The Influence of Cervical Spondylolisthesis on Clinical Presentation and Surgical Outcome in Patients With DCM: Analysis of a Multicenter Global Cohort of 458 Patients.

STUDY DESIGN: Ambispective study with propensity matching. OBJECTIVE: To assess the impact of cervical spondylolisthesis (CS) on clinical presentation and surgical outcome in patients with degenerative cervical myelopathy (DCM). METHODS: A total of 458 magnetic resonance images (MRIs) from the AOSpine CSM-NA and CSM-I studies were reviewed and CS was identified. Patients with DCM were divided into 2 cohorts, those with CS and those without, and propensity matching was performed. Patient demographics, neurological and functional status at baseline and 2-year follow-up were compared. RESULTS: Compared with nonspondylolisthesis (n = 404), CS patients (n = 54) were 8.8 years older (P < .0001), presented with worse baseline neurological and functional status (mJOA [modified Japanese Orthopaedic Association Assessment Scale], P = .008; Nurick, P = .008; SF-36-PCS [Short Form-36 Physical Component Score], P = .01), more commonly presented with ligamentum flavum enlargement (81.5% vs 53.5%, P < .0001), and were less commonly from Asia (P = .0002). Surgical approach varied between cohorts (P = .0002), with posterior approaches favored in CS (61.1% vs 37.4%). CS patients had more operated levels (4.3 ± 1.4 vs 3.6 ± 1.2, P = .0002) and tended to undergo longer operations (196.6 ± 89.2 vs 177.2 ± 75.6 minutes, P = .087). Neurological functional recovery was lower with CS (mJOA [1.5 ± 3.6 vs 2.8 ± 2.7, P = .003]; Nurick [-0.8 ± 1.4 vs -1.5 ± 1.5, P = .002]), and CS was an independent predictor of worse mJOA recovery ratio at 2 years (B = -0.190, P < .0001). After propensity matching, improvement of neurological function was still lower in CS patients (mJOA [1.5 ± 3.6 vs 3.2 ± 2.8, P < .01]; Nurick [-0.8 ± 1.4 vs -1.4 ± 1.6, P = .02]). CONCLUSIONS: CS patients are older, present with worse neurological/functional impairment, and receive surgery on more levels and more commonly from the posterior. CS may indicate a more advanced state of DCM pathology and is more likely to result in a suboptimal surgical outcome.

Transient Dorsal Column Dysfunction After Extreme Cervical Deformity Correction: Report of 3 Cases.

BACKGROUND: Chin-on-chest kyphotic cervical deformity can be debilitating. Surgical deformity correction serves to decompress neural elements and restore lordosis. This can be achieved through multiple osteotomies with instrumentation and fusion, sometimes requiring a staged approach. Such procedures carry a high risk of neurologic injury. Here we present examples of transient neurologic dysfunction not previously reported in the common literature. CASE DESCRIPTION: The authors present 3 patients who underwent extreme cervical deformity correction for chin-on-chest deformity. Deformity correction in all cases was obtained through multiple osteotomies with multilevel cervicothoracic posterior instrumentation and arthrodesis. On postoperative examination, all 3 patients developed transient ataxia, dysmetria, and decreased proprioception in all 4 extremities-examination findings consistent with dorsal column dysfunction. All symptoms resolved within 2-3 weeks postoperatively. CONCLUSIONS: Incomplete spinal cord syndromes such as posterior cord syndrome can be caused by compression or stretching of the ascending dorsal spinal tracts. Considering the large degree of correction obtained, we hypothesize the resulting shortening of the dorsal columns as the pathomechanism. Providers should be aware, and patients should be counseled preoperatively that these symptoms may occur. If these symptoms are present postoperatively, appropriate diligence is warranted with the understanding that these deficits may be transient.

Prevalence of anemia and its relationship with neurological status in patients undergoing surgery for degenerative cervical myelopathy and radiculopathy: A retrospective study of 2 spine centers.

