An autopsy case of adult-onset neuronal intranuclear inclusion disease with perivascular preservation in cerebral white matter.

Neuronal intranuclear inclusion disease (NIID) is a neurodegenerative disease characterized by appearance of eosinophilic hyaline intranuclear inclusions. While the main symptoms of adult-onset NIID are dementia or limb weakness, some patients present with encephalitic episodes and transient neurological symptoms. The pathophysiology of these acute, transient symptoms, however, remains unknown. Here, we describe an autopsy case of adult-onset NIID with progressive dementia and transient hemiparesis. The patient was a 70-year-old man without a relevant family history, and initially presented with progressive dementia. He then exhibited transient left hemiparesis at 75 years of age and died of ureteral cancer at 77 years of age. Neuropathological examination revealed the presence of multiple areas of focal spongiosis in the subcortical white matter and patchy myelin pallor of the white matter, as in previous reports. However, perivascular areas were preserved even in the damaged white matter. In addition, dense glial fibrillary acidic protein (GFAP)-immunoreactive astrocytic processes were observed in these areas. [Correction added on 23 January 2022, after first online publication: the preceding sentence has been corrected to improve readability.] GFAP immunohistochemistry revealed decreased density and morphological abnormalities of astrocytes in the affected white matter. These pathological findings might reflect blood-brain barrier impairment and dysregulation of blood flow, which may be related to the pathophysiology of the acute, transient symptoms observed in NIID.

Circuit-Specific Early Impairment of Proprioceptive Sensory Neurons in the SOD1G93A Mouse Model for ALS.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease in which motor neurons degenerate, resulting in muscle atrophy, paralysis, and fatality. Studies using mouse models of ALS indicate a protracted period of disease development with progressive motor neuron pathology, evident as early as embryonic and postnatal stages. Key missing information includes concomitant alterations in the sensorimotor circuit essential for normal development and function of the neuromuscular system. Leveraging unique brainstem circuitry, we show in vitro evidence for reflex circuit-specific postnatal abnormalities in the jaw proprioceptive sensory neurons in the well-studied SOD1G93A mouse. These include impaired and arrhythmic action potential burst discharge associated with a deficit in Nav1.6 Na+ channels. However, the mechanoreceptive and nociceptive trigeminal ganglion neurons and the visual sensory retinal ganglion neurons were resistant to excitability changes in age-matched SOD1G93A mice. Computational modeling of the observed disruption in sensory patterns predicted asynchronous self-sustained motor neuron discharge suggestive of imminent reflexive defects, such as muscle fasciculations in ALS. These results demonstrate a novel reflex circuit-specific proprioceptive sensory abnormality in ALS.SIGNIFICANCE STATEMENT Neurodegenerative diseases have prolonged periods of disease development and progression. Identifying early markers of vulnerability can therefore help devise better diagnostic and treatment strategies. In this study, we examined postnatal abnormalities in the electrical excitability of muscle spindle afferent proprioceptive neurons in the well-studied SOD1G93A mouse model for neurodegenerative motor neuron disease, amyotrophic lateral sclerosis. Our findings suggest that these proprioceptive sensory neurons are exclusively afflicted early in the disease process relative to sensory neurons of other modalities. Moreover, they presented Nav1.6 Na+ channel deficiency, which contributed to arrhythmic burst discharge. Such sensory arrhythmia could initiate reflexive defects, such as muscle fasciculations in amyotrophic lateral sclerosis, as suggested by our computational model.

Heating sensation in patients with and without spinal fixation devices during MRI examination at different magnetic field strengths.

