Pharmacological Interventions for Sialorrhoea in People with Parkinson's Disease: A Systematic Review and Meta-Analysis.

Background/objectives: Sialorrhoea is a common non motor complication experienced by people with Parkinson's disease (PD). Despite its prevalence there is conflicting evidence on how to effectively treat it. Our aim was to establish the efficacy and safety outcomes of pharmacological interventions used to treat sialorrhoea in people with idiopathic PD. Methods: We registered and conducted a systematic review and meta-analysis (PROSPERO: CRD42016042470). We searched seven electronic databases from inception until July 2022. Quantitative synthesis was performed where data allowed using random effects models. Results: From 1374 records we included 13 studies (n = 405 participants). Studies were conducted in Europe, North America and China. There was marked heterogeneity in the interventions used, follow up times and outcome measures investigated. The main source of risk of bias identified was reporting bias. Five studies were included in the quantitative synthesis. Summary estimates showed administration of botulinum toxin significantly reduced saliva production, improved patient reported functional outcomes and was associated with an increase in adverse events. Conclusion: Sialorrhoea in PD is an important condition, but current data does not allow for strong recommendations on optimal pharmacological treatments. There is significant heterogeneity in outcomes measures used to evaluate the burden of sialorrhoea with lack of consensus on what constitutes clinically meaningful change. More research is required to better understand the underlying mechanism and potential treatments of sialorrhoea in idiopathic PD.

Epidemiological and cohort study finds no association between COVID-19 and Guillain-Barré syndrome.

Reports of Guillain-Barré syndrome (GBS) have emerged during the Coronavirus disease 2019 (COVID-19) pandemic. This epidemiological and cohort study sought to investigate any causative association between COVID-19 infection and GBS. The epidemiology of GBS cases reported to the UK National Immunoglobulin Database was studied from 2016 to 2019 and compared to cases reported during the COVID-19 pandemic. Data were stratified by hospital trust and region, with numbers of reported cases per month. UK population data for COVID-19 infection were collated from UK public health bodies. In parallel, but separately, members of the British Peripheral Nerve Society prospectively reported incident cases of GBS during the pandemic at their hospitals to a central register. The clinical features, investigation findings and outcomes of COVID-19 (definite or probable) and non-COVID-19 associated GBS cases in this cohort were compared. The incidence of GBS treated in UK hospitals from 2016 to 2019 was 1.65-1.88 per 100 000 individuals per year. GBS incidence fell between March and May 2020 compared to the same months of 2016-19. GBS and COVID-19 incidences during the pandemic also varied between regions and did not correlate with one another (r = 0.06, 95% confidence interval: -0.56 to 0.63, P = 0.86). In the independent cohort study, 47 GBS cases were reported (COVID-19 status: 13 definite, 12 probable, 22 non-COVID-19). There were no significant differences in the pattern of weakness, time to nadir, neurophysiology, CSF findings or outcome between these groups. Intubation was more frequent in the COVID-19 affected cohort (7/13, 54% versus 5/22, 23% in COVID-19-negative) attributed to COVID-19 pulmonary involvement. Although it is not possible to entirely rule out the possibility of a link, this study finds no epidemiological or phenotypic clues of SARS-CoV-2 being causative of GBS. GBS incidence has fallen during the pandemic, which may be the influence of lockdown measures reducing transmission of GBS inducing pathogens such as Campylobacter jejuni and respiratory viruses.

Emergency presentations of movement disorders.

Movement disorders are typically perceived as being gradually progressive conditions that are managed in outpatient settings. However, they may manifest de novo with an acute severe phenotype or an acute decompensation. A movement disorder becomes an emergency when it evolves acutely or subacutely over hours to days; delays in its diagnosis and treatment may cause significant morbidity and mortality. Here we address the clinical presentation, diagnosis and management of those movement disorder emergencies that are principally encountered in emergency departments, in acute receiving units or in intensive care units. We provide practical guidance for management in the acute setting where there are several treatable causes not to be missed. The suggested medication doses are predominantly based on expert opinion due to limited higher-level evidence. In spite of the rarity of movement disorder emergencies, neurologists need to be familiar with the phenomenology, potential causes and treatments of these conditions. Movement disorder emergencies divide broadly into two groups: hypokinetic and hyperkinetic, categorised according to their phenomenology. Most acute presentations are hyperkinetic and some are mixed.

Syncope in a new mother: a case of long-QT syndrome presenting after childbirth.

Diagnosis of inherited arrhythmia syndromes, including long-QT syndrome (LQTS), is challenging; however, early detection and initiation of therapies can reduce otherwise high rates of mortality. Two months following the birth of her first child a previously well 21-year-old female experienced four episodes of transient loss of consciousness (TLOC). The history was atypical for seizures but a video electroencephalogram (EEG) captured an episode with abnormal bifrontal epileptic discharge. She was commenced on levetiracetam. Within weeks of the birth of her second child she experienced five further episodes. During the subsequent hospital admission an electrocardiogram (ECG) recorded polymorphic ventricular tachycardia (VT) during a typical TLOC event. Other ECGs recorded a prolonged QT interval. A diagnosis of LQTS was made and TLOC episodes ceased on commencement of nadolol. The patient experienced 22 TLOC episodes before diagnosis - most likely from self-terminating VT. With widespread availability of effective treatments to reduce the risk of sudden cardiac death in such conditions, clinicians should always remember how the ECG is an essential investigation every time a patient presents with TLOC.

