Management of asymptomatic cervical spinal stenosis in the setting of symptomatic tandem lumbar stenosis: a review

INTRODUCTION: This article reviews the literature regarding tandem asymptomatic cervical stenosis in the setting of symptomatic lumbar stenosis. The presenting features of cervical spondylotic myelopathy are insidious and consistent with upper motor neuron loss. Often, asymptomatic cervical stenosis is encountered in the clinical setting during the workup of a symptomatic lumbar stenosis and degenerative disease. METHODS: A PubMed (1966 to July 2013) electronic database search was conducted for articles pertaining to the diagnosis of incidentally discovered cervical cord compression. Keywords and MESH terms were limited to asymptomatic cervical stenosis, asymptomatic cervical compression, asymptomatic spinal stenosis, asymptomatic cervical spondylosis, and asymptomatic cervical cord signal. The primary literature topics for manuscript inclusion were the development of symptomatic myelopathy from asymptomatic cord signal edema, as well as the presence of tandem stenosis as defined above by incidental cervical stenosis during the workup of lumbar degenerative disease. RESULTS: There were no previous systematic reviews, randomized trials, or prospective studies on the management of tandem cervical and thoracic stenosis. Five studies, all retrospective reviews containing relevant data were included in the review. Asymptomatic cervical stenosis encountered in the investigation of lumbar symptoms was had a 23% incidence. A risk of 5% per year of development of myelopathy previously reported. CONCLUSIONS: There is insufficient evidence in the literature to support the need for preemptive decompression for asymptomatic cervical cord compression with or without a correlative T2 hyperintense cord signal. Early diagnosis of radiculopathy or myelopathy in patients with cervical stenosis (i.e., through conversion of asymptomatic to symptomatic state) is important as each patient with in this clinical setting should be followed closely, as the literature shows the tendency for a clinical progression to eventual cervical myelopathy

Optomechanical Thermometry of Nanoribbon Cantilevers

Cadmium sulfide (CdS) nanostructures have attracted a significant amount of attention for a variety of optoelectronic applications including photovoltaic cells, semiconductor lasers, and solid-state laser refrigeration due to their direct bandgap around 2.42 eV and high radiative quantum efficiency. Nanoribbons (NRs) of CdS have been claimed to laser cool following excitation at 514 and 532 nm wavelengths by the annihilation of optical phonons during anti-Stokes photoluminescence. To explore this claim, we demonstrate a novel optomechanical experimental technique for microthermometry of a CdSNR cantilever using Young’s modulus as the primary temperature-dependent observable. Measurements of the cantilever’s fundamental acoustic eigenfrequency at low laser powers showed a red-shift in the eigenfrequency with increasing power, suggesting net heating. At high laser powers, a decrease in the rate of red-shift of the eigenfrequency is explained using Euler–Bernoulli elastic beam theory, considering Hookean optical-trapping force. A predicted imaginary refractive index for CdSNR based on experimental temperature measurement agrees well with a heat transfer analysis that predicts the temperature distribution within the cantilever and the time required to reach steady state (<100 μs). This approach is useful for investigating solid-state laser refrigeration of a wide variety of material systems without the need for complex pump/probe spectroscopy

Efficacy of the pharmacologic chaperone migalastat in a subset of male patients with the classic phenotype of Fabry disease and migalastat-amenable variants: data from the phase 3 randomized, multicenter, double-blind clinical trial and extension study

Purpose: Outcomes in patients with Fabry disease receiving migalastat during the phase 3 FACETS trial (NCT00925301) were evaluated by phenotype. Methods: Data were evaluated in two subgroups of patients with migalastat-amenable GLA variants: “classic phenotype” (n = 14; males with residual peripheral blood mononuclear cell αgalactosidase A <3% normal and multiorgan system involvement) and “other patients” (n = 36; males not meeting classic phenotype criteria and all females). Endpoints included estimated glomerular filtration rate (eGFR), left ventricular mass index (LVMi), Gastrointestinal Symptoms Rating Scale diarrhea subscale (GSRS-D), renal peritubular capillary (PTC) globotriaosylceramide (GL-3) inclusions, and plasma globotriaosylsphingosine (lyso-Gb3). Results: Baseline measures in the classic phenotype patients suggested a more severe phenotype. At month 24, mean (SD) annualized change in eGFRCKD-EPI with migalastat was −0.3 (3.76) mL/min/1.73 m2 in the classic phenotype subgroup; changes in LVMi, GSRS-D, and lyso-Gb3 were −16.7 (18.64) g/m2 , −0.9 (1.66), and −36.8 (35.78) nmol/L, respectively. At month 6, mean PTC GL-3 inclusions decreased with migalastat (−0.8) and increased with placebo (0.3); switching from placebo to migalastat, PTC inclusions decreased by −0.7. Numerically smaller changes in these endpoints were observed in the other patients. Conclusion: Migalastat provided clinical benefit to patients with Fabry disease and amenable variants, regardless of disease severity

Oral pharmacological chaperone migalastat compared with enzyme replacement therapy in Fabry disease: 18-month results from the randomised phase III ATTRACT study.

BackgroundFabry disease is an X-linked lysosomal storage disorder caused by GLA mutations, resulting in α-galactosidase (α-Gal) deficiency and accumulation of lysosomal substrates. Migalastat, an oral pharmacological chaperone being developed as an alternative to intravenous enzyme replacement therapy (ERT), stabilises specific mutant (amenable) forms of α-Gal to facilitate normal lysosomal trafficking.MethodsThe main objective of the 18-month, randomised, active-controlled ATTRACT study was to assess the effects of migalastat on renal function in patients with Fabry disease previously treated with ERT. Effects on heart, disease substrate, patient-reported outcomes (PROs) and safety were also assessed.ResultsFifty-seven adults (56% female) receiving ERT (88% had multiorgan disease) were randomised (1.5:1), based on a preliminary cell-based assay of responsiveness to migalastat, to receive 18 months open-label migalastat or remain on ERT. Four patients had non-amenable mutant forms of α-Gal based on the validated cell-based assay conducted after treatment initiation and were excluded from primary efficacy analyses only. Migalastat and ERT had similar effects on renal function. Left ventricular mass index decreased significantly with migalastat treatment (-6.6 g/m2 (-11.0 to -2.2)); there was no significant change with ERT. Predefined renal, cardiac or cerebrovascular events occurred in 29% and 44% of patients in the migalastat and ERT groups, respectively. Plasma globotriaosylsphingosine remained low and stable following the switch from ERT to migalastat. PROs were comparable between groups. Migalastat was generally safe and well tolerated.ConclusionsMigalastat offers promise as a first-in-class oral monotherapy alternative treatment to intravenous ERT for patients with Fabry disease and amenable mutations.Trial registration numberNCT00925301; Pre-results