Both degenerative cervical myelopathy (DCM) and anemia are common among older patients, however insufficient data exists evaluating their co-occurrence and the influence of anemia on baseline neurological status. To address this, we examined a retrospective multicenter series of patients treated for DCM or radiculopathy. Myelopathy was graded using the Nurick scale. Established criteria for diagnosing abnormalities were used to identify blood abnormalities, including macrocytic and microcytic anemia. Multivariable regression was used to determine the impact of hematological anomalies on Nurick grades. In our analysis, we included 725 patients (age of 57.1 ± 11.7), of whom 398 presented with myelopathy and 327 presented with radiculopathy alone. Twenty six percent of all patients were anemic at baseline and the mean preoperative Nurick grade across all patients was 2.09 ± 1.29; mean Nurick grade amongst those with DCM was 2.98 ± 1.12. Compared to those with myelopathy, patients with radiculopathy were significantly younger (53.8 ± 11.0 vs 59.8 ± 11.6, p < 0.001) and less likely to be anemic (16.8% vs 33.7%, p < 0.0001). Nurick grading was significantly higher in myelopathy patients with anemia (3.13 ± 1.19 vs 2.91 ± 1.07, p = 0.05) and macrocytic anemia (4.00 ± 1.41 vs 2.97 ± 1.11, p = 0.04). Multivariate regression demonstrated that anemia (p < 0.001), age (p < 0.0001), and posterior surgical approach (p < 0.0001) were related to worse preoperative Nurick grade. In sum, these data suggest that anemia and degenerative cervical spine pathologies commonly co-occur. Anemia, and macrocytic anemia specifically, is associated with poorer neurological status in myelopathic patients. These data suggest anemia may influence baseline neurological status and impact surgical recovery in patients treated for DCM or radiculopathy.

Complications in Children with Ehlers-Danlos Syndrome Following Spine Surgery: Analysis of the Pediatric National Surgery Quality Improvement Program Database.

BACKGROUND: Ehlers-Danlos syndrome (EDS) is a group of rare congenital disorders of connective tissue that result in tissue fragility and joint hyperextensibility. Owing to its rarity, outcomes of pediatric spine surgery in patients with EDS are poorly characterized. Although it has been suggested that complication rates are high, few studies have characterized these complications. METHODS: Pediatric National Surgery Quality Improvement Program data from 2012-2016 were analyzed. Patients with EDS undergoing spine surgery were identified along with patients without EDS undergoing the same surgeries using International Classification of Diseases, Ninth Revision and Current Procedural Terminology codes. RESULTS: Of 369,176 total patients, 279 were determined to have EDS. Of these, 56 patients underwent spine surgery; 46% were male and 54% were female (P = 0.108). Mean age at surgery was 11.59 years (P = 0.888) with a range of 1.77-17.33 years. The most common procedure was arthrodesis (n = 37). There were no differences in unplanned reoperations (n = 4, P = 0.119), wound infections or disruptions (n = 2, P = 0.670), or overall complications (n = 25, P = 0.751). Blood transfusions were required in 41% of patients with EDS, but this was not significant compared with patients without EDS undergoing the same procedures (n = 23, P = 0.580). The total amount of blood transfused (P = 0.508), length of hospital stay (P = 0.396), and total operative time (P = 0.357) were not different from control subjects. CONCLUSIONS: Pediatric patients with EDS do not appear to be at a higher risk of bleeding or other complications during spine surgery as reported in past case series. This is the largest retrospective review of its kind that has been performed in this patient population.

Application of emerging technologies to improve access to ischemic stroke care.

During the past 20 years, the traditional supportive treatment for stroke has been radically transformed by advances in catheter technologies and a cohort of prominent randomized controlled trials that unequivocally demonstrated significant improvement in stroke outcomes with timely endovascular intervention. However, substantial limitations to treatment remain, among the most important being timely access to care. Nonetheless, stroke care has continued its evolution by incorporating technological advances from various fields that can further reduce patients' morbidity and mortality. In this paper the authors discuss the importance of emerging technologies-mobile stroke treatment units, telemedicine, and robotically assisted angiography-as future tools for expanding access to the diagnosis and treatment of acute ischemic stroke.

