Cervical ossification of the posterior longitudinal ligament: Biomechanical analysis of the influence of static and dynamic factors

Objective

Cervical myelopathy due to ossification of the posterior longitudinal ligament (OPLL) is induced by static factors, dynamic factors, or a combination of both. We used a three-dimensional finite element method (3D-FEM) to analyze the stress distributions in the cervical spinal cord under static compression, dynamic compression, or a combination of both in the context of OPLL.

Methods

Experimental conditions were established for the 3D-FEM spinal cord, lamina, and hill-shaped OPLL. To simulate static compression of the spinal cord, anterior compression at 10, 20, and 30% of the anterior–posterior diameter of the spinal cord was applied by the OPLL. To simulate dynamic compression, the OPLL was rotated 5°, 10°, and 15° in the flexion direction. To simulate combined static and dynamic compression under 10 and 20% anterior static compression, the OPLL was rotated 5°, 10°, and 15° in the flexion direction.

Results

The stress distribution in the spinal cord increased following static and dynamic compression by cervical OPLL. However, the stress distribution did not increase throughout the entire spinal cord. For combined static and dynamic compression, the stress distribution increased as the static compression increased, even for a mild range of motion (ROM).

Conclusion

Symptoms may appear under static or dynamic compression only. However, under static compression, the stress distribution increases with the ROM of the responsible level and this makes it very likely that symptoms will worsen. We conclude that cervical OPLL myelopathy is induced by static factors, dynamic factors, and a combination of both.     

A novel tract imaging technique of the brainstem using phase difference enhanced imaging: normal anatomy and initial experience in multiple system atrophy

Objectives

To develop a new tract imaging technique for visualising small fibre tracts of the brainstem and for detecting the abnormalities in multiple system atrophy of the cerebellar type (MSA-C) using a phase difference enhanced (PADRE) imaging technique, in which the phase difference between the target and surrounding tissue is selectively enhanced.

Methods

Two neuroradiologists compared the high-spatial-resolution PADRE imaging, which was acquired from six healthy volunteers, three patients with MSA-C, and 7 patients with other types of neurodegenerative diseases involving the brainstem or cerebellum.

Results

Various fine fibre tracts in the brainstem, the superior and inferior cerebellar peduncles, medial lemniscus, spinothalamic tract, medial longitudinal fasciculus, central tegmental tract, corticospinal tract and transverse pontine fibres, were identified on PADRE imaging. PADRE imaging from MSA-C demonstrated the disappearance of transverse pontine fibres and significant atrophy of the inferior cerebellar peduncles, while the superior cerebellar peduncles were intact. PADRE imaging also demonstrated that the transverse pontine fibres and inferior cerebellar peduncle were not involved in the other neurodegenerative diseases.

Conclusion

PADRE imaging can offer a new form of tract imaging of the brainstem and may have the potential to reinforce the clinical utility of MRI in differentiating MSA from other conditions.     

Differentiation of tumor recurrence from radiation-induced pulmonary fibrosis after stereotactic ablative radiotherapy for lung cancer: characterization of 18F-FDG PET/CT findings

Objective

Stereotactic ablative radiotherapy (SABR), also known as stereotactic body radiotherapy (SBRT), is now a standard treatment option for patients with stage I non-small cell lung cancer or oligometastatic lung tumor who are medically inoperable or medically operable but refuse surgery. When mass-like consolidation is observed on follow-up CT after SABR, it is sometimes difficult to differentiate tumor recurrence from SABR-induced pulmonary fibrosis. In this study, we evaluated the role of ¹⁸F-fluorodeoxyglucose positron emission tomography combined with computed tomography (FDG-PET/CT) in differentiating tumor recurrence from radiation fibrosis after SABR.

Methods

Between June 2006 and June 2009, 130 patients received SABR for stage I non-small cell lung cancer or metastatic lung cancer at our institution. Fifty-nine patients of them were imaged with FDG-PET/CT after SABR. There were a total of 137 FDG-PET/CT scans for retrospective analysis. The FDG uptake in the pulmonary region was assessed qualitatively using a 3-point scale (0, none or faint; 1, mild; or 2, moderate to intense), and the shape (mass-like or non mass-like) was evaluated. For semi-quantitative analysis, the maximum standardized uptake value (SUV_max) was calculated.

Results

Sixteen of 59 patients had local failure. In recurrent tumor, the combination of intensity grade 2 and mass-like shape was most common (21/23; 91 %). By contrast, in cases of radiation fibrosis, the combination of intensity grade 0 or 1 and non mass-like shape was most common (48/59; 81 %). The SUV_max of tumor recurrence after 12 months was significantly higher than that of radiation fibrosis (8.0 ± 3.2 vs. 2.1 ± 0.9, p < 0.001), and all tumor recurrence showed the SUV_max > 4.5 at diagnosis of local failure. At ≥12 months after SABR, these two variables, the combination of intensity 2 and mass-like FDG uptake or SUV_max > 4.5 acquired a significant high predictive value of local recurrence, finding sensitivity 100 % and specificity 100 % for both of them.

