COVID-19 in Multiple Sclerosis: Clinically reported outcomes from the UK Multiple Sclerosis Register.

BACKGROUND: In March 2020, the United Kingdom Multiple Sclerosis Register (UKMSR) established an electronic case return form, designed collaboratively by MS neurologists, to record data about COVID-19 infections in people with MS (pwMS). OBJECTIVES: Examine how hospital admission and mortality are affected by disability, age and disease modifying treatments (DMTs) in people with Multiple Sclerosis with COVID-19. METHODS: Anonymised data were submitted by clinical teams. Regression models were tested for predictors of hospitalisation and mortality outcomes. Separate analyzes compared the first and second 'waves' of the pandemic. RESULTS: Univariable analysis found hospitalisation and mortality were associated with increasing age, male gender, comorbidities, severe disability, and progressive MS; severe disability showed the highest magnitude of association. Being on a DMT was associated with a small, lower risk. Multivariable analysis found only age and male gender were significant. Post hoc analysis demonstrated that factors were significant for hospitalisation but not mortality. In the second wave, hospitalisation and mortality were lower. Separate models of the first and second wave using age and gender found they had a more important role in the second wave. CONCLUSIONS: Features associated with poor outcome in COVID-19 are similar to other populations and being on a DMT was not found to be associated with adverse outcomes, consistent with smaller studies. Once in hospital, no factors were predictive of mortality. Reassuringly, mortality appears lower in the second wave.

Sensitivity of multi-shell NODDI to multiple sclerosis white matter changes: a pilot study.

Diffusion tensor imaging (DTI) is sensitive to white matter (WM) damage in multiple sclerosis (MS), not only in focal lesions but also in the normal-appearing WM (NAWM). However, DTI indices can also be affected by natural spatial variation in WM, as seen in crossing and dispersing white matter fibers. Neurite orientation dispersion and density imaging (NODDI) is an advanced diffusion-weighted imaging technique that provides distinct indices of fiber density and dispersion. We performed NODDI of lesion tissue and NAWM in five MS patients and five controls, comparing the technique with traditional DTI. Both DTI and NODDI identified tissue damage in NAWM and in lesions. NODDI was able to detect additional changes and it provided better contrast in MS-NAWM microstructure, because it distinguished orientation dispersion and fiber density better than DTI. We showed that NODDI is viable in MS patients and that it offers, compared with DTI parameters, improved sensitivity and possibly greater specificity to microstructure features such as neurite orientation.

Neuromyelitis optica spectrum disorder related tonic spasms responsive to lacosamide.

Paroxysmal tonic spasms [PTS] are common in patients with neuromyelitis optica spectrum disorder (NMOSD).1 2 In patients with demyelinating disease, PTS can significantly reduce the quality of life, limit activities of daily living and the rehabilitative process following an acute relapse 3. As in patients with multiple sclerosis (MS), paroxysmal tonic spasms in NMOSD usually respond well to treatment with carbamazepine.2 However, the optimal treatment in patients where carbamazepine is contraindicated or poorly tolerated is unclear. We describe a patient with NMOSD with severe paroxysmal tonic spasms who did not tolerate carbamazepine but was successfully treated with lacosamide (Vimpat).

Antecedent anti-NMDA receptor encephalitis in two patients with multiple sclerosis.

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is an autoimmune disorder characterised by psychiatric symptoms, movement disorder and seizures often evolving into a severe encephalopathy. An overlap has recently been recognised between anti-NMDAR encephalitis and inflammatory demyelinating disorders, particularly neuromyelitis optical spectrum disorder (NMOSD). In this case report, we describe two patients with an initial presentation consistent with anti-NMDAR encephalitis who have subsequently developed relapsing-remitting multiple sclerosis (MS) and discuss the literature pertaining to potential overlap between NMDAR encephalitis and inflammatory demyelinating disorders.

Association of asymptomatic spinal cord lesions and atrophy with disability 5 years after a clinically isolated syndrome.