BACKGROUND: Radiofrequency (RF) heating during MRI theoretically increases with magnetic field strength. In addition, implanted metallic devices are reported to further increase RF heating. However, a detailed evaluation of this type of heating remains scarce in clinical practice. PURPOSE: To assess possible risks and discomfort related to RF heating during MRI examinations of patients with and without metallic implantable devices. STUDY TYPE: A retrospective study of previous questionnaire results on the heating sensation during MRI examinations of the lumbar spine. SUBJECTS: In all, 715 patients, of whom 101 had implanted lumbar spine fixation devices. FIELD STRENGTH/SEQUENCE: 1T and 3T/T1 - and T2 -weighted imaging. ASSESSMENT: The number of patients who perceived heating around the lumbar spine or other regions during the MRI examination. STATISTICAL TESTS: A chi-square test with respect to static field strength B0 , presence of lumbar spine fixation devices, and duration of the MRI examination. RESULTS: The number of patients who perceived heating around the lumbar spine during the MRI examination significantly increased from 5.0% at 1T to 47.5% at 3T (P < 0.001), without a significant difference between patients with and without lumbar spine fixation devices (P = 0.23 at 1T, P = 0.48 at 3T), and regardless of the duration of the MRI examination (P = 0.88 at 1T, P = 0.15 at 3T). DATA CONCLUSION: Sensation of RF heating increased by around 10 times from 1T to 3T MRI examination, but the influence of implanted lumbar spine fixation devices on the RF heating sensation has not been observed. LEVEL OF EVIDENCE: 4 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;49:525-533.

Torque property of titanium alloy cerebral aneurysm clips in a magnetic resonance scanner.

Titanium (Ti) alloys have been introduced in magnetic resonance (MR) safe implantable medical devices because the susceptibility of Ti is approximately 1/10 that of the Co-Cr-Ni alloy (Elgiloy), which was the previously preferred MR-safe material. The torque applied to metallic materials in an MR imaging (MRI) scanner is commonly believed to increase with the susceptibility of the material. However, a visual inspection showed that the torque applied to Ti alloy cerebral aneurysm clips is comparable with that in the case of those of Elgiloy. In this study, we measured the torque applied to the small test pieces of rods and aneurysm clips quantitatively in a 3-T MRI using an accurate self-developed torque measurement apparatus. The maximum torques of Ti alloy and Elgiloy rod test pieces were comparable as 1.1 and 1.2 µN·m, respectively. The values for Ti alloy aneurysm clips were distinctly higher than the values for those of Elgiloy. These contradictory results of a larger torque for smaller-susceptibility products could be explained by our new theory, which takes into account the crystal susceptibility anisotropy in addition to the conventional torque due to the shape anisotropy.

Noninvasive electrical conductivity measurement by MRI: a test of its validity and the electrical conductivity characteristics of glioma.

OBJECTIVES: This study noninvasively examined the electrical conductivity (σ) characteristics of diffuse gliomas using MRI and tested its validity. METHODS: MRI including a 3D steady-state free precession (3D SSFP) sequence was performed on 30 glioma patients. The σ maps were reconstructed from the phase images of the 3D SSFP sequence. The σ histogram metrics were extracted and compared among the contrast-enhanced (CET) and noncontrast-enhanced tumour components (NCET) and normal brain parenchyma (NP). Difference in tumour σ histogram metrics among tumour grades and correlation of σ metrics with tumour grades were tested. Validity of σ measurement using this technique was tested by correlating the mean tumour σ values measured using MRI with those measured ex vivo using a dielectric probe. RESULTS: Several σ histogram metrics of CET and NCET of diffuse gliomas were significantly higher than NP (Bonferroni-corrected p ≤ .045). The maximum σ of NCET showed a moderate positive correlation with tumour grade (r = .571, Bonferroni-corrected p = .018). The mean tumour σ measured using MRI showed a moderate positive correlation with the σ measured ex vivo (r = .518, p = .040). CONCLUSIONS: Tissue σ can be evaluated using MRI, incorporation of which may better characterise diffuse gliomas. KEY POINTS: • This study tested the validity of noninvasive electrical conductivity measurements by MRI. • This study also evaluated the electrical conductivity characteristics of diffuse glioma. • Gliomas have higher electrical conductivity values than the normal brain parenchyma. • Noninvasive electrical conductivity measurement can be helpful for better characterisation of glioma.

Dependence of Scan Parameters on Nerve Fiber Crossing Depiction in Diffusion Spectrum Imaging in Clinical Practice.

