35 research outputs found
Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome : a slowly progressive disorder with stereotypical presentation
No full textCerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS) is a newly described condition with onset in adulthood, characterized by progressive balance impairment and sensory disturbances in the lower limbs, which can severely affect patients' quality of life. Its pathogenesis remains obscure and the diagnosis challenging. We described four patients complaining of slowly progressive gait unbalance and sensory disturbances at the feet followed, after a period ranging 2-6 years, by cerebellar dysfunction. All patients showed gait and limb ataxia, positive Romberg sign, cerebellar dysarthria, gaze-evoked nystagmus, absent deep tendon reflexes, and impaired vibratory sensation. Nerve conduction studies revealed axonal sensory neuropathy, brain magnetic resonance imaging showed cerebellar atrophy, and otoneurological investigation demonstrated bilateral vestibular areflexia with impaired vestibulo-ocular reflexes. The diagnosis of CANVAS should be suspected on clinical ground based on homogeneous course of symptoms and signs, and addressed by video-oculography eye movement recording
Mutation of the small HSP27/HSPB1 causes CMT neuropathy with abnormal neurofilament assembly
No full textShort-Form Charlson Comorbidity Index for Assessment of Perioperative Mortality After Radical Cystectomy
No full textBackground: The Deyo adaptation of the Charlson comorbidity index (DaCCI), which relies on 17 comorbid condition groupings, represents one of the most frequently used baseline comorbidity assessment tools in retrospective database studies. However, this index is not specific for patients with bladder cancer (BCa) treated with radical cystectomy (RC). The goal of this study was to develop a short-form of the original DaCCI (DaCCI-SF) that may specifically predict 90-day mortality after RC, with equal or better accuracy. Patients and Methods: Between 2000 and 2009, we identified 7,076 patients in the SEER-Medicare database with stage T1 through T4 nonmetastatic BCa treated with RC. We randomly divided the population into development (n= 6,076) and validation (n= 1,000) cohorts. Within the development cohort, logistic regression models tested the ability to predict 90-day mortality with various iterations of the DaCCI-SF, wherein 75 years), stage (organ-confined vs non-organ-confined), type of diversion (ilealconduit vs non-ileal-conduit), and treatment period. Conclusions: DaCCI-SF relies on 17.6% of the original comorbid condition groupings and provides higher accuracy for predicting 90-day mortality after RC compared with the original DaCCI, especially in most contemporary patients
Development of a New Comorbidity Assessment Tool for Specific Prediction of Perioperative Mortality in Contemporary Patients Treated with Radical Cystectomy
No full textPurpose: The Deyo adaptation of the Charlson comorbidity index (DaCCI), which relies on 17 comorbid condition groupings defined with 200 ICD-9-CM diagnostic codes, lacks specificity in the context of radical cystectomy (RC) for bladder cancer (BCa). We attempted to develop a new comorbidity assessment tool based on individual comorbid conditions and/or BCa manifestations for specific prediction of perioperative mortality after RC. Methods: We relied on 7076 T1–T4 nonmetastatic BCa patients treated with RC between 2000 and 2009 in the SEER-Medicare linked database. Within the development cohort (n = 6076), simulated annealing (SA) was used to identify (1) individual comorbid conditions, (2) individual BCa manifestations, and (3) the combination of both, that satisfy the criteria of maximal accuracy and parsimony for prediction of 90-day mortality after RC, after adjusting for several confounders. The accuracy of the newly identified groups of individual comorbid conditions and/or BCa manifestations and of the original DaCCI was tested in a 1000-patient external validation cohort. Results: The combination of six individual comorbid conditions and two individual BCa disease manifestations (type II diabetes without complications, anemia, chronic obstructive pulmonary disease, congestive heart failure, aortocoronary bypass, cardiomegaly, urinary tract infection, and hydronephrosis), and seven individual comorbid conditions (type II diabetes without complications, anemia, chronic obstructive pulmonary disease, congestive heart failure, aortocoronary bypass, osteoarthrosis, and cardiomegaly) respectively showed 71.1 and 70.2% accuracy versus 68.0% for the original DaCCI. Conclusions: These new approaches are specific to contemporary RC patients and represent simpler methods compared with the original DaCCI, without any compromise in accuracy
The extracellular matrix affects axonal regeneration in peripheral neuropathies
No full textObjective: Recent evidence in animal models suggests that components of the extracellular ma- trix (ECM) play a primary role in peripheral nerve degeneration and regeneration. Methods: We investigated the expression of several ECM molecules in human sural nerves by immunohistochemistry, Western blot, and reverse transcriptase PCR analysis. To unravel the pos- sible role of these molecules in nerve regeneration, we compared results obtained from nerves with abundant signs of regeneration with those with complete absence of axonal regeneration. The role of some ECM components on neurite extension was further tested in dorsal root ganglion cultures. Results: We observed that the ECM composition significantly differs in regenerating compared with nonregenerating nerves, independently from their etiologic background. Fibronectin was abundantly expressed in regenerating nerves, whereas vitronectin and fibrin(ogen) prevailed in nonregenerating nerves. Whereas fibronectin is secreted by endoneurial cells, in vivo and vitro studies showed that the source of vitronectin and fibrin(ogen) is the bloodstream. Conclusions: These data indicate that nerve regeneration is impaired in the presence of breaches in the blood–nerve barrier or impaired extracellular matrix (ECM) degradation that leads to accumula- tion of plasma vitronectin and fibrin(ogen). The transformation into mature, fibronectin-enriched ECM is necessary for efficient nerve regeneration in humans
Epidermal innervation morphometry by immunofluorescence and bright-field microscopy
No full textWe investigated the agreement between simple indirect immunofluorescence (IF) and bright-field immunohistochemistry (BFI) on free-floating sections for intraepidermal nerve fiber density (IENFD) quantification. Fifty-five healthy subjects and 63 patients with probable small fiber neuropathy (SFN) underwent two adjacent skin biopsies at the distal leg processed by IF and BFI technique. Agreement between IENFD pairs obtained by each method was assessed by Bland-Altman testing. The area under the curve of the receiving operating characteristics (ROC) curves was used to compare the discrimination ability. The diagnostic judgment was based on sex and age-adjusted normative values. IF and BFI showed good correlation (r = 0.81), with a ratio of about 2:1 and a mean difference of 5.5 ± 3.0 IENF per millimeter between paired measures, as demonstrated by linear regression and Bland-Altman test analyses. The square root transformation confirmed a Poisson distribution of the data and a fixed bias between IF and BFI measurements. The ROC curves analysis demonstrated a striking overlap between IF and BFI (0.83 and 0.82; p = 0.72). The diagnosis of SFN disagreed in only 6.7% of cases when the judgment was based on a difference of >1 IENF from 5% cut-off value. IF and BFI showed comparable diagnostic efficiency when referred to appropriate normative reference values
