Autoantibodies to Low-Density Lipoprotein Receptor-Related Protein 4 in Double Seronegative Myasthenia Gravis: A Systematic Review.

BACKGROUND: Myasthenia gravis (MG) is an autoimmune disorder of the neuromuscular junction in which a clinical diagnosis may be confirmed with serological testing. The most common autoantibodies used to support a diagnosis of MG are anti-acetylcholine receptor antibodies and anti-muscle-specific tyrosine kinase antibodies. In cases in which both of these autoantibodies are negative (termed double-seronegative [dSNMG]), other autoantibodies such as low-density lipoprotein receptor-related protein 4 (LRP4) may be used to aid in diagnosis. METHODS: We have undertaken a systematic literature review to identify studies that have assessed the frequency of anti-LRP4 antibodies in dSNMG patients and the characteristics of anti-LRP4+ dSNMG patients (epidemiology, clinical features, electromyographic findings, or management). PubMed, EMBASE, Medline, and Scopus were searched on January 14, 2017, using the medical subject headings "myasthenia gravis" and "low-density lipoprotein receptor-related protein 4" or "LRP4." RESULTS: The initial search identified 367 articles. Fourteen publications met the inclusion criteria. There were ten cross-sectional research studies, three were case series, and one was a case report. The majority of studies were limited by small sample sizes of LRP4+ dSNMG. There has been a wide range of frequencies of anti-LRP4 antibodies detected in different MG patient populations, some involving different laboratory techniques. CONCLUSIONS: LRP4+ dSNMG is more likely than LRP4- dSNMG to have a younger onset of disease and occur in females. LRP4+ dSNMG most often is mild in severity and often involves isolated ocular weakness. It typically responds well to pyridostigmine or prednisone.

Domperidone for Hypotension in Parkinson's Disease: A Systematic Review.

BACKGROUND: Domperidone is a proposed treatment of orthostatic hypotension (OH) in Parkinson's disease (PD). However, domperidone use in PD is tempered by concerns regarding QT prolongation and ventricular tachyarrhythmia and sudden cardiac death (VT/SCD). OBJECTIVE: The aim is to identify peer-reviewed studies in which either (1) the effect of domperidone on blood pressure in patients with PD, or (2) the adverse effects associated with domperidone use in PD patients has been reported. METHODS: PubMed, EMBASE, Medline and Scopus were searched using the terms Parkinson's disease and domperidone. RESULTS: Twenty-two articles fulfilled the inclusion criteria. One study was a randomized placebo-controlled trial with domperidone administration independent of the commencement of dopaminergic medications. This study identified a non-statistically significant trend that domperidone may be beneficial for OH in PD. Several studies identified statistically significant differences in BP with domperidone in the setting of initiating dopaminergic medication. There is currently the most evidence to support domperidone use with apomorphine commencement. Studies reporting domperidone adverse effects in PD patients were largely retrospective or cross-sectional. The identified studies demonstrated that domperidone may cause QT prolongation and is associated with increased risk of VT/SCD in PD patients with preexisting cardiac disease. CONCLUSIONS: Domperidone may help to ameliorate OH associated with dopaminergic medications in PD, namely when used in conjunction with apomorphine. When considering whether to use domperidone in PD, factors that should be taken into account include pre-existing heart disease and drug interactions, as well as the impact of OH on mobility, cognition and quality of life.