OBJECTIVE: The objective of this study was to show the effect of the number of sampling points (NS) and the maximum b value (bmax) on fiber crossing detection in diffusion spectrum imaging (DSI) in clinical practice. METHODS: We performed 3-Tesla DSI in which we changed the NS (62-258) while keeping bmax at 8000 s/mm and in which we changed the bmax (4000-8000 s/mm) while keeping the NS at 129. The superior longitudinal fasciculus volume and the proportion of nerve voxels in which at least 2 (Rcr2) or 3 (Rcr3) nerve fiber bundles crossed were calculated. RESULTS: When bmax was set to 8000 s/mm, mean Rcr2 and Rcr3 values and superior longitudinal fasciculus volumes significantly increased with higher NSs, but they did not significantly change when we varied bmax with 129 NS. CONCLUSIONS: Depiction sensitivity of nerve fiber crossing in DSI improves at higher NS and bmax settings, but a bmax insensitivity appears at an intermediate NS such as 129.

Characteristic microglial features in patients with hereditary diffuse leukoencephalopathy with spheroids.

OBJECTIVE: To clarify the histopathological alterations of microglia in the brains of patients with hereditary diffuse leukoencephalopathy with spheroids (HDLS) caused by mutations of the gene encoding the colony stimulating factor-1 receptor (CSF-1R). METHODS: We examined 5 autopsied brains and 1 biopsy specimen from a total of 6 patients with CSF-1R mutations. Detailed immunohistochemical, biochemical, and ultrastructural features of microglia were examined, and quantitative analyses were performed. RESULTS: In layers 3 to 4 of the frontal cortex in HDLS brains, microglia showed relatively uniform and delicate morphology, with thin and winding processes accompanying knotlike structures, and significantly smaller areas of Iba1 immunoreactivity and lower numbers of Iba1-positive cells were evident in comparison with control brains. On the other hand, in layers 5 to 6 and the underlying white matter, microglia were distributed unevenly; that is, in some areas they had accumulated densely, whereas in others they were scattered. Immunoblot analyses of microglia-associated proteins, including CD11b and DAP12, revealed that HDLS brains had significantly lower amounts of these proteins than diseased controls, although Ki-67-positive proliferative microglia were not reduced. Ultrastructurally, the microglial cytoplasm and processes in HDLS showed vesiculation of the rough endoplasmic reticulum and disaggregated polyribosomes, indicating depression of protein synthesis. On the other hand, macrophages were immunonegative for GLUT-5 or P2ry12, indicating that they were derived from bone marrow. INTERPRETATION: The pathogenesis of HDLS seems to be associated with microglial vulnerability and morphological alterations. Ann Neurol 2016;80:554-565.

Clinical characteristics of external iliac artery branch injury in pelvic trauma.

INTRODUCTION: The clinical characteristics of an injury of external iliac artery branches in blunt pelvic trauma have not yet been sufficiently studied. We evaluated the relationship between injury characteristics and the presence of an injury to external iliac artery branches in blunt pelvic trauma. MATERIALS AND METHODS: A retrospective review of patients admitted with blunt pelvic trauma was conducted over an 11-year period. Charts were reviewed for age, gender, injury characteristics, injury severity score, length of stay in the intensive care unit, transfusion requirements, and fracture pattern. RESULTS: Of 286 blunt pelvic trauma patients, 90 patients (31%) underwent pelvic angiography. Of those patients, 10 (11%) had the injuries of the branches of external iliac artery and 88 (97%) had the injuries of the branches of internal iliac artery. Those patients with external iliac artery branch injuries were significantly associated with hemodynamic instability, when compared to those without external iliac artery branch injuries. There were no significant differences between the patients with and without external iliac artery branch injury with regard to the anatomical characteristics of pelvic trauma. CONCLUSION: Blunt pelvic trauma with hemodynamic instability may be associated with concomitant external iliac artery branch injury.

Anesthetic Management of a Patient With Takayasu Arteritis.

