Nonpharmacological interventions to reduce respiratory viral transmission: an evidence-based review with recommendations.

BACKGROUND: Viral respiratory infections are a leading cause of worldwide mortality and exert the potential to cause global socioeconomic crises. However, inexpensive, efficacious, and rapidly deployable strategies to reduce viral transmission are increasingly important in the setting of an ongoing pandemic, though not entirely understood. This article provides a comprehensive review of commonly employed nonpharmacological interventions to interrupt viral spread and provides evidence-based recommendations for their use. METHODOLOGY: A systematic review of three databases was performed. Studies with defined endpoints of subjects receiving one of five interventions (nasal washing, gargling, personal protective equipment (PPE), social distancing, and hand hygiene) were included. An evidence-based review of the highest level of evidence, with recommendations, was created in accordance with a previously described, rigorous, iterative process. RESULTS: Fifty-four primary studies were included. The most commonly studied intervention was hand hygiene, followed by PPE, gargling, saline nasal washing, and social distancing. CONCLUSIONS: Mask use and hand hygiene are strong recommendations for prevention of viral transmission. Donning gloves, gowns, and eye protection are a recommendation in healthcare settings. Saline nasal washing and gargling are options in selected populations. Although an aggregate level of evidence is not provided, the authors recommend social distancing.

Safety and clinical activity of the Notch inhibitor, crenigacestat (LY3039478), in an open-label phase I trial expansion cohort of advanced or metastatic adenoid cystic carcinoma.

Background Deregulated Notch signaling is implicated in multiple cancers. The phase I trial (I6F-MC-JJCA) investigated the safety and anti-tumor activity of crenigacestat (LY3039478), a selective oral Notch inhibitor, in an expansion cohort of patients with adenoid cystic carcinoma (ACC) who received the dose-escalation-recommended phase 2 dose (RP2D), established previously (Massard C, et al., Annals Oncol 2018, 29:1911-17). Methods Patients with advanced or metastatic cancer, measurable disease, ECOG-PS ≤1, and baseline tumor tissue were enrolled. Primary objectives were to identify a safe RP2D, confirm this dose in expansion cohorts, and document anti-tumor activity. Secondary objectives included safety and progression-free survival (PFS). The ACC expansion cohort received the RP2D regimen of 50 mg crenigacestat thrice per week in a 28-day cycle until disease progression or other discontinuation criteria were met. Results Twenty-two patients with ACC were enrolled in the expansion cohort (median age of 60 years). Median treatment duration was 3 cycles with 6 patients remaining on treatment. There were no objective responses; 1 (5%) patient had an unconfirmed partial response. Disease control rate was 73% and 4 patients had stable disease ≥6 months. Median PFS was 5.3 months (95%CI: 2.4-NE)) for the 22 patients; and 7.7 months (95%CI: 4.0-NR) and 2.4 months (95%CI: 1.1-NE) in the subgroup of patients in second-line (n = 7) or ≥ third-line (n = 9), respectively. Frequent treatment-related-adverse events (all grades) included diarrhea, fatigue, vomiting, decreased appetite, dry mouth, and dry skin. There were no new safety signals. Conclusion The crenigacestat RP2D regimen induced manageable toxicity and limited clinical activity, without confirmed responses, in heavily pretreated patients with ACC.

First-in-human study of LY3039478, an oral Notch signaling inhibitor in advanced or metastatic cancer.

