The Restless Spinal Cord in Degenerative Cervical Myelopathy.

BACKGROUND AND PURPOSE: The spinal cord is subject to a periodic, cardiac-related movement, which is increased at the level of a cervical stenosis. Increased oscillations may exert mechanical stress on spinal cord tissue causing intramedullary damage. Motion analysis thus holds promise as a biomarker related to disease progression in degenerative cervical myelopathy. Our aim was characterization of the cervical spinal cord motion in patients with degenerative cervical myelopathy. MATERIALS AND METHODS: Phase-contrast MR imaging data were analyzed in 55 patients (37 men; mean age, 56.2 [SD,12.0] years; 36 multisegmental stenoses) and 18 controls (9 men, P = .368; mean age, 62.2 [SD, 6.5] years; P = .024). Parameters of interest included the displacement and motion pattern. Motion data were pooled on the segmental level for comparison between groups. RESULTS: In patients, mean craniocaudal oscillations were increased manifold at any level of a cervical stenosis (eg, C5 displacement: controls [n = 18], 0.54 [SD, 0.16] mm; patients [n = 29], monosegmental stenosis [n = 10], 1.86 [SD, 0.92] mm; P < .001) and even in segments remote from the level of the stenosis (eg, C2 displacement: controls [n = 18], 0.36 [SD, 0.09] mm; patients [n = 52]; stenosis: C3, n = 21; C4, n = 11; C5, n = 18; C6, n = 2; 0.85 [SD, 0.46] mm; P < .001). Motion at C2 differed with the distance to the next stenotic segment and the number of stenotic segments. The motion pattern in most patients showed continuous spinal cord motion throughout the cardiac cycle. CONCLUSIONS: Patients with degenerative cervical myelopathy show altered spinal cord motion with increased and ongoing oscillations at and also beyond the focal level of stenosis. Phase-contrast MR imaging has promise as a biomarker to reveal mechanical stress to the cord and may be applicable to predict disease progression and the impact of surgical interventions.

Extrapyramidal plasticity predicts recovery after spinal cord injury.

Spinal cord injury (SCI) leads to wide-spread neurodegeneration across the neuroaxis. We explored trajectories of surface morphology, demyelination and iron concentration within the basal ganglia-thalamic circuit over 2 years post-SCI. This allowed us to explore the predictive value of neuroimaging biomarkers and determine their suitability as surrogate markers for interventional trials. Changes in markers of surface morphology, myelin and iron concentration of the basal ganglia and thalamus were estimated from 182 MRI datasets acquired in 17 SCI patients and 21 healthy controls at baseline (1-month post injury for patients), after 3, 6, 12, and 24 months. Using regression models, we investigated group difference in linear and non-linear trajectories of these markers. Baseline quantitative MRI parameters were used to predict 24-month clinical outcome. Surface area contracted in the motor (i.e. lower extremity) and pulvinar thalamus, and striatum; and expanded in the motor thalamus and striatum in patients compared to controls over 2-years. In parallel, myelin-sensitive markers decreased in the thalamus, striatum, and globus pallidus, while iron-sensitive markers decreased within the left caudate. Baseline surface area expansions within the striatum (i.e. motor caudate) predicted better lower extremity motor score at 2-years. Extensive extrapyramidal neurodegenerative and reorganizational changes across the basal ganglia-thalamic circuitry occur early after SCI and progress over time; their magnitude being predictive of functional recovery. These results demonstrate a potential role of extrapyramidal plasticity during functional recovery after SCI.

Segmental differences of cervical spinal cord motion: advancing from confounders to a diagnostic tool.

