Modern Look at Transverse Myelitis and Inflammatory Myelopathy: Epidemiology of the National Veterans Health Administration Population.

BACKGROUND AND OBJECTIVES: To characterize population-level data associated with transverse myelitis (TM) within the US Veterans Health Administration (VHA). METHODS: This retrospective review used VHA electronic medical record from 1999 to 2015. We analyzed prevalence, disease characteristics, modified Rankin Scale (mRS) scores, and mortality data in patients with TM based on the 2002 Diagnostic Criteria. RESULTS: We identified 4,084 patients with an International Classification of Diseases (ICD) code consistent with TM and confirmed the diagnosis in 1,001 individuals (90.7% males, median age 64.2, 67.7% Caucasian, and 31.4% smokers). The point prevalence was 7.86 cases per 100,000 people. Less than half of the cohort underwent a lumbar puncture, whereas only 31.8% had a final, disease-associated TM diagnosis. The median mRS score at symptom onset was 3 (interquartile range 2-4), which remained unchanged at follow-up, although less than half (43.2%) of the patients received corticosteroids, IVIg, or plasma exchange. Approximately one-quarter of patients (24.3%) had longitudinal extensive TM, which was associated with poorer outcomes (p = 0.002). A total of 108 patients (10.8%) died during our review (94.4% males, median age 66.5%, and 70.4% Caucasian). Mortality was associated with a higher mRS score at follow-up (OR 1.94, 95% CI, 1.57-2.40) and tobacco use (OR 1.87, 95% CI, 1.17-2.99). DISCUSSION: This national TM review highlights the relatively high prevalence of TM in a modern cohort. It also underscores the importance of a precise and thorough workup in this disabling disorder to ensure diagnostic precision and ensure optimal management for patients with TM in the future.

Bowel, bladder, and sudomotor symptoms in ALS patients.

OBJECTIVES: To describe prevalence rates of bowel, bladder, and sudomotor symptoms in patients with amyotrophic lateral sclerosis (ALS) in relation to disease onset and progression. Treatment strategies and efficacies were also assessed. METHODS: A pilot patient cohort revealed increased incidences of bowel/bladder and sudomotor symptoms. Questionnaires derived from formal bowel and bladder survey instruments were administered to a second cohort of patients during multidisciplinary ALS clinic visits. RESULTS: The pilot cohort of 30 patients reported an increase in bowel symptoms from 17% prior to 70% after the diagnosis of ALS, and an increase in urinary symptoms from 24% to 76%. In the second cohort of 66 patients an increase in constipation from 33% prior to 64.7% after the diagnosis of ALS was reported. 25.4% of patients reported bowel urgency initially, which increased to 33.3% over time. Constipation was most commonly treated with docusate, dietary fiber supplementation, fluid/exercise, and polyethylene glycol. In the second cohort the prevalence of overactive bladder symptoms increased from 3.1% prior to 25.0% after the diagnosis of ALS. Urinary symptoms are most commonly treated with catheters and oxybutynin. A sudomotor survey found stinging eyes in 17.2% of patients, oily/greasy skin in 14.1% of patients, and flaking of the skin in 29.7% of patients. CONCLUSIONS: Bowel and bladder symptoms are common in the ALS population and respond to treatment. Sudomotor symptoms are also common. Inquiring about these symptoms at clinic visits and initiating treatment can significantly improve the patients' quality of life.

A case of ictal burst-suppression.

"Burst-suppression" pattern consists of complete attenuation of background between bursts of mixed frequencies, variable morphology and waveforms. It is a subgroup of periodic patterns seen in severe cerebral damage, anesthesia or prematurity. Here, we present a 46-year-old woman with post-anoxic encephalopathy on cooling protocol with two electrographically similar patterns of burst-suppression (one with a clinical ictal correlate of isolated eye movements), as well as three electroclinical seizures. The literature on rare clinical phenomenon of isolated eye movements associated with burst-suppression is reviewed, with the conclusion that the presented case suggests an ictal origin.

CD36-triggered cell invasion and persistent tissue colonization by tumor microvesicles during metastasis.

Tumor microvesicles are a peculiar type of extracellular vesicles that circulate in the blood of patients with metastatic cancer. The itineraries and immune cell interactions of tumor microvesicles during the intravascular and extravascular stages of metastasis are largely unknown. We found that the lipid receptor CD36 is a major mediator of the engulfment of pancreatic tumor microvesicles by myeloid immune cells in vitro and critically samples circulating tumor microvesicles by resident liver macrophages in mice in vivo. Direct nanoscopic imaging of individual tumor microvesicles shows that the microvesicles rapidly decay during engulfment whereby their cargo is targeted concomitantly to the plasma membrane and the cytoplasm excluding lysosomal compartments. CD36 also promotes internalization of blood cell (nontumor) microvesicles, which involves endolysosomal pathways. A portion of tumor microvesicles circulating in the liver microcirculation traverses the vessel wall in a CD36-dependent way. Extravasated microvesicles colonize distinct perivascular Ly6C- macrophages for at least 2 wk. Thus, the microvesicles are increasingly integrated into CD36-induced premetastatic cell clusters and enhance development of liver metastasis. Hence, promotion of metastasis by pancreatic tumor microvesicles is associated with CD36-regulated immune cell invasion and extravasation of microvesicles and persistent infiltration of specific tissue macrophages by microvesicle cargo.-Pfeiler, S., Thakur, M., Grünauer, P., Megens, R. T. A., Joshi, U., Coletti, R., Samara, V., Müller-Stoy, G., Ishikawa-Ankerhold, H., Stark, K., Klingl, A., Fröhlich, T., Arnold, G. J., Wörmann, S., Bruns, C. J., Algül, H., Weber, C., Massberg, S., Engelmann, B. CD36-triggered cell invasion and persistent tissue colonization by tumor microvesicles during metastasis.

