Shakti Agrawal

Paediatric autoimmune encephalopathies: clinical features, laboratory investigations and outcomes in patients with or without antibodies to known central nervous system autoantigens

Objective To report the clinical and investigative features of children with a clinical diagnosis of probable autoimmune encephalopathy, both with and without antibodies to central nervous system antigens. Method Patients with encephalopathy plus one or more of neuropsychiatric symptoms, seizures, movement disorder or cognitive dysfunction, were identified from 111 paediatric serum samples referred from five tertiary paediatric neurology centres to Oxford for antibody testing in 2007–2010. A blinded clinical review panel identified 48 patients with a diagnosis of probable autoimmune encephalitis whose features are described. All samples were tested/retested for antibodies to N-methyl-D-aspartate receptor (NMDAR), VGKC-complex, LGI1, CASPR2 and contactin-2, GlyR, D1R, D2R, AMPAR, GABA(B)R and glutamic acid decarboxylase. Results Seizures (83%), behavioural change (63%), confusion (50%), movement disorder (38%) and hallucinations (25%) were common. 52% required intensive care support for seizure control or profound encephalopathy. An acute infective organism (15%) or abnormal cerebrospinal fluid (32%), EEG (70%) or MRI (37%) abnormalities were found. One 14-year-old girl had an ovarian teratoma. Serum antibodies were detected in 21/48 (44%) patients: NMDAR 13/48 (27%), VGKC-complex 7/48(15%) and GlyR 1/48(2%). Antibody negative patients shared similar clinical features to those who had specific antibodies detected. 18/34 patients (52%) who received immunotherapy made a complete recovery compared to 4/14 (28%) who were not treated; reductions in modified Rankin Scale for children scores were more common following immunotherapies. Antibody status did not appear to influence the treatment effect. Conclusions Our study outlines the common clinical and paraclinical features of children and adolescents with probable autoimmune encephalopathies. These patients, irrespective of positivity for the known antibody targets, appeared to benefit from immunotherapies and further antibody targets may be defined in the future.

N-methyl-D-aspartate receptor antibody-mediated neurological disease: results of a UK-based surveillance study in children

Objective N-methyl-D-aspartate receptor antibody (NMDAR-Ab) encephalitis is a well-recognised clinico-immunological syndrome that presents with neuropsychiatric symptoms cognitive decline, movement disorder and seizures. This study reports the clinical features, management and neurological outcomes of paediatric NMDAR-Ab-mediated neurological disease in the UK. Design A prospective surveillance study. Children with NMDAR-Ab-mediated neurological diseases were voluntarily reported to the British Neurological Surveillance Unit (BPNSU) from November 2010 to December 2011. Initial and follow-up questionnaires were sent out to physicians. Results Thirty-one children fulfilled the criteria for the study. Eight presented during the study period giving an incidence of 0.85 per million children per year (95% CI 0.64 to 1.06); 23 cases were historical. Behavioural change and neuropsychiatric features were present in 90% of patients, and seizures and movement disorders both in 67%. Typical NMDAR-Ab encephalitis was reported in 24 children and partial phenotype without encephalopathy in seven, including predominantly psychiatric (four) and movement disorder (three). All patients received steroids, 22 (71%) received intravenous immunoglobulin, 9 (29%) received plasma exchange,and 10 (32%) received second-line immunotherapy. Of the 23 patients who were diagnosed early, 18 (78%) made a full recovery compared with only 1 of 8 (13%) of the late diagnosed patients (p=0.002, Fishers exact test). Seven patients relapsed, with four needing additional second-line immunotherapy. Conclusions Paediatric NMDAR-Ab-mediated neurological disease appears to be similar to adult NMDAR-Ab encephalitis, but some presented with a partial phenotype. Early treatment was associated with a quick and often full recovery.

Successful treatment of antiN-methyl-d-aspartate receptor limbic encephalitis in a 22-monthold child with plasmapheresis and pharmacological immunomodulation

We report the case of a previously healthy 22-month-old girl who presented with the full clinical spectrum of anti-N-methyl-daspartate receptor (NMDAR) encephalitis with seizures, agitation, stupor, autonomic instability, dysphagia and relentless choreoathetoid movements. Schimmel et al describe a 12-year-old girl with typical clinical symptoms of the recently described NMDAR encephalitis.1 Their patient was the youngest reported case with this condition to date. The symptoms in our patient began 1 week after a meningitis C booster vaccination. Cerebrospinal fluid (CSF) examination on admission showed raised lymphocyte count and oligoclonal bands with no oligoclonal bands in a paired blood sample. All other investigations including PCR for …

Movement disorders associated with complex regional pain syndrome in children.

