Preserving fertility: using cyclophosphamide and other cytotoxics in young people.

Cytotoxic agents such as cyclophosphamide are infrequently used in neurological practice. When they are, it is commonly in critically ill patients or in those with refractory inflammatory disorders. Cyclophosphamide in particular has a well-recognised negative impact on both female and male long-term fertility. This article summarises the data with regards the impact of cytotoxics on long-term fertility and describes the current options to preserve fertility in these patients. We hope this will provide neurologists with a useful aid for counselling patients for whom they are considering these treatments.

Crowned dens syndrome.

Crowned dens syndrome is a rare presentation of calcium pyrophosphate deposition disease. It is characterised by severe occipital pain and neck stiffness. Acute presentations are typically accompanied by fever and an inflammatory response and hence can be misdiagnosed as polymyalgia rheumatica or meningitis. Chronic relapsing presentations may be misdiagnosed as cervicogenic neck pain or occipital neuralgia. We present a patient who presented with a chronic relapsing form of crowned dens syndrome and discuss the epidemiology, typical presentation and management of this eminently treatable condition.

Parkinson's, where are we heading?

The prevalence of Parkinson's disease has rapidly increased over the last decade. This editorial discusses our current understanding of the pathophysiological basis for the condition, with a particular focus on the potential role of α-synuclein, and the consequent implications this has for both the development of new investigations and disease-modifying therapies. Specifically, the article discusses the development of a new diagnostic test for cerebrospinal fluid α-synuclein, the development of a new staging system for Parkinson's disease, which takes into account the α-synuclein, genetic and neuro-imaging status, and the results of two recently completed clinical trials, using monoclonal antibodies wherein α-synuclein is the principal target. We also discuss the increasing awareness of the importance of non-motor symptoms in Parkinson's disease including hyposmia, rapid eye movement sleep behaviour disorder, and autonomic and cognitive symptoms.

The longitudinal progression of autonomic dysfunction in Parkinson's disease: A 7-year study.

Background: Autonomic dysfunction, including gastrointestinal, cardiovascular, and urinary dysfunction, is often present in early Parkinson's Disease (PD). However, the knowledge of the longitudinal progression of these symptoms, and the connection between different autonomic domains, is limited. Furthermore, the relationship between the presence of autonomic symptoms in early-stage PD and olfactory dysfunction, a possible marker of central nervous system involvement, has not been fully investigated. Objectives: We aimed to investigate the occurrence and progression of autonomic dysfunction in recently diagnosed (< 2 years) untreated PD patients and determine any coexistence of symptoms in individual patients. We also investigated the relationship between autonomic symptoms, olfactory dysfunction, and motor impairment. Methods: Data were obtained from the Parkinson's Progression Markers Initiative (PPMI) database. Autonomic dysfunction was measured using the Scales for Outcomes in Parkinson's Disease (SCOPA-AUT). Symptom frequency and mean scores over 7 years were determined. The simultaneous occurrence of different autonomic symptoms was also examined. Finally, the relationships between SCOPA-AUT scores, olfactory dysfunction, and motor impairment were investigated using the University of Pennsylvania Smell Identification Test (UPSIT) and the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS), respectively. Results: Follow-up data were available for 7 years for 171 PD patients and for 5 years for 136 HCs. Mean SCOPA-AUT score increased significantly from baseline to the 7-year follow-up for each autonomic domain, except for female sexual dysfunction. Most patients reported three or more autonomic symptoms. Common clusters of symptoms were composed of combinations of gastrointestinal, urinary, thermoregulatory, and sexual dysfunction. At baseline, greater SCOPA-AUT total score was associated with lower UPSIT scores (r = -0.209, p = 0.006) and with greater total MDS-UDPRS III score (r = 0.218, p = 0.004). Conclusions: Autonomic dysfunction, often with coexistence of autonomic manifestations, is common in early PD and progressively worsens over the first 7 years of disease, suggesting that these symptoms should be addressed with appropriate treatments early in the disease. The association between greater autonomic dysfunction and greater olfactory impairment, coupled with the association with more severe motor scores at baseline, indicates that patients who show more severe autonomic dysfunction could also have more severe involvement of the central nervous system at the time of diagnosis.

Corrigendum: The longitudinal progression of autonomic dysfunction in Parkinson's disease: a 7-year study.

[This corrects the article DOI: 10.3389/fneur.2023.1155669.].

Focal myositis and contracture secondary to amiodarone extravasation from a peripheral cannula.

A 63-year-old man underwent cardioversion of atrial fibrillation with intravenous amiodarone through an antecubital fossa cannula. Mid-infusion, the cannula tissued. He developed immediate pain and swelling. At 3 weeks, he continued to have significant pain and had developed a fixed flexion deformity. MRI demonstrated focal myositis of the biceps and brachialis muscles. Treatment included physiotherapy and plastic surgery but sadly in spite of this, the patient has had minimal symptomatic improvement at 1 year. Amiodarone extravasation is well recognised to cause local injection site reactions. Involvement of deeper tissues is rare. To our knowledge, this is only the second description of a consequent focal myositis in the literature.

Positive anti-MOG antibodies in a patient with Sjögren's syndrome and transverse myelitis.

Twenty percent of patients with Sjögren's syndrome experience associated neurological disease. Transverse myelitis (TM) frequently forms part of a neuromyelitis optica spectrum disorder associated with the presence of anti-aquaporin 4 (AQP4) antibodies. We report the first described case of a patient who developed TM and the presence of a newly recognized antibody, anti-myelin oligodendrocyte protein (MOG), who went on to develop Sjögren's syndrome. AQP4 and MOG antibodies should be tested to guide prognostically the chances of further relapse as well as the type and duration of immunotherapy in patients with coexisting Sjögren's syndrome and TM.

