Abnormal Static Sagittal Cervical Curvatures following Motor Vehicle Collisions: A Retrospective Case Series of 41 Patients before and after a Crash Exposure.

Previous investigations have found a correlation between abnormal curvatures and a variety of patient complaints such as cervical pain and disability. However, no study has shown that loss of the cervical curve is a direct result of exposure to a motor vehicle collision (MVC). This investigation presents a retrospective consecutive case series of patients with both a pre-injury cervical lateral radiograph (CLR) and a post-injury CLR after exposure to an MVC. Computer analysis of digitized vertebral body corners on CLRs was performed to investigate the possible alterations in the geometric alignment of the sagittal cervical curve. METHODS: Three spine clinic records were reviewed over a 2-year period, looking for patients where both an initial lateral cervical X-ray and an examination were performed prior to the patient being exposed to a MVC; afterwards, an additional exam and radiographic analysis were obtained. A total of 41 patients met the inclusion criteria. Examination records of pain intensity on numerical pain rating scores (NPRS) and neck disability index (NDI), if available, were analyzed. The CLRs were digitized and modeled in the sagittal plane using curve fitting and the least squares error approach. Radiographic variables included total cervical curve (ARA C2-C7), Chamberlain's line to horizontal (skull flexion), horizontal translation of C2 relative to C7, segmental translations (retrolisthesis and anterolisthesis), and circular modelling radii. RESULTS: There were 15 males and 26 females with an age range of 8-65 years. Most participants were drivers (28) involved in rear-end impacts (30). The pre-injury NPRS was 2.7 while the post injury was 5.0; p < 0.001. The NDI was available on 24/41 (58.5%) patients and increased after the MVC from 15.7% to 32.8%, p < 0.001. An altered cervical curvature was identified following exposure to MVC, characterized by an increase in the mean radius of curvature (265.5 vs. 555.5, p < 0.001) and an approximate 8° reduction of lordosis from C2-C7; p < 0.001. The mid-cervical spine (C3-C5) showed the greatest curve reduction with an averaged localized mild kyphosis at these levels. Four participants (10%) developed segmental translations that were just below the threshold of instability, segmental translations < 3.5 mm. CONCLUSIONS: The post-exposure MVC cervical curvature was characterized by an increase in radius of curvature, an approximate 8° reduction in C2-C7 lordosis, a mild kyphosis of the mid-cervical spine, and a slight increase in anterior translation of C2-C7 sagittal balance. The modelling result indicates that the post-MVC cervical sagittal alignment approximates a second-order buckling alignment, indicating a significant alteration in curve geometry. Future biomechanics experiments and clinical investigations are needed to confirm these findings.

Crafting Sequences of Sight and Sound: A Behavior Analysis of Filmmaking.

The discipline of film studies often engages in analyses of the functions of filmmakers' decisions in terms of their effects on viewers. Behavior analysis uses a similar, functional-analytic approach toward understanding the relationship between individuals' behavior and the environmental effects that maintain their behavior. Given converging similarities between the two disciplines, a functional analysis of filmmaking is provided, using Skinner (1957)'s Verbal Behavior as a guiding framework. Similar to behavioral conceptualizations of language and speaker-listener verbal episodes, the analysis prioritizes functional explanation of the controlling variables and conditions that underlie the meaning of filmmakers' behavior and behavioral products, rather than solely focusing on their topographical description. Viewers' responses to the audiovisual stimuli of the film are emphasized as key controlling variables, through rules specifying contingency relations as well as through contingency shaping, including when the filmmaker acts as a self-viewer who directly shapes their own behavior. Their responding as a self-viewer during the production and editing of a film is explored as a problem-solving process, similar to other artists who serve as their own audience when creating and editing their behavioral products.

Non-Surgical Management of Upper Cervical Instability via Improved Cervical Lordosis: A Case Series of Adult Patients.

Injury to the head and neck resulting from whiplash trauma can result in upper cervical instability (UCIS), in which excessive movement at C1 on C2 is observed radiologically. In some cases of UCIS there is also a loss of normal cervical lordosis. We postulate that improvement or restoration of the normal mid to lower cervical lordosis in patients with UCIS can improve the biomechanical function of the upper cervical spine, and thus potentially improve symptoms and radiographic findings associated with UCIS. Nine patients with both radiographically confirmed UCIS and loss of cervical lordosis underwent a chiropractic treatment regimen directed primarily at the restoration of the normal cervical lordotic curve. In all nine cases, significant improvements in radiographic indicators of both cervical lordosis and UCIS were observed, along with symptomatic and functional improvement. Statistical analysis of the radiographic data revealed a significant correlation (R2 = 0.46, p = 0.04) between improved cervical lordosis and reduction in measurable instability, determined by C1 lateral mass overhang on C2 with lateral flexion. These observations suggest that enhancing cervical lordosis can contribute to improvement in signs and symptoms of upper cervical instability secondary to traumatic injury.

