Wilbrand Knee Revisited.

BACKGROUND: Over a century ago, German ophthalmologist Hermann Wilbrand reported inferonasal crossing fibers within the chiasm curve anteriorly into the contralateral optic nerve. This anatomic bend, "Wilbrand knee," is classically cited as the explanation for the "junctional scotoma," a contralateral superotemporal visual field defect associated with lesions affecting the optic nerve at its junction with the chiasm. More recent reports have called into question the existence of Wilbrand knee or suggested that it may simply be an artifact. METHODS: Four human optic chiasms (obtained from cadaver donors with no reported premortem visual pathology) and 2 monkey chiasms were fixed and thin sectioned (40 µm), then examined using anisotropic scattering imaging, a novel technique that takes advantage of the fact that light reflects off well-defined linear structures (i.e., axonal tracts) in a predictable manner based on their orientation. Using this technique, tissue structures oriented in different directions can be distinguished at high resolution without the need for tissue staining. RESULTS: In all 4 human optic chiasms, thin fiber tracts consistent with, but less prominent than, those Wilbrand had described were observed. No such tracts were found in the monkey chiasms. CONCLUSIONS: Wilbrand knee exists in humans but is modest in its anterior projection. Wilbrand knee does not seem to be present in monkeys, however, which may explain conflicting reports in the literature regarding its existence.

Demyelination as a harbinger of lymphoma: a case report and review of primary central nervous system lymphoma preceded by multifocal sentinel demyelination.

BACKGROUND: Primary central nervous system lymphoma (PCNSL) may rarely be preceded by "sentinel demyelination," a pathologic entity characterized by histologically confirmed demyelinating inflammatory brain lesions that mimic multiple sclerosis (MS) or acute disseminated encephalomyelitis (ADEM). Interpreting the overlapping radiologic and clinical characteristics associated with each of these conditions-contrast-enhancing demyelination of white matter and relapsing and remitting steroid-responsive symptoms respectively-can be a significant diagnostic challenge. CASE PRESENTATION: We describe a 57-year-old woman with an unusual clinical course who presented with multi-focal enhancing white matter lesions demonstrated to be inflammatory demyelination by brain biopsy. Despite a good initial response to steroids and rituximab for treatment of presumed tumefactive multiple sclerosis, the patient's condition rapidly deteriorated, and a repeat brain biopsy six months later was consistent with a diagnosis of diffuse large B-cell lymphoma. CONCLUSIONS: Early clinical suspicion for PCNSL and awareness that biopsied lesions may initially show sentinel demyelination suggestive of alternate diagnoses may be essential for early initiation of appropriate therapies and mitigation of disease progression. Clinical, pathophysiological, and diagnostic aspects of sentinel demyelination and PCNSL are discussed.

Transient ocular motor nerve palsies associated with presumed cranial nerve schwannomas.

BACKGROUND: Cranial nerve schwannomas are radiologically characterized by nodular cranial nerve enhancement on magnetic resonance imaging (MRI). Schwannomas typically present with gradually progressive symptoms, but isolated reports have suggested that schwannomas may cause fluctuating symptoms as well. METHODS: This is a report of ten cases of presumed cranial nerve schwannoma that presented with transient or recurring ocular motor nerve deficits. RESULTS: Schwannomas of the third, fourth, and fifth nerves resulted in fluctuating deficits of all 3 ocular motor nerves. Persistent nodular cranial nerve enhancement was present on sequential MRI studies. Several episodes of transient oculomotor (III) deficts were associated with headaches, mimicking ophthalmoplegic migraine. CONCLUSIONS: Cranial nerve schwannomas may result in relapsing and remitting cranial nerve symptoms.

Traumatic optic neuropathy: facial CT findings affecting visual acuity.

