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Journal of Inherited Metabolic Disease Feb 2024The balance between a protective and a destructive immune response can be precarious, as exemplified by inborn errors in nucleotide metabolism. This class of inherited...
The balance between a protective and a destructive immune response can be precarious, as exemplified by inborn errors in nucleotide metabolism. This class of inherited disorders, which mimics infection, can result in systemic injury and severe neurologic outcomes. The most common of these disorders is Aicardi Goutières syndrome (AGS). AGS results in a phenotype similar to "TORCH" infections (Toxoplasma gondii, Other [Zika virus (ZIKV), human immunodeficiency virus (HIV)], Rubella virus, human Cytomegalovirus [HCMV], and Herpesviruses), but with sustained inflammation and ongoing potential for complications. AGS was first described in the early 1980s as familial clusters of "TORCH" infections, with severe neurology impairment, microcephaly, and basal ganglia calcifications (Aicardi & Goutières, Ann Neurol, 1984;15:49-54) and was associated with chronic cerebrospinal fluid (CSF) lymphocytosis and elevated type I interferon levels (Goutières et al., Ann Neurol, 1998;44:900-907). Since its first description, the clinical spectrum of AGS has dramatically expanded from the initial cohorts of children with severe impairment to including individuals with average intelligence and mild spastic paraparesis. This broad spectrum of potential clinical manifestations can result in a delayed diagnosis, which families cite as a major stressor. Additionally, a timely diagnosis is increasingly critical with emerging therapies targeting the interferon signaling pathway. Despite the many gains in understanding about AGS, there are still many gaps in our understanding of the cell-type drivers of pathology and characterization of modifying variables that influence clinical outcomes and achievement of timely diagnosis.
PubMed: 38421058
DOI: 10.1002/jimd.12721 -
Journal of Clinical Virology : the... Dec 2023HTLV-1 infection is a neglected disease. Over 10 million people are infected worldwide, with hot spots of high endemicity across all continents. Roughly 5% of HTLV-1...
BACKGROUND
HTLV-1 infection is a neglected disease. Over 10 million people are infected worldwide, with hot spots of high endemicity across all continents. Roughly 5% of HTLV-1 carriers develop HTLV-1-associated myelopathy (HAM), a progressive subacute neurological disabling disease.
METHODS
We report the main features of patients diagnosed with HAM up to date in Spain, a non-endemic country with a relatively high migrant flow from Latin America and Equatorial Africa, where HTLV-1 is endemic.
RESULTS
A total of 451 cases of HTLV-1 had been recorded in Spain until the end of year 2022. HAM had been diagnosed in 58 (12.9%). The current incidence is of 2-3 new cases per year. Women represent 76%. Mean age at diagnosis is 49 years-old. Nearly 60% are Latin Americans. Although sexual transmission is the most likely route of HTLV-1 acquisition, up to 6 individuals had been infected following solid organ transplantation. Rapid onset myelopathy developed in all but one of these transplant recipients from three HTLV-1-positive donors. HTLV-1 subtype 1a transcontinental was the only variant recognized in HAM patients. HTLV-1 proviral load was significantly greater in HAM patients than in asymptomatic HTLV-1 carriers (677 vs 104 HTLV-1 DNA copies/10 PBMC; p = 0.012). Symptom relief medications and physiotherapy have been the only treatment providing some benefit to HAM patients. Neither significant clinical nor virological efficacy was noticed using antiretrovirals in at least 9 HAM patients. Two thirds of HAM patients ended up in a wheelchair and with urinary/fecal sphincter incontinence.
CONCLUSION
HAM is the most frequent clinical manifestation of HTLV-1 infection in Spain, a non-endemic country. Middle aged women migrants from Latin America are the most frequently affected. Two thirds end up in a wheelchair despite using antiretroviral therapy.
Topics: Middle Aged; Humans; Female; Paraparesis, Tropical Spastic; Spain; Leukocytes, Mononuclear; HTLV-I Infections; Human T-lymphotropic virus 1; Viral Load
PubMed: 38000189
DOI: 10.1016/j.jcv.2023.105619 -
Frontiers in Immunology 2023Extracellular vesicles and particles (EVPs) are released from virtually all cell types, and may package many inflammatory factors and, in the case of infection, viral...