Background: Deregulated Notch signaling due to mutation or overexpression of ligands and/or receptors is implicated in various human malignancies. γ-Secretase inhibitors inhibit Notch signaling by preventing cleavage of transmembrane domain of Notch protein. LY3039478 is a novel, potent Notch inhibitor decreases Notch signaling and its downstream biologic effects. In this first-in-human study, we report the safety, pharmacokinetic (PK) profile, pharmacodynamic effects, and antitumor activity of LY3039478 in patients with advanced or metastatic cancer. Methods: This phase I, open-label, multicenter, nonrandomized, and dose-escalation phase study determined and confirmed the recommended phase II dose of LY3039478 (oral dose: 2.5-100 mg, thrice weekly (TIW) on a 28-day cycle). The primary objectives are to determine (part A) and confirm (part B) a recommended phase II dose that may be safely administered to patients with advanced or metastatic cancer, and secondary objectives include evaluation of safety, tolerability, PK parameters, and preliminary antitumor activity of LY3039478. Results: A total of 110 patients were treated with LY3039478 monotherapy between 31 October 2012 and 15 July 2016. Dose-limiting toxicities were thrombocytopenia, colitis, and nausea. Most adverse events were gastrointestinal. The recommended phase II dose was 50 mg TIW, because of its better tolerability compared with 75 mg. The PKs of LY3039478 appeared dose proportional. Pharmacodynamic data indicate an ∼80% inhibition of plasma Aß, and >50% inhibition of Notch-regulated genes hairy and enhancer of split-1, cyclin D1, and Notch-regulated ankyrin repeat at 45-100-mg dose. Clinical activity (tumor necrosis, metabolic response, or tumor shrinkage) was observed in patients with breast cancer, leiomyosarcoma, and adenoid cystic carcinoma. Conclusion: Potent inhibition of Notch signaling by LY3039478 was well tolerated at doses associated with target engagement, and demonstrated evidence of clinical activity in heavily pretreated patients. Further investigation with LY3039478 as monotherapy and in combination with targeted agent or chemotherapy is ongoing. Clinicaltrials.gov ID: NCT01695005.

A Comparison of Request Process and Outcomes in Donation After Cardiac Death and Donation After Brain Death: Results From a National Study.

Available literature points to healthcare providers' discomfort with donation after cardiac death (DCD) and their perception of public reluctance toward the procedure. Using a national sample, we report on the communication content of actual DCD and donation after brain death (DBD) approaches by organ procurement organization (OPO) requesters and compare family decision makers' (FDMs') experiences of both modalities. We recruited 1601 FDMs using a validated protocol; 347 (21.7%) were of potential DCD donors. Semistructured telephone interviews yielded FDMs' sociodemographic data, donation attitudes, assessment of approach, final outcomes, and substantiating reasons. Initial analysis consisted of bivariate analyses. Multilevel mixture models compared groups representing authorization outcome and DCD/DBD status. No significant differences in family authorization were found between DCD and DBD cases. Statistically significant associations were found between sociodemographic characteristics and authorization, with white FDMs more likely to authorize DCD or DBD than black FDMs. FDMs of both modalities had similar evaluations of requester skills, topics discussed, satisfaction, and refusal reasons. The findings suggest that the DCD/DBD distinction may not be notable to families. We recommend the use of similar approach strategies and communication skills and the development of education campaigns about the public's acceptance of DCD.

Development of a conceptual model of cancer caregiver health literacy.

Caregivers play a vital role in caring for people diagnosed with cancer. However, little is understood about caregivers' capacity to find, understand, appraise and use information to improve health outcomes. The study aimed to develop a conceptual model that describes the elements of cancer caregiver health literacy. Six concept mapping workshops were conducted with 13 caregivers, 13 people with cancer and 11 healthcare providers/policymakers. An iterative, mixed methods approach was used to analyse and synthesise workshop data and to generate the conceptual model. Six major themes and 17 subthemes were identified from 279 statements generated by participants during concept mapping workshops. Major themes included: access to information, understanding of information, relationship with healthcare providers, relationship with the care recipient, managing challenges of caregiving and support systems. The study extends conceptualisations of health literacy by identifying factors specific to caregiving within the cancer context. The findings demonstrate that caregiver health literacy is multidimensional, includes a broad range of individual and interpersonal elements, and is influenced by broader healthcare system and community factors. These results provide guidance for the development of: caregiver health literacy measurement tools; strategies for improving health service delivery, and; interventions to improve caregiver health literacy.

Estrogen protects against the detrimental effects of repeated stress on glutamatergic transmission and cognition.