The purpose of this study was to determine the relationship between admission visual acuity (VA) and facial computed tomographic (CT) findings of traumatic optic neuropathy (TON). We retrospectively evaluated CT findings in 44 patients with TON. Mid-facial fractures, extraconal and intraconal hematomas, hematomas along the optic nerve and the posterior globe, optic canal fracture, nerve impingement by optic canal fracture fragment, and extraconal and intraconal emphysema were evaluated. CT variables of patients with and without available VA were compared. VA was converted into logarithm of the minimum angle of resolution (logMAR) to provide a numeric scale for the purpose of statistical analysis. The risk factors related to poor VA on univariate analysis were as follows: intraconal hematoma [median logMAR -4.7 versus -1.15, p = 0.016] and hematoma along the optic nerve [median -4.7 versus -1.3, p = 0.029]. Intraconal hematoma was the best predictor of poor VA (coefficient, 1.01; SE, 0.34; and p = 0.008). Receiver operating characteristic (ROC) curve analysis showed that the presence of intraconal hematoma and hematoma along the optic nerve predicted poor VA (logMAR of -3.7 or lower) with an area under the curve of 0.8 and 0.85, respectively. TON patients at higher risk of severe visual impairment may be identified based on admission facial CT.

Traumatic optic neuropathy prediction after blunt facial trauma: derivation of a risk score based on facial CT findings at admission.

PURPOSE: To determine the specific facial computed tomographic (CT) findings that can be used to predict traumatic optic neuropathy (TON) in patients with blunt craniofacial trauma and propose a scoring system to identify patients at highest risk of TON. MATERIALS AND METHODS: This study was compliant with HIPAA, and permission was obtained from the institutional review board. Facial CT examination findings in 637 consecutive patients with a history of blunt facial trauma were evaluated retrospectively. The following CT variables were evaluated: midfacial fractures, extraconal hematoma, intraconal hematoma, hematoma along the optic nerve, hematoma along the posterior globe, optic canal fracture, nerve impingement by optic canal fracture fragment, extraconal emphysema, and intraconal emphysema. A prediction model was derived by using regression analysis, followed by receiver operating characteristic analysis to assess the diagnostic performance. To examine the degree of overfitting of the prediction model, a k-fold cross-validation procedure (k = 5) was performed. The ability of the cross-validated model to allow prediction of TON was examined by comparing the mean area under the receiver operating characteristic curve (AUC) from cross-validations with that obtained from the observations used to create the model. RESULTS: The five CT variables with significance as predictors were intraconal hematoma (odds ratio, 12.73; 95% confidence interval [CI]: 5.16, 31.42; P < .001), intraconal emphysema (odds ratio, 5.21; 95% CI: 2.03, 13.36; P = .001), optic canal fracture (odds ratio, 4.45; 95% CI: 1.91, 10.35; P = .001), hematoma along the posterior globe (odds ratio, 0.326; 95% CI: 0.111, 0.958; P = .041), and extraconal hematoma (odds ratio, 2.36; 95% CI: 1.03, 5.41; P = .042). The AUC was 0.818 (95% CI: 0.734, 0.902) for the proposed model based on the observations used to create the model and 0.812 (95% CI: 0.723, 0.9) after cross-validation, excluding substantial overfitting of the model. CONCLUSION: The risk model developed may help radiologists suggest the possibility of TON and prioritize ophthalmology consults. However, future external validation of this prediction model is necessary.

Diagnosis of traumatic optic neuropathy: application of diffusion tensor magnetic resonance imaging.

