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Transplantation Proceedings May 2024Familial hemophagocytic lymphohistiocytosis (FHL) is a rare inherited autosomal recessive immune deficiency that usually manifests during infancy or early childhood,...
Familial hemophagocytic lymphohistiocytosis (FHL) is a rare inherited autosomal recessive immune deficiency that usually manifests during infancy or early childhood, rarely occurring in adults. Hematopoietic stem cell transplantation (HSCT) is the only curative treatment for FHL. However, optimal conditioning regimens for adult-onset FHL have not yet been established. Herein, we report a case of adult-onset FHL. A 37-year-old man presented with fever, liver dysfunction, and pancytopenia, which improved temporarily with corticosteroid therapy. However, he later developed encephalitis and myelitis. Genetic analysis revealed rare variants of UNC13D (c.2367+1 g>a and c.2588 g>a), which were compound heterozygous pathogenic mutations. FHL type 3 was diagnosed, and treatment based on the hemophagocytic lymphohistiocytosis (HLH) 1994 protocol was initiated. The patient underwent cord blood transplantation (CBT) with myeloablative conditioning using fludarabine, melphalan, and total-body irradiation (TBI), which resulted in graft rejection. The patient was successfully rescued by a second CBT following reduced-intensity conditioning with fludarabine, cyclophosphamide, and TBI. Although graft failure is an important complication especially in CBT, it could be managed by appropriate treatment, and that cord blood would be a promising alternative source with the advantages of rapidity and avoidance of related donors with a high risk of harboring the same genetic mutation.
PubMed: 38811303
DOI: 10.1016/j.transproceed.2024.05.011 -
Current Therapeutic Research, Clinical... 2024Complementary and alternative medications (CAM) are common among patients with multiple sclerosis (MS) for physical and psychological support. However, there is...
Use of Complementary and Alternative Medicine in Patients With Idiopathic Inflammatory Demyelinating Diseases of the Central Nervous System: A Cross-Sectional Study in Thailand.
BACKGROUND
Complementary and alternative medications (CAM) are common among patients with multiple sclerosis (MS) for physical and psychological support. However, there is insufficient data regarding the application of CAM in the different cultures and beliefs of each community as well as patient's status.
OBJECTIVE
To evaluate the prevalence and modalities of the use of CAM among patients with central nervous system idiopathic inflammatory demyelinating diseases (CNS-IIDD) in a tertiary care hospital.
METHODS
A cross-sectional study was conducted at Siriraj Hospital from June to December 2021 involving patients with MS, neuromyelitis optic spectrum disorders (NMOSD), myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), idiopathic transverse myelitis (iTM), and optic neuritis (ON) to examine the prevalence and mode of CAM use and its correlation with patient characteristics.
RESULTS
There were 107 patients. The diagnoses were MS (38), NMOSD (55), MOGAD (5), iTM (7), and ON (2). Most of the patients were female (89.7%), and 61.7% were diagnosed over 5 years. The mean Expanded Disability Status Scale was 2.63 (S.D., 2.38), and the median ambulation index was 0 (range 0-8.5). There were 68 patients (63.6%) with a history of CAM use for at least 3 months, while those with current use decreased to 62 (58.5%). Vitamins and minerals were the most commonly used, particularly vitamin D (97.1%) and calcium (47.7%). Both treatments were primarily prescribed (95.3%) rather than self-administered (24.3%). The main reasons for the use of CAM were to strengthen their health (48.6%) and relieve existing symptoms (28.0%).
CONCLUSIONS
The use of CAM is common among patients with Thai CNS-IIDD. Further exploration of patient perspectives and preferences regarding CAM usage may contribute to a more comprehensive management approach for patients with CNS-IIDD.
PubMed: 38808155
DOI: 10.1016/j.curtheres.2024.100749 -
Cureus Apr 2024Immunotherapies are powerful disease-modifying agents in treating autoimmune diseases like rheumatoid arthritis (RA). However, their unique mechanisms of action confer a...
