A double-blind, placebo-controlled study of rituximab in patients with stiff person syndrome.

Objective: In stiff person syndrome (SPS), an antibody-mediated impaired γ-aminobutyric acidergic (GABAergic) neurotransmission is believed to cause muscle stiffness and spasms. Most patients improve with GABA-enhancing drugs and intravenous immunoglobulin, but some respond poorly and remain disabled. The need for more effective therapy prompted a trial with the anti-CD20 monoclonal antibody rituximab.

99mTc-sestamibi scintigraphy to monitor the long-term efficacy of enzyme replacement therapy on bone marrow infiltration in patients with Gaucher disease.

Unlabelled: Assessing the skeletal response to enzyme replacement therapy (ERT) in Gaucher disease (GD) is problematic. We investigated the reliability of (99m)Tc-sestamibi scintigraphy in monitoring changes in bone marrow involvement induced by ERT.

Methods: In 52 GD patients, the efficacy of ERT on bone marrow disease was monitored using at least 2 sequential (99m)Tc-sestamibi scans; 17 patients were receiving ERT at enrollment, and 35 were ERT-naïve.

Effect of Alemtuzumab (CAMPATH 1-H) in patients with inclusion-body myositis.

Sporadic inclusion-body myositis (sIBM) is the most common disabling, adult-onset, inflammatory myopathy histologically characterized by intense inflammation and vacuolar degeneration. In spite of T cell-mediated cytotoxicity and persistent, clonally expanded and antigen-driven endomysial T cells, the disease is resistant to immunotherapies. Alemtuzumab is a humanized monoclonal antibody that causes an immediate depletion or severe reduction of peripheral blood lymphocytes, lasting at least 6 months.

Placebo-controlled trial of rituximab in IgM anti-myelin-associated glycoprotein antibody demyelinating neuropathy.

Objective: Report a double-blind, placebo-controlled study of rituximab in patients with anti-MAG demyelinating polyneuropathy (A-MAG-DP).

Methods: Twenty-six patients were randomized to four weekly infusions of 375 mg/m(2) rituximab or placebo. Sample size was calculated to detect changes of > or = 1 Inflammatory Neuropathy Course and Treatment (INCAT) leg disability scores at month 8.

Effect of housing density on reproductive parameters and corticosterone levels in nursing mice.

The Guide for the Care and Use of Laboratory Animals (Guide) recommends minimum floor space per mouse based on weight, with no other factors considered. We conducted a randomized experiment to evaluate the effect of housing density on reproductive indices and corticosterone levels in lactating mice. Female mice matched for age, strain, and date-of-pregnancy were housed individually.

Mechanisms of morbid hearing loss associated with tumors of the endolymphatic sac in von Hippel-Lindau disease.

Context: Endolymphatic sac tumors (ELSTs) are associated with von Hippel-Lindau disease and cause irreversible sensorineural hearing loss (SNHL) and vestibulopathy. The underlying mechanisms of audiovestibular morbidity remain unclear and optimal timing of treatment is not known.

Objective: To define the mechanisms underlying audiovestibular pathophysiology associated with ELSTs.

N-CoR pathway targeting induces glioblastoma derived cancer stem cell differentiation.

Nuclear receptor corepressor (N-CoR) is a critical regulator of neural stem cell differentiation. Nuclear localization of N-CoR is a feature of undifferentiated neural stem cells and cytoplasmic translocation of N-CoR leads to astrocytic differentiation. Comparative proteomic analysis of microdissected glioblastoma multiforme (GBM) specimens and matched normal glial tissue reveals increased expression of N-CoR in GBM.

Genetic polymorphisms and spontaneous preterm birth.

Objective: To examine whether selected genetic polymorphisms in the infant are associated with spontaneous preterm birth (less than 37 weeks) among children with or without later-diagnosed cerebral palsy.

Methods: Exploratory case-control study investigating the relationship of gestational age at delivery to 31 single nucleotide polymorphisms measured in newborn screening bloodspots. Among all 443 children with later-diagnosed cerebral palsy born to white women in South Australia in 1986-1999, 234 were born after spontaneous onset of labor, and 108 of these were preterm (gestational age less than 37 weeks).

Long-term natural history of hemangioblastomas in patients with von Hippel-Lindau disease: implications for treatment.

Object: In the course of their lives most patients with von Hippel-Lindau (VHL) disease require treatment for several symptom-producing hemangioblastomas of the cerebellum, brainstem, or spinal cord. However, many tumors never produce symptoms and do not require treatment. Detection at an early stage of lesions that will later produce symptoms and ultimately require treatment would allow for earlier excision of hemangioblastomas of the spinal cord, brainstem, or cerebellum, and may identify cerebellar hemangioblastomas that can be treated with radiosurgery at a stage before treatment is contraindicated because of tumor size or the presence of an associated cyst.

A prospective evaluation of the role for intraoperative x-ray in lumbar discectomy. Predictors of incorrect level exposure.

Background: Lumbar discectomy is among the most frequently performed procedures by spine surgeons. Among the potential difficulties encountered during this procedure, incorrect spinal level surgery remains a significant concern for surgeons and patients. Multiple groups have advocated the use of intraoperative x-ray to reduce the incidence of incorrect level surgery; however, this technique has not been prospectively evaluated.

Selected neurotrophins, neuropeptides, and cytokines: developmental trajectory and concentrations in neonatal blood of children with autism or Down syndrome.

Using a double-antibody immunoaffinity assay (Luminex) and ELISA technology, we measured concentrations of certain neurotrophins, neuropeptides, and cytokines in pooled samples (one to three subjects per sample) eluted from archived neonatal blood of children with later-diagnosed autism, Down syndrome, very preterm birth, or term control infants. We also measured analytes in blood from healthy adult controls. Case or control status for infant subjects was ascertained by retrospective review of service agency medical records.