BACKGROUND: Using diffusion tensor imaging, we evaluated the directional diffusivities of the optic nerve in patients with traumatic optic neuropathy (TON). METHODS: Our study consisted of 12 patients with unilateral TON, 6 patients with severe traumatic brain injury (comparison group A), and 6 patients with normal conventional brain magnetic resonance imaging (comparison group B). The contralateral optic nerve in patients with TON also was evaluated (comparison group C). Two trauma radiologists, blinded to the clinical diagnosis, independently obtained the directional diffusivities. The intraorbital optic nerve was divided into anterior and posterior segments to evaluate intersegmental differences in directional diffusivities. RESULTS: The mean axial diffusivity (AD) in both optic nerve segments and the mean diffusivity (ADC) in the posterior segment on the affected side were significantly lower and differentiated subjects with TON from those in comparison groups A and B. Area under the receiver operating characteristic curve was 0.762, 0.746, and 0.737 for posterior AD, anterior AD, and posterior ADC, respectively. The mean AD, mean diffusivity, and radial diffusivity were lower in the affected nerves in comparison to the contralateral nerve (comparison group C), but the values did not reach statistical significance. CONCLUSION: Decreased AD and mean diffusivity in the posterior segment of the optic nerve may serve as a biomarker of axonal damage in patients with TON and merits further investigation as a predictor of initial visual acuity and potential visual recovery.

A 28-Year-Old Woman With Left-Sided Weakness and Atypical MRI Lesions: From the National Multiple Sclerosis Society Case Conference Proceedings.

A 28-year-old woman presented with subacute relapsing left-sided weakness. MRI demonstrated both enhancing C3-C6 and nonenhancing T2-T4 lesions. Initial provisional diagnosis was inflammatory/autoimmune. Her left-sided weakness progressed despite immunosuppressive therapies. We reassessed our original suspected diagnosis because of an atypical clinicoradiologic course, leading to biopsy and a definitive diagnosis.

Aberrant regeneration of the third nerve (oculomotor synkinesis).

Aberrant regeneration of a third nerve palsy (oculomotor synkinesis) excludes an ischaemic cause and in the absence of relevant trauma strongly suggests a compressive aetiology. A scan is mandatory in such cases. We describe the case of a 52-year-old woman who presented with complete pupil-involving third nerve palsy from a posterior communicating artery aneurysm, who later developed widespread aberrant regeneration of pupil, eyelid and third nerve territory rectus muscles.

Podcast on B Cell-Targeting Therapies and Other Multiple Sclerosis Concerns During COVID-19.

The ongoing coronavirus disease 2019 (COVID-19) pandemic continues to raise questions for people living with multiple sclerosis (MS) and their healthcare providers. Common questions have included whether people living with MS are at higher risk of COVID-19 or of severe disease, whether certain disease-modifying therapies (DMTs) for MS heighten COVID-19 risk, and if/how COVID-19 vaccinations should be administered in relation to MS treatments. Anti-CD20 therapies, which target B cells, have been of particular interest given the role B cells play in the response to both the virus that causes COVID-19 (SARS-CoV-2) and vaccines. As more data surfaces and the pandemic evolves, additional questions have emerged regarding the administration of booster shots and differences between B cell-targeting therapies and other DMTs in terms of their immunomodulatory effects. In this podcast article, MS specialists discuss these challenges to MS care during the COVID-19 pandemic and the recent data which are currently informing their clinical decision-making. As the pandemic evolves, providers should continually partner with people living with MS to achieve MS treatment goals informed by the latest developments in COVID-19. Video: Podcast Video (MP4 388175 KB).

Developing a Digital Solution for Remote Assessment in Multiple Sclerosis: From Concept to Software as a Medical Device.

There is increasing interest in the development and deployment of digital solutions to improve patient care and facilitate monitoring in medical practice, e.g., by remote observation of disease symptoms in the patients' home environment. Digital health solutions today range from non-regulated wellness applications and research-grade exploratory instruments to regulated software as a medical device (SaMD). This paper discusses the considerations and complexities in developing innovative, effective, and validated SaMD for multiple sclerosis (MS). The development of SaMD requires a formalised approach (design control), inclusive of technical verification and analytical validation to ensure reliability. SaMD must be clinically evaluated, characterised for benefit and risk, and must conform to regulatory requirements associated with device classification. Cybersecurity and data privacy are also critical. Careful consideration of patient and provider needs throughout the design and testing process help developers overcome challenges of adoption in medical practice. Here, we explore the development pathway for SaMD in MS, leveraging experiences from the development of Floodlight™ MS, a continually evolving bundled solution of SaMD for remote functional assessment of MS. The development process will be charted while reflecting on common challenges in the digital space, with a view to providing insights for future developers.