Immunotherapies are powerful disease-modifying agents in treating autoimmune diseases like rheumatoid arthritis (RA). However, their unique mechanisms of action confer a broad spectrum of immune-related adverse events (irAEs), which tend to be rare but complex, with significant risk for morbidity and mortality. We report a case of transverse myelitis in a patient with RA whose joint disease had been well-controlled with long-term intravenous abatacept. Suspicion of an unusual irAE in this elderly patient, whose neurologic symptomatology was gradual and protracted, prompted the discontinuation of abatacept and the rapid initiation of corticosteroid therapy. These interventions yielded a favorable clinical outcome for the patient. We must draw clinicians' attention to this rare but potentially consequential adverse drug reaction.
PubMed: 38807813
DOI: 10.7759/cureus.59201 -
BMC Infectious Diseases May 2024To assess the immunogenicity of the current primary polio vaccination schedule in China and compare it with alternative schedules using Sabin or Salk-strain IPV (sIPV,...
BACKGROUND
To assess the immunogenicity of the current primary polio vaccination schedule in China and compare it with alternative schedules using Sabin or Salk-strain IPV (sIPV, wIPV).
METHODS
A cross-sectional investigation was conducted at four sites in Chongqing, China, healthy infants aged 60-89 days were conveniently recruited and divided into four groups according to their received primary polio vaccination schedules (2sIPV + bOPV, 2wIPV + bOPV, 3sIPV, and 3wIPV). The sero-protection and neutralizing antibody titers against poliovirus serotypes (type 1, 2, and 3) were compared after the last dose.
RESULTS
There were 408 infants completed the protocol. The observed seropositivity was more than 96% against poliovirus types 1, 2, and 3 in all groups. IPV-only groups induced higher antibody titers(GMT) against poliovirus type 2 (Median:192, QR: 96-384, P<0.05) than the "2IPV + bOPV" group. While the "2IPV + bOPV" group induced significantly higher antibody titers against poliovirus type 1 (Median:2048, QR: 768-2048, P<0.05)and type 3 (Median:2048, QR: 512-2048, P<0.05) than the IPV-only group.
CONCLUSIONS
Our findings have proved that the two doses of IPV with one dose of bOPV is currently the best polio routine immunization schedule in China.
Topics: Humans; Poliovirus Vaccine, Inactivated; Poliomyelitis; Infant; Poliovirus Vaccine, Oral; Male; Immunization Schedule; Female; Antibodies, Viral; Cross-Sectional Studies; China; Antibodies, Neutralizing; Poliovirus; Immunogenicity, Vaccine; Vaccination
PubMed: 38807038
DOI: 10.1186/s12879-024-09389-8 -
BMJ Case Reports May 2024A woman in her 40s presented with thoracic banding dysaesthesia and lower motor neuron weakness. Spinal imaging revealed a short segment of transverse myelitis and...
A woman in her 40s presented with thoracic banding dysaesthesia and lower motor neuron weakness. Spinal imaging revealed a short segment of transverse myelitis and neurophysiology was suggestive of concurrent acute inflammatory demyelinating polyneuropathy. The patient improved with consecutive intravenous immunoglobulin and methylprednisolone treatment. Acute inflammatory demyelinating polyneuropathy is a progressive immune-mediated peripheral neuropathy which responds to intravenous immunoglobulin or plasmapheresis, whereas transverse myelitis is a central inflammatory syndrome usually treated with corticosteroid. We highlight differentiating features of the clinical presentation and the utility of investigations such as neurophysiology and MRI along with a review of treatment and the role for corticosteroid therapy.
Topics: Humans; Myelitis, Transverse; Female; Immunoglobulins, Intravenous; Methylprednisolone; Guillain-Barre Syndrome; Adult; Magnetic Resonance Imaging; Diagnosis, Differential
PubMed: 38806395
DOI: 10.1136/bcr-2024-259732 -
Current Neurology and Neuroscience... May 2024Myelin oligodendrocyte glycoprotein antibody disease (MOGAD) is a distinct neuroinflammatory condition characterized by attacks of optic neuritis, transverse myelitis,... (Review)
Review
PURPOSE OF REVIEW
Myelin oligodendrocyte glycoprotein antibody disease (MOGAD) is a distinct neuroinflammatory condition characterized by attacks of optic neuritis, transverse myelitis, and other demyelinating events. Though it can mimic multiple sclerosis and neuromyelitis optica spectrum disorder, distinct clinical and radiologic features which can discriminate these conditions are now recognized. This review highlights recent advances in our understanding of clinical manifestations, diagnosis, and treatment of MOGAD.