Increased cranio-caudal spinal cord motion is associated with clinical impairment in degenerative cervical myelopathy. However, whether spinal cord motion holds potential as a neuroimaging biomarker requires further validation. Different confounders (i.e. subject characteristics, methodological problems such as phase drift, etc.) on spinal cord motion readouts have to be considered. Twenty-two healthy subjects underwent phase contrast MRI, a subset of subjects (N = 9) had repeated scans. Parameters of interest included amplitude of velocity signal, maximum cranial respectively maximum caudal velocity, displacement (=area under curve of the velocity signal). The cervical spinal cord showed pulse synchronic oscillatory motions with significant differences in all readouts across cervical segments, with a maximum at C5. The Inter-rater reliability was excellent for all readouts. The test-retest reliability was excellent for all parameters at C2 to C6, but not for maximum cranial velocity at C6 and all readouts at C7. Spinal cord motion was correlated with spinal canal size, heart rate and body size. This is the first study to propose a standardized MRI measurement of spinal cord motion for further clinical implementation based on satisfactory phase drift correction and excellent reliability. Understanding the influence of confounders (e.g. structural conditions of the spine) is essential for introducing cord motion into the diagnostic work up.

O-GlcNAcylation of STAT5 controls tyrosine phosphorylation and oncogenic transcription in STAT5-dependent malignancies.

The signal transducer and activator of transcription 5 (STAT5) regulates differentiation, survival, proliferation and transformation of hematopoietic cells. Upon cytokine stimulation, STAT5 tyrosine phosphorylation (pYSTAT5) is transient, while in diverse neoplastic cells persistent overexpression and enhanced pYSTAT5 are frequently found. Post-translational modifications might contribute to enhanced STAT5 activation in the context of transformation, but the strength and duration of pYSTAT5 are incompletely understood. We found that O-GlcNAcylation and tyrosine phosphorylation act together to trigger pYSTAT5 levels and oncogenic transcription in neoplastic cells. The expression of a mutated hyperactive gain-of-function (GOF) STAT5 without O-GlcNAcylation resulted in decreased tyrosine phosphorylation, oligomerization and transactivation potential and complete loss of oncogenic transformation capacity. The lack of O-GlcNAcylation diminished phospho-ERK and phospho-AKT levels. Our data show that O-GlcNAcylation of STAT5 is an important process that contributes to oncogenic transcription through enhanced STAT5 tyrosine phosphorylation and oligomerization driving myeloid transformation. O-GlcNAcylation of STAT5 could be required for nutrient sensing and metabolism of cancer cells.

Discrepancy between perceived pain and cortical processing: A voxel-based morphometry and contact heat evoked potential study.

OBJECTIVES: The purpose of this study was to determine if local gray and white matter volume variations between subjects could account for variability in responses to CHEP stimulation. METHODS: Structural magnetic resonance imaging was used to perform voxel-based morphometry (VBM) of gray and white matter in 30 neurologically healthy subjects. Contact heat stimulation was performed on the dorsum of the right hand at the base of the thumb. Evoked potentials were acquired from a vertex-recording electrode referenced to linked ears. RESULTS: Controlling for age, total intracranial volume, and skull/scalp thickness, CHEP amplitude and pain rating were not significantly correlated between subjects. A VBM region of interest approach demonstrated a significant interaction between pain rating and N2 amplitude in the right insular cortex (p<0.05, family-wise error corrected, FWE). In white matter, a significant interaction was localized in the right inferior frontal occipital fasciculus (IFOF, p<0.05 FWE). CONCLUSIONS: Accounting for gray matter volume in the right insular cortex, resulted in a significant relationship between CHEP amplitude and pain rating. SIGNIFICANCE: This finding suggests that the discrepancy between pain ratings and the amplitude of evoked potentials is not solely related to measurement artifact, but rather attributable, in part, to anatomical differences between subjects.

Fate of rubrospinal neurons after unilateral section of the cervical spinal cord in adult macaque monkeys: effects of an antibody treatment neutralizing Nogo-A.

The present study describes in primates the effects of a spinal cord injury on the number and size of the neurons in the magnocellular part of the red nucleus (RNm), the origin of the rubrospinal tract, and evaluates whether a neutralization of Nogo-A reduces the lesioned-induced degenerative processes observed in RNm. Two groups of monkeys were subjected to unilateral section of the spinal cord affecting the rubrospinal tract; one group was subsequently treated with an antibody neutralizing Nogo-A; the second group received a control antibody. Intact animals were also included in the study. Counting neurons stained with a monoclonal antibody recognizing non-phosphorylated epitopes on neurofilaments (SMI-32) indicated that their number in the contralesional RNm was consistently inferior to that in the ipsilesional RNm, in a proportion amounting up to 35%. The lesion also induced shrinkage of the soma of the neurons detected in the contralesional RNm. Infusing an anti-Nogo-A antibody at the site of the lesion did not increase the proportion of SMI-32 positive rubrospinal neurons in the contralesional RNm nor prevent shrinkage.