Lumbar Facet Tropism: A Comprehensive Review.

BACKGROUND: Scattered reports exist in the medical literature regarding facet tropism. However, this finding has had mixed conclusions regarding its origin and impact on the normal spine. METHODS: We performed a literature review of the anatomy, embryology, biomechanics, and pathology related to lumbar facet tropism. RESULTS: Facet tropism is most commonly found at L4-L5 vertebral segments and there is some evidence that this condition may lead to facet degenerative spondylolisthesis, intervertebral disc disease, and other degenerative conditions. CONCLUSION: Long-term analyses of patients are necessary to elucidate relationships between associated findings and facet tropism. In addition, a universally agreed definition that is more precise should be developed for future investigative studies.

Vascular Diseases of the Spinal Cord: Infarction, Hemorrhage, and Venous Congestive Myelopathy.

Vascular pathologies of the spinal cord are rare and often overlooked. This article presents clinical and imaging approaches to the diagnosis and management of spinal vascular conditions most commonly encountered in clinical practice. Ischemia, infarction, hemorrhage, aneurysms, and vascular malformations of the spine and spinal cord are discussed. Pathophysiologic mechanisms, clinical classification schemes, clinical presentations, imaging findings, and treatment modalities are considered. Recent advances in genetic and syndromic vascular pathologies of the spinal cord are also discussed. Clinically relevant spinal vascular anatomy is reviewed in detail.

Activation of mGluR5 and inhibition of NADPH oxidase improves functional recovery after traumatic brain injury.

Abstract Traumatic brain injury (TBI) induces microglial activation, which can contribute to secondary tissue loss. Activation of mGluR5 reduces microglial activation and inhibits microglial-mediated neurodegeneration in vitro, and is neuroprotective in experimental models of CNS injury. In vitro studies also suggest that the beneficial effects of mGluR5 activation involve nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibition in activated microglia. We hypothesized that activation of mGluR5 by the selective agonist CHPG after TBI in mice is neuroprotective and that its therapeutic actions are mediated by NADPH oxidase inhibition. Vehicle, CHPG, or CHPG plus the mGluR5 antagonist (MPEP), were administered centrally, 30 minutes post-TBI, and functional recovery and lesion volume was assessed. CHPG significantly attenuated post-traumatic sensorimotor and cognitive deficits, and reduced lesion volumes; these effects were blocked by MPEP, thereby indicating neuroprotection involved selective activation of mGluR5. CHPG treatment also reduced NFκB activity and nitrite production in lipopolysaccharide-stimulated microglia and the protective effects of CHPG treatment were abrogated in NADPH oxidase deficient microglial cultures (gp91(phox-/-)). To address whether the neuroprotective effects of CHPG are mediated via the inhibition of NADPH oxidase, we administered the NADPH oxidase inhibitor apocynin with or without CHPG treatment after TBI. Both apocynin or CHPG treatment alone improved sensorimotor deficits and reduced lesion volumes when compared with vehicle-treated mice; however, the combined CHPG + apocynin treatment was not superior to CHPG alone. These data suggest that the neuroprotective effects of activating mGluR5 receptors after TBI are mediated, in part, via the inhibition of NADPH oxidase.

Bioinformatic profiling of the transcriptional response of adult rat cardiomyocytes to distinct fatty acids.