Short-latency afferent inhibition during selective finger movement.

During individual finger movement, two opposite phenomena occur at the level of the central nervous system that could affect other intrinsic hand muscle representations, unintentional co-activation, and surround inhibition (SI). At rest, excitability in the motor cortex (M1) is inhibited at about 20 ms after electric stimulation of a peripheral nerve [short-latency afferent inhibition (SAI)]. We sought to determine whether SAI changes during selective index finger movement.

Long-latency afferent inhibition during selective finger movement.

Stimulation of a peripheral nerve of a hand at rest modulates excitability in the motor cortex and, in particular, leads to inhibition when applied at an interval of approximately 200 ms (long-latency afferent inhibition; LAI). Surround inhibition (SI) is the process that inhibits neighboring muscles not involved in a particular task. The neuronal mechanisms of SI are not known, and it is possible that LAI might contribute to it.

Interferon-beta1a therapy in human T-lymphotropic virus type I-associated neurologic disease.

Human T-lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is an immune-mediated inflammatory disorder of the central nervous system. Immune activation in the host, which results from high levels of persistent antigenic stimulation and from transactivation of host immunoregulatory genes by HTLV-I, appears important in the pathogenesis of HAM/TSP. In a single-center, open-label trial, 12 patients with HAM/TSP were treated with doses of interferon-beta1a of up to 60mug twice weekly, based on its antiviral and immunomodulatory effects.

Genetic polymorphisms and cerebral palsy in very preterm infants.

In the present study, we examine whether selected genetic polymorphisms contribute to the development of cerebral palsy (CP) in very preterm infants. Subjects were 96 singleton infants with later-diagnosed CP and 119 control children, white non-Hispanic (n for CP=74, controls=88) or white Hispanic (CP=22, controls=31), born <32 wk gestation. Presence of CP was identified through state service agencies, with review of medical records.

Pediatric Fabry disease.

Background: Fabry disease is an underdiagnosed, treatable, X-linked, multisystem disorder.

Objectives: To test the hypothesis that quality of life and sweating are decreased among pediatric patients with Fabry disease, compared with control subjects, and to provide quantitative natural history data and novel clinical end points for therapeutic trials.

Design: Prospective, cross-sectional, observational study.

Motor training as treatment in focal hand dystonia.

Focal hand dystonia may arise as a result of aberrant plasticity from excessive repetitive use. Improvement might be possible with appropriate motor training. Focusing on trying to decrease abnormal overflow of movement to fingers not involved in a task, we developed a motor training program for individualized finger movements.

Rising statin use and effect on ischemic stroke outcome.

Background: Statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) have neuroprotective effects in experimental stroke models and are commonly prescribed in clinical practice. The aim of this study was to determine if patients taking statins before hospital admission for stroke had an improved clinical outcome.

Methods: This was an observational study of 436 patients admitted to the National Institutes of Health Suburban Hospital Stroke Program between July 2000 and December 2002.

Enzyme replacement therapy improves peripheral nerve and sweat function in Fabry disease.

Fabry disease is an X-linked disorder caused by a deficiency of lysosomal alpha-galactosidase A resulting in accumulation of alpha-D-galatosyl conjugated glycosphingolipids. Clinical manifestations include a small-fiber neuropathy associated with debilitating pain and hypohidrosis. We report the effect of a 3-year open-label extension of a previously reported 6-month placebo-controlled enzyme replacement therapy (ERT) trial in which 26 hemizygous patients with Fabry disease received 0.

Early ischemic lesion recurrence within a week after acute ischemic stroke.

Previous observations suggested that multiple ischemic lesions on diffusion-weighted imaging (DWI) are common in acute stroke patients. We hypothesized that a source of these multiple lesions was the recurrence of ischemic lesions within a week after a clinically symptomatic stroke. We analyzed 99 acute ischemic stroke patients scanned within 6 hours of onset and at subsequent times within the first week.

High frequency of human herpesvirus 6 DNA in multiple sclerosis plaques isolated by laser microdissection.

The frequency of human herpesvirus 6 (HHV-6) DNA was assessed in autopsy material from multiple sclerosis (MS) plaques and normal-appearing white matter (NAWM) from brains of persons with MS, healthy brains, and brains of persons with other neurologic diseases. Specific areas from formalin-fixed, paraffin-embedded brain tissue samples were isolated by laser microscope. DNA was extracted from laser microdissected brain material, and HHV-6 genomic sequences were amplified by nested polymerase chain reaction.

Evaluation of essential tremor with multi-voxel magnetic resonance spectroscopy.

The pathologic substrate of essential tremor (ET) remains unknown. The authors studied 10 patients with ET and 10 volunteers using a multislice MR spectroscopy imaging sequence. Left and right cerebellar hemisphere NAA/CR and NAA/Cho ratios were significantly smaller in the ET patients than healthy subjects.

Neonatal cytokines and cerebral palsy in very preterm infants.

To examine the relationship of cytokines in blood of very preterm neonates with later diagnosis of spastic cerebral palsy (CP) compared with infants of similar gestational age without CP, we measured concentrations of inflammatory cytokines and other substances in archived neonatal blood by recycling immunoaffinity chromatography. Subjects were surviving children born before 32 wk gestational age (GA) to women without preeclampsia, 64 with later diagnoses of CP and 107 control children. The initial analyses were augmented by measurement of 11 cytokines by a bead-based flow analytic system (Luminex) in an additional 37 children with CP and 34 control children from the same cohort.