RECENT FINDINGS
Studies have identified subtleties of common clinical attacks and identified more rare phenotypes, including cerebral cortical encephalitis, which have broadened our understanding of the clinicoradiologic spectrum of MOGAD and culminated in the recent publication of proposed diagnostic criteria with a familiar construction to those diagnosing other neuroinflammatory conditions. These criteria, in combination with advances in antibody testing, should simultaneously lead to wider recognition and reduced incidence of misdiagnosis. In addition, recent observational studies have raised new questions about when to treat MOGAD chronically, and with which agent. MOGAD pathophysiology informs some of the relatively unique clinical and radiologic features which have come to define this condition, and similarly has implications for diagnosis and management. Further prospective studies and the first clinical trials of therapeutic options will answer several remaining questions about the peculiarities of this condition.
PubMed: 38805147
DOI: 10.1007/s11910-024-01344-z -
Paediatric Drugs Jul 2024Neuropsychiatric systemic lupus erythematosus (NPSLE) is a potentially serious and life-threatening complication of SLE. The presentation and severity of... (Review)
Review
Neuropsychiatric systemic lupus erythematosus (NPSLE) is a potentially serious and life-threatening complication of SLE. The presentation and severity of neuropsychiatric involvement in SLE may show considerable variability. The disease can affect the neural tissue directly or may be associated with vascular involvement, mainly associated with anti-phospholipid (aPL) antibodies. A direct causal link with SLE may sometimes be challenging since there are many confounding factors and the symptoms may be non-specific. Despite its remarkable sensitivity in detecting hemorrhagic and ischemic stroke, transverse myelitis and ischemic infarction, magnetic resonance imaging (MRI) lacks the spatial resolution required to identify microvascular involvement. When standard MRI fails to detect a suspicious lesion, it is advisable to use advanced imaging modalities such as positron emission tomography (PET), single photon emission computed tomography (SPECT) or quantitative MRI, if available. Even with these advanced modalities, the specificity of neuroimaging in NPSLE remains inadequate (60-82% for MRI). Neuropsychiatric syndromes, such as cerebrovascular events, seizures and cognitive impairments appear to be associated with serum aPL antibodies. Some studies have shown that anti-ribosomal P antibodies have a low sensitivity for NPSLE and a limited contribution to the differentiation of different clinical entities. Treatment has two main goals: symptomatic relief and treatment of the disease itself. Commonly used immunosuppressants for NPSLE include cyclophosphamide (CYC), azathioprine (AZA), and mycophenolate mofetil (MMF). According to EULAR's current recommendation, strong immunosuppressants such as CYC and rituximab (RTX) should be preferred. Biologics have also been used in NPSLE. Fingolimod, eculizumab, and JAK inhibitors are potential drugs in the pipeline. Developing targeted therapies will be possible by a better understanding of the pathological mechanisms.
Topics: Humans; Lupus Vasculitis, Central Nervous System; Child; Immunosuppressive Agents
PubMed: 38805115
DOI: 10.1007/s40272-024-00632-y -
Antibodies (Basel, Switzerland) May 2024Clinical syndromes associated with antibodies against myelin oligodendrocyte glycoprotein (MOG) are now recognized as a distinct neurological disease entity, and are... (Review)
Review
Clinical syndromes associated with antibodies against myelin oligodendrocyte glycoprotein (MOG) are now recognized as a distinct neurological disease entity, and are gaining increasing attention. The pathogenic mechanisms underlying MOG-antibody disease (MOGAD) remain incompletely understood. Case series, facilitated by registries, and observational studies over the past few years have shed increasing light on the clinical aspects and therapeutic approaches of MOGAD. MOGAD may manifest with a variety of clinical syndromes, including acute disseminated encephalomyelitis (ADEM), autoimmune encephalitis, optic neuritis (ON) and transverse myelitis (TM). MOGAD can be either monophasic or relapsing. This review aims to provide a comprehensive updated description of the clinical spectrum, paraclinical features, and prognosis of MOG-antibody disease, as well as summarize its therapeutic considerations. Randomized clinical trials, standardized diagnostic criteria and treatment guidelines are the steps forward.