Converging evidence suggests that females and males show different responses to stress; however, little is known about the mechanism underlying the sexually dimorphic effects of stress. In this study, we found that young female rats exposed to 1 week of repeated restraint stress show no negative effects on temporal order recognition memory (TORM), a cognitive process controlled by the prefrontal cortex (PFC), which was contrary to the impairment in TORM observed in stressed males. Concomitantly, normal glutamatergic transmission and glutamate receptor surface expression in PFC pyramidal neurons were found in repeatedly stressed females, in contrast to the significant reduction seen in stressed males. The detrimental effects of repeated stress on TORM and glutamate receptors were unmasked in stressed females when estrogen receptors were inhibited or knocked down in PFC, and were prevented in stressed males with the administration of estradiol. Blocking aromatase, the enzyme for the biosynthesis of estrogen, revealed the stress-induced glutamatergic deficits and memory impairment in females, and the level of aromatase was significantly higher in the PFC of females than in males. These results suggest that estrogen protects against the detrimental effects of repeated stress on glutamatergic transmission and PFC-dependent cognition, which may underlie the stress resilience of females.

Mice deficient in Six5 develop cataracts: implications for myotonic dystrophy.

Expansion of a CTG trinucleotide repeat in the 3' UTR of the gene DMPK at the DM1 locus on chromosome 19 causes myotonic dystrophy, a dominantly inherited disease characterized by skeletal muscle dystrophy and myotonia, cataracts and cardiac conduction defects. Targeted deletion of Dm15, the mouse orthologue of human DMPK, produced mice with a mild myopathy and cardiac conduction abnormalities, but without other features of myotonic dystrophy, such as myotonia and cataracts. We, and others, have demonstrated that repeat expansion decreases expression of the adjacent gene SIX5 (refs 7,8), which encodes a homeodomain transcription factor. To determine whether SIX5 deficiency contributes to the myotonic dystrophy phenotype, we disrupted mouse Six5 by replacing the first exon with a beta-galactosidase reporter. Six5-mutant mice showed reporter expression in multiple tissues, including the developing lens. Homozygous mutant mice had no apparent abnormalities of skeletal muscle function, but developed lenticular opacities at a higher rate than controls. Our results suggest that SIX5 deficiency contributes to the cataract phenotype in myotonic dystrophy, and that myotonic dystrophy represents a multigenic disorder.

Mechanisms for acute stress-induced enhancement of glutamatergic transmission and working memory.

Corticosteroid stress hormones have a strong impact on the function of prefrontal cortex (PFC), a central region controlling cognition and emotion, though the underlying mechanisms are elusive. We found that behavioral stressor or short-term corticosterone treatment in vitro induces a delayed and sustained potentiation of the synaptic response and surface expression of N-methyl-D-aspartic acid receptors (NMDARs) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) in PFC pyramidal neurons through a mechanism depending on the induction of serum- and glucocorticoid-inducible kinase (SGK) and the activation of Rab4, which mediates receptor recycling between early endosomes and the plasma membrane. Working memory, a key function relying on glutamatergic transmission in PFC, is enhanced in acutely stressed animals through an SGK-dependent mechanism. These results suggest that acute stress, by activating glucocorticoid receptors, increases the trafficking and function of NMDARs and AMPARs through SGK/Rab4 signaling, which leads to the potentiated synaptic transmission, thereby facilitating cognitive processes mediated by the PFC.

Reliability of shear wave ultrasound elastography for neck lesions identified in routine clinical practice.