Diabetes mellitus, obesity, and dyslipidemia increase risk for cardiovascular disease, and expose the heart to high plasma fatty acid (FA) levels. Recent studies suggest that distinct FA species are cardiotoxic (e.g., palmitate), while others are cardioprotective (e.g., oleate), although the molecular mechanisms mediating these observations are unclear. The purpose of the present study was to investigate the differential effects of distinct FA species (varying carbon length and degree of saturation) on adult rat cardiomyocyte (ARC) gene expression. ARCs were initially challenged with 0.4 mM octanoate (8:0), palmitate (16:0), stearate (18:0), oleate (18:1), or linoleate (18:2) for 24 h. Microarray analysis revealed differential regulation of gene expression by the distinct FAs; the order regarding the number of genes whose expression was influenced by a specific FA was octanoate (1,188) > stearate (740) > palmitate (590) > oleate (83) > linoleate (65). In general, cardioprotective FAs (e.g., oleate) increased expression of genes promoting FA oxidation to a greater extent than cardiotoxic FAs (e.g., palmitate), whereas the latter induced markers of endoplasmic reticulum and oxidative stress. Subsequent RT-PCR analysis revealed distinct time- and concentration-dependent effects of these FA species, in a gene-specific manner. For example, stearate- and palmitate-mediated ucp3 induction tended to be transient (i.e., initial high induction, followed by subsequent repression), whereas oleate-mediated induction was sustained. These findings may provide insight into why diets high in unsaturated FAs (e.g., oleate) are cardioprotective, whereas diets rich in saturated FAs (e.g., palmitate) are not.

Disruption of the circadian clock within the cardiomyocyte influences myocardial contractile function, metabolism, and gene expression.

Virtually every mammalian cell, including cardiomyocytes, possesses an intrinsic circadian clock. The role of this transcriptionally based molecular mechanism in cardiovascular biology is poorly understood. We hypothesized that the circadian clock within the cardiomyocyte influences diurnal variations in myocardial biology. We, therefore, generated a cardiomyocyte-specific circadian clock mutant (CCM) mouse to test this hypothesis. At 12 wk of age, CCM mice exhibit normal myocardial contractile function in vivo, as assessed by echocardiography. Radiotelemetry studies reveal attenuation of heart rate diurnal variations and bradycardia in CCM mice (in the absence of conduction system abnormalities). Reduced heart rate persisted in CCM hearts perfused ex vivo in the working mode, highlighting the intrinsic nature of this phenotype. Wild-type, but not CCM, hearts exhibited a marked diurnal variation in responsiveness to an elevation in workload (80 mmHg plus 1 microM epinephrine) ex vivo, with a greater increase in cardiac power and efficiency during the dark (active) phase vs. the light (inactive) phase. Moreover, myocardial oxygen consumption and fatty acid oxidation rates were increased, whereas cardiac efficiency was decreased, in CCM hearts. These observations were associated with no alterations in mitochondrial content or structure and modest mitochondrial dysfunction in CCM hearts. Gene expression microarray analysis identified 548 and 176 genes in atria and ventricles, respectively, whose normal diurnal expression patterns were altered in CCM mice. These studies suggest that the cardiomyocyte circadian clock influences myocardial contractile function, metabolism, and gene expression.

Generation of the beta-amyloid peptide and the amyloid precursor protein C-terminal fragment gamma are potentiated by FE65L1.

Members of the FE65 family of adaptor proteins, FE65, FE65L1, and FE65L2, bind the C-terminal region of the amyloid precursor protein (APP). Overexpression of FE65 and FE65L1 was previously reported to increase the levels of alpha-secretase-derived APP (APPs alpha). Increased beta-amyloid (A beta) generation was also observed in cells showing the FE65-dependent increase in APPs alpha. To understand the mechanism for the observed increase in both A beta and APPs alpha given that alpha-secretase cleavage of a single APP molecule precludes A beta generation, we examined the effects of FE65L1 overexpression on APP C-terminal fragments (APP CTFs). Our data show that FE65L1 potentiates gamma-secretase processing of APP CTFs, including the amyloidogenic CTF C99, accounting for the ability of FE65L1 to increase generation of APP C-terminal domain and A beta 40. The FE65L1 modulation of these processing events requires binding of FE65L1 to APP and APP CTFs and is not because of a direct effect on gamma-secretase activity, because Notch intracellular domain generation is not altered by FE65L1. Furthermore, enhanced APP CTF processing can be detected in early endosome vesicles but not in endoplasmic reticulum or Golgi membranes, suggesting that the effects of FE65L1 occur at or near the plasma membrane. Finally, although FE65L1 increases APP C-terminal domain production, it does not mediate the APP-dependent transcriptional activation observed with FE65.