PubMed: 38804311
DOI: 10.3390/antib13020043 -
European Journal of Neurology May 2024Glucose transporter-1 (GLUT1) deficiency syndrome (GLUT1-DS) is a metabolic disorder due to reduced expression of GLUT1, a glucose transporter of the central nervous...
BACKGROUND AND PURPOSE
Glucose transporter-1 (GLUT1) deficiency syndrome (GLUT1-DS) is a metabolic disorder due to reduced expression of GLUT1, a glucose transporter of the central nervous system. GLUT1-DS is caused by heterozygous SLC2A1 variants that mostly arise de novo. Here, we report a large family with heterogeneous phenotypes related to a novel SLC2A1 variant.
METHODS
We present clinical and genetic features of a five-generation family with GLUT1-DS.
RESULTS
The 14 (nine living) affected members had heterogeneous phenotypes, including seizures (11/14), behavioral disturbances (5/14), mild intellectual disability (3/14), and/or gait disabilities (2/14). Brain magnetic resonance imaging revealed hippocampal sclerosis in the 8-year-old proband, who also had drug-responsive absences associated with attention-deficit/hyperactivity disorder. His 52-year-old father, who had focal epilepsy since childhood, developed paraparesis related to a reversible myelitis associated with hypoglycorrhachia. Molecular study detected a novel heterozygous missense variant (c.446C>T) in exon 4 of SLC2A1 (NM: 006516.2) that cosegregated with the illness. This variant causes an amino acid replacement (p.Pro149Leu) at the fourth transmembrane segment of GLUT1, an important domain located at its catalytic core.
CONCLUSIONS
Our study illustrates the extremely heterogenous phenotypes in familial GLUT1-DS, ranging from milder classic phenotypes to more subtle neurological disorder including paraparesis. This novel SLC2A1 variant (c.446C>T) provides new insight into the pathophysiology of GLUT1-DS.
PubMed: 38803061
DOI: 10.1111/ene.16325 -
European Journal of Clinical... May 2024To describe the clinical characteristics and factors associated with disease severity in a Norwegian cohort of hospitalized patients with tick-borne encephalitis (TBE).
PURPOSE
To describe the clinical characteristics and factors associated with disease severity in a Norwegian cohort of hospitalized patients with tick-borne encephalitis (TBE).
METHODS
This observational multicenter study included hospitalized patients with TBE in the endemic area in the southeastern region of Norway from 2018 to 2022. Clinical signs and findings from laboratory tests, EEG, CT and MRI scans were recorded. Patient characteristics were compared among those with mild, moderate, and severe TBE, and factors associated with disease severity were identified.
RESULTS
Nearly all eligible patients were included in the final cohort (153/189 participants, 81%). The median age was 56 years, 63% were men, and 7% were vaccinated against TBE; no participants were fully vaccinated. TBE presented as mild (meningeal) disease in 31% of patients and as moderate or severe (encephalitic) disease in 54% and 14% of patients, respectively. We found that 46% of the patients had a monophasic course, 64% had hyponatremia, and 7% presented with central nervous system (CNS) symptoms without pleocytosis in cerebrospinal fluid (CSF). Dysesthesia, a symptom previously not described, was reported in 10% of the patients. Most objective findings were related to the CNS. Preexisting comorbidities, CRP and CSF protein levels were predictors of more severe disease.
CONCLUSION
This novel presentation of a large Norwegian cohort supports TBE as a serious disease in the southeastern region of Norway. The majority of hospitalized patients presented with encephalitis, and fewer presented with meningitis. Comorbidities, CRP and CSF protein levels were associated with more severe disease.
TRIAL REGISTRATION
Prosjekt #2,296,959 - The Norwegian Tick-borne Encephalitis Study - NOTES. Acute phase characteristics and long-term outcomes. - Cristin.
PubMed: 38801484
DOI: 10.1007/s10096-024-04855-2