Publications by authors named "Saiju Jacob"

A newly identified subtype of hereditary axonal motor neuropathy, characterized by early proximal limb involvement, has been discovered in a cohort of 34 individuals with biallelic variants in von Willebrand factor A domain-containing 1 (). This study further delineates the disease characteristics in a cohort of 20 individuals diagnosed through genome or exome sequencing, incorporating neurophysiological, laboratory and imaging data, along with data from previously reported cases across three different studies. Newly reported clinical features include hypermobility/hyperlaxity, axial weakness, dysmorphic signs, asymmetric presentation, dystonic features and, notably, upper motor neuron signs.

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Stiff-person syndrome.

Pract Neurol

September 2024

Article Synopsis
  • * Symptoms arise from abnormal neuronal excitability due to disrupted GABA and glycine neurotransmission, and SPS can overlap with other autoimmune conditions such as autoimmune epilepsy and progressive encephalomyelitis.
  • * Early diagnosis is crucial to prevent irreversible disabilities; the review provides insights into clinical signs that may indicate SPS, along with a diagnostic algorithm and treatment options including immunotherapy and GABA-ergic medications.
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Myasthenia gravis (MG) is one of the most well characterised autoimmune disorders affecting the neuromuscular junction with autoantibodies targeting the acetylcholine receptor (AChR) complex. The vast majority of patients present with ocular symptoms including double vision and ptosis, but may progress on to develop generalised fatiguable muscle weakness. Severe involvement of the bulbar muscles can lead to dysphagia, dysarthria and breathing difficulties which can progress to myasthenic crisis needing ventilatory support.

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Background: There are limited data on the real-world healthcare resource use (HCRU) and management costs of myasthenia gravis (MG) in England.

Objective: This study aims to assess the burden of disease for patients with MG in England.

Design: A retrospective, observational cohort study of adult patients diagnosed with MG, using data from the Hospital Episode Statistics data warehouse.

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Article Synopsis
  • Azathioprine is the first choice medicine for treating myasthenia gravis, but many people also use mycophenolate and methotrexate as alternatives.
  • A survey of 235 people found that azathioprine caused liver problems in 23% of users, mycophenolate led to diarrhea in 14%, and methotrexate made 18% feel tired.
  • Women generally have more side effects from these medicines, and azathioprine is often stopped more often than the other two due to these side effects, showing there’s a need for better treatments.
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Patient-reported quality-of-life (QoL) and carer impacts are not reported after leucine-rich glioma-inactivated 1-antibody encephalitis (LGI1-Ab-E). From 60 patients, 85% (51 out of 60) showed one abnormal score across QoL assessments and 11 multimodal validated questionnaires. Compared to the premorbid state, QoL significantly deteriorated (p < 0.

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Article Synopsis
  • * A comprehensive review of published studies highlights the need for updated definitions, consistent patient assessments, and new treatment algorithms to better tailor therapies to individual patients.
  • * The impact of gMG extends beyond physical symptoms, affecting mental health and quality of life, but innovative therapies and biomarkers could lead to improved management and outcomes for patients.
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Article Synopsis
  • * Patients often experience varying degrees of muscle weakness that can become severe and life-threatening if it affects muscles necessary for breathing and swallowing.
  • * The article discusses how complement system involvement contributes to the damage at the neuromuscular junction and reviews current therapies targeting this pathway, highlighting their efficacy and safety based on recent studies.
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Susac syndrome is a likely autoimmune microangiopathy affecting the brain, retina and inner ear. Due to the rarity of this condition, diagnosis and treatment can be challenging. Diagnosis is based on the presence of the clinical triad of central nervous system dysfunction, branch retinal artery occlusions and sensorineural hearing loss.

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Myasthenia gravis (MG), a prototype autoimmune neurological disease, had its therapy centred on corticosteroids, non-steroidal broad-spectrum immunotherapy and cholinesterase inhibitors for several decades. Treatment-refractory MG and long-term toxicities of the medications have been major concerns with the conventional therapies. Advances in the immunology and pathogenesis of MG have ushered in an era of newer therapies which are more specific and efficacious.

