IgG4-related disease in the nervous system.

IgG4-related disease (IgG4-RD) is a recently described multisystemic disorder with a spectrum of manifestations that continue to be described. Nonetheless, there are recognised distinct patterns of disease. Neurological involvement is rare, particularly in isolation, but IgG4-RD may present with orbital disease, hypophysitis or pachymeningitis.

Can reproductive health services be used to screen for sexual and gender-based violence in post-conflict Northern Uganda? - a pilot study.

Background: Sexual and gender-based violence (SGBV), including rape and child sexual abuse, remains a significant challenge in post-conflict northern Uganda. Many victims have never sought help. Consequently, the scale of the problem is not known, and SGBV victims' injuries, both psychological and physical, remain hidden and unresolved.

Efficacy and safety of autologous haematopoietic stem cell transplantation versus alemtuzumab, ocrelizumab, ofatumumab or cladribine in relapsing remitting multiple sclerosis (StarMS): protocol for a randomised controlled trial.

Introduction: Autologous haematopoietic stem cell transplantation (aHSCT) is increasingly used as treatment for patients with active multiple sclerosis (MS), typically after failure of disease-modifying therapies (DMTs). A recent phase III trial, 'Multiple Sclerosis International Stem Cell Transplant, MIST', showed that aHSCT resulted in prolonged time to disability progression compared with DMTs in patients with relapsing remitting MS (RRMS). However, the MIST trial did not include many of the current high-efficacy DMTs (alemtuzumab, ocrelizumab, ofatumumab or cladribine) in use in the UK within the control arm, which are now offered to patients with rapidly evolving severe MS (RES-MS) who are treatment naïve.

The Bone Marrow Microenvironment in Immune-Mediated Inflammatory Diseases: Implications for Mesenchymal Stromal Cell-Based Therapies.

Bone marrow (BM)-derived mesenchymal stromal cells (MSCs) are promising candidates for cell-based therapy for several immune-mediated inflammatory diseases (IMIDs) due to their multiplicity of immunomodulatory and reparative properties and favorable safety profile. However, although preclinical data were encouraging, the clinical benefit demonstrated in clinical trials of autologous MSC transplantation in a number of conditions has been less robust. This may be explained by the growing body of evidence pointing to abnormalities of the bone marrow microenvironment in IMIDs, including impaired MSC function.

Acute flaccid myelitis: not uncommon in rural Uganda?

Acute Flaccid Myelitis is a paralytic illness with significant similarities to poliomyelitis, and which affects predominantly children. It was first fully delineated only in 2014 in the USA, occurring in epidemic clusters with a likely overall increasing incidence. It has subsequently rapidly been identified in Europe, the UK, and Australasia and the Far East, confirming it to be an emerging, global, infectious neurological disease.

An open-label pilot study of recombinant granulocyte-colony stimulating factor in Friedreich's ataxia.

Friedreich's ataxia (FA) is an inherited progressive neurodegenerative disease for which there is no proven disease-modifying treatment. Here we perform an open-label, pilot study of recombinant human granulocyte-colony stimulating factor (G-CSF) administration in seven people with FA (EudraCT: 2017-003084-34); each participant receiving a single course of G-CSF (Lenograstim; 1.28 million units per kg per day for 5 days).

The neurology of chronic nodding syndrome.

Nodding syndrome is an uncommon disorder of childhood onset and unknown cause, presenting with nodding seizures, and which appears to occur exclusively in clusters in sub-Saharan Africa. An endemic pattern of disease was initially described in Tanzania and in Liberia; epidemic occurrences were later reported in South Sudan and northern Uganda. Not the least significant of the many questions remaining about nodding syndrome concerns the common presence or otherwise of neurological features other than seizures-clearly relevant to the core issue of whether this is a focal, primary epileptic disease, or a multi-system CNS disorder, with, in turn implications for its aetiology.

Evaluating the feasibility of a real world pharmacovigilance study (OPTIMISE:MS).

Background: Clinical trial populations do not fully reflect routine practice. The power of routinely collected data to inform clinical practice is increasingly recognised.

Methods: The OPTIMISE:MS pharmacovigilance study is a prospective, pragmatic observational study, conducted across 13 UK MS centres.

Repeat infusion of autologous bone marrow cells in progressive multiple sclerosis - A phase I extension study (SIAMMS II).

Background: During the safety and feasibility 'Study of Intravenous Autologous Marrow in Multiple Sclerosis (SIAMMS)', intravenous infusion of autologous marrow was well tolerated. The efficacy of the approach is being explored in a placebo-controlled randomised controlled trial (ACTiMuS, NCT01815632) but it is not known whether repeated infusions will be required to optimise benefit. The objective of the current study was to explore the safety and feasibility of repeat treatment with intravenous autologous bone marrow for patients with progressive multiple sclerosis (MS).

