Iatrogenic myelodysplastic syndrome complicating multiple sclerosis: A case report.

After 1.5 years of treatment with dimethyl fumarate (DMF) for multiple sclerosis, preceded 8 years earlier by intravenous (IV) cladribine and 1 year earlier by natalizumab, our patient developed myelodysplastic syndrome (MDS). The initial manifestation was a severe drop in absolute neutrophil and lymphocyte counts. Repeat bone marrow biopsy demonstrated a new unbalanced translocation (between the chromosome 1 long arm and chromosome 7 short arm). This case report, to our knowledge, is the first linking iatrogenic MDS to DMF and cladribine, while also suggesting caution with immunosuppressants in multiple sclerosis patients.

Clinical Reasoning: A 47-Year-Old Man With an Upper Respiratory Infection, Acute Confusion, Dysarthria, and Ataxia.

A patient presenting with acute confusion, dysarthria, and appendicular ataxia with gait instability warrants a broad differential including emergent consideration of acute ischemic or hemorrhagic stroke. Moreover, in acute to subacute presentations, a wide array of etiologies including infectious causes, toxins, or autoimmune conditions may be considered. This article features a 47-year-old man who presented acutely with confusion, severe dysarthria, left upper extremity dysmetria, and unsteady gait. In this case, these neurologic signs were preceded by symptoms of an upper respiratory infection. In addition, MRI brain without contrast demonstrated a small focus of hyperintensity on diffusion-weighted imaging in the splenium of the corpus callosum with apparent diffusion coefficient match. The article illustrates a diagnostic approach in evaluating a patient with this constellation of clinical and radiologic findings, as well as pertinent management considerations. A comprehensive overview of other potential causative factors of the imaging findings is described to augment the reader's differential diagnosis. Finally, a literature review pertaining to the revealed diagnosis highlights the epidemiologic relevance and important clinical pearls.

Targeted epidural blood patch through a catheter in the treatment of spontaneous intracranial hypotension.

OBJECTIVE: Spontaneous intracranial hypotension (SIH) can be effectively treated by epidural blood patch (EBP) following the primary unsuccessful conservative therapy. Nevertheless, multi-site cerebrospinal fluid (CSF) leaks or those originating at the cervical or thoracic spine remain therapeutically challenging. Therefore, this study aimed to present our experience in the treatment of thoracic CSF leaks using epidural catheters for the EBP infusion. METHODS: Three patients presenting with typical orthostatic headaches were qualified for an EBP procedure. Preoperative MRI scans, myelography, and CT myelography were performed. Additionally, delayed CT myelography was repeated after 3 h to identify the CSF leakage site. Patients were followed-up clinically and radiologically for three months. RESULTS: The CT myelography identified CSF leak at the T2-3 (case 1), T5-12 (case 2), and T3-7 level (Case 3). A 0.06" diameter lumbar drainage catheter (Case 1 and 2) or Abbot's spinal cord stimulation (SCS) catheter (Case 3) was inserted epidurally through the lower thoracic/lumbar single-entry point and advanced into the identified thoracic leak site. The average volume of injected blood was 15.7 ml. No procedure-related complications were observed, and all patients improved clinically. CONCLUSIONS: Epidural catheters remain safe and effective in treating thoracic and multi-site CSF leaks. In addition, Abbot's SCS catheter was found superior to the lumbar drainage catheter due to higher rigidity and bigger diameter despite being shorter than the lumbar drainage catheter.

LGALS3 (galectin 3) mediates an unconventional secretion of SNCA/α-synuclein in response to lysosomal membrane damage by the autophagic-lysosomal pathway in human midbrain dopamine neurons.

Numerous lines of evidence support the premise that the misfolding and subsequent accumulation of SNCA/α-synuclein (synuclein alpha) is responsible for the underlying neuronal pathology observed in Parkinson disease (PD) and other synucleinopathies. Moreover, the cell-to-cell transfer of these misfolded SNCA species is thought to be responsible for disease progression and the spread of cellular pathology throughout the brain. Previous work has shown that when exogenous, misfolded SNCA fibrils enter cells through endocytosis, they can damage and rupture the membranes of their endocytotic vesicles in which they are trafficked. Rupture of these vesicular membranes exposes intralumenal glycans leading to galectin protein binding, subsequent autophagic protein recruitment, and, ultimately, their introduction into the autophagic-lysosomal pathway. Increasing evidence indicates that both pathological and non-pathological SNCA species undergo autophagy-dependent unconventional secretion. While other proteins have also been shown to be secreted from cells by autophagy, what triggers this release process and how these specific proteins are recruited to a secretory autophagic pathway is largely unknown. Here, we use a human midbrain dopamine (mDA) neuronal culture model to provide evidence in support of a cellular mechanism that explains the cell-to-cell transfer of pathological forms of SNCA that are observed in PD. We demonstrate that LGALS3 (galectin 3) mediates the release of SNCA following vesicular damage. SNCA release is also dependent on TRIM16 (tripartite motif containing 16) and ATG16L1 (autophagy related 16 like 1), providing evidence that secretion of SNCA is mediated by an autophagic secretory pathway.