Takayasu arteritis is a rare chronic progressive panendarteritis involving the aorta and its main branches. Anesthesia in patients with this disease can be complicated by severe uncontrolled hypertension, end-organ dysfunction, and stenosis of major blood vessels. In this case, general anesthesia was induced with sevoflurane and remifentanil without complications. To prevent intraoperative complications, we conducted intubation with a rigid video laryngoscope with careful consideration of the concentrations of analgesics and sedatives used. This case demonstrates the importance of anesthetic techniques for maintaining adequate tissue perfusion without hemodynamic changes in the anesthetic management of patients with Takayasu arteritis.

A preclinical large animal study on a novel intervertebral fusion cage covered with high porosity titanium sheets with a triple pore structure used for spinal fusion.

PURPOSE: To evaluate the osteoconductivity and the bonding strength of the newly developed interbody cage covered with the porous titanium sheet (porous Ti cage) to vertebral bodies in a sheep model. METHODS: Twelve sheep underwent anterior lumbar interbody fusion at L2-3 and L4-5 using either the new porous Ti cages (Group-P) or conventional Ti cages with autogenous iliac bone (Group-C). The animals were euthanized at 2 or 4 months postoperatively and subjected to radiological, biomechanical, and histological examinations. RESULTS: Computed tomography analyses showed that the ratio of bone contact area in Group-P was significantly increased at 4 months compared with that at 2 months (p = 0.01). Although the ratio of bone contact area in Group-C was significantly higher than Group-P at 2 months (p < 0.001), there was no statistically significant difference between the two groups at 4 months. Biomechanical test showed that there was no significant difference in bonding strength between the two groups at either 2 or 4 months. Histological analyses revealed that the bone apposition ratio increased significantly with time in Group-P (p < 0.001). Although Group-C showed significantly higher bone apposition ratio than Group-P at 2 months (p = 0.001), there was no statistical difference between the two groups at 4 months. CONCLUSIONS: There was bone ingrowth into the porous Ti sheet, and bonding capacity of the porous Ti cage to the host bone increased with time. However, the speed of union to the bone with a porous Ti cage was marginally lower than a conventional cage along with an autogenous bone graft. Although it needs further experiment with a larger sample size, the results of the current study suggested that this material could achieve interbody fusion without the need for bone grafts.

Magnetic displacement force and torque on dental keepers in the static magnetic field of an MR scanner.

PURPOSE: To evaluate the effect of the static magnetic field of magnetic resonance (MR) scanners on keepers (ie, ferromagnetic stainless steel plate adhered to the abutment tooth of dental magnetic attachments). MATERIALS AND METHODS: Magnetically induced displacement force and torque on keepers were measured using 1.5 Tesla (T) and 3.0 T MR scanners and a method outlined by American Society for Testing and Materials (ASTM). Changes in magnetic flux density before and after exposure to scanner static magnetic field were examined. RESULTS: The maximum magnetically induced displacement forces were calculated to be 10.3 × 10(-2) N at 1.5 T and 13.9 × 10(-2) N at 3.0 T on the cover surface. The maximum torques exerted on the keeper (4 mm in diameter) were 0.83 N × 4 mm at 1.5 T and 0.85 N × 4 mm at 3.0 T. These forces were considerably higher than the gravitational force (7.7 × 10(-4) N) of the keeper but considerably lower than the keeper-root cap proper adhesive force. The keepers' magnetic flux density remained less than that of the Earth. CONCLUSION: Magnetically induced displacement force and torque on the keeper in the MR scanner do not influence the keeper-root cap proper adhesive force.

Tracheal Deviation and Airway Management: Clinical Considerations From a Cadaver.

Severe tracheal deviation detected on preoperative chest radiographs is one of the risk factors for difficult tracheal intubation and difficulty in ventilation using an endotracheal tube after tracheal intubation when managing the airway through tracheal intubation under general anesthesia. In this report, we describe the cadaver of an 81-year-old woman with marked tracheal deviation due to meandering multiple aortas. This report details the importance of anatomical knowledge in developing a detailed airway management plan. The deviated trachea was removed from the cadaver and the tracheal tube was inserted at the glottis to the proximal end of the glottal marker. The tube tip was in contact with the tracheal wall, suggesting ventilation difficulty during intubation. The tortuous brachiocephalic artery passed in front of the trachea, which posed a risk of massive aortic hemorrhage and postoperative trachea-brachiocephalic artery fistula during percutaneous tracheostomy for emergency airway management. The anatomical location of the trachea and carotid artery must be confirmed before surgery/anesthesia to ensure safe airway management.