Static mechanical allodynia (SMA) is a paradoxical painful hypo-aesthesia: observations derived from neuropathic pain patients treated with somatosensory rehabilitation.

The present study aimed at investigating the time span it takes to remove a static mechanical allodynia (SMA) in humans suffering from chronic peripheral neuropathic pain. Forty-three subjects were included in the study and, during somatosensory rehabilitation, their SMA territory was precisely mapped. They then underwent distant vibrotactile counter stimulation (DVCS) treatment. It was observed that, with DVCS, SMA disappeared in all cases, and was transformed into an underlying hypoaesthesia. It was found that the "tenderness to touch" symptom (which is SMA) was located in the same territory as the underlying hypoaesthesia, which was located on a part of the cutaneous territory of a partially damaged nerve. These results demonstrate that treating patients suffering from neuropathic pain with DVCS revealed a skin territory of denervation that was previously masked by SMA. Thus, SMA can be considered as a paradoxical painful hypoaesthesia. Furthermore, mapping SMA is a valuable source of information for our understanding of abnormal sensory processing in neuropathic pain patients. We conclude that the mapping of the zone of hypersensitivity on the skin in humans suffering from chronic peripheral neuropathic pain improves diagnosis. The mapping of the zone of hypersensitivity is a tool to presume which branch of the peripheral nerve is damaged. The location of the axonal lesions is at the periphery, while the mechanism of pain sensitization is probably central and referred peripherally to the skin by a painful hypoaesthesia.

Omega- and Omega+ production in central Pb + Pb collisions at 40 and 158A GeV.

Results are presented on Omega production in central Pb+Pb collisions at 40 and 158A GeV beam energy. For the first time in heavy ion reactions, rapidity distributions and total yields were measured for the sum Omega(-) + Omega(+) at 40A GeV and for Omega(-) and Omega(+) separately at 158A GeV. The yields are strongly underpredicted by the string-hadronic UrQMD model but agree better with predictions from hadron gas models.

System-size dependence of strangeness production in nucleus-nucleus collisions at squareroot[sNN]=17.3 GeV.

Emission of pi+/-, K+/-, phi, and Lambda was measured in near-central C+C and Si+Si collisions at 158 AGeV beam energy. Together with earlier data for p+p, S+S, and Pb+Pb, the system-size dependence of relative strangeness production in nucleus-nucleus collisions is obtained. Its fast rise and the saturation observed at about 60 participating nucleons can be understood as the onset of the formation of coherent systems of increasing size.

Lambda and lambda production in central Pb-Pb collisions at 40, 80, and 158A GeV.

Production of Lambda and Antilambda hyperons was measured in central Pb-Pb collisions at 40, 80, and 158A GeV beam energy on a fixed target. Transverse mass spectra and rapidity distributions are given for all three energies. The Lambda/pi ratio at midrapidity and in full phase space shows a pronounced maximum between the highest BNL Alternating Gradient Synchrotron and 40A GeV CERN Super Proton Synchrotron energies, whereas the Lambda/pi ratio exhibits a monotonic increase.

Evidence for an exotic S= -2, Q= -2 baryon resonance in proton-proton collisions at the CERN SPS.

Results of resonance searches in the Xi(-)pi(-), Xi(-)pi(+), Xi;(+)pi(-), and Xi;(+)pi(+) invariant mass spectra in proton-proton collisions at sqrt[s]=17.2 GeV are presented. Evidence is shown for the existence of a narrow Xi(-)pi(-) baryon resonance with mass of 1.862+/-0.002 GeV/c(2) and width below the detector resolution of about 0.018 GeV/c(2). The significance is estimated to be above 4.2sigma. This state is a candidate for the hypothetical exotic Xi(--)(3/2) baryon with S=-2, I=3 / 2, and a quark content of (dsdsu). At the same mass, a peak is observed in the Xi(-)pi(+) spectrum which is a candidate for the Xi(0)(3/2) member of this isospin quartet with a quark content of (dsus[-]d). The corresponding antibaryon spectra also show enhancements at the same invariant mass.