BACKGROUND AND OBJECTIVES
Extracellular vesicles and particles (EVPs) are released from virtually all cell types, and may package many inflammatory factors and, in the case of infection, viral components. As such, EVPs can play not only a direct role in the development and progression of disease but can also be used as biomarkers. Here, we characterized immune signatures of EVPs from the cerebrospinal fluid (CSF) of individuals with HTLV-1-associated myelopathy (HAM), other chronic neurologic diseases, and healthy volunteers (HVs) to determine potential indicators of viral involvement and mechanisms of disease.
METHODS
We analyzed the EVPs from the CSF of HVs, individuals with HAM, HTLV-1-infected asymptomatic carriers (ACs), and from patients with a variety of chronic neurologic diseases of both known viral and non-viral etiologies to investigate the surface repertoires of CSF EVPs during disease.
RESULTS
Significant increases in CD8+ and CD2+ EVPs were found in HAM patient CSF samples compared to other clinical groups ( = 0.0002 and = 0.0003 compared to HVs, respectively, and = 0.001 and = 0.0228 compared to MS, respectively), consistent with the immunopathologically-mediated disease associated with CD8+ T-cells in the central nervous system (CNS) of HAM patients. Furthermore, CD8+ ( < 0.0001), CD2+ ( < 0.0001), CD44+ ( = 0.0176), and CD40+ ( = 0.0413) EVP signals were significantly increased in the CSF from individuals with viral infections compared to those without.
DISCUSSION
These data suggest that CD8+ and CD2+ CSF EVPs may be important as: 1) potential biomarkers and indicators of disease pathways for viral-mediated neurological diseases, particularly HAM, and 2) as possible meditators of the disease process in infected individuals.
Topics: Humans; Paraparesis, Tropical Spastic; Central Nervous System; Extracellular Vesicles; Nervous System Diseases; CD40 Antigens; Chronic Disease
PubMed: 37622115
DOI: 10.3389/fimmu.2023.1235791 -
Pediatric Neurology Oct 2023TANGO2 deficiency disorder is a rare genetic disease caused by biallelic defects in TANGO2 gene.
BACKGROUND
TANGO2 deficiency disorder is a rare genetic disease caused by biallelic defects in TANGO2 gene.
METHODS
We report the clinical phenotype of two children with TANGO2 deficiency disorder.
RESULTS
Patient 1 is a female child presenting with developmental delay and microcephaly during the second year of life, who evolved with severe cognitive impairment, facial dysmorphisms, spastic paraparesis, and atonic seizures. At age 13 years, she was hospitalized due to an episode of rhabdomyolysis complicated with cardiac arrhythmia and hypothyroidism. Patient 2 is a female child with dysmorphic facial features, cleft palate, and developmental delay who was diagnosed with DiGeorge syndrome. At age three years, she presented with an acute episode of severe rhabdomyolysis in the context of human herpesvirus 6 infection. After the resolution of this acute episode, she maintained recurrent muscle weakness with axial hypotonia and progressive spasticity of the lower extremities. In both patients, diagnosis of TANGO2 deficiency disorder was only confirmed after an acute metabolic crisis.
CONCLUSIONS
A high index of suspicion for TANGO2 deficiency disorder is needed in patients with developmental delay or other neurological symptoms and episodic rhabdomyolysis.
Topics: Child; Humans; Female; Adolescent; Child, Preschool; Microcephaly; Seizures; Phenotype; DiGeorge Syndrome; Rhabdomyolysis
PubMed: 37562170
DOI: 10.1016/j.pediatrneurol.2023.07.010 -
Journal of Vascular Surgery Apr 2024Since its inception in the early 2000s, hybrid arch repair (HAR) has evolved from novel approach to well-established treatment modality for aortic arch pathology in...
OBJECTIVE
Since its inception in the early 2000s, hybrid arch repair (HAR) has evolved from novel approach to well-established treatment modality for aortic arch pathology in appropriately selected patients. Despite this nearly 20-year history of use, long-term results of HAR remain to be determined. As such, objectives of this study are to detail the long-term outcomes for HAR within an expanded classification scheme.
METHODS
From August 2005 to August 2022, 163 consecutive patients underwent HAR at a single referral institution. Operative approach was selected according to an institutional algorithm and included zone 0/1 HAR in 25% (n = 40), type I HAR in 34% (n = 56), and type II/III HAR in 41% (n = 67). Specific zone 0/1 technique was zone 1 HAR in 31 (78%), zone 0 with innominate snorkel (zone 0 HAR) in 7 (18%), and zone 0 with single side-branch endograft (zone 0 HAR) in 2 (5%). The 30-day and long-term outcomes, including overall and aortic-specific survival, as well as freedom from reintervention, were assessed.
