Paroxysmal dysarthria-ataxia syndrome.

Paroxysmal dysarthria ataxia syndrome presents with recurrent, brief, stereotyped events of dysarthria, limb clumsiness, unsteady gait and vertigo or dizziness that can occur in association with lesions in the midbrain. We describe a case of a woman presenting with paroxysmal dysarthria and ataxia secondary to a midbrain lesion, treated successfully with carbamazepine.

Multiple sclerosis and the risk of infection: Association of British Neurologists consensus guideline.

Infection in people with multiple sclerosis (MS) is of major concern, particularly for those receiving disease-modifying therapies. This article explores the risk of infection in people with MS and provides guidance-developed by Delphi consensus by specialists involved in their management-on how to screen for, prevent and manage infection in this population.

Missense mutations in small muscle protein X-linked (SMPX) cause distal myopathy with protein inclusions.

Using deep phenotyping and high-throughput sequencing, we have identified a novel type of distal myopathy caused by mutations in the Small muscle protein X-linked (SMPX) gene. Four different missense mutations were identified in ten patients from nine families in five different countries, suggesting that this disease could be prevalent in other populations as well. Haplotype analysis of patients with similar ancestry revealed two different founder mutations in Southern Europe and France, indicating that the prevalence in these populations may be higher. In our study all patients presented with highly similar clinical features: adult-onset, usually distal more than proximal limb muscle weakness, slowly progressing over decades with preserved walking. Lower limb muscle imaging showed a characteristic pattern of muscle involvement and fatty degeneration. Histopathological and electron microscopic analysis of patient muscle biopsies revealed myopathic findings with rimmed vacuoles and the presence of sarcoplasmic inclusions, some with amyloid-like characteristics. In silico predictions and subsequent cell culture studies showed that the missense mutations increase aggregation propensity of the SMPX protein. In cell culture studies, overexpressed SMPX localized to stress granules and slowed down their clearance.

A practical approach to the patient presenting with dropped head.

Head drop, or having a dropped head, is an uncommon condition in which patients present with a disabling inability to lift their head. It may arise in many neurological conditions that can be divided into those with neuromuscular weakness of neck extensors and those with increased tone of neck flexors. The most common neuromuscular causes include myasthenia gravis, motor neurone disease and myositis, while neck dystonia secondary to movement disorders can cause an increased tone. Investigations should include blood tests, imaging, muscle biopsy and neurophysiological studies. Here, we present a man with dropped head and discuss the investigation and management of this condition.

Interpretation of vaccine associated neurological adverse events: a methodological and historical review.

As a result of significant recent scientific investment, the range of vaccines available for COVID-19 prevention continues to expand and uptake is increasing globally. Although initial trial safety data have been generally reassuring, a number of adverse events, including vaccine induced thrombosis and thrombocytopenia (VITT), have come to light which have the potential to undermine the success of the vaccination program. However, it can be difficult to interpret available data and put these into context and to communicate this effectively. In this review, we discuss contemporary methodologies employed to investigate possible associations between vaccination and adverse neurological outcomes and why determining causality can be challenging. We demonstrate these issues by discussing relevant historical exemplars and explore the relevance for the current pandemic and vaccination program. We also discuss challenges in understanding and communicating such risks to clinicians and the general population within the context of the 'infodemic' facilitated by the Internet and other media.

Cocaine-induced toxic leucoencephalopathy with complete clinical recovery.

A 45-year-old man, a regular cocaine user, presented with confusion and unusual behaviour to the emergency room. On examination he was unable to perform simple tasks or follow commands. He was treated for possible central nervous system infection. MRI of the brain showed multiple bilateral T2 hyperintense periventricular and deep white matter foci, best appreciated on FLAIR with contrast enhancement. He continued deteriorating, eventually becoming catatonic with extensor posturing and increased tone, requiring intensive therapy unit management. Repeat MRIs were also noted to show worsening changes. He was treated for a presumed inflammatory leucoencephalopathy with intravenous methylprednisolone, immunoglobulins, as well as plasmapheresis. After 2 weeks, the patient started to show clinical improvement with eventual transfer to a rehabilitation hospital. A year after his first presentation, the patient scored 30 out of 30 on the MMSE and his neurological examination was normal.

The Effects of Cold Arm Width and Metal Deposition on the Performance of a U-Beam Electrothermal MEMS Microgripper for Biomedical Applications.