Biomarker Supervised G-CSF (Filgrastim) Response in ALS Patients.

Objective: To evaluate safety, tolerability and feasibility of long-term treatment with Granulocyte-colony stimulating factor (G-CSF), a well-known hematopoietic stem cell factor, guided by assessment of mobilized bone marrow derived stem cells and cytokines in the serum of patients with amyotrophic lateral sclerosis (ALS) treated on a named patient basis. Methods: 36 ALS patients were treated with subcutaneous injections of G-CSF on a named patient basis and in an outpatient setting. Drug was dosed by individual application schemes (mean 464 Mio IU/month, range 90-2160 Mio IU/month) over a median of 13.7 months (range from 2.7 to 73.8 months). Safety, tolerability, survival and change in ALSFRS-R were observed. Hematopoietic stem cells were monitored by flow cytometry analysis of circulating CD34+ and CD34+CD38- cells, and peripheral cytokines were assessed by electrochemoluminescence throughout the intervention period. Analysis of immunological and hematological markers was conducted. Results: Long term and individually adapted treatment with G-CSF was well tolerated and safe. G-CSF led to a significant mobilization of hematopoietic stem cells into the peripheral blood. Higher mobilization capacity was associated with prolonged survival. Initial levels of serum cytokines, such as MDC, TNF-beta, IL-7, IL-16, and Tie-2 were significantly associated with survival. Continued application of G-CSF led to persistent alterations in serum cytokines and ongoing measurements revealed the multifaceted effects of G-CSF. Conclusions: G-CSF treatment is feasible and safe for ALS patients. It may exert its beneficial effects through neuroprotective and -regenerative activities, mobilization of hematopoietic stem cells and regulation of pro- and anti-inflammatory cytokines as well as angiogenic factors. These cytokines may serve as prognostic markers when measured at the time of diagnosis. Hematopoietic stem cell numbers and cytokine levels are altered by ongoing G-CSF application and may potentially serve as treatment biomarkers for early monitoring of G-CSF treatment efficacy in ALS in future clinical trials.

FGFR3 Antibodies in Neuropathy: What to Do With Them?

OBJECTIVES: To describe the variability of fibroblast growth factor receptor 3 (FGFR3) antibody titers in a small series of patients. METHODS: We performed a retrospective review of patients with neuropathy and positive FGFR3 antibodies. RESULTS: We report 7 patients (3 women) with an age range 44-81 years. Symptoms were acute onset in 3 and subacute onset in 4 patients. Five had neuropathic pain. Examination revealed normal large fiber function to mild/moderate predominantly sensory neuropathy and ataxia in one patient. Electrodiagnostic studies revealed normal large fiber function (3), demyelinating neuropathy (1), and mild/moderate axonal neuropathy (3). Four patients had high and 3 patients had low FGFR3 titers. Repeat testing revealed absence of antibodies in 2 patients and a significant reduction in one patient without any intervening immunotherapy. CONCLUSIONS: Our case series highlights the variability and inconsistency in FGFR3 antibody titers through enzyme-linked immunosorbent assay testing. These antibody titers should always be interpreted with caution in clinical context.

Rare case of severe serotonin syndrome leading to bilateral compartment syndrome.

The term 'serotonin syndrome' describes a constellation of symptoms caused by serotonergic overstimulation. Its characteristic clinical presentation consists of encephalopathy, neuromuscular signs and autonomic hyperactivity. After removal of the offending agent, the clinical course is usually self-limited but can occasionally lead to severe symptoms. We report the case of a 68-year-old woman who presented emergently with encephalopathy. Home medications included paroxetine and dextroamphetamine/amphetamine. Physical examination revealed tachycardia, tachypnoea, diaphoresis, rigidity, hyperreflexia and clonus. Given the fast onset of symptoms, a diagnosis of serotonin syndrome was made. Laboratory studies showed acute-on-chronic kidney injury and elevated creatine kinase. The patient's mental status quickly returned to baseline with supportive care. Her rhabdomyolysis, however, persisted and led to acute compartment syndrome in her lower extremities. After bilateral leg fasciotomies and treatment of a severe wound infection with intravenous antibiotics, the patient has now recovered with complete resolution of her symptoms.

Rare case of T-cell lymphoma presenting as acute myelopathy.

Acute myelopathy is a rare presentation of systemic T-cell lymphoma. We present the case of a man aged 68 years with a diffuse erythematous maculopapular rash, followed by lower extremity paresthesias and progressive lower extremity weakness. Spinal MRI showed longitudinally extensive T2 hyperintensity with diffuse contrast enhancement. An atypical clonal T-lymphocyte population was identified in cerebrospinal fluid, peripheral blood and bone marrow aspirate, indicating a malignant T-cell lymphoproliferative disorder. The patient was treated with intrathecal and systemic chemotherapy. Unfortunately, he was not responsive to chemotherapy.