Accuracy of Parkinson's disease diagnosis in 610 general practice patients in the West of Scotland.

UK-based community studies have found high rates of misdiagnosis in Parkinson's disease (PD). Searches of prescription databases and case records identified 610 patients taking antiparkinson therapy for a PD diagnosis in 92 West of Scotland General Practices. Patients with no documented progression of parkinsonism and/or no increase in antiparkinson medication for 3 years were assessed by two movement disorder specialists. FP-CIT SPECT scanning was performed in clinically uncertain cases. Those considered unlikely to have PD had antiparkinson drugs tapered then stopped, with a minimum of 6 months follow-up. Age, sex and disease duration matched controls were also assessed. 64 of 89 (71.9%) patients meeting selection criteria were assessed, of whom 36 (56.3%) were appropriate for therapy withdrawal. Thirty three of those 36 patients (91.7%) and 3 of 64 (4.7%) controls stopped antiparkinson therapy without deterioration giving an overall total of 36 of 610 (5.9%). The revised diagnoses in this group were mainly essential tremor (ET) (n = 14) and vascular parkinsonism (VP) (n = 10). Patients managed in Primary Care were significantly more likely to complete therapy withdrawal than those attending a specialist clinic (15.3% vs. 2.6%, P < 0.0001). The total annual cost of antiparkinson medication for these 36 patients was 13,400 pounds; the mean duration of diagnosis was 6.8 years (SD 5.6). At least 1 in every 20 patients taking medication for PD is misdiagnosed. Nearly all of these patients can be identified by simple screening of prescription databases and case records in Primary Care, followed by clinical review, which allows withdrawal of unnecessary medication.

Geographical difference in Parkinson's disease prevalence within West Scotland.

The wide range in reported prevalence of Parkinson's disease (PD) in the United Kingdom (between 108 and 164 per 100,000) is usually attributed to differences in study methodology. We report prevalence of PD in four geographic areas within West Scotland, which was calculated using the same methodology, from prescription database searches within primary care, combined with full case record review. Crude prevalence was 119.2 per 100,000 (95% CI 109.7-128.6) and age-adjusted prevalence was 129.5 (95% CI 119.6-139.4) in 92 General Practices covering a population of 511,927. Prevalence was significantly lower in South Glasgow (men 98.3, CI 78.7-117.9; women 83.9, CI 65.6-102.2) than South Lanarkshire (men 202.7, CI 175.0-230.4; women 151.1, CI 127.7-174.5), age-adjusted rates, both P < 0.001. Factors associated with higher prevalence of PD, such as lower cigarette smoking rates, higher education level, and rural living, were higher in South Lanarkshire than South Glasgow, but the magnitude of the difference was greater than expected considering studies describing relative risk for these factors. Access to services, and specialist clinic attendance were both higher for South Glasgow, which may influence diagnostic accuracy, time to diagnosis, and time to initiating antiparkinson therapy. Exploration of these factors is justified to explain further such wide variation in PD prevalence.

The parkinsonism-hyperpyrexia syndrome.

The parkinsonism-hyperpyrexia syndrome (PHS) is a rare but potentially fatal complication seen in Parkinson's disease (PD) patients, most commonly following reduction or cessation of antiparkinson medications. Clinically it resembles neuroleptic malignant syndrome with rigidity, pyrexia, and reduced conscious level. There may be features of autonomic instability, and serum creatine kinase (CK) may be elevated. Complications of PHS include acute renal failure, aspiration pneumonia, deep venous thrombosis/pulmonary embolism, and disseminated intravascular coagulation (DIC). Management consists of dopaminergic drug replacement, supportive measures, and treatment of complications. The prognosis is improved with early recognition and management. Mortality of up to 4% has been reported, but an additional one-third of patients have permanent sequelae. Patients and physicians should be warned against sudden reduction in antiparkinson medications. PHS should always be considered in a patient with parkinsonism who presents with an acute deterioration in symptoms.

Elevated serum urate concentration independently predicts poor outcome following stroke in patients with diabetes.

BACKGROUND: Type 2 diabetes is a risk factor for stroke and confers increased risk of poor outcome and further vascular events following stroke. Hyperuricaemia occurs commonly in patients with type 2 diabetes, but its significance as a predictor of outcome following stroke is uncertain. We sought to investigate the prognostic significance of elevated serum urate concentration in diabetic subjects following stroke. METHODS: We studied a cohort of type 2 diabetes patients presenting to our unit with computed tomography-confirmed acute stroke. Fasting blood samples were drawn within 24 h of admission for urate concentration and standard battery of biochemistry and hematological tests. Information on age, stroke type, prior hypertension, smoking status, resolution time of symptoms and National Institutes of Health Stroke Score was collated. The main outcome event was time to myocardial infarction, recurrent stroke or vascular death, as defined in the CAPRIE trial. Stepwise proportional hazards regression was used to estimate the effect of the above variables on event-free survival following stroke. RESULTS: One hundred and forty patients were studied. Median follow-up duration was 974 days (IQR 163 to 1830 days). Sixty-four patients suffered an outcome event. Urate levels of greater than 0.42 mmol/L (p < 0.001) and an increasing NIHSS score (p < 0.001) independently predicted increased likelihood of suffering an event. CONCLUSION: Elevated urate concentration is significantly and independently associated with increased risk of future vascular events in diabetic stroke patients. Further studies to elucidate the mechanism of this observation are required.