RESULTS
The mean age was 63 ± 13 years and almost one-half of patients (47% [n = 77]) had prior sternotomy. Presenting pathology included degenerative aneurysm in 44% (n = 71), residual dissection after prior type A repair in 38% (n = 62), chronic type B dissection in 12% (n = 20), and other indications in 6% (n = 10). Operative outcomes included 9% mortality (n = 14) at 30 days, 5% mortality (n = 8) in hospital, 4% stroke (n = 7), 2% new dialysis (n = 3), and 2% permanent paraparesis/plegia (n = 3). The median follow-up was 44 month (interquartile range, 12-84 months). Overall survival was 59% and 47% at 5 and 10 years, respectively, whereas aorta-specific survival was 86% and 84% at the same time points. At 5 and 10 years, freedom from major reintervention was 92% and 91%, respectively. Institutional experience had a significant impact on both early and late outcomes: comparing the first (2005-2012) and second (2013-2022) halves of the series, 30-day mortality decreased from 14% to 1% (P = .01) and stroke from 6% to 3% (P = .62). Improved operative outcomes were accompanied by improved late survival, with 78% of patients in the later era vs 45% in the earlier era surviving to 5 years.
CONCLUSIONS
HAR is associated with excellent operative outcomes, as well as sustained protection from adverse aortic events as evidenced by high long-term aorta-specific survival and freedom from reintervention. However, surgeon and institutional experience appear to play a major role in achieving these superior outcomes, with a five-fold decrease in operative mortality and a two-fold decrease in stroke rate in the latter half of the series. These long-term results expand on prior midterm data and continue to support use of HAR for properly selected patients with arch disease.
Topics: Humans; Middle Aged; Aged; Aorta, Thoracic; Aortic Aneurysm, Thoracic; Treatment Outcome; Blood Vessel Prosthesis Implantation; Risk Factors; Retrospective Studies; Kaplan-Meier Estimate; Postoperative Complications; Stroke; Endovascular Procedures
PubMed: 38008268
DOI: 10.1016/j.jvs.2023.11.032 -
The Journal of the Association of... Oct 2023Statins are drugs for preventing cardiac events in the elderly population. Statins are well tolerated with a lower reported incidence of serious side effects (<0.15%)...
Statins are drugs for preventing cardiac events in the elderly population. Statins are well tolerated with a lower reported incidence of serious side effects (<0.15%) like myopathy and elevated transaminases [>3× upper limit of normal (ULN)]. Serious adverse effects of statins like statin-associated myopathy range from mild muscle pain to rhabdomyolysis. Drug-induced liver injury (DILI) is another adverse effect of statin use, typically presenting with an acute hepatocellular liver injury pattern as mixed or cholestatic injury. Symptoms usually disappear after 3 months of discontinuation of statins. Some patients require immunosuppression with steroids, intravenous immunoglobulin, or rituximab for management of rhabdomyolysis. DILI can be rapidly reversed by the stoppage of the statins if the enzyme elevation is more than twice the normal. Elderly patients are particularly at increased risk of such adverse effects, emphasizing a need for rational prescription of statins in older adults and close monitoring. We report a case of an elderly presenting with paraparesis and later diagnosed to be a case of statin-induced myositis that significantly improved with prompt management. : Kashyap K, Bisht K, Dhar M, Atorvastatin-induced Myositis and Drug-induced Liver Injury. J Assoc Physicians India 2023;71(10):96-98.
Topics: Humans; Atorvastatin; Chemical and Drug Induced Liver Injury; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Myositis; Aged; Male; Female
PubMed: 38716533
DOI: 10.59556/japi.71.0309 -
Expert Review of Anti-infective Therapy May 2024Human T-cell leukemia virus type 1 (HTLV-1) carriers may develop adult T-cell leukemia (ATL), or HTLV-1-associated myelopathy (HAM)/tropical spastic paraparesis (TSP)....
INTRODUCTION
Human T-cell leukemia virus type 1 (HTLV-1) carriers may develop adult T-cell leukemia (ATL), or HTLV-1-associated myelopathy (HAM)/tropical spastic paraparesis (TSP). The evidence is limited regarding other diseases potentially associated with HTLV-1, such as HTLV-1-associated autoimmune diseases.
AREA COVERED
We summarized the available information on complications associated with HTLV-1 infection.