PURPOSE: To evaluate the reliability of shear wave ultrasound elastography (SWE) in the neck. MATERIALS AND METHODS: 176 neck lesions (40 thyroid, 56 lymph nodes, 46 salivary, 34 miscellaneous) identified in a routine US clinic underwent SWE by one or two blinded radiologists. For this study, SWE required the operator to acquire three 10 second dynamic colour-coded SWE cineloops per lesion, select one static image per cineloop, and place circular regions-of-interest within the entire lesion and stiffest part to generate 3 SWE measurements per static image. For logistical reasons, one radiologist evaluated all 176 lesions and the other evaluated 58 lesions. Both radiologists also reviewed 27 archived cineloops independently to assess SWE excluding practical technique. Reliability was assessed using intraclass correlation coefficients (ICCs) concordance correlation coefficients (CCCs) and coefficients of repeatability (CORs). RESULTS: Test-retest ICCs for the radiologist evaluating 176 lesions were 0.78 - 0.85 (fair-excellent agreement), CCCs were 0.85 - 0.88 (substantial agreement), and CORs were 14.9 - 36.1 kPa. For both radiologists evaluating 58 lesions, intra-rater and inter-rater ICCs were 0.65 - 0.78 and 0.72 - 0.77 respectively. For SWE excluding practical technique, inter-rater ICCs were 0.97 - 0.98 (excellent agreement). ICCs differed according to tissue, being higher in thyroid lesions than lymph nodes (p < 0.001), and higher in benign than malignant lesions (p values < 0.001). CONCLUSION: Intra- and inter-rater reliability of SWE is fair to excellent according to ICCs. SWE reliability is influenced appreciably by acquisition technique. Nevertheless, CORs for SWE are not negligible. To determine whether these results are acceptable clinically, further research is required to establish SWE stiffness values of normal and pathological tissues in the neck.

A phase 1b study of crenigacestat (LY3039478) in combination with gemcitabine and cisplatin or gemcitabine and carboplatin in patients with advanced or metastatic solid tumors.

BACKGROUND: Notch signaling plays an integral role in development and tissue homeostasis. Inhibition of Notch signaling has been identified as a reasonable target for oncotherapy. Crenigacestat (LY3039478) is a potent Notch inhibitor that decreases Notch signaling and its downstream biologic effects. METHODS: I6F-MC-JJCD was a multicenter, nonrandomized, open-label, phase 1b study with 5 separate, parallel dose escalations in patients with advanced or metastatic cancer from a variety of solid tumors followed by a dose-confirmation phase in pre-specified tumor types. This manuscript reports on 2 of 5 groups. The primary objective was to determine the recommended phase 2 dose of crenigacestat combined with other anticancer agents (gemcitabine/cisplatin or gemcitabine/carboplatin). Secondary objectives included evaluation of safety, tolerability, preliminary efficacy, and pharmacokinetics. RESULTS: Patients (N = 31) received treatment between November 2016 and July 2019. Dose-limiting toxicities occurred in 6 patients. The recommended phase 2 dose for crenigacestat was 50 mg TIW in Part 1 (combined with gemcitabine/cisplatin) and not established in Part 2 (combined with gemcitabine/carboplatin) due to poor tolerability. Patients had at least one treatment-emergent adverse event (TEAE), and most had Grade ≥ 3 TEAEs. Over 50% of the patients experienced gastrointestinal disorders (Grade ≥ 3). No patient had complete response; 5 patients had a partial response. Disease control rates were 62.5% (Part 1) and 60.0% (Part 2). CONCLUSION: This study demonstrated that the Notch inhibitor, crenigacestat, combined with different anticancer agents (gemcitabine, cisplatin, and carboplatin) was poorly tolerated and resulted in disappointing clinical activity in patients with advanced or metastatic solid tumors. CLINICALTRIALS: gov Identification Number: NCT02784795.

Biopsy of deep-seated head and neck lesions under intraoral ultrasound guidance.

Although transcutaneous ultrasound combined with fine-needle aspiration is often used as initial modality for evaluating superficial neck masses, its role in management of deep-seated neck masses is limited. Intraoral ultrasound and guided biopsy helps in obtaining tissue from deep-seated neck masses for an accurate histologic diagnosis, providing useful information in treatment planning. This article discusses the role of intraoral ultrasound and presents 3 cases in which biopsy of deep-seated neck masses under intraoral ultrasound guidance helped in diagnosis and management.

