Change in Mortality of Generalized Convulsive Status Epilepticus in High-Income Countries Over Time: A Systematic Review and Meta-analysis.

IMPORTANCE: Status epilepticus (SE) is associated with significant morbidity and mortality. Since the late 1990s, a more aggressive management of prolonged convulsive seizures lasting longer than 5 minutes has been advocated. OBJECTIVE: To determine if convulsive SE mortality has decreased during a time of increasing advocacy for out-of-hospital treatment and escalating and earlier treatment protocols for prolonged seizures and SE. DATA SOURCE: This systemic review and meta-analysis on studies focused on the mortality of convulsive status epilepticus was conducted by searching MEDLINE, Embase, PsychINFO, CINAHL Plus, and the Cochrane Database of Systematic Reviews between January 1, 1990, and June 30, 2017. STUDY SELECTION: Studies were excluded if they had fewer than 30 participants (<20 for refractory SE), were limited to SE of single specific etiology or an evaluation of a single treatment modality, or were studies of nonconvulsive SE. DATA EXTRACTION AND SYNTHESIS: Data were abstracted and their quality was assessed via a modified Newcastle-Ottawa scale independently by 2 reviewers (A.N. and T.D.G.) using the Meta-analyses of Observational Studies in Epidemiology (MOOSE) guidelines. Data were pooled using a random-effects model. MAIN OUTCOMES AND MEASURES: The main outcome measure was in-hospital mortality or 30-day case fatality expressed as proportional mortality. RESULTS: Sixty-one studies were included in the analysis. The pooled mortality ratios were 15.9% (95% CI, 12.7-19.2) for adult studies, 13.0% (95% CI, 7.2-19.0) for all-age population studies, 3.6% (95% CI, 2.0%-5.2%) for pediatric studies, and 17.3% (95% CI, 9.8-24.7) for refractory SE studies, with very high between-study heterogeneity. We found no evidence of a change in prognosis over time nor by the definition of SE used. CONCLUSIONS AND RELEVANCE: The mortality of convulsive SE is higher in adults than in children and there was no evidence for improved survival over time. Although there are many explanations for these findings, they can be explained by aetiology of SE being the major determinant of mortality. However, there are potential confounders, including differences in case ascertainment and study heterogeneity. This meta-analysis highlights the need for strict international guidelines for the study of this condition.

The prodromes of Parkinson's disease.

Whilst the diagnosis of Parkinson's disease (PD) relies on the motor triad of bradykinesia, rigidity and tremor, the underlying pathological process starts many years before these signs are overt. In this prodromal phase of PD, a diverse range of non-motor and motor features can occur. Individually they do not allow a diagnosis of PD, but when considered together, they reflect the gradual development of the clinical syndrome. Different subgroups within the prodromal phase may exist and reflect different underlying pathology. Here, we summarise the evidence on the prodromal phase of PD in patient groups at increased risk of PD with well described prodromal features: patients with idiopathic rapid eye movement sleep behaviour disorder, patients with idiopathic anosmia and families with monogenic mutations that are closely linked to PD pathology. In addition, we discuss the information on prodromal features from ongoing studies aimed at detecting prodromal PD in the general population. It is likely that better delineation of the clinical prodromes of PD and their progression in these high-risk groups will improve understanding of the underlying pathophysiology.

An early diagnosis is not the same as a timely diagnosis of Parkinson's disease.

Parkinson's disease is a common neurodegenerative condition that has significant costs to the individual patient and to society. The pathology starts up to a decade before symptoms are severe enough to allow a diagnosis using current criteria. Although the search for disease-modifying treatment continues, it is vital to understand what the right time is for diagnosis. Diagnosis of Parkinson's disease is based on the classic clinical criteria, but the presence of other clinical features and disease biomarkers may allow earlier diagnosis, at least in a research setting. In this review, we identify the benefits of an early diagnosis, including before the classic clinical features occur. However, picking the right point for a "timely" diagnosis will vary depending on the preferences of the individual patient, efficacy (or existence) of disease-modifying treatment, and the ability for health systems to provide support and management for individuals at every stage of the disease. Good evidence for the quality-of-life benefits of existing symptomatic treatment supports the argument for earlier diagnosis at a time when symptoms are already present. This argument would be significantly bolstered by the development of disease-modifying treatments. Benefits of early diagnosis and treatment would affect not only the individual (and their families) but also the wider society and the research community. Ultimately, however, shared decision-making and the principles of autonomy, beneficence, and non-maleficence will need to be applied on an individual basis when considering a "timely" diagnosis.

Lupus myelopathy.

Although neurological manifestations of systemic lupus erythematosus (SLE) are well recognised, myelopathy complicating SLE is rare. A 35-year-old woman presented with non-specific symptoms and a respiratory tract infection but had serological evidence of SLE. She subsequently deteriorated rapidly, developing a catastrophic spinal cord syndrome. Her initial MRI was normal; but after 1 month, her encephalopathy having progressed, repeat imaging showed characteristic myelitic changes. She responded only slowly to a combination of cyclophosphamide and corticosteroids. This case exemplifies the mixed presentations of SLE, including the under-recognised 'subpial leukomyelopathy' of central nervous system lupus. It highlights the challenges in managing lupus-related myelopathy and the benefits of a multidisciplinary approach to care.

The prediagnostic phase of Parkinson's disease.

The field of prediagnostic Parkinson's disease (PD) is fast moving with an expanding range of clinical and laboratory biomarkers, and multiple strategies seeking to discover those in the earliest stages or those 'at risk'. It is widely believed that the highest likelihood of securing neuroprotective benefit from drugs will be in these subjects, preceding current point of diagnosis of PD. In this review, we outline current knowledge of the prediagnostic phase of PD, including an up-to-date review of risk factors (genetic and environmental), their relative influence, and clinical features that occur prior to diagnosis. We discuss imaging markers across a range of modalities, and the emerging literature on fluid and peripheral tissue biomarkers. We then explore current initiatives to identify individuals at risk or in the earliest stages that might be candidates for future clinical trials, what we are learning from these initiatives, and how these studies will bring the field closer to realistically commencing primary or secondary preventive trials for PD. Further progress in this field hinges on greater clinical and biological description, and understanding of the prediagnostic, peridiagnostic and immediate postdiagnostic stages of PD. Identifying subjects 3-5 years before they are currently diagnosed may be an ideal group for neuroprotective trials. At the very least, these initiatives will help clarify the stage before and around diagnosis, enabling the field to push into unchartered territory at the earliest stages of disease.

Bone health in chronic neurological diseases: a focus on multiple sclerosis and parkinsonian syndromes.

The importance of bone health is increasingly recognised, and there is mounting evidence that neurological conditions are associated with a significantly increased risk of osteoporosis and fractures. This increase in risk is likely to be multifactorial. Multiple sclerosis and Parkinson's disease were identified in the Global Longitudinal Study of Osteoporosis in Women study as significantly associated with osteoporosis. Here, we discuss the literature on bone health, falls and fractures in MS and akinetic-rigid syndromes, and suggest strategies to investigate and manage bone health in the neurology clinic.