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.
View Article and Find Full Text PDFBone 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.
View Article and Find Full Text PDFThe European Stroke Organisation (ESO) guideline on Primary Angiitis of the Central Nervous System (PACNS), developed according to ESO standard operating procedures (SOP) and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology, was elaborated to assist clinicians in the diagnostic and treatment pathway of patients with PACNS in their decision making. A working group involving vascular neurologists, neuroradiologists, rheumatologists, a neuropathologist and a methodologist identified 17 relevant clinical questions; these were addressed according to the patient/population, intervention, comparison and outcomes (PICO) framework and systematic literature reviews were performed. Notably, each PICO was addressed with respect to large vessel (LV)-PACNS and small vessel (SV)-PACNS.
View Article and Find Full Text PDFFriedreich'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).
View Article and Find Full Text PDFBackground: 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).
View Article and Find Full Text PDFContext: Neurological disease can affect the rate of urine production and bladder storage function, increasing nocturia severity, with additional risks if mobility or cognition is impaired.
Objective: To conduct a systematic review (SR) of nocturia in neurological diseases and achieve expert consensus for management in clinics without neurologist input.
Evidence Acquisition: Four databases were searched from January 2000 to April 2020.
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.
Background: The cytotoxic T-lymphocyte antigen-4 (CTLA-4) pathway acts as a negative immune regulator of T-cell activation and promotes self-tolerance.
Case: We report the first case of biopsy-proven central nervous system inflammatory demyelination in the context of primary immunodeficiency and a novel variant.
Conclusion: This case has significant implications for the development of novel treatments for autoimmune conditions including multiple sclerosis and further emphasises the need for caution with clinical use of CTLA-4 immune checkpoint inhibitors in those with a history of inflammatory demyelination.
Objective: Takotsubo stress cardiomyopathy is characterized by dysfunction of the left ventricle of the heart including apical ballooning and focal wall-motion abnormalities. Although reported in association with seizures and intracerebral hemorrhage, there are no studies reporting its occurrence in patients having stereoelectroencephalography (sEEG).
Methods: A 38-year-old lady with no prior history of cardiac disease experienced sudden onset chest pain and acute left ventricular failure 4 hours following explantation of stereoelectroencephalogram electrodes.
Rhomboencephalitis-inflammation of the brainstem and cerebellum-has myriad clinical presentations including encephalopathy, cranial neuropathies, long tract signs and cerebellar dysfunction and is associated with significant morbidity and mortality. There are a variety of potential underlying causes that respond variably to treatment, including infections, parainfective syndromes, inflammatory disorders including autoimmune encephalitis and paraneoplastic syndromes. Here, we review its clinical presentation and outline a practical approach to its investigation, aiming to facilitate prompt diagnosis and confirmation of the underlying cause, to start appropriate management early and optimise the clinical outcome.
View Article and Find Full Text PDFCoronavirus disease of 2019 (COVID-19) is associated with hypercoagulopathy, but haemorrhage, including spontaneous intracerebral parenchymal haemorrhage and diffuse petechial cerebral haemorrhage, has also been reported. We present two cases of nonaneurysmal subarachnoid haemorrhage (SAH) in patients with severe COVID-19. Careful review of neuroimaging for haemorrhagic complications of COVID-19 should be undertaken, particularly for those patients receiving enhanced prophylaxis for venous thromboembolism.
View Article and Find Full Text PDFThe 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.
View Article and Find Full Text PDFThe 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.
View Article and Find Full Text PDFGiven the intuitive potential of stem cell therapy and limitations of current treatment options for progressive multiple sclerosis (MS), it is not surprising that patients consider undertaking significant clinical and financial risks to access stem cell transplantation. However, while increasing evidence supports autologous haematopoietic stem cell transplantation (AHSCT) in aggressive relapsing-remitting MS, interventions employing haematopoietic or other stem cells should otherwise be considered experimental and recommended only in the context of a properly regulated clinical study. Understandably, most neurologists are unfamiliar with AHSCT procedures and the specific requirements for quality assurance and safety standards, as well as post-procedure precautions and follow-up.
View Article and Find Full Text PDFObjective: Friedreich's ataxia is an incurable inherited neurological disease caused by frataxin deficiency. Here, we report the neuroreparative effects of myeloablative allogeneic bone marrow transplantation in a humanized murine model of the disease.
Methods: Mice received a transplant of fluorescently tagged sex-mismatched bone marrow cells expressing wild-type frataxin and were assessed at monthly intervals using a range of behavioral motor performance tests.