Correlation of malrotation deformity in distal radius fractures with radiographic analysis: cadaveric study.

PURPOSE: The radiographic parameters commonly used for evaluating distal radius fractures are radial length, palmar tilt, radial inclination, and articular congruity. Rotation of the distal fragment is not routinely evaluated after distal radius fractures. The purpose of this study was to define the appearance of distal fragment malrotation on conventional radiographs and to correlate varying degrees of malrotation with the corresponding radiographic findings. METHODS: Six distal radiuses from embalmed cadavers were cut and stabilized in 10 degrees, 20 degrees, and 30 degrees of pronated malrotation. Posteroanterior, lateral, and oblique (45 degrees pronated view) radiographs were taken and radiographic measurements were made of radial length, palmar tilt, radial inclination, and rotation. RESULTS: With malrotation, the visible cortical width of the distal fragment mismatched the visible cortical width of the proximal fragment. This was most evident on the oblique view (p < .05) and measured 2.2 mm for 10 degrees of rotation (standard deviation [SD] 0.6), 3.4 mm for 20 degrees of rotation (SD 0.8), and 5.3 mm for 30 degrees of rotation (SD 2.2). CONCLUSIONS: The radiographic parameter of rotation should be considered when evaluating distal radius fracture reduction. Malrotation is best seen on a 45 degrees oblique pronated radiographic view as a mismatch of the cortical width of the distal fragment compared with the cortical width of the proximal fragment. In the absence of radial shortening, a 5.3-mm mismatch is associated with 30 degrees of malrotation and is the upper limit of acceptability.

Saccadic palsy after cardiac surgery: characteristics and pathogenesis.

OBJECTIVE: To characterize the syndrome of saccadic palsy that may follow cardiac surgery, and to interpret the findings using current concepts of the neurobiology of fast eye movements. METHODS: Using the magnetic search coil technique, we measured eye, eyelid, and head movements of 10 patients who developed selective palsy of saccades after cardiac surgery. RESULTS: Patients showed varying degrees of slowing and hypometria of saccades in the vertical plane or both horizontal and vertical planes, with complete loss of all saccades in one patient. Quick phases of nystagmus were also affected, but smooth pursuit, vergence, and the vestibuloocular reflex were usually spared. The smallest saccades were less slowed than larger saccades. Affected patients were visually disabled by loss of ability to voluntarily shift their direction of gaze. Blinks and head thrusts modestly improved the range and speed of voluntary movement. The syndrome usually followed aortic valve replacement. Common accompanying features included dysarthria, labile emotions, and unsteady gait. The saccadic palsy either improved during the early part of the course or remained static. INTERPRETATION: Selective loss of all forms of saccades, with sparing of other eye movements, indicates malfunction of the brainstem machinery that generates saccades. A current model of brainstem circuits could account for both hypometria and slowing. This syndrome and the visual disability it causes often go unrecognized unless saccades are systematically tested at the bedside.

A survey regarding physician recommendations regarding return to work.

PURPOSE: Returning patients to work may be influenced by subjective factors and physician bias. The purpose of this study was to determine whether factors such as complaints of pain and patient motivation influence physicians' recommendations regarding return to work or activity. METHODS: One hundred twenty-five members of the American Society for Surgery of the Hand completed an online survey describing a 25-year-old patient with surgically treated diaphyseal fractures of the radius and ulna. Physicians were asked whether the patient could be returned to work in 4 distinct scenarios varying with occupation, time since injury, radiographic union, patient motivation, and pain. RESULTS: Logistic regression analysis demonstrated that all 5 predictor variables were highly significant predictors of return to work. Pain and diminished motivation were associated with a significantly lower probability of return to work. CONCLUSIONS: Although in the scenario depicted, objective factors such as radiographic union and job demands are the major determinants of physician clearance to return to work, physicians are also influenced by patient motivation and complaints of pain.