Progress in Understanding Radiofrequency Heating and Burn Injuries for Safer MR Imaging.

RF electromagnetic wave exposure during MRI scans induces heat and occasionally causes burn injuries to patients. Among all the types of physical injuries that have occurred during MRI examinations, RF burn injuries are the most common ones. The number of RF burn injuries increases as the static magnetic field of MRI systems increases because higher RFs lead to higher heating. The commonly believed mechanisms of RF burn injuries are the formation of a conductive loop by the patient's posture or cables, such as an electrocardiogram lead; however, the mechanisms of RF burn injuries that occur at the contact points, such as the bore wall and the elbow, remain unclear. A comprehensive understanding of RF heating is needed to address effective countermeasures against all RF burn injuries for safe MRI examinations. In this review, we summarize the occurrence of RF burn injury cases by categorizing RF burn injuries reported worldwide in recent decades. Safety standards and regulations governing RF heating that occurs during MRI examinations are presented, along with their theoretical and physiological backgrounds. The experimental assessment techniques for RF heating are then reviewed, and the development of numerical simulation techniques is explained. In addition, a comprehensive theoretical interpretation of RF burn injuries is presented. By including the results of recent experimental and numerical simulation studies on RF heating, this review describes the progress achieved in understanding RF heating from the standpoint of MRI burn injury prevention.

Tracheal Bronchus Detected During General Anesthesia: A Case Report.

A tracheal bronchus is a congenital abnormality of the tracheobronchial tree in which a displaced or accessory bronchus arises from the trachea superior to its bifurcation. We herein report a case in which a tracheal bronchus was incidentally found after induction of general anesthesia, and we discuss the potential airway management problems that may have ensued. An 80-year-old man was scheduled for buccal mucosa resection and abdominal skin grafting for treatment of squamous cell carcinoma of the left buccal mucosa. Because of trismus and anticipated airway difficulty, an awake intubation was performed under sedation. A 3-branched structure was incidentally observed at the first branching site that was supposed to be the carina. The tip of the endotracheal tube was repositioned 3 cm above the tracheal trifurcation, and the rest of the procedure proceeded uneventfully. A flexible fiberoptic scope is not used in many anesthesia cases, making the identification of such tracheal or bronchial abnormalities more difficult. Therefore, it is important to carefully check the bronchial morphology on any available chest radiographs before surgery, listen to lung sounds after intubation, and assess thoracic lung compliance without neglecting routine safety checks.

SARS-CoV-2 recombinant spike protein induces cell apoptosis in rat taste buds.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections can cause loss or alteration of taste and smell as early symptoms or sequelae, but the detailed mechanism behind this phenomenon remains unclear. Here, we investigated whether the SARS-CoV-2 spike protein induces taste cell apoptosis and expression of the apoptosis-related cytokine TNF-α in male Sprague-Dawley rats. Terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP)-fluorescein nick end labeling (TUNEL) assay results revealed a significantly higher apoptosis index for taste cells in the SARS-CoV-2 group than for those in the control group. An immunohistochemistry analysis indicated significantly more TNF-α-positive cells in the SARS-CoV-2 group compared with the control group. These data suggest that the SARS-CoV-2 spike protein promotes taste cell apoptosis and the release of apoptosis-related cytokine TNF-α, implicating its contribution to the taste malfunction caused by coronavirus disease 2019 (COVID-19).

Expert consensus on difficult airway assessment.