BACKGROUND: Spinal cord pathology is an important substrate for long-term disability in multiple sclerosis (MS). OBJECTIVE: To investigate longitudinal changes in spinal cord lesions and atrophy in patients with a non-spinal clinically isolated syndrome (CIS), and how they relate to the development of disability. METHODS: In all, 131 patients with a non-spinal CIS had brain and spinal cord imaging at the time of CIS and approximately 5 years later (median: 5.2 years, range: 3.0-7.9 years). Brain magnetic resonance imaging (MRI) measures consisted of T2-hyperintense and T1-hypointense lesion loads plus brain atrophy. Spinal cord MRI measures consisted of lesion number and the upper cervical cord cross-sectional area (UCCA). Disability was measured using the Expanded Disability Status Scale (EDSS). Multiple linear regression was used to identify independent predictors of disability after 5 years. RESULTS: During follow-up, 93 (71%) patients were diagnosed with MS. Baseline spinal cord lesion number, change in cord lesion number and change in UCCA were independently associated with EDSS ( R2 = 0.53) at follow-up. Including brain T2 lesion load and brain atrophy only modestly increased the predictive power of the model ( R2 = 0.64). CONCLUSION: Asymptomatic spinal cord lesions and spinal cord atrophy contribute to the development of MS-related disability over the first 5 years after a non-spinal CIS.

Developmental programming of polycystic ovary syndrome (PCOS): prenatal androgens establish pancreatic islet α/ß cell ratio and subsequent insulin secretion.

Exogenous androgenic steroids applied to pregnant sheep programmes a PCOS-like phenotype in female offspring. Via ultrasound guidance we applied steroids directly to ovine fetuses at d62 and d82 of gestation, and examined fetal (day 90 gestation) and postnatal (11 months old) pancreatic structure and function. Of three classes of steroid agonists applied (androgen - Testosterone propionate (TP), estrogen - Diethystilbesterol (DES) and glucocorticoid - Dexamethasone (DEX)), only androgens (TP) caused altered pancreatic development. Beta cell numbers were significantly elevated in prenatally androgenised female fetuses (P = 0.03) (to approximately the higher numbers found in male fetuses), whereas alpha cell counts were unaffected, precipitating decreased alpha:beta cell ratios in the developing fetal pancreas (P = 0.001), sustained into adolescence (P = 0.0004). In adolescence basal insulin secretion was significantly higher in female offspring from androgen-excess pregnancies (P = 0.045), and an exaggerated, hyperinsulinaemic response to glucose challenge (P = 0.0007) observed, whereas prenatal DES or DEX treatment had no effects upon insulin secretion. Postnatal insulin secretion correlated with beta cell numbers (P = 0.03). We conclude that the pancreas is a primary locus of androgenic stimulation during development, giving rise to postnatal offspring whose pancreas secreted excess insulin due to excess beta cells in the presence of a normal number of alpha cells.

Neurological complications of acute multifocal placoid pigment epitheliopathy.

Acute multifocal placoid pigment epitheliopathy (AMPPE) is an autoimmune chorioretinal disease that can be complicated by neurological involvement. There is limited information on this potentially treatable condition in the neurological literature. The objective of this patient series is to describe the neurological complications of AMPPE. We retrospectively identified patients with neurological complications of AMPPE seen at Auckland Hospital between 2008 and 2013 and summarised cases in the literature between 1976 and 2013. We identified five patients with neurological complications of AMPPE at Auckland Hospital and 47 reported patients. These patients demonstrated a spectrum of neurological involvement including isolated headache, stroke or transient ischaemic attack, seizures, venous sinus thrombosis, optic neuritis, sensorineural hearing loss and peripheral vestibular disorder. We propose criteria to define AMPPE with neurological complications. A cerebrospinal fluid (CSF) lymphocytosis in a patient with isolated headache may predict the development of cerebrovascular complications of AMPPE. Patients with cerebrovascular complications of AMPPE have a poor prognosis with high rates of death and neurological disability among survivors. Predictors of poor outcome in those who develop neurological complications of AMPPE are a relapsing course, generalised seizures and multifocal infarction on MRI. All patients with neurological complications of AMPPE, including headache alone, should be investigated with an MRI brain and CSF examination. Patients with focal neurological symptoms should receive intravenous (IV) methylprednisolone followed by a tapering course of oral steroids for at least 3months. Patients with AMPPE and an isolated headache with a CSF pleocytosis should be treated with oral steroids.

Intravenous thrombolysis is unsafe in stroke due to infective endocarditis.

Embolic stroke is the most common neurological complication of infective endocarditis and a major source of morbidity and mortality. Septic embolism is considered a contraindication to intravenous thrombolysis in patients with ischaemic stroke because of concerns over an increased risk of intracranial haemorrhage. We describe a patient with occult endocarditis who was treated with thrombolysis for acute stroke and review other cases reported in the literature.