The effect of bispectral index monitoring on end-tidal gas concentration and recovery duration after outpatient anesthesia.

We performed this study to determine whether instituting monitoring of bispectral index (BIS) throughout an entire operating room would affect end-tidal gas concentration (as a surrogate for anesthetic use) or speed of recovery after outpatient surgery. Primary caregivers (n = 69) were randomly assigned to a BIS or non-BIS Control group with cross-over at 1-mo intervals for 7 mo. Data were obtained in all outpatients except for those having head-and-neck surgery. Mean end-tidal gas concentration and total recovery duration were compared by unpaired t-test. Overall, 469 patients (80%) received propofol for induction and sevoflurane for maintenance. This homogeneous group was selected for statistical analysis. Mean end-tidal sevoflurane concentration was 13% less in the BIS group (BIS, 1.23%; Control, 1.41%; P < 0.0001); differences were most evident when anesthesia was administered by first-year trainees. Mean BIS values were 47 in the BIS-Monitored group. Total recovery was 19 min less with BIS monitoring in men (BIS group, 147 min; Controls, 166 min; P = 0.035), but not different in women. We conclude that routine application of BIS monitoring is associated with a modest reduction in end-tidal sevoflurane concentration. In men, this may correlate with a similar reduction (11%) in recovery duration.

Event-by-event fluctuations of the Kaon-to-Pion ratio in central Pb+Pb collisions at 158 GeV per nucleon.

We present the first measurement of fluctuations from event to event in the production of strange particles in collisions of heavy nuclei. The ratio of charged kaons to charged pions is determined for individual central Pb+Pb collisions. After accounting for the fluctuations due to detector resolution and finite number statistics we derive an upper limit on genuine nonstatistical fluctuations, which could be related to a first- or second-order QCD phase transition. Such fluctuations are shown to be very small.

Trends in quality of anesthesia care associated with changing staffing patterns, productivity, and concurrency of case supervision in a teaching hospital.

BACKGROUND: The authors used continuous quality improvement (CQI) program data to investigate trends in quality of anesthesia care associated with changing staffing patterns in a university hospital. METHODS: The monthly proportion of cases performed by solo attending anesthesiologists versus attending-resident teams or attending-certified registered nurse anesthetist (CRNA) teams was used to measure staffing patterns. Anesthesia team productivity was measured as mean monthly surgical anesthesia hours billed per attending anesthesiologist per clinical day. Supervisory ratios (concurrency) were measured as mean monthly number of cases supervised concurrently by attending anesthesiologists. Quality of anesthesia care was measured as monthly rates of critical incidents, patient injury, escalation of care, operational inefficiencies, and human errors per 10,000 cases. Trends in quality at increasing productivity and concurrency levels from 1992 to 1997 were analyzed by the one-sided Jonckheere-Terpstra test. RESULTS: Productivity was positively correlated with concurrency (r = 0.838; P<0.001). Productivity levels ranged from 10 to 17 h per anesthesiologist per clinical day. Concurrency ranged from 1.6 to 2.2 cases per attending anesthesiologist. At higher productivity and concurrency levels, solo anesthesiologists conducted a smaller percentage of cases, and the proportion of cases with CRNA team members increased. The patient injury rate decreased with increased productivity levels (P = 0.002), whereas the critical incident rate increased (P = 0.001). Changes in operational inefficiency, escalation of care, and human error rates were not statistically significant (P = 0.072, 0.345, 0.320, respectively). CONCLUSIONS: Most aspects of quality of anesthesia care were apparently not effected by changing anesthesia team composition or increased productivity and concurrency. Only team performance was measured; the role of individuals (attending anesthesiologist, resident, or CRNA) in quality of care was not directly measured. Further research is needed to explain lower patient injury rates and increases in critical incident reporting at higher concurrency and productivity levels.