Improvements in Cervical Spinal Canal Diameter and Neck Disability Following Correction of Cervical Lordosis and Cervical Spondylolistheses Using Chiropractic BioPhysics Technique: A Case Series.

Cervical spondylolisthesis indicates instability of the spine and can lead to pain, radiculopathy, myelopathy and vertebral artery stenosis. Currently degenerative cervical spondylolisthesis is a wait-and-watch condition with no treatment guidelines. A literature review and discussion will be provided. 8 females presented with neck pain, disability, and history of motor vehicle collision. Radiographs revealed abnormal cervical alignment, spinal canal narrowing, and spondylolistheses. After 30 sessions of Chiropractic BioPhysics® care over 12 weeks, patients reported improved symptoms and disabilities. Radiographs revealed improvements in cervical alignment, spondylolistheses, and spinal canal diameter. Motor vehicle collision may cause instability and abnormal alignment of the cervical spine leading to cervical spondylolisthesis. Improving spinal alignment may be an effective treatment to reduce vertebral subluxation and cervical spondylolistheses and improve neck disability as a result of improved spinal alignment.

Diagnostic Accuracy of Videofluoroscopy for Symptomatic Cervical Spine Injury Following Whiplash Trauma.

BACKGROUND: Intervertebral instability is a relatively common finding among patients with chronic neck pain after whiplash trauma. Videofluoroscopy (VF) of the cervical spine is a potentially sensitive diagnostic tool for evaluating instability, as it offers the ability to examine relative intervertebral movement over time, and across the entire continuum of voluntary movement of the patient. At the present time, there are no studies of the diagnostic accuracy of VF for discriminating between injured and uninjured populations. METHODS: Symptomatic (injured) study subjects were recruited from consecutive patients with chronic (>6 weeks) post-whiplash pain presenting to medical and chiropractic offices equipped with VF facilities. Asymptomatic (uninjured) volunteers were recruited from family and friends of patients. An ethical review and oversight were provided by the Spinal Injury Foundation, Broomfield, CO. Three statistical models were utilized to assess the sensitivity, specificity, positive and negative predictive values (PPV and NPV) of positive VF findings to correctly discriminate between injured and uninjured subjects. RESULTS: A total of 196 subjects (119 injured, 77 uninjured) were included in the study. All three statistical models demonstrated high levels of sensitivity and specificity (i.e., receiver operating characteristic (ROC) values of 0.71 to 0.95), however, the model with the greatest practical clinical utility was based on the number of abnormal VF findings. For 2+ abnormal VF findings, the ROC was 0.88 (93% sensitivity, 79% specificity) and the PPV and NPV were both 88%. The highest PPV (1.0) was observed with 4+ abnormal findings. CONCLUSIONS: Videofluoroscopic examination of the cervical spine provides a high degree of diagnostic accuracy for the identification of vertebral instability in patients with chronic pain stemming from whiplash trauma.

Increase in cerebral blood flow indicated by increased cerebral arterial area and pixel intensity on brain magnetic resonance angiogram following correction of cervical lordosis.

CONTEXT: Loss of cervical lordosis is associated with decreased vertebral artery hemodynamics. AIM: The aim of this study is to evaluate cerebral blood flow changes on brain magnetic resonance angiogram (MRA) in patients with loss of cervical lordosis before and following correction of cervical lordosis. SETTINGS AND DESIGN: This study is a retrospective consecutive case series of patients in a private practice. MATERIALS AND METHODS: Cervical lordosis of seven patients (five females and two males, 28-58 years) was measured on lateral cervical radiographs ranging from -13.1° to 19.0° (ideal is -42.0°). Brain MRAs were analyzed for pixel intensities representing blood flow. Pixel intensity of the cerebral vasculature was quantified, and percentage change was determined. STATISTICAL ANALYSIS USED: A Student's t-test established significance of the percentage change in cerebral blood flow between pre- and postcervical lordosis adjustment images. Regression analysis was performed. An a priori analysis determined correlation between cervical lordosis and change in MRA pixel intensity. The statistician was blinded to the cervical lordosis. RESULTS: Pixel intensity increased 23.0%-225.9%, and a Student's t-test determined that the increase was significant (P < 0.001). Regression analysis of the change in pixel intensity versus the cervical lordosis showed that as the deviation from a normal cervical lordosis increases, percentage change in pixel intensity on MRA decreases. CONCLUSION: These results indicate that correction of cervical lordosis may be associated with an immediate increase in cerebral blood flow. Further studies are needed to confirm these findings and understand clinical implications.