Inhibition of elastase by N-sulfonylaryl beta-lactams: anatomy of a stable acyl-enzyme complex.

beta-Lactam inhibitors of transpeptidase enzymes involved in cell wall biosynthesis remain among the most important therapeutic agents in clinical use. beta-Lactams have more recently been developed as inhibitors of serine proteases including elastase. All therapeutically useful beta-lactam inhibitors operate via mechanisms resulting in the formation of hydrolytically stable acyl-enzyme complexes. Presently, it is difficult to predict which beta-lactams will form stable acyl-enzyme complexes with serine enzymes. Further, the factors that result in the seemingly special nature of beta-lactams versus other acylating agents are unclear-if indeed they exist. Here we present the 1.6 A resolution crystal structure of a stable acyl-enzyme complex formed between porcine pancreatic elastase and a representative monocyclic beta-lactam, which forms a simple acyl-enzyme. The structure shows that the ester carbonyl is not located within the oxyanion hole and the "hydrolytic" water is displaced. Combined with additional kinetic and mass spectrometric data, the structure allows the rationalization of the low degree of hydrolytic lability observed for the beta-lactam-derived acyl-enzyme complex.

Left atrial ball thrombus: review of clinical and echocardiographic manifestations with suggestions for management.

Left atrial ball thrombus is an infrequent clinical syndrome, which can have a catastrophic outcome but can be readily treated when recognized. It is usually a complication of long-standing rheumatic mitral stenosis. Symptomatic presentation is variable: fragmentation of the thrombus followed by peripheral embolization will produce ischemia or infarction of myocardium, brain, viscera, or extremities; random, intermittent, partial, or total occlusion of the mitral valve orifice may cause syncope, pulmonary congestion, and occasionally sudden death in other patients. Embolic and obstructive phenomena may also occur together. Cardiac physical findings usually suggest mitral stenosis; variability in the intensity of the diastolic rumble is common. Two-dimensional echocardiography is the gold standard for identifying ball thrombus. Cardiac catheterization provides assessment of coronary artery status when needed. The outcome of untreated ball thrombus is unlikely to be favorable. The results of anticoagulation and thrombolysis are unpredictable and potentially as harmful as no treatment at all. Current evidence although scant suggests that prompt surgical removal of the free thrombus, often in conjunction with mitral valve repair or replacement, is the appropriate therapeutic course in most patients.

Massive left atrial thrombus: a possible paraneoplastic complication of breast carcinoma.

We describe a patient with long-standing rheumatic mitral valve disease, left atrial dilatation, and a precommissurotomy history of left atrial thrombus. Following operation she was maintained on daily aspirin as an antithrombotic measure. For 6 years she had no evidence, echocardiographically, of left atrial thrombus. She underwent surgery for apparently nonmetastatic breast cancer in early 1986. In May 1986 the left atrium was echocardiographically clear. At approximately the same time, recurrence was found at the suture line. In October 1987, two metastatic lung lesions and a very large left atrial mass were detected by computed tomography. The atrial mass was surgically removed and found to be a thrombus. There was a striking temporal correlation between dissemination of carcinoma and development of a massive atrial thrombus.

Percutaneous removal of ventricular pacemaker electrodes using a Dormier basket.

Four permanent ventricular endocardial pacemaker electrodes which could not be removed via their insertion site have been retrieved via the femoral vein using a Dormier basket. Apart from short-lived ventricular arrhythmias no complications occurred in any case. Where removal of an otherwise unaccessible ventricular pacemaker electrode is considered essential the use of a Dormier basket percutaneously appears to be effective and more acceptable than surgical removal.

Aortic dissection: morphology and differential flow velocity patterns demonstrated by magnetic resonance imaging.

A case of chronic aortic dissection is presented, in which computed tomography and magnetic resonance imaging both demonstrated the abnormality non-invasively. Velocity flow patterns within the true and false lumens obtained by magnetic resonance imaging, using a flow-mapping technique, gave a more thorough analysis.

Cross-sectional echocardiographic demonstration of biventricular thrombus.

Nine months following extensive myocardial infarction, a 60-year-old man presented with intermittent right heart failure. Cross-sectional echocardiography demonstrated biventricular thrombi, the right ventricular thrombus being very close to the tricuspid valve and possibly interfering with its function. Post-mortem examination confirmed the echocardiographic findings.