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Autoimmune encephalitis can be classified into antibody-defined subtypes, which can manifest with immunotherapy-responsive movement disorders sometimes mimicking non-inflammatory aetiologies. In the elderly, anti-LGI1 and contactin associated protein like 2 (CASPR2) antibody-associated diseases compose a relevant fraction of autoimmune encephalitis. Patients with LGI1 autoantibodies are known to present with limbic encephalitis and additionally faciobrachial dystonic seizures may occur.

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Background: Patients with generalized myasthenia gravis (MG) often experience debilitating exacerbations, with the possibility of life-threatening respiratory crises requiring hospitalization. Long-term longitudinal studies are needed to understand the burden of MG, including in patients whose disease is refractory to conventional treatment.

Methods: A retrospective, longitudinal, cohort study was conducted of patients in England aged ≥ 18 years with treatment-refractory or non-refractory MG, using data recorded during 1997-2016 in the Clinical Practice Research Datalink and the Hospital Episode Statistics databases.

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Background: There are few studies exploring the prognostic factors in patients with aquaporin-4 (AQP4)-IgG positive neuromyelitis optica spectrum disorder (NMOSD).

Objective: To assess the predictors of outcome in patients with AQP4-antibody positive NMOSD from a United Kingdom (UK) population.

Methods: A retrospective study of 52 patients from 2 neuroscience centres in the UK Midlands.

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Article Synopsis
  • Autoimmune neurological disorders often require immunosuppressive therapies, but some patients with refractory conditions may not fully recover with standard treatments and need alternative therapies.
  • Common alternative treatments include intravenous immunoglobulin, plasma exchange (PLEX), and immune-modulating therapies, particularly for conditions discussed at the 2018 Midlands Neurological Society meeting.
  • Accurate diagnosis is crucial since misdiagnoses can lead to ineffective treatments; for example, POEMS syndrome can be incorrectly identified as CIDP, which responds favorably to PLEX, whereas POEMS does not.
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Background: Stiff person syndrome (SPS) is an autoimmune condition involving antibodies against several components of the inhibitory synapse in the spinal cord, with glutamic acid decarboxylase antibodies being the predominant immune marker. SPS affects approximately 1 patient per million population per year. The effect of intravenous immunoglobulin (IVIG) has been established, but studies on the long-term efficacy of regular IVIG are limited.

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Article Synopsis
  • MRI is crucial for evaluating brain lesions, but conventional MRI lacks specificity.
  • Multiparametric MRI, which includes advanced techniques like diffusion and perfusion-weighted imaging, offers better insights into tissue conditions.
  • This review aims to illustrate the effectiveness of multiparametric MRI in diagnosing and planning treatment, showcasing cases that highlight its superior ability to distinguish between cancerous and non-cancerous lesions compared to standard MRI.
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Background: In the phase III eculizumab for refractory generalized myasthenia gravis REGAIN study [ClinicalTrials.gov identifier: NCT01997229] and its open-label extension (OLE) [ClinicalTrials.gov identifier: NCT02301624], patients with treatment-refractory antiacetylcholine receptor antibody-positive generalized myasthenia gravis had clinically meaningful improvements with eculizumab placebo.

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Background: The efficacy and tolerability of eculizumab were assessed in REGAIN, a 26-week, phase 3, randomized, double-blind, placebo-controlled study in anti-acetylcholine receptor antibody-positive (AChR+) refractory generalized myasthenia gravis (gMG), and its open-label extension.

Methods: Attainment of 'minimal symptom expression' was evaluated using patient-reported outcome measures of gMG symptoms [MG activities of daily living scale (MG-ADL), 15-item MG quality of life questionnaire (MG-QOL15)] at the completion of REGAIN and during the open-label extension. 'Minimal symptom expression' was defined as MG-ADL total score of 0-1 or MG-QOL15 total score of 0-3.

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Neocortical-hippocampal interactions support new episodic (event) memories, but there is conflicting evidence about the dependence of remote episodic memories on the hippocampus. In line with systems consolidation and computational theories of episodic memory, evidence from model organisms suggests that the cornu ammonis 3 (CA3) hippocampal subfield supports recent, but not remote, episodic retrieval. In this study, we demonstrated that recent and remote memories were susceptible to a loss of episodic detail in human participants with focal bilateral damage to CA3.

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