[Symptomatic venous angioma. Report of a case]. / Angiome veineux symptomatique. A propos d'un cas.

We report a case of venous angioma revealed by seizure after a non hemorrhagic venous infarct. The initial neuroradiological work-up with CT scan, angiography and brain MRI evidenced the venous infarction with abnormal contrast uptake. The control MRI 3 months later showed clear involution of the venous infarct. Non-hemorrhagic venous infarction on venous angiomas are exceptional. Only 2 cases have been reported in the literature. Impaired venous drainage could be implicated.

[Capillary telangiectasis, angiographically occult vascular malformations. MRI symptomatology apropos of 7 cases]. / Les télangiectasies capillaires, malformations vasculaires angiographiquement occultes. Sémiologie IRM à propos de 7 observations.

OBJECTIVE: Describe the MRI findings in capillary telangiectasias. MATERIALS AND METHODS: Between 1996 and 1999, we observed 9 cases of capillary telangiectasia in 7 patients explored 5 times for posterior fossa symptoms. In two cases capillary telangiectasia was a fortuitous discovery. All patients were explored by MRI with T1 sequences with and without gadolinium injections, turbo spin echo T2 coupled in 5 cases with a double echo gradient echo T2 sequence (TR: 970 ms, TE: 15 and 35 ms). Two patients also underwent vertebral angiography. RESULTS: The telangiectasia gave a low intensity signal on T1 sequences in 2 of the 9 cases and a discretely high intensity signal on T2 sequences in all cases. After gadolinium injection, 9 telangiectasias showed homogeneous or speckled enhancement. The echo-gradient T2 images showed a very low intensity signal in 7 out of 7 cases on the second echo. At the first echo, 4 capillary telangiectasias were undetectable. The two vertebral angiographies were normal and the follow-up MRI in 5 patients showed lesion stability. CONCLUSION: Pontile lesions with no mass effect showing enhancement after gadolinium injection and with or without a discrete T2 high intensity signal but with a frank echo-gradient T2 signal strongly suggest capillary telangiectasia.

[Current imaging of an "aberrant course" of the internal carotid artery]. / Imagerie actuelle d'un "trajet aberrant" de l'artère carotide interne.

Blood flow via an aberrant internal carotid artery within the tympanic cavity is a rare pathogenic embryonic variation causing pulsatile tintinus and a vascularized tympanum. CT-scan provides the diagnosis. MRI and 3D time-of-flight MRA appear ideal for exploring aberrant flow both for diagnostic purposes and to establish the vascular morphology.

Cost-effective reduction of neuromuscular-blocking drug expenditures.

BACKGROUND: Anesthetic drug expenditures have been a focus of cost-containment efforts. The aim of this study was to determine whether expenditures for neuromuscular-blocking agents could be reduced without compromising outcome, and to determine whether such a cost-effective pattern of neuromuscular blocker use could be sustained. METHODS: Education, practice guidelines, and paperwork barriers were used to persuade anesthesiologists to substitute low-cost neuromuscular-blocking drugs (pancuronium or a metocurine-pancuronium combination) for a more costly neuromuscular-blocking drug (vecuronium). Neuromuscular-blocking drug use in all patients during a historical control period (6 months; n = 4,804) was compared with that during two consecutive 1-yr periods of intervention (n = 9,761/n = 10,695). Expenditures for vecuronium and for all neuromuscular-blocking drugs were compared for the control and intervention periods. The rate of complications related to neuromuscular-blocking drugs was determined by an ongoing continuous quality improvement program. RESULTS: Vecuronium use decreased by 76% during the first and second yr of intervention, compared with the historical period (P < 0.01). The cost of neuromuscular-blocking drugs decreased by 31% (P < 0.01) and 47% (P < 0.01) for the first and second yr, respectively. The complication rate related to neuromuscular-blocking drugs was 0.081% in the historical period and 0.11% and 0.093% during the intervention periods (P = 0.29 and 0.41). CONCLUSION: Practice guidelines, education, and paperwork barriers used together substantially reduced the expenditures for neuromuscular-blocking drugs for 2 yr without adversely affecting clinical outcome.