Microelectromechanical systems (MEMS) have established themselves within various fields dominated by high-precision micromanipulation, with the most distinguished sectors being the microassembly, micromanufacturing and biomedical ones. This paper presents a horizontal electrothermally actuated 'hot and cold arm' microgripper design to be used for the deformability study of human red blood cells (RBCs). In this study, the width and layer composition of the cold arm are varied to investigate the effects of dimensional and material variation of the cold arm on the resulting temperature distribution, and ultimately on the achieved lateral displacement at the microgripper arm tips. The cold arm widths investigated are 14 µ m, 30 µ m, 55 µ m, 70 µ m and 100 µ m. A gold layer with a thin chromium adhesion promoter layer is deposited on the top surface of each of these cold arms to study its effect on the performance of the microgripper. The resultant ten microgripper design variants are fabricated using a commercially available MEMS fabrication technology known as a silicon-on-insulator multi-user MEMS process (SOIMUMPs)™. This process results in an overhanging 25 µ m thick single crystal silicon microgripper structure having a low aspect ratio (width:thickness) value compared to surface micromachined structures where structural thicknesses are of the order of 2 µ m. Finite element analysis was used to numerically model the microgripper structures and coupled electrothermomechanical simulations were implemented in CoventorWare ® . The numerical simulations took into account the temperature dependency of the coefficient of thermal expansion, the thermal conductivity and the electrical conductivity properties in order to achieve more reliable results. The fabricated microgrippers were actuated under atmospheric pressure and the experimental results achieved through optical microscopy studies conformed with those predicted by the numerical models. The gap opening and the temperature rise at the cell gripping zone were also compared for the different microgripper structures in this work, with the aim of identifying an optimal microgripper design for the deformability characterisation of RBCs.

Analytical, Numerical and Experimental Study of a Horizontal Electrothermal MEMS Microgripper for the Deformability Characterisation of Human Red Blood Cells.

Microgrippers are typical microelectromechanical systems (MEMS) that are widely used for micromanipulation and microassembly in both biological and micromanufacturing fields. This paper presents the design, modelling, fabrication and experimental testing of an electrothermal microgripper based on a 'hot and cold arm' actuator design that is suitable for the deformability characterisation of human red blood cells (RBCs). The analysis of the mechanical properties of human RBCs is of great interest in the field of medicine as pathological alterations in the deformability characteristics of RBCs have been linked to a number of diseases. The study of the microgripper's steady-state performance is initially carried out by the development of a lumped analytical model, followed by a numerical model established in CoventorWare® (Coventor, Inc., Cary, NC, USA) using multiphysics finite element analysis. Both analytical and numerical models are based on an electothermomechanical analysis, and take into account the internal heat generation due to the applied potential, as well as conduction heat losses through both the anchor pads and the air gap to the substrate. The models are used to investigate key factors of the actuator's performance including temperature distribution, deflection and stresses based on an elastic analysis of structures. Results show that analytical and numerical values for temperature and deflection are in good agreement. The analytical and computational models are then validated experimentally using a polysilicon microgripper fabricated by the standard surface micromachining process, PolyMUMPs™ (Durham, NC, USA). The microgripper's actuation is characterised at atmospheric pressure by optical microscopy studies. Experimental results for the deflection of the microgripper arm tips are found to be in good agreement with the analytical and numerical results, with process-induced variations and the non-linear temperature dependence of the material properties accounting for the slight discrepancies observed. The microgripper is shown to actuate to a maximum opening displacement of 9 µ m at an applied voltage of 3 V, thus being in line with the design requirement of an approximate opening of 8 µ m for securing and characterising a RBC.

A time and motion study of patients presenting at the accident and emergency department at Mater Dei Hospital.

BACKGROUND: To carry out a time and motion study of patients presenting at the Emergency Department (ED) by measuring waiting times at the ED dept throughout the day. The objectives were:• to determine whether waiting times are prolonged, and• if prolonged, at which station(s) bottlenecks occur most often in terms of duration and frequency.Results will be compared to the United Kingdom guidelines of stay at the emergency department. METHODS: A group of 11 medical students monitored all patients who attended ED between 0600 hours on the 25th August and 0600 hours on the 1st September 2008. For each 24 hour period, students were assigned to the triage room and the 3 priority areas where they monitored all patient-related activity, movement and waiting times so that length of stay (LOS) could be recorded. The key data recorded included patient characteristics, waiting times at various ED process stages, tests performed, specialist consultations and follow up until admitted, discharged, or referred to another hospital area. Average waiting times were calculated for each priority area. Bottle-necks and major limiting factors were identified. Results were compared against the United Kingdom benchmarks - i.e. 1 hour until first assessment, and 4 hours before admitting/discharge. RESULTS: 1779 patients presented to the ED in the week monitored. As expected, patients in the lesser priority areas (i.e. 2 & 3) waited longer before being assessed by staff. Patients requiring laboratory and imaging investigations had a prolonged length of stay, which varied depending on specific tests ordered. Specialty consultation was associated with longer waiting times. A major bottleneck identified was waiting times for inpatient admission. CONCLUSIONS: In conclusion, it was found that 30.3% of priority 1 patients, 86.3% of priority 2 patients and 76.8% of priority 3 patients waited more than 1 hour for first assessment. We conclude by proposing several changes that may expedite throughput.