Conclusions

The combination of FDG uptake patterns and SUV_max was useful for distinguishing tumor recurrence from radiation fibrosis after SABR.     

Clinical features and varieties of non-motor fluctuations in Parkinson's disease: A Japanese multicenter study

ObjectiveThis multicenter cross-sectional study aimed to investigate the clinical features and varieties of non-motor fluctuation in Parkinson's disease (PD).MethodsTo identify motor and non-motor fluctuation, we employed the wearing-off questionnaire of 19 symptoms (WOQ-19) in 464 PD patients. We compared the frequency of levodopa-related fluctuation as identified by the WOQ-19 with recognition by neurologists. We compared patients with both motor and non-motor fluctuations with those who only had motor fluctuations. Non-motor fluctuations were separated into psychiatric, autonomic, and sensory categories for further analysis.ResultsThe patients' average age was 70.8 ± 8.4 years (mean ± SD) and disease duration was 6.6 ± 5.0 years. The frequency of motor fluctuations was 69% and for non-motor fluctuation 40%. Fifty-three percent of patients with motor fluctuations also had non-motor fluctuations, whereas 93% of patients with non-motor fluctuations also had motor fluctuations. The WOQ-19 showed a sensitivity of 82% but a specificity of only 40%. The patients with both non-motor and motor fluctuations exhibited more severe motor symptoms, more non-motor symptoms and higher levodopa daily doses (p < 0.05). Patients had significantly higher fluctuation rates if they had psychiatric (49%) and sensory (45%) symptoms than patients with autonomic symptoms (32%, p < 0.01). Forty-eight percent of patients with non-motor fluctuations exhibited more than one type of non-motor fluctuation.ConclusionForty percent of PD patients presented with non-motor fluctuations, and almost half of these exhibited more than one type. Appropriate recognition of levodopa-related fluctuations, both motor and non-motor, can lead to treatment modifications in PD patients.     

Functional connectivity between amygdala and facial regions involved in recognition of facial threat

The recognition of threatening faces is important for making social judgments. For example, threatening facial features of defendants could affect the decisions of jurors during a trial. Previous neuroimaging studies using faces of members of the general public have identified a pivotal role of the amygdala in perceiving threat. This functional magnetic resonance imaging study used face photographs of male prisoners who had been convicted of first-degree murder (MUR) as threatening facial stimuli. We compared the subjective ratings of MUR faces with those of control (CON) faces and examined how they were related to brain activation, particularly, the modulation of the functional connectivity between the amygdala and other brain regions. The MUR faces were perceived to be more threatening than the CON faces. The bilateral amygdala was shown to respond to both MUR and CON faces, but subtraction analysis revealed no significant difference between the two. Functional connectivity analysis indicated that the extent of connectivity between the left amygdala and the face-related regions (i.e. the superior temporal sulcus, inferior temporal gyrus and fusiform gyrus) was correlated with the subjective threat rating for the faces. We have demonstrated that the functional connectivity is modulated by vigilance for threatening facial features.     

Cardiac parasympathetic dysfunction concurrent with cardiac sympathetic denervation in Parkinson's disease

We aimed to characterize the relationship between cardiac sympathetic and parasympathetic dysfunction employing cardiac (123)I-meta-iodobenzylguanidine (MIBG) uptake and other autonomic function parameters in Parkinson's disease (PD). 79 PD patients were studied. We performed (123)I-MIBG myocardial scintigraphy to assess the extent of cardiac sympathetic denervation. Electrocardiogram readings at rest and postural change in blood pressure were also examined. Coefficient variation of RR intervals (CVR-R) was used as an index for cardiac parasympathetic activity. Cardiac (123)I-MIBG uptake did not vary significantly among the Hoehn-Yahr (H-Y) stages. There was a significant correlation between cardiac (123)I-MIBG uptake and CVR-R (early, r=0.457, p<0.001; late, r=0.442, p<0.001). While the correlation was present among the patients who had had the disease less than two years (early, r=0.558, p<0.001; late, r=0.530, p<0.001), the patients with the disease duration longer than two years did not have such a significant correlation. Age, disease duration, corrected QT interval, or postural blood pressure change did not correlate with cardiac (123)I-MIBG uptake. Orthostatic hypotension was observed in 13 out of 72 subjects, and reduced CVR-R was a major determinant for the development of orthostatic hypotension. We conclude that cardiac parasympathetic dysfunction occurs concurrent with sympathetic denervation as revealed by (123)I-MIBG myocardial scintigraphy in PD and contributes to the development of orthostatic hypotension.     

