Chisa Yamada

Effects of Noninvasive Facial Nerve Stimulation in the Dog Middle Cerebral Artery Occlusion Model of Ischemic Stroke

Background and Purpose— Facial nerve stimulation has been proposed as a new treatment of ischemic stroke because autonomic components of the nerve dilate cerebral arteries and increase cerebral blood flow when activated. A noninvasive facial nerve stimulator device based on pulsed magnetic stimulation was tested in a dog middle cerebral artery occlusion model. Methods— We used an ischemic stroke dog model involving injection of autologous blood clot into the internal carotid artery that reliably embolizes to the middle cerebral artery. Thirty minutes after middle cerebral artery occlusion, the geniculate ganglion region of the facial nerve was stimulated for 5 minutes. Brain perfusion was measured using gadolinium-enhanced contrast MRI, and ATP and total phosphate levels were measured using 31P spectroscopy. Separately, a dog model of brain hemorrhage involving puncture of the intracranial internal carotid artery served as an initial examination of facial nerve stimulation safety. Results— Facial nerve stimulation caused a significant improvement in perfusion in the hemisphere affected by ischemic stroke and a reduction in ischemic core volume in comparison to sham stimulation control. The ATP/total phosphate ratio showed a large decrease poststroke in the control group versus a normal level in the stimulation group. The same stimulation administered to dogs with brain hemorrhage did not cause hematoma enlargement. Conclusions— These results support the development and evaluation of a noninvasive facial nerve stimulator device as a treatment of ischemic stroke.

Report of the ASFA apheresis registry study on Wilson's disease

Wilsons disease is a rare autosomal recessive genetic disorder that results in accumulation of copper in the liver, brain, cornea and kidney. Therapeutic plasma exchange (TPE) has been used to remove copper and provide a bridge to liver transplantation. We report here the collective experiences through the ASFA apheresis registry on Wilsons disease.

Effect of pulsed magnetic stimulation of the facial nerve on cerebral blood flow

In these experiments we define an effective means of pulsed magnetic stimulation of the facial nerve for the purpose of increasing cerebral blood flow (CBF). In normal anesthetized dog and sheep, a focal magnetic field was directed toward the facial nerve within the temporal bone by placing a 6.5 cm figure-8 stimulation coil over the ear. In an initial set of experiments, CBF was measured by laser Doppler flowmetry and the cerebral vasculature was visualized by angiography. The effect of facial nerve stimulation was found to be dependent on stimulation power, frequency, and the precise positioning of the stimulation coil. Furthermore, an increase in CBF was not observed after direct electrical stimulation in the middle ear space, indicating that non-specific stimulation of the tympanic plexus, an intervening neural structure with vasoactive effects, was not responsible for the increase in CBF after pulsed magnetic stimulation. Subsequent experiments using perfusion MRI demonstrated reproducible increases in CBF throughout the forebrain that manifested bilaterally, albeit with an ipsilateral predominance. These experiments support the development of a non-invasive pulsed magnetic facial nerve stimulator that will increase CBF as a treatment of ischemic stroke.

Fatal Cryocrystalglobulinemia With Intravascular and Renal Tubular Crystalline Deposits

Cryocrystalglobulinemia is a rare variant of cryoglobulinemia in which monoclonal immunoglobulins self-assemble into crystalline arrays. We report a case of a 53-year-old man who presented with systemic thrombotic microangiopathy causing multiorgan failure, including decreased kidney, lung, and gastrointestinal function; skin necrosis; and mental status changes. Skin and kidney biopsy specimens showed intravascular thrombi, along with intravascular, intratubular, and periglomerular crystalline deposits. Typical morphologic features of cryoglobulinemia, such as a leukocytoclastic vasculitis and pseudothrombi, were absent. Spindled crystals precipitated in the cryoglobulin assay, and immunofixation showed them to be composed of monoclonal immunoglobulin G κ light chains. Ultrastructural analysis demonstrated deposits to have an array-like substructure. The patient was successfully treated with a combination of plasmapheresis, steroids, and bortezomib, but experienced a relapse and died 12 months after his initial diagnosis. Cryocrystalglobulinemia causes significant morbidity and mortality and should be classified as a monoclonal gammopathy of renal significance when it occurs in patients not meeting diagnostic criteria for multiple myeloma.

Procedure-related complications and adverse events associated with pediatric autologous peripheral blood stem cell collection

Autologous peripheral blood hematopoietic progenitor cell collection (A‐HPCC) in pediatric patients is considered relatively safe although technically challenging. Very little is known regarding the incidence, risk factors and impact of procedure‐related adverse events (AE) on pediatric A‐HPCC outcomes. Methods: Prospective 4.5‐year review of AE associated with pediatric A‐HPCC. AE were graded by severity and type. Potential demographic and procedural risk factors, and the impact on product quality, were compared by t‐test, chi‐square, and linear regression. Results: Sixty‐two children underwent 110 A‐HPCC, including 36 (58%) under 20 kg. Fifty‐five AE were documented in 25.4% A‐HPCCs and 39% of children (citrate 25%, access 19%, technical 11%, cardiovascular 0%, allergic 1.8%). No AE were noted in children < 10 kg anticoagulated with heparin. Access and technical AE accounted for 73% of severe AE, with line‐related problems underlying most technical AE (87.5%, P = 0.006). AE were more likely in older (P = 0.012), heavier patients (P = 0.02), who frequently required more than one A‐HPCC (P = 0.012). In contrast, young children were more likely to experience citrate AE with gastrointestinal symptoms (median age, 6 years; P = 0.076). AE had no impact on CD34 collection rates; however, mean CD34 yields (4.2 vs. 20.4 million/kg; P = 0.0035) were decreased in patients with technical AE due to lower peripheral CD34 counts and a high number of aborted procedures (37%). Conclusion: Venous access and flow‐related issues are a major factor associated with moderate and severe AE, effecting ∼10% of patients. AE are more frequent with increasing patient age, weight, and number of procedures. J. Clin. Apheresis 32:35–48, 2017.

