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The monoamine neurotransmitter disorders are increasingly recognized as an expanding group of inherited neurometabolic syndromes caused by disturbances in the synthesis, transport and metabolism of the biogenic amines, including the catecholamines (dopamine, norepinephrine, and epinephrine) and serotonin. Disturbances in monoamine metabolism lead to neurological syndromes that frequently mimic other conditions, such as hypoxic ischemic encephalopathy, cerebral palsy, parkinsonism-dystonia syndromes, primary genetic dystonia and paroxysmal disorders. As a consequence, neurotransmitter disorders are frequently misdiagnosed. Early and accurate diagnosis of these neurotransmitter disorders is important, as many are highly amenable to, and some even cured by, therapeutic intervention. In this review, we highlight recent advances in the field, particularly the recent extensive characterization of known neurotransmitter disorders and identification of novel neurotransmitter disorders. We also provide an overview of current and future research in the field focused on developing novel treatment strategies.

Aim The aim of this study was to evaluate the number of children with acute arterial ischaemic stroke (AIS) who would have been eligible for hyperacute thrombolysis in the authors' unit (Great Ormond Street Hospital, London, UK) and to identify barriers to this treatment. Method We compared the characteristics of children with a diagnosis of acute AIS, identified from neuroimaging databases, seen at our centre between January 2006 and December 2011. The criteria for hyperacute thrombolysis were predefined by us: age ≥8y; imaging‐confirmed diagnosis of acute AIS and arrival at our centre within 6 hours of symptom onset; occluded major artery on computed tomography (CT) or magnetic resonance angiography; no contraindications. Factors that precluded therapy were examined. Results Of a total of 107 children with acute AIS identified on MRI (n=64; 33 females, 31 males; median age 4y, range 1mo–17y) or CT databases (n=43; 14 females, 29 males; median age 1y, range 1mo–15y), none would have been eligible for hyperacute thrombolysis. The major barriers to this were (1) delayed diagnosis, (2) delayed transfer to the tertiary centre, (3) age, and (4) medical comorbidities. Of 107 children, three (2.8%) would have been eligible for thrombolysis if diagnosis and transfer had occurred in a timely manner. An additional 11 children (10.3%) would have been eligible if the age criterion was 28 days or more and if diagnosis and transfer had occurred promptly. Interpretation Although hyperacute thrombolysis is, as yet, an unproven treatment in childhood AIS, at least a subset of patients could potentially benefit. This audit has identified that clinical factors preclude treatment in a high percentage of children. Furthermore, in our specialist unit, without an emergency department, we identified major logistic barriers that will need to be addressed to enable access to hyperacute therapies. These results could inform future trial design and service delivery.

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