P72 Riluzole causing pancytopenia: a clinically important rarity

DesignCase Report: An 83-year-old lady, was admitted with progressive speech and swallowing difficulty and wasting of small muscles of hand for 3 months. EMG revealed widespread anterior horn cell disease. With a diagnosis of MND, She was started on Riluzole 50 mg, LFT and FBC were normal before and 2 days after 1 st dose and the dose increased to a recommended dose of 50 mg twice a day. While waiting for PEG tube insertion, within 7 days, FBC showed a significant drop in Hb of 23 g/L ( from 125 to 102 g/L), Platelet dropped to 150×x10^9/L from 208 × 10^9/L, leucopenica ( 2.4 × 10^9/L) without any significant neutropenia. Her follow up haemogram showed persistent pancytopenia with more evident leucopenia and thrombocytopenia over next 7 days. She had no symptoms and signs of infection with normal infection screen. Her medication history was unremarkable apart from riluzole and thyroxine. No past history of liver disease or haematological conditions. Serum electrophoresis, Vitamin B12 and Folate were completely normal. A diagnosis of riluzole induced pancytopenia was made. A study by FDA suggests out of 861 patients, 3 patients (0.35%) developed Pancytopenia and 100% of them had it in the 1 st month. The aim of this case report to highlight the importance of considering Pancytopenia as an adverse reaction of riluzole. Patient may develop overt sepsis as a part of the spectrum. In that case, risk and benefit of riluzole prescription needs to addressed as an individual case basis.

Specific conditions

This chapter adopts a systematic approach to common diagnoses in paediatric neurology, aetiologies, management to include investigation and treatment, and outcome. For each condition current knowledge on cause and underlying biology is summarized. A rational approach to investigation and treatment is summarized for each topic. These include: acquired brain injury; autoimmune and autoinflammatory disease of the CNS; cerebral palsy and neurodisability which covers feeding, communication, special senses, and respiratory disease; demyelinating disease; epilepsy including its impact on daily life; non-epileptic paroxysmal phenomena; functional illness, illness behaviour; headache; hydrocephalus; spina bifida and related disorders; idiopathic intracranial hypertension; infection of the CNS; congenital infection; mitochondrial disease; movement disorders; neuromuscular disease which covers neuropathy, anterior horn cell disease, and myasthenic syndromes; neurocutaneous syndromes; neurodegenerative conditions; late presentations of metabolic disease; neurotransmitter disorders; sleep disorders; stroke and intracerebral haemorrhage; tumours of the CNS; and vitamin-responsive disorders.

Survival Beyond the Perinatal Period Expands the Phenotypes Caused by Mutations in GLE1

Mutations in GLE1 underlie Lethal Congenital Contracture syndrome (LCCS1) and Lethal Arthrogryposis with Anterior Horn Cell Disease (LAAHD). Both LCCS1 and LAAHD are characterized by reduced fetal movements, congenital contractures, and a severe form of motor neuron disease that results in fetal death or death in the perinatal period, respectively. Via trio-exome sequencing, we identified bi-allelic mutations in GLE1 in two unrelated individuals with motor delays, feeding difficulties and respiratory insufficiency who survived beyond the perinatal period. Each affected child had missense variants predicted to result in amino acid substitutions near the C-terminus of GLE1 that are predicted to disrupt protein-protein interaction or GLE1 protein targeting. We hypothesize that mutations that preserve function of the coiled-coil domain of GLE1 cause LAAHD whereas mutations that abolish the function of the coiled-coil domain cause LCCS1. The phenotype of LAAHD is now expanded to include multiple individuals surviving into childhood suggesting that LAAHD is a misnomer and should be re-named Arthrogryposis with Anterior Horn Cell Disease (AAHD). Too few cases have been reported to identify significant genotype-phenotype relationships, but given that perinatal lethality in AAHD typically resulted from respiratory failure, it is possible that early or aggressive airway management such as early tracheostomy and ventilation may enable survival beyond the perinatal period.