EXPERT OPINION
Previous studies showed that HTLV-1 carriers have an increased incidence of collagen diseases including Sjögren's syndrome, as well as dysthyroidism, diabetes mellitus, and atherosclerosis. Furthermore, cognitive deficits are observed in asymptomatic carriers and in symptomatic carriers who develop HAM/TSP. It is hypothesized that altered immunoregulation occurs as a result of persistent HTLV-1 infection. A systematic review and meta-analysis demonstrated that HTLV-1 infection itself has an adverse impact on overall survival. ATL alone cannot entirely explain the adverse impact of HTLV-1 infection on overall mortality, because the incidence is low, and therefore HTLV-1-associated diseases as a whole may contribute to the inferior clinical outcome. However, there are insufficient data to determine the causal relationship between HTLV-1 infection and each complication. While non-cancerous events linked to HTLV-1 infection are not fatal, they are likely to reduce quality of life. Large prospective studies should be conducted by international collaborators.
Topics: Humans; Autoimmune Diseases; Carrier State; HTLV-I Infections; Human T-lymphotropic virus 1; Leukemia-Lymphoma, Adult T-Cell; Paraparesis, Tropical Spastic
PubMed: 38536666
DOI: 10.1080/14787210.2024.2336547 -
Journal of the American Veterinary... Nov 2023
Topics: Dogs; Animals; Low Back Pain; Lumbosacral Region; Paraparesis; Magnetic Resonance Imaging; Dog Diseases
PubMed: 37468125
DOI: 10.2460/javma.23.05.0278 -
Brain & Development Aug 2023Late-onset Krabbe disease is a disorder with autosomal recessive inheritance caused by a deficiency in galactocerebrosidase (GALC) activity. Its late-onset form usually...
BACKGROUND
Late-onset Krabbe disease is a disorder with autosomal recessive inheritance caused by a deficiency in galactocerebrosidase (GALC) activity. Its late-onset form usually shows slow disease progression with atypical symptoms including spastic paresis. The efficacy of hematopoietic stem cell transplantation (HSCT) in late-onset Krabbe disease has not been fully established.
CASE REPORT
We describe the case of a patient with late-onset Krabbe disease showing progressive spastic paraparesis. At the age of 18, one and a half years after the development of symptoms, the patient underwent HSCT. After HSCT, the patient's GALC activity returned to a normal level and the lesions in the brain and spinal cord became faint on images. Over two and a half years after the HSCT, the patient's gait remained spastic, however, an improvement in gait speed and modified Rankin Scale score was observed. No severe adverse events occurred during this period.
CONCLUSION
Our experience reported herein provides additional evidence for a favorable course in HSCT conducted in the early course of late-onset Krabbe disease.
Topics: Humans; Leukodystrophy, Globoid Cell; Muscle Spasticity; Hematopoietic Stem Cell Transplantation; Brain; Syncope; Galactosylceramidase
PubMed: 37080866
DOI: 10.1016/j.braindev.2023.04.001 -
Cureus Sep 2023A 71-year-old female with a past medical history of hypertension, seizure disorder, chronic obstructive pulmonary disease, coronary artery disease, chronic kidney...
A 71-year-old female with a past medical history of hypertension, seizure disorder, chronic obstructive pulmonary disease, coronary artery disease, chronic kidney disease, open abdominal aortic aneurysm repair complicated by spinal cord infarction resulting in lower extremity paraparesis with chronic urinary retention, and sacral decubitus ulcer initially presented to the emergency department (ED) complaining of a one-week history of chest pain. During her inpatient stay, acute myocardial infarction and pulmonary embolism were ruled out and the patient was hemodynamically stable for discharge until she started experiencing new-onset nausea and dyspnea. Bedside electrocardiogram demonstrated ST elevations in the anterior leads with concomitant T-wave inversions in the inferolateral leads as well as a prolonged QTc. Troponin-HS was elevated at 907.69. Bedside transthoracic echocardiogram (TTE) demonstrated a severely decreased left ventricular ejection fraction of 10%-15% (representing an acute decrease from a left ventricular ejection fraction of 55%-60% from a TTE performed seven days prior). Cardiac catheterization demonstrated mild non-obstructive coronary artery disease and no interventions were conducted. Such signs and symptoms of acute myocardial infarction, without demonstrable coronary artery stenosis, are consistent with stress induced or Takotsubo cardiomyopathy. This phenomenon occurs in approximately 1%-2% of patients presenting with troponin-positive suspected acute coronary syndrome (ACS) or suspected ST-elevation myocardial infarction (STEMI).
PubMed: 37846235
DOI: 10.7759/cureus.45285