The aim of the present study was to review the history, clinical course, treatment, and outcome of movement disorders in children and young people with complex regional pain syndrome (CRPS). Case notes were reviewed retrospectively of children and young people who presented with movement disorders in CRPS to our tertiary paediatric pain service over a period of 13 years. Ten children with CRPS presented with movement disorders (eight females, two males). The age at first presentation with symptoms of CRPS ranged from 8 to 15 years (mean 11y 2mo, median 13y). The most common movement disorder was dystonia (n=8), followed by tremors (n=3) and myoclonus (n=3); two patients had all three movement disorders. The movement disorder affected mainly the lower limb (n=9) with a predilection for the foot (n=7) and was frequently initiated by minor trauma (n=7). Follow‐up ranged from 6 months to 14 years. The outcome was variable, with good prognosis in nearly half of the cases: four children experienced complete resolution of symptoms. Two children showed a slight improvement. Four children showed no improvement. Movement disorders in CRPS are under‐recognized in children. The management has to be multidisciplinary with an expertize in paediatric pain.

Recessive ITPA mutations cause an early infantile encephalopathy

To identify the etiology of a novel, heritable encephalopathy in a small group of patients.

Management of children and young people with headache

Headache is very common in children and young people. The correct advice and treatment requires consideration of a wide differential diagnosis between primary and secondary headaches, and also of the different types of primary headache. The International Classification of Headache Disorders gives useful descriptions and diagnostic criteria that are especially useful for primary headaches. The National Institute for Health and Care Excellence (NICE) Clinical Guideline 150 provides evidence-based recommendations on treatments for adults and young people from age 12 years. However, the same principles can be applied to younger children when a specific diagnosis can be made. Key recommendations from the NICE Quality Standards include, establishing a precise diagnosis if possible, avoiding, diagnosing and treating medication overuse headache, and combining a triptan with a non-steroidal anti-inflammatory drug or paracetamol as the first-line acute/rescue treatment for migraine with or without aura. Although rare in children and young people, it is important to diagnose new daily persistent headache, as it responds poorly or not at all to medication; and paroxysmal hemicrania as it responds very well to indomethacin but not to other commonly used analgesics. When faced with difficulties in reaching a precise diagnosis or in finding effective therapies, further advice should be sought from a childrens headache clinic or specialist.

Clinical features, course, and outcomes of a UK cohort of pediatric moyamoya

Objective To describe characteristics and course of a large UK cohort of children with moyamoya from multiple centers and examine prognostic predictors. Methods Retrospective review of case notes/radiology, with use of logistic regression to explore predictors of outcome. Results Eighty-eight children (median presentation age 5.1 years) were included. Thirty-six presented with arterial ischemic stroke (AIS) and 29 with TIA. Eighty had bilateral and 8 unilateral carotid circulation disease; 29 patients had posterior circulation involvement. Acute infarction was present in 36/176 hemispheres and chronic infarction in 86/176 hemispheres at the index presentation. Sixty-two of 82 with symptomatic presentation had at least one clinical recurrence. Fifty-five patients were treated surgically, with 37 experiencing fewer recurrences after surgery. Outcome was categorized as good using the Recovery and Recurrence Questionnaire in 39/85 patients. On multivariable analysis, presentation with TIA (odds ratio [OR] 0.09, 95% confidence interval [CI] 0.02–0.35), headache (OR 0.10, 95% CI 0.02–0.58), or no symptoms (OR 0.08, 95% CI 0.01–0.68) was less likely to predict poor outcome than AIS presentation. Posterior circulation involvement predicted poor outcome (OR 4.22, 95% CI 1.23–15.53). Surgical revascularization was not a significant predictor of outcome. Conclusions Moyamoya is associated with multiple recurrences, progressive arteriopathy, and poor outcome in half of patients, especially with AIS presentation and posterior circulation involvement. Recurrent AIS is rare after surgery. Surgery was not a determinant of overall outcome, likely reflecting surgical case selection and presentation clinical status.

046 EAST syndrome: probable closure in many an adult case

Introduction It is frustrating for patients, families and clinicians when a unifying diagnosis for the constellations of neurological signs and symptoms remains elusive. Two recent reports, working independently, have hypothesised that KCNJ10 mutations on Chrosome 1q23.2 are responsible for Epilepsy, Ataxia, Sensorineural deafness and Tubulopathy (EAST syndrome/ SeSAME syndrome). We present a series of six patients with ages ranging from 3-22 years from three families. Case series We describe three Asian siblings, two Caribbean siblings, and one Caucasian child who have epilepsy, ataxia, sensorineural hearing loss, and tubulopathy. Consanguinity was present only in the Asian family. Seizures were a presenting symptom in four with onset as early as 3–7 months of age. Development delay and learning difficulties were present in all of the cases. Ataxia was evident from early on. Sensorineural hearing loss was identified at different ages and in some cases was asymptomatic. In some cases, tubulopathy was an incidental finding. In the five children who have been extensively investigated, metabolic and mitochondrial investigations, magnetic resonance images, and electroencephalograms were normal. All six children had biochemical evidence of a tubulopathy with hypokalaemia, hypomagnesaemia, and alkalosis. KCNJ10 DNA mutations have since been identified in all of them. Conclusion This condition does not seem to be life limiting as is evident from the early reports and our own experience. Three patients from our series have moved on to the adult services. We hypothesise that there are adult patients with similar findings who are still waiting for a closure.