Migraine and stroke]

Both migraine and stroke are common illness. However, each disorder usually occurs in different generation, migraine in younger, while stroke in elder, and seems to have little in common. Migraine has been supposed to be benign, not life-threatening illness occurring throughout the life-time. Whereas, stroke is an acute illness with certain degree of disabilities consequently, even fatal in case. In spite of such differences, some of recent studies suggested migraine as a risk factor of stroke or subclinical brain damage. There seems to be several types of stroke associated with migraine. One is "migrainous infarction", which is defined as one or more migrainous aura symptoms associated with an ischemic brain lesion in appropriate territory demonstrated neuroimaging, in the International Classification of Headache Disorders (ICHD-II). The other is stroke occurring in those who had been suffering from migraine in their younger time. The former is seldom to observe, and the latter is in dispute. Recent elaborate epidemiological studies disclosed the risk of stroke is increase in people with migraine, particularly marked in those with migraine with aura, further increased in those taking oral contraceptives. However, several issues such as strict diagnostic criteria for stroke and migraine, history of medication for migraine treatment, etc. for those studies should be settled. The well organized prospective studies for the issue "migraine as a risk factor of stroke" should be considered necessary.     

Mechanical properties of nerve roots and rami radiculares isolated from fresh pig spinal cords

No reports have described experiments designed to determine the strength characteristics of spinal nerve roots and rami radiculares for the purpose of explaining the complexity of symptoms of medullary cone lesions and cauda equina syndrome. In this study, to explain the pathogenesis of cauda equina syndrome, monoaxial tensile tests were performed to determine the strength characteristics of spinal nerve roots and rami radiculares, and analysis was conducted to evaluate the stress-strain relationship and strength characteristics. Using the same tensile test device, the nerve root and ramus radiculares isolated from the spinal cords of pigs were subjected to the tensile test and stress relaxation test at load strain rates of 0.1, 1, 10, and 100 s^-1 under identical settings. The tensile strength of the nerve root was not rate dependent, while the ramus radiculares tensile strength tended to decrease as the strain rate increased. These findings provide important insights into cauda equina symptoms, radiculopathy, and clinical symptoms of the medullary cone.     

FCGR3A‐158V/F polymorphism may correlate with the levels of immunoglobulin in patients with non‐Hodgkin’s lymphoma after rituximab treatment as an adjuvant to autologous stem cell transplantation

Objectives: Recent studies have indicated that patients who receive stem cell transplantation (SCT) and rituximab demonstrate an increased risk of developing hypogammaglobulinemia. Such hypogammaglobulinemia has been found to be due to delayed recovery of memory B cells with an abnormal cell marker expression and impaired immunoglobulin production in vitro. However, no predictive factors for the levels of immunoglobulin after autologous SCT and rituximab therapy have been reported. The aim of this study is to clarify the relationships between the FCGR3A‐158V/F genotype and the levels of serum immunoglobulin after SCT. Methods: A total of 24 non‐Hodgkin’s lymphoma (NHL) patients received autologous SCT with an adjuvant rituximab. The FCGR3A‐158V/F genotype was determined in these patients. We also included ten NHL patients who received an identical conditioning regimen and autologous SCT but no rituximab as control patients. Results: The levels of IgG were significantly lower in FCGR3A‐158F homozygous patients (n = 9) in comparison to those in FCGR3A‐158V carriers (n = 15). Moreover, the levels of IgG and IgA of FCGR3A‐158F homozygous patients, but not those of FCGR3A‐158V carriers, were significantly lower than those of control patients. Conclusions: The genotype of FCGR3A determines not only the response to rituximab, but also the levels of immunoglobulin after SCT and an adjuvant rituximab.     

Recommendations for Responsible Development and Application of Neurotechnologies

Advancements in novel neurotechnologies, such as brain computer interfaces (BCI) and neuromodulatory devices such as deep brain stimulators (DBS), will have profound implications for society and human rights. While these technologies are improving the diagnosis and treatment of mental and neurological diseases, they can also alter individual agency and estrange those using neurotechnologies from their sense of self, challenging basic notions of what it means to be human. As an international coalition of interdisciplinary scholars and practitioners, we examine these challenges and make recommendations to mitigate negative consequences that could arise from the unregulated development or application of novel neurotechnologies. We explore potential ethical challenges in four key areas: identity and agency, privacy, bias, and enhancement. To address them, we propose (1) democratic and inclusive summits to establish globally-coordinated ethical and societal guidelines for neurotechnology development and application, (2) new measures, including “Neurorights,” for data privacy, security, and consent to empower neurotechnology users’ control over their data, (3) new methods of identifying and preventing bias, and (4) the adoption of public guidelines for safe and equitable distribution of neurotechnological devices.