In a recent Lancet Neurology article, the Global Burden of Disease Nervous System Disorders Collaborators reviewed the global burden of 37 nervous system diseases (in 2021) and estimated that 3.4 billion people (43% of the total population) suffered from a nervous system condition.
The accompanying morbidity and mortality come at immense economic and personal cost. The 37 conditions analysed caused 443 million DALYs and were the top-ranked contributors to global DALYs, with cardiovascular disease coming second.
The top three nervous system conditions were headaches (migraines and tension type, 3.17 billion), diabetic neuropathy (206 million) and stroke (93.8 million). There are differences in the disease burdens of these conditions, however, the ability to accurately diagnose, manage, on-refer and educate patients in a timely way are vital in reducing disease burden and disability.
Understanding migraine has advanced, in particular, the discovery of the role of calcitonin gene-related peptide (CGRP) in the pathophysiology of migraine symptoms, and its neuromodulatory effects. This has led to the development of the new generation of Gepants and CGRP monoclonal antibody (MAB) migraine therapies, including Olcegepant (2000) and Erenumab (2017) which have significant efficacy.
The 60% of patients treated with CGRP MABs have their headache days reduced by ~50%. However, Gepants are still not available on the PBS schedule, while MABs are listed and accessible for patients who have failed multiple standard therapies. These new approaches and correct headache diagnosis will contribute significantly to reducing migraine disease burden.
Diabetic neuropathy (DN) is common, with complications including falls, foot ulcers and potentially amputation. Its development is associated with raised triglyceride levels, obesity, smoking and hypertension. A high haemoglobin A1c is a significant predictor.
The ACCORD study and EDIC trial found that intensive treatment reduced DN. Beside pharmacological control of diabetes, exercise even over 10 weeks improved nerve function and neuropathy symptoms. Screening for DN is important and can be done easily using a Semmes-Weinstein 10 monofilament.
Screening questionnaires and multi-faceted screening tools such as the Toronto Clinical Neuropathy Score (TCNS) help improve diagnostic accuracy and selection of patients for more specialised testing. A correlation between DN and corneal nerve fibre density was reported, leading to utilisation of corneal confocal microscopy as a surrogate marker for DN. The ultimate mainstay of prevention remains good diabetic control.
Over the past 25 years, stroke treatment has expanded beyond the conservative use of aspirin. The ECASS and NINDS tPA trials first showed the benefits of thrombolysis for acute ischaemic stroke. Mechanical thrombectomy has cemented itself as one of the most effective treatments in medicine, with the NNT to prevent disability in one patient with stroke being only 2.3.
Early studies were designed to select patients with the greatest benefit so those with established core infarcts were often omitted. More trials are now examining the utility of mechanical thrombectomy in patients with large core infarcts. A recent meta-analysis of 6 newly completed RCTs using mechanical thrombectomy in patients with medium/large core infarcts showed significant benefits on the Rankin Scale and higher rates of functional independence.
Stroke rates in Australia have decreased by 27% since 2004. Between 1980 and 2021, annual stroke deaths declined in rate (104 to 24 per 100,000) and number (10,000 to 8500, 16%), driven by several factors, including improved risk factor management and breakthroughs in stroke treatments.
Nonetheless, the opportunity to rescue brain tissue in acute ischaemic stroke is limited by the time to reperfusion (approximately six hours). There remains a continued push to develop novel therapeutic options to prolong this window of opportunity, especially in the Australian clinical setting, where the time and distance to access treatment centres can be long.
The Australian-led phase II, double-blinded, randomised, placebo-controlled multicentre study (SEANCON) to determine the safety, preliminary efficacy and pharmacokinetics of the neuroprotective agent ARG-007 in acute ischaemic stroke patients has recently commenced patient recruitment.
The crux of improving patient outcomes is still early diagnosis and most importantly, patient and community education which will allow patients and doctors to identify and treat these conditions, faster, better and with reduced burdens to patients.
Led by the Institute for Health Metrics and Evaluation at the University of Washington, the Global Burden of Disease study involved researchers from over 150 countries and territories, including Professor Graeme Hankey (Perron Institute Chair in Stroke Research at The University of Western Australia).
Key messages
- Nervous system conditions are the most prevalent global causes of Disability Adjusted Life Years (DALYs)
- Headaches, diabetic neuropathy and stroke are amongst the top five causes.
Author competing interests – nil