Clarion call for histopathological clot analysis in "cryptogenic" ischemic stroke: implications for diagnosis and treatment.

Diagnosis, treatment, and secondary management of cryptogenic stroke patients pose a formidable challenge. The scenario is further complicated in patients with native and prosthetic valvular heart disease. We present a case study of a 36-year-old man who received intravenous thrombolysis (IV-tPA) and endovascular thrombectomy (EVT) for presumed "cryptogenic" complete middle cerebral artery infarction who made a surprisingly excellent clinical recovery despite poor baseline and postintervention neuroimaging. Retrospective gram stain of his clot confirmed a diagnosis of infective endocarditis. This raises an important issue regarding need for more routine histopathological analysis of clot retrieved after EVT in "cryptogenic" stroke patients particularly those with valvular heart disease.

The dangers of iodine-based contrasts in an elderly patient with thyroid disease.

Iodine-based contrast agents are widely used in angiographic and other radiological procedures. Clinicians are familiar with many of the potential adverse events from contrast agents including allergic reactions and contrast-induced nephropathy. This case describes a lesser known adverse event: 'contrast-induced thyrotoxicosis' and its implications on the presentation and management of a patient with severe coronary artery disease. The management of this case was difficult and required a long inpatient admission with use of prednisolone, propylthiouracil and planned treatment with radioiodine to control the thyrotoxicosis, as well as the use of several rate-limiting agents and antianginal medications to control atrial fibrillation and prevent further episodes of angina.

Heyde's syndrome: exploring the link between aortic stenosis and an acquired bleeding disorder.

Heyde's syndrome was first proposed in 1958. It refers to gastrointestinal haemorrhage resulting from a combination of aortic stenosis with angiodysplasia. This report explores the case of a 93-year-old lady who was admitted to hospital following a neck of femur fracture. She suffered from multiple comorbidities including renal failure and congestive heart failure secondary to critical aortic stenosis. As an inpatient she suffered an exacerbation of both her heart and renal failure postoperatively. A week later she suffered from heavy upper gastro-intestinal bleeding, which failed to respond to pharmacological and endoscopic therapies as well as angiographic embolisation. The pathophysiology of Heyde's syndrome: an acquired von Willebrand deficiency syndrome has a much wider impact than was commonly thought, both in terms of how common it is and in how the association may be extrapolated to a wide range of bleeding disorders, rather than simply angiodysplasia associated gastrointestinal haemorrhage.

Cardiovascular health monitoring in patients with psychotic illnesses: A project to investigate and improve performance in primary and secondary care.

Patients with psychotic illnesses are predicted to die 15 years younger than the national average. The chief cause is cardiovascular disease (1). Evidence-based guidelines including those produced by the National Institute of Health and clinical Excellence and the Quality Outcomes Framework, recommend regular monitoring of their cardiovascular risk (2,3,4). Primary health care audits were undertaken in an urban and a rural setting. These looked at the proportion of patients who had their physical health regularly monitored in line with NICE guidelines. Following an audit in general practice, it became clear that there was a group of patients that were chronic non-attenders. It was not clear whether these patients were the responsibility of the general practices or psychiatric services. An audit in secondary care then looked at the level of cardiovascular health monitoring in that setting, and the communication of results to primary care. These audits demonstrated that monitoring of cardiovascular health did not meet standards as set by NICE. Further to this, communication of findings between primary and secondary care was also poor. Primary care interventions included setting up Alert reminder boxes on the computer system and sending invitations for clinic attendance to 'at risk' patients. In secondary care interventions included redesign of the patient lists to include a way of monitoring cardiovascular health and generation of a new discharge summary to facilitate communication of cardiovascular indicators to primary care. These interventions have resulted in marked improvements in cardiovascular health monitoring in primary care, however, there is still room for considerable improvement. Discussions about further intervention strategies, and further audit cycles, are ongoing.

Perampanel: What is its Place in the Management of Partial Onset Epilepsy?

INTRODUCTION: Current pathways for treatment of partial onset epilepsy are diverse and include 14 new antiepileptic drugs (AEDs) licensed for use as either monotherapy or adjunctive therapy. However, the impact of these new AEDs on the treatment of partial epilepsy has so far been disappointing and there persists a need for additional drugs. Recently, perampanel, a first-in-class AED was licensed as an adjunct for the management of refractory partial onset seizures with or without secondary generalization in patients 12 years and older. This review highlights the current management of partial epilepsy and analyses the published clinical and preclinical data of perampanel to consider its potential role in the treatment of partial epilepsy. METHODS: A literature review of Embase, Medline and PubMed was conducted in April 2013 using the search terms 'perampanel' and 'AMPA receptor antagonist/blocker'. Publications were included if they discussed perampanel in the context of preclinical or clinical epilepsy. RESULTS: Perampanel acts on the glutamate pathway. It is a novel highly selective non-competitive alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist. This is a previously untargeted post-synaptic glutamate receptor. It is responsible for mediating rapid trans-synaptic signal transduction and hence believed to play a major role in seizure propagation. The three pivotal placebo-controlled trials of adjunctive perampanel demonstrated that the effective dosing range is 4-12 mg/day. The drug can be prescribed once daily, and its adverse effect profile is minimal with dizziness, fatigue, headache, and somnolence being the most commonly reported. CONCLUSIONS: Perampanel is a welcome addition as it represents an alternative approach in the management of epilepsy with potential to have a significant impact on the prognosis of intractable epilepsy. However, it has only recently been licensed for clinical use in Europe, the USA, and Canada, and there are no data directly comparing it with other AEDs; hence, it remains far too early to ascertain its place in the treatment of patients with partial epilepsy.