The prognostic significance of T cell receptor beta gene rearrangements and idiotype-reactive T cells in multiple myeloma.

Clonal T cell populations with idiotype specificity are present in the peripheral blood of a proportion of patients with multiple myeloma. We have identified the presence of both T cell subpopulations with a specificity for autologous immunoglobin fragments and T cell receptor beta gene rearrangements in peripheral blood samples of patients with myeloma. T cell receptor beta gene rearrangements were detected in 38 of 119 patient samples (32%) and were more common in progressive disease (70%), than at diagnosis (25%) or in stable disease (23%). The 38 patients who had T cell receptor beta gene rearrangements detected at any time had a better overall survival (median not yet achieved) than the patients who never had rearrangements detected (median 45 months, n = 49; chi2 = 6.2, P < 0.01). All 12 patients with T cell receptor beta gene rearrangements at diagnosis are still alive whereas the median survival for 28 patients with a germline configuration at diagnosis was 40 months (chi2 = 5.8, P > 0.01). The presence of T cell receptor beta gene rearrangements even conferred a survival advantage during progressive disease (median survival 44 months vs 19 months; chi2 = 8.7, P < 0.003). Two colour flow cytometry with biotinylated autologous immunoglobulin fragments demonstrated idiotype-reactive T cells in the peripheral blood of five out of 15 patients all of whom had T cell gene rearrangements. The remaining 10 patients had neither idiotype-reactive T cells nor a detectable T cell receptor beta gene rearrangement in concurrent samples. Thus in patients with myeloma there was a good correlation between the presence of T cell receptor beta gene rearrangements and idiotype-reactive T cells. Patients with a rearranged T cell receptor beta gene had a significantly better prognosis.

Human bone marrow progenitor cells stimulated by cord blood.

Agar cultures of human bone marrow cells stimulated by cord plasma or irradiated cord blood feeder layers demonstrated the presence of a multilineage hemopoietic growth factor in cord blood. When bone marrow cultures stimulated with giant cell tumor-conditioned medium (GCT-CM) were supplemented with this cord blood-derived growth factor, total colony numbers increased by more than 50% after day 23 and persisted in culture for approximately 40 days. Marrow cultures stimulated by the cord blood-derived growth factor formed colonies of neutrophils, monocyte-macrophages, eosinophils, mast cells, and a few colonies containing a mixed cell population. The results suggest that, while GCT-CM contains granulocyte-monocyte colony-stimulating factor (GM-CSF), cord blood contains a high concentration of a multilineage hemopoietic growth factor, which may be multi-CSF.

Identification and characterization of human hemopoietic mast cell colonies.

Persisting mast cell colonies from human bone marrow and cord blood cells grown in semisolid agar cultures for over 56 days have been positively identified and characterized using morphology and cytochemistry. Mast cells demonstrated the following features: Cytoplasmic granules frequently contained the specific and characteristic papyrus rolls (transmission electron microscopy); mature cells were positive to the mouse monoclonal antibody YB5.B8 specific for human mast cells (raised against acute myeloid leukemia cells) and RPA-M1 specific for human monocytes but negative to the human basophil monoclonal antibody Bsp-1; morphologically the cells were large (diameter 20-25 micron), deeply basophilic, and contained granules that measured up to 2 micron in diameter (May-Grünwald-Giemsa stain); the presence of heparin by the thrombin clotting time and positive staining with toluidine blue and alcian blue; the presence of histamine by a positive fluorescent o-phthalaldehyde stain; the presence of IgE receptor sites with human IgE and a rabbit anti-human IgE second antibody; and a unique zone of lysis around mast cell colonies occurred when cultured on peripheral blood feeder layers in agar plates that was not present around monocytic, neutrophilic, or eosinophilic colonies under the same culture conditions. Our results identify the cells in persisting colonies as mast cells and describe some specific characteristics that distinguish these cells from basophils.

Immunophenotypic analyses of cultured hemopoietic mast cells.