Clinical Features and Treatment Response in Immune-Mediated Small Fiber Neuropathy with Trisulfated Heparin Disaccharide or Fibroblast Growth Factor Receptor 3 Antibodies.

OBJECTIVE: Novel antibodies to trisulfated heparin disaccharide (TS-HDS) and fibroblast growth factor receptor 3 (FGFR-3) have been recently described in otherwise cryptogenic small fiber neuropathy (SFN) cases. Our goal was to further describe clinical features in such cases and to analyze treatment responses. METHODS: In a retrospective analysis, 40 cases of cryptogenic SFN in a university neuropathy clinic were identified. Of these, TS-HDS and FGFR-3 cases were identified, and clinical features and treatment responses were analyzed. RESULTS: In this cohort, 95% were women, and 55% had either TS-HDS or FGFR-3 antibodies (77% of these had TS-HDS). Of the seropositive group, 41% had a nonlength dependent epidermal nerve fiber density on skin punch biopsy (OR = 1.80). In the seropositive group, 82% had neuropathic pain as their primary symptom (OR = 1.73). Also 32% of seropositive patients reported widespread pain (OR = 1.63). 63% of seropositive cases presented acutely (OR = 11.0). In the seropositive group, 23% had an initial erroneous diagnosis (OR = 1.47). Eight seropositive patients improved on intravenous immunoglobulin treatment, with a 42% reduction in pain scores (P = 0.02), a 44% reduction in the Utah Neuropathy Score, and improved epidermal nerve fiber density post-treatment. CONCLUSIONS: TS-HDS and FGFR-3 antibodies may be present in a high proportion of cryptogenic SFN cases with acute onset, nonlength dependent pathology, and primary neuropathic and widespread pain. They are often misdiagnosed as other conditions including fibromyalgia. These cases may be responsive to immune treatment, especially with intravenous immunoglobulin.

Dual-Energy Computed Tomography in Loosening of Revision Hip Prosthesis: A Comparison Between MARS and non-MARS Images.

PURPOSE: The aim of the study was to assess potential endoprosthesis loosening in patients after revision total hip arthroplasty, based on monochromatic dual-energy computed tomography (DECT) images obtained with and without metal artifact reduction software (MARS) and comparison with the clinical examination and hip function. MATERIALS AND METHODS: Twenty-five consecutive patients underwent DECT examinations. Two monochromatic data sets were generated: with MARS (75-keV MARS) and without MARS (140-keV non-MARS) and evaluated for signs of loosening, using a dedicated radiological score. The Harris Hip Score (HHS) was used to evaluate patients' hip function. RESULTS: The mean radiological score for loosening in the non-MARS group was 16.2, in the MARS group 17.0 and was significantly higher (P < 0.001). Radiological loosening evaluation in non-MARS images correlated with the HHS score (ρ = 0.43, P = 0.03), whereas there was no correlation between MARS images and HHS (ρ = 0.15, P = 0.47). New MARS-related artifacts, which hinder implant-bone interface evaluation, were found in 75-keV MARS images ("pseudo-loosening" in 33 of 34 prostheses, "ground-glass blurring" in 20 of 32). CONCLUSIONS: High-energy monochromatic DECT images are superior to low-energy DECT MARS images in assessment of the potential loosening and correlate better with the clinical examination outcomes. For revision total hip arthroplasty evaluation, 2 data sets should be assessed inseparably because of extra artifacts in MARS images.

Interest in Babies Negatively Predicts Testosterone Responses to Sexual Visual Stimuli Among Heterosexual Young Men.

Men's testosterone may be an important physiological mechanism mediating motivational and behavioral aspects of the mating/parenting trade-off not only over time but also in terms of stable differences between mating-oriented and parenting-oriented individuals. In this study, we tested the hypothesis that self-reported interest in babies is inversely related to testosterone reactivity to cues of short-term mating among heterosexual young men. Among 100 participants, interest in babies was related to a slow life-history strategy, as assessed by the Mini-K questionnaire, and negatively related to testosterone responses to an erotic video. Interest in babies was not associated with baseline testosterone levels or with testosterone reactivity to nonsexual social stimuli. These results provide the first evidence that differential testosterone reactivity to sexual stimuli may be an important aspect of individual differences in life-history strategies among human males.