The validation of pharmacogenetics for the identification of Fabry patients to be treated with migalastat.

PURPOSE: Fabry disease is an X-linked lysosomal storage disorder caused by mutations in the α-galactosidase A gene. Migalastat, a pharmacological chaperone, binds to specific mutant forms of α-galactosidase A to restore lysosomal activity. METHODS: A pharmacogenetic assay was used to identify the α-galactosidase A mutant forms amenable to migalastat. Six hundred Fabry disease-causing mutations were expressed in HEK-293 (HEK) cells; increases in α-galactosidase A activity were measured by a good laboratory practice (GLP)-validated assay (GLP HEK/Migalastat Amenability Assay). The predictive value of the assay was assessed based on pharmacodynamic responses to migalastat in phase II and III clinical studies. RESULTS: Comparison of the GLP HEK assay results in in vivo white blood cell α-galactosidase A responses to migalastat in male patients showed high sensitivity, specificity, and positive and negative predictive values (≥0.875). GLP HEK assay results were also predictive of decreases in kidney globotriaosylceramide in males and plasma globotriaosylsphingosine in males and females. The clinical study subset of amenable mutations (n = 51) was representative of all 268 amenable mutations identified by the GLP HEK assay. CONCLUSION: The GLP HEK assay is a clinically validated method of identifying male and female Fabry patients for treatment with migalastat.Genet Med 19 4, 430-438.

A pharmacogenetic approach to identify mutant forms of α-galactosidase A that respond to a pharmacological chaperone for Fabry disease.

Fabry disease is caused by mutations in the gene (GLA) that encodes α-galactosidase A (α-Gal A). The iminosugar AT1001 (GR181413A, migalastat hydrochloride, 1-deoxygalactonojirimycin) is a pharmacological chaperone that selectively binds and stabilizes α-Gal A, increasing total cellular levels and activity for some mutant forms (defined as "responsive"). In this study, we developed a cell-based assay in cultured HEK-293 cells to identify mutant forms of α-Gal A that are responsive to AT1001. Concentration-dependent increases in α-Gal A activity in response to AT1001 were shown for 49 (60%) of 81 mutant forms. The responses of α-Gal A mutant forms were generally consistent with the responses observed in male Fabry patient-derived lymphoblasts. Importantly, the HEK-293 cell responses of 19 α-Gal A mutant forms to a clinically achievable concentration of AT1001 (10 µM) were generally consistent with observed increases in α-Gal A activity in peripheral blood mononuclear cells from male Fabry patients orally administered AT1001 during Phase 2 clinical studies. This indicates that the cell-based responses can identify mutant forms of α-Gal A that are likely to respond to AT1001 in vivo. Thus, the HEK-293 cell-based assay may be a useful aid in the identification of Fabry patients with AT1001-responsive mutant forms.

Total cervical translation as a function of impact vector as measured by flexion-extension radiography.

BACKGROUND: Clinical and cadaveric studies have implicated that sub-failure cervical instability likely occurs in a subset of whiplash injury patients. Cadaveric studies have suggested that female specimens suffer from more ligamentous stretch injury than males when exposed to simulated rear end crash vectors. However, these findings have never been tested in an in-vivo clinical setting. DESIGN: A prospective evaluation of total cervical translation on sagittal flexion radiographs versus impact vector in a late whiplash population. OBJECTIVES: To determine if total cervical translation on radiographs is correlated with impact crash vector. METHODS: Consecutive late whiplash patients in a subspecialty pain clinic setting were sent for radiographs using a strict stress flexion-extension protocol. Information concerning crash vector and damage was recorded. Vertebral translation was read by a blinded reader and recorded. RESULTS: Males did not significantly differ in total translation in flexion-extension radiographs when involved in sagittal plane crashes (n=75) compared to coronal plane crashes (n=10). In a front end collision, males (n=16) and females (n=26) did not differ in total translation in flexion-extension radiographs. In a rear end collision, females (mean translation 4.61 mm, n=103) did differ significantly in total translation in flexion-extension radiographs from their male counterparts (mean translation 3.29, n=48) (P<0.001). CONCLUSION: This investigation suggests that specific crash vectors lead to particular patterns of radiographic translation in female subjects. A realization that sub-failure cervical instability occurs in whiplash may help design more effective treatments.