduced rCBF and rCMRglc in related frontal brain regions, and consistent, although small, reductions in rCBF and rCMRglc in the anterior cingulate cortex (ACC) in HIV, a finding of potential clinical significance. There was no significant interaction between HIV status and the ageing process, and no significant HIV‐related changes elsewhere in the brain on PET or ASL. This is the first paper to combine evidence from ASL and PET method in HIV participants. These finding provide evidence of crossvalidity between the two techniques, both in ageing and a clinical condition (HIV). Hum Brain Mapp 34:2484–2493, 2013. © 2012 Wiley Periodicals, Inc.

Abnormalities in brain structure and brain function have been described in schizophrenia. It is not yet known whether these are caused by an abnormality of brain development, some form of birth injury, or a neurodegenerative process. Using immunocytochemical methods and a marker for neurodegeneration (ubiquitin), we examined an area of prefrontal cortex from elderly schizophrenic and control subjects for the presence of ubiquitin-positive degeneration products. There was no statistical difference in the degree of ubiquitination between the control and the patient samples. The findings provide no evidence to support a neurodegenerative process.

We report the case of a patient presenting with abdominal pain as a result of a thoracic disc prolapse. The literature is reviewed, highlighting the associated morbidity by the often extensive and invasive procedures patients may undergo when a thoracic disc prolapse presents with abdominal pain.

Background There is evidence that at least 5% of Multiple sclerosis (MS) cases manifest in childhood. Children with MS present with a demyelinating episode involving single or multiple symptoms prior to developing a second event (usually within two years) to then meet criteria for diagnosis. There is evidence from adult cohorts that the incidence and sex ratios of MS are changing and that children of immigrants have a higher risk for developing MS. A paediatric population should reflect the vanguard of such changes and may reflect trends yet to be observed in adult cohorts. Studying a paediatric population from the first demyelinating event will allow us to test these hypotheses, and may offer further valuable insights into the genetic and environmental interactions in the pathogenesis of MS. Methods/Design The Paediatric UK Demyelinating Disease Longitudinal Study (PUDDLS) is a prospective longitudinal observational study which aims to determine the natural history, predictors and outcomes of childhood CNS inflammatory demyelinating diseases. PUDDLS will involve centres in the UK, and will establish a cohort of children affected with a first CNS inflammatory demyelinating event for long-term follow up by recruiting for approximately 5 years. PUDDLS will also establish a biological sample archive (CSF, serum, and DNA), allowing future hypothesis driven research. For example, the future discovery of a biomarker will allow validation within this dataset for the evaluation of novel biomarkers. Patients will also be requested to consent to be contacted in the future. A secondary aim is to collaborate internationally with the International Paediatric Multiple Sclerosis Study Group when future collaborative studies are proposed, whilst sharing a minimal anonymised dataset. PUDDLS is the second of two jointly funded studies. The first (UCID-SS) is an epidemiological surveillance study that already received ethical approvals, and started on the 1st September 2009. There is no direct patient involvement, and UCID-SS aims to determine the UK and Ireland incidence of CNS inflammatory demyelinating disorders in children under 16 years. Discussion A paediatric population should reflect the vanguard of MS epidemiological changes and may reflect trends yet to be observed in adult MS cohorts. The restricted window between clinical expression of disease and exposure to environmental factors in children offers a unique research opportunity. Studying a paediatric population from the first demyelinating event will allow us to investigate the changing epidemiology of MS, and may offer further valuable insights into the genetic and environmental interactions in the pathogenesis of MS.