Background: Identifying a potentially difficult airway is crucial both in anaesthesia in the operating room (OR) and non-operation room sites. There are no guidelines or expert consensus focused on the assessment of the difficult airway before, so this expert consensus is developed to provide guidance for airway assessment, making this process more standardized and accurate to reduce airway-related complications and improve safety. Methods: Seven members from the Airway Management Group of the Chinese Society of Anaesthesiology (CSA) met to discuss the first draft and then this was sent to 15 international experts for review, comment, and approval. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) is used to determine the level of evidence and grade the strength of recommendations. The recommendations were revised through a three-round Delphi survey from experts. Results: This expert consensus provides a comprehensive approach to airway assessment based on the medical history, physical examination, comprehensive scores, imaging, and new developments including transnasal endoscopy, virtual laryngoscopy, and 3D printing. In addition, this consensus also reviews some new technologies currently under development such as prediction from facial images and voice information with the aim of proposing new research directions for the assessment of difficult airway. Conclusions: This consensus applies to anesthesiologists, critical care, and emergency physicians refining the preoperative airway assessment and preparing an appropriate intubation strategy for patients with a potentially difficult airway.

Cerebral hypoperfusion accelerates cerebral amyloid angiopathy and promotes cortical microinfarcts.

Cortical microinfarcts (CMIs) observed in brains of patients with Alzheimer's disease tend to be located close to vessels afflicted with cerebral amyloid angiopathy (CAA). CMIs in Alzheimer's disease are preferentially distributed in the arterial borderzone, an area most vulnerable to hypoperfusion. However, the causal association between CAA and CMIs remains to be elucidated. This study consists of two parts: (1) an observational study using postmortem human brains (n = 31) to determine the association between CAA and CMIs, and (2) an experimental study to determine whether hypoperfusion worsens CAA and induces CMIs in a CAA mouse model. In postmortem human brains, the density of CMIs was 0.113/cm(2) in mild, 0.584/cm(2) in moderate, and 4.370/cm(2) in severe CAA groups with a positive linear correlation (r = 0.6736, p < 0.0001). Multivariate analysis revealed that, among seven variables (age, disease, senile plaques, neurofibrillary tangles, CAA, atherosclerosis and white matter damage), only the severity of CAA was a significant multivariate predictor of CMIs (p = 0.0022). Consistent with the data from human brains, CAA model mice following chronic cerebral hypoperfusion due to bilateral common carotid artery stenosis induced with 0.18-mm diameter microcoils showed accelerated deposition of leptomeningeal amyloid ß (Aß) with a subset of them developing microinfarcts. In contrast, the CAA mice without hypoperfusion exhibited very few leptomeningeal Aß depositions and no microinfarcts by 32 weeks of age. Following 12 weeks of hypoperfusion, cerebral blood flow decreased by 26% in CAA mice and by 15% in wild-type mice, suggesting impaired microvascular function due to perivascular Aß accumulation after hypoperfusion. Our results suggest that cerebral hypoperfusion accelerates CAA, and thus promotes CMIs.

Early embolization without external fixation in pelvic trauma.

PURPOSES: In this retrospective study, we reviewed our protocol consisting of early embolization without acute external fixation in patients with pelvic fracture. PATIENTS AND METHODS: Eighty-eight patients with pelvic fracture were identified by reviewing the records of the Fukui Prefectural Hospital from April 2005 through September 2009. We managed the patients with a treatment protocol consisting of hemodynamic resuscitation and early pelvic embolization. Patients with hemodynamic instability without nonpelvic hemorrhage or extravasation of contrast in the pelvis by computed tomography (CT) were indicated to angiography and embolization. External fixation of the pelvic ring was not used in our protocol. RESULTS: Of the 88 patients with pelvic fractures, 43 underwent angiography. Twenty-eight patients (65%) were hemodynamically unstable. Twenty-five patients (58%) had major ligamentous disruption. Computed tomography detected extravasation in 21 patients (48%). Of the 43 patients who underwent angiography, 29 (67%) were positive. The average time from hospital arrival to angiography was 76.3 ± 34.5 minutes. The packed red blood cell requirement in the initial 24 hours was 8.4 ± 8.2 U, required in the embolization group. There was no complication-related embolization. Repeat angiography was not required in all patients. The mortality rate of patients requiring angiography was 11%. CONCLUSIONS: Early pelvic embolization without external fixation may be useful for the initial treatment for patients with hemodynamic instability without nonpelvic hemorrhage or with extravasation of contrast in the pelvis by CT.