Immunophenotypic analyses of immature stage (day 19-23), intermediate stage (day 28-32), mature stage (day 34-37), and older stage (day 42-44) human hemopoietic mast cells from colonies grown in semi-solid agar cultures were performed to study the ontogeny and identity of this cell type and its relationship to other leukocytes. Intermediate to mature stage mast cells were positive with the YB5.B8 mouse monoclonal antibody, (McAb) specific for human mast cells, whereas the reactivity of immature mast cells with this McAb was inconsistent and older cells were generally negative. Mast cells at all stages of maturation were strongly positive for IgE receptor sites and negative with the Bsp-1 McAb, specific for human basophils. Mast cells at all stages of maturation were also strongly positive with the monocyte McAbs RPA-M1 (CD11), positive with the monocyte McAb OKM5 and the monocyte/granulocyte McAbs BMA-210 and MY7 (CD13), strongly positive with the B-cell markers J5 (CD10) and anti-IgM, and positive with the plasma cell marker PCA-1 and to a lesser extent with the activated B-cell marker CD23. The mast cells were also strongly positive with anti-CD45 to the common leukocyte antigen and positive with an antibody to HLA-DR and an antibody to FVIIIC. They were negative for specific T-cell markers. The diversity of this phenotype supports the current concept that mast cells originate from the pluripotential progenitor cells in the bone marrow.

Longitudinal study of fiber density and motor unit number estimate in patients with amyotrophic lateral sclerosis.

We examined fiber density, compound muscle action potential (CMAP) amplitude, and motor unit number estimate (MUNE) of the abductor digiti minimi and grip strength longitudinally. We sought to determine the effects of ALS on these measurements and to evaluate which of these tests may be more sensitive in evaluating progression of ALS and possibly predicting survival. Ten patients were examined at months 0, 3, and 6. A significant decrease in MUNE and increase in fiber density were observed at months 3 and 6 (p < 0.02) compared with baseline (month 0). Mean CMAP and grip strength declined, but not significantly. The decrease in MUNE over 6 months was significantly greater than that of CMAP and grip strength (p < 0.025). The significant changes in MUNE and fiber density over time suggest that they are more sensitive in measuring the rate of progression of ALS. To evaluate further the utility of these tests, we arbitrarily divided the patients into equal groups based on length of survival. MUNE declined significantly in the group with shorter survival (p < 0.01). Conversely, fiber density increased significantly in patients with longer survival (p < 0.01). With similar statistical analysis there were no significant differences in decline of CMAP or grip strength in either subgroup over 6 months. Our study suggests that MUNE and fiber density are more sensitive than CMAP and grip strength in detecting progression of ALS. Furthermore, we raise the hypotheses that a greater increase in fiber density identifies a group of patients with ALS who will have longer survival, and that a greater decline in MUNE identifies a group with a worse prognosis.

Electrodiagnostic features of hereditary neuropathy with liability to pressure palsies.

OBJECTIVE: Because diagnosis of hereditary neuropathy with liability to pressure palsies (HNPP) frequently is missed or delayed, we looked for electrodiagnostic features that raise suspicion of the disorder by making comparisons with two more common diseases that mimic it electrophysiologically: chronic inflammatory demyelinating polyneuropathy (CIDP) and diabetic polyneuropathy. METHODS: A retrospective review of the neuromuscular laboratory database was performed. RESULTS: Nine HNPP subjects, 22 with CIDP and 49 with diabetic polyneuropathy. Of all the HNPP nerves studied, abnormally slow sensory nerve conduction velocity (SNCV) was found in 93%, prolonged distal motor latencies (DML) in 78%, slow motor nerve conduction velocity in 31%, and prolonged F-wave latencies in 90%. Mean SNCV for HNPP was 85.6%+/-10.6% of the lower limit of normal and significantly slower than for CIDP (114.3%+/-20.1%; p<0.0001) or diabetes (108.1%+/-14.8%; p<0.0001). Excluding the carpal tunnel site from the analysis did not alter this observation: Mean DML were more prolonged in HNPP, even without median nerve data in the analysis (118.5%+/-31.0% of the upper limit of normal), than in CIDP (103.2%+/-31.6%; p<0.05) or diabetes (86.3%+/-18.3%; p<0.0001). Mean HNPP motor nerve conduction velocity was within normal limits. CONCLUSIONS: According to findings, hereditary neuropathy with liability to pressure palsies (HNPP) has a distinctive background polyneuropathy independent of superimposed entrapment neuropathy. It is characterized by diffuse sensory nerve conduction velocity (SNCV) slowing and prolongation of distal motor latencies with relatively infrequent and minor reduction of motor nerve conduction velocities. This indicates disproportionate distal conduction slowing in the disorder.