Reduced expression of mitochondrial fumarate hydratase in progressive multiple sclerosis contributes to impaired in vitro mesenchymal stromal cell-mediated neuroprotection.

Background: Cell-based therapies for multiple sclerosis (MS), including those employing autologous bone marrow-derived mesenchymal stromal cells (MSC) are being examined in clinical trials. However, recent studies have identified abnormalities in the MS bone marrow microenvironment.

Objective: We aimed to compare the secretome of MSC isolated from control subjects (C-MSC) and people with MS (MS-MSC) and explore the functional relevance of findings.

OPTIMISE: MS study protocol: a pragmatic, prospective observational study to address the need for, and challenges with, real world pharmacovigilance in multiple sclerosis.

Introduction: The power of 'real world' data to improve our understanding of the clinical aspects of multiple sclerosis (MS) is starting to be realised. Disease modifying therapy (DMT) use across the UK is driven by national prescribing guidelines. As such, the UK provides an ideal country in which to gather MS outcomes data.

CNS involvement in systemic vasculitides.

Both the CNS and the PNS can be involved in almost all of the vasculitides - including the primary systemic vasculitic disorders, such as microscopic polyangiitis and polyarteritis nodosa, and in non-vasculitic systemic disorders, such as systemic lupus erythematosis and sarcoidosis. The latter diseases also include infections and toxininduced disorders - particularly drugs of abuse such as cocaine and amphetamines. Here we will summarise the spectrum of these disorders as they affect the CNS, concentrating in particular on their distinguishing clinical and investigational features.

Tetanus in a rural low-income intensive care unit setting.

Tetanus is a potentially severe but preventable infection. In resource-rich settings, vaccination programmes have reduced tetanus to a rare disease, though still carrying an overall mortality of some 13%. However, in low-income settings, tetanus remains common, and is a significant cause of mortality-though major World Health Organisation programmes are successfully targeting neonatal and maternal disease.

Prolonged disorders of consciousness: a critical evaluation of the new UK guidelines.

In March 2020, the Royal College of Physicians in the UK published national guidelines on the management of patients with prolonged disorders of consciousness, updating their 2013 guidance 'particularly in relation to recent developments in assessment and management and … changes in the law governing … the withdrawal of clinically assisted nutrition and hydration'. The report's primary focus is on patients who could live for many years with treatment and care. This update, by a neurologist, an imaging neuroscientist, and a lawyer-ethicist, questions the document's rejection of any significant role for neuroimaging techniques including functional MRI and/or bedside EEG to detect covert consciousness in such patients.

Nodding syndrome: a concise review.

Nodding syndrome is an uncommon epileptic disorder of childhood onset, which appears to occur exclusively in clusters in sub-Saharan Africa. It was first reported in the 1960s, in what is now southern Tanzania, then in Liberia, and later in South Sudan and northern Uganda, with both epidemic and endemic patterns described. The cause remains unknown.

Maternal micro-chimeric cells in the multiple sclerosis brain.

Maternal microchimeric cells (MMC) pass across the placenta from a mother to her baby during pregnancy. MMC have been identified in healthy adults, but have been reported to be more frequent and at a higher concentration in individuals with autoimmune diseases. MMC in brain tissue from individuals with autoimmune neurological disease has never previously been explored.

The diagnosis of primary central nervous system vasculitis.

The diagnosis of primary central nervous system (CNS) vasculitis is often difficult. There are neither specific clinical features nor a classical clinical course, and no blood or imaging investigations that can confirm the diagnosis. Contrast catheter cerebral angiography is neither specific nor sensitive, yet still underpins the diagnosis in many published studies.

Association of Initial Disease-Modifying Therapy With Later Conversion to Secondary Progressive Multiple Sclerosis.

Importance: Within 2 decades of onset, 80% of untreated patients with relapsing-remitting multiple sclerosis (MS) convert to a phase of irreversible disability accrual termed secondary progressive MS. The association between disease-modifying treatments (DMTs), and this conversion has rarely been studied and never using a validated definition.

Objective: To determine the association between the use, the type of, and the timing of DMTs with the risk of conversion to secondary progressive MS diagnosed with a validated definition.

Dysregulation of Mesenchymal Stromal Cell Antioxidant Responses in Progressive Multiple Sclerosis.

The potential of autologous cell-based therapies including those using multipotent mesenchymal stromal cells (MSCs) is being investigated for multiple sclerosis (MS) and other neurological conditions. However, the phenotype of MSC in neurological diseases has not been fully characterized. We have previously shown that MSC isolated from patients with progressive MS (MS-MSC) have reduced expansion potential, premature senescence, and reduced neuroprotective potential in vitro.