Efficacy of plasmapheresis on donor-specific antibody reduction by HLA specificity in post–kidney transplant recipients

Donor‐specific antibodies (DSAs) to HLA antigens can cause acute antibody‐mediated rejection (AMR) after kidney transplantation (Txp). Therapeutic plasma exchange (TPE) has been used for AMR treatment; however, DSA reduction rates are inconsistent. We investigated DSA reduction rates by HLA specificity and clinical outcome.

Report of the ASFA apheresis registry on muscle specific kinase antibody positive myasthenia gravis

Background: Anti‐muscle specific kinase antibody positive (MuSK Ab) myasthenia gravis (MG) patients are known to have different clinical course compared to anti‐acetylcholine receptor Ab positive MG patients. Therapeutic plasma exchange (TPE) has been reported to be effective; however, little is known of the response and of TPE procedural information. An ASFA Apheresis Registry was developed to analyze those data. Methods: The study collected detailed de‐identified patient data, TPE procedures, and treatment outcome/complications. Collected data was described in aggregate. Results: A total of 15 MuSK Ab MG patients with exacerbation of MG symptoms, 13 females/2 males, median age 44, were investigated. Thirty TPE courses (median 5 procedures/course, total 145 procedures) were evaluated. All TPE procedures were performed with citrate anticoagulation, 1 − 1.25 plasma volume exchange in 100% fluid balance, and 90% of courses used only albumin as replacement. Calcium was added to albumin or given orally as needed. TPE was performed every other day in 55% of courses. Adverse events occurred in 3.4% of procedures. Ten patients (67%) experienced relapses within a median of 7 weeks. Objective symptoms were resolved in more than 75% of courses. Overall subjective improvement rates were 94.1%/93.3% after 3/4 TPE procedures, respectively. Thirty‐one percent of patients responded poorly with minimal recovery. Conclusion: Overall subjective improvement was seen up to 94% of patients after one course of TPE. Some patients were poor‐responders. Five TPE may be adequate for initial course with additional TPE as needed. Based upon this preliminary data, we will modify our future data collection. J. Clin. Apheresis 32:5–11, 2017.

Effects of the search technique on the measurement of the change in quality of randomized controlled trials over time in the field of brain injury

BackgroundTo determine if the search technique that is used to sample randomized controlled trial (RCT) manuscripts from a field of medical science can influence the measurement of the change in quality over time in that field.MethodsRCT manuscripts in the field of brain injury were identified using two readily-available search techniques: (1) a PubMed MEDLINE search, and (2) the Cochrane Injuries Group (CIG) trials registry. Seven criteria of quality were assessed in each manuscript and related to the year-of-publication of the RCT manuscripts by regression analysis.ResultsNo change in the frequency of reporting of any individual quality criterion was found in the sample of RCT manuscripts identified by the PubMed MEDLINE search. In the RCT manuscripts of the CIG trials registry, three of the seven criteria showed significant or near-significant increases over time.ConclusionsWe demonstrated that measuring the change in quality over time of a sample of RCT manuscripts from the field of brain injury can be greatly affected by the search technique. This poorly recognized factor may make measurements of the change in RCT quality over time within a given field of medical science unreliable.

Performance and safety of femoral central venous catheters in pediatric autologous peripheral blood stem cell collection

Autologous peripheral blood hematopoietic progenitor cell collection (A‐HPCC) in children typically requires placement of a central venous catheter (CVC) for venous access. There is scant published data regarding the performance and safety of femoral CVCs in pediatric A‐HPCC.

Maintenance plasma exchange treatment for muscle specific kinase antibody positive myasthenia gravis patients.

Background:Anti‐muscle specific kinase antibody positive myasthenia gravis (MuSK MG) is often characterized by a relatively severe and progressive course, refractoriness to standard myasthenia gravis (MG) medications, and an increased risk of myasthenic crisis. We report here successful management of three MuSK MG patients using maintenance therapeutic plasma exchange (TPE) treatment for up to 4.5 years. Materials: The study was a 5‐year retrospective review of all MG patients treated with TPE between 2008 and 2013 at University of Michigan. Inclusion criteria of MuSK MG were positive for anti‐MuSK antibodies and a diagnosis of MuSK MG by staff neurologists. Patient data included age, gender, diagnostic testing results, medications, and the dates and response to TPE treatments. Results: A total of 153 MG patients underwent at least one course of TPE between 2008 and 2013. A total of 12 patients (7.8%) were positive for anti‐MuSK antibodies. Patients were predominantly female (83.3%) and a median age of onset was 46‐years old. Three MuSK MG patients were successfully managed with maintenance TPE. Conclusion: Maintenance TPE may be an effective option for MuSK MG patients. The key of successful maintenance treatment at our institution has been to tailor the TPE frequency for each individual, and to modify the treatment interval in conjunction with medical management. J. Clin. Apheresis 30:314–319, 2015.