Sciatic neuropathy: clinical and prognostic features in 73 patients.

We examined the clinical features of patients with sciatic neuropathy and the factors that influence prognosis. Of 92 consecutive patients referred for EMG evaluation of sciatic neuropathy, 73 fulfilled strict inclusion and exclusion criteria and had adequate clinical and electrophysiologic information. The etiologies included hip arthroplasty (21.9%), acute external compression (13.7%), infarction (9.6%), gunshot wound (9.6%), hip fracture/dislocation (9.6%), femur fracture (4.1%), contusion (4.1%), and uncertain (16.4%). We used life table analysis to determine outcome and to identify prognostic factors in patients with acute or subacute onset. Moderate or better recovery (improvement to grade 2 or by two of six clinical grades) occurred in most patients (30% by 1 year, 50% by 2 years, 75% by 3 years). A subgroup experienced excellent improvement (by three of six grades, or to grade 2) less frequently (33% by 2 and 3 years). Of the nine factors tested, two predicted an earlier or better recovery: a recordable compound muscle action potential of the extensor digitorum brevis (p < 0.025), and an initial absence of paralysis of muscles controlling ankle plantar flexion and dorsiflexion (p < 0.05). Thus, good but incomplete recovery occurs over 2 to 3 years in most patients with sciatic neuropathy, particularly in those without severe motor axonal loss.

Recurrent multifocal demyelinating neuropathy with febrile illness and IgG subset deficiency.

We describe a unique syndrome of recurrent multifocal demyelinating motor greater than sensory deficits in cranial and peripheral nerve distributions with rapid, spontaneous improvement. Three patients presented with episodes over a period of 7 to 24 years, largely accompanied by febrile illness. Variably decreased IgG1 and IgG3 subclass levels were found. We postulate an immune-mediated process based upon the clinical presentation and presence of decreased IgG subclass levels.

Neurologic complications of lumbar epidural anesthesia and analgesia.

We reviewed the clinical features of 12 patients with neurologic complications following lumbar epidural anesthesia or analgesia. Eleven patients experienced lumbosacral radiculopathy or polyradiculopathy and, of these, 10 received epidural anesthesia or analgesia and one received subarachnoid injection of medication after intended epidural anesthesia. One patient suffered a moderately severe thoracic myelopathy in the setting of unintended spinal anesthesia. The two patients with more severe polyradiculopathy had severe lumbar spinal stenosis on MRI. The other patients experienced mild to moderate neurologic deficits most often involving the L-2 root, and MRIs, when performed, were unremarkable. EMG on three patients helped to localize the lesions to the lumbosacral roots and to quantify the extent of axonal loss. Ten patients were ambulatory upon discharge from the hospital and had good neurologic outcome. One patient with severe polyradiculopathy did not improve after 4 years and had severe motor axonal loss based upon electrodiagnostic studies. The patient with a thoracic myelopathy was ambulatory 4 months after onset. Although generally a safe procedure with low frequency of complications, lumbar epidural anesthesia or analgesia occasionally causes neurologic sequelae such as radiculopathy or myelopathy. Neurologic complications may be more severe in the presence of spinal stenosis or after inadvertent subarachnoid injection of anesthetic or analgesic agent.