ToxRefDB version 2.0: Improved utility for predictive and retrospective toxicology analyses.

The Toxicity Reference Database (ToxRefDB) structures information from over 5000 in vivo toxicity studies, conducted largely to guidelines or specifications from the US Environmental Protection Agency and the National Toxicology Program, into a public resource for training and validation of predictive models. Herein, ToxRefDB version 2.0 (ToxRefDBv2) development is described. Endpoints were annotated (e.g. required, not required) according to guidelines for subacute, subchronic, chronic, developmental, and multigenerational reproductive designs, distinguishing negative responses from untested. Quantitative data were extracted, and dose-response modeling for nearly 28,000 datasets from nearly 400 endpoints using Benchmark Dose (BMD) Modeling Software were generated and stored. Implementation of controlled vocabulary improved data quality; standardization to guideline requirements and cross-referencing with United Medical Language System (UMLS) connects ToxRefDBv2 observations to vocabularies linked to UMLS, including PubMed medical subject headings. ToxRefDBv2 allows for increased connections to other resources and has greatly enhanced quantitative and qualitative utility for predictive toxicology.

Expert Perspectives on COVID-19 Vaccination for People Living with Multiple Sclerosis.

COVID-19 vaccines are safe for people living with MS on or off disease-modifying therapies and are important for the prevention of COVID-19. Antibody responses for individuals on certain DMTs may be diminished, however, T-cell responses may be preserved in those individuals. Data are lacking regarding optimal timing of vaccinations, and delaying disease-modifying therapies may increase the risk of disease activity and progression. In this perspective podcast, the authors recommend COVID-19 vaccination as soon as possible, regardless of timing considerations, in most cases.

Evaluation of the learning curve for laparoscopic Roux-en-Y gastric bypass surgery.

BACKGROUND: The literature reports that the learning curve for laparoscopic Roux-en-Y gastric bypass (LRYGBP) is approximately 75-100 cases. This aim of the present study was to evaluate the safety and feasibility of shortening the learning curve for performing LRYGBP by an experienced laparoscopic surgeon. METHODS: This study analyzed retrospectively the first 100 consecutive LRYGBP cases performed by an experienced laparoscopic surgeon between April 2003 and September 2003. The surgeon performed these cases after first assisting in 30 cases, and the first 4 cases were proctored by an experienced laparoscopic bariatric surgeon. Two cases done after previous gastric stapling and Nissen fundoplication were excluded from the study. Outcome variables included operative time, complications, conversion, and mortality. RESULTS: For the first 100 LRYGBP patients, the mean age was 42.6 years (range, 22-62 years) and mean body mass index (BMI) was 47.6 kg/m2 (range, 36-71.8). The complications included 1 case of intestinal leak, 1 case of small bowel obstruction, 6 cases of gastrojejunal stenosis, 8 cases of wound infection, 1 case of wound seroma, and 2 cases of pulmonary embolism, resulting in 1 mortality. One case was converted to an open technique. Over the second 50 cases, there was a significant reduction in mean operative time, to 73 minutes (range, 39-145 minutes) from 113 minutes (range, 54-238 minutes) (P < .0001). However, despite the reduction in complication frequency (no gastrointestinal leak or obstruction, 2 cases of gastrojejunal stenosis, 2 cases of wound infection, no pulmonary embolism/deep venous thrombosis, and no mortality), there was no significant correlation between the mortality, conversion, and complication rates and the surgeon's experience. CONCLUSION: A bariatric surgical practice incorporating LRYGBP can be safely done by an experienced laparoscopic surgeon. With appropriate advanced laparoscopic skills, preparatory steps, proctorship, and adequate volume of cases, the learning curve for performing LRYGBP can be reduced to 50 cases. Further experience is associated with a significant reduction in operative time with acceptable mortality, complication, and conversion rates.

Posterior capsulorrhaphy for treatment of recurrent posterior glenohumeral instability.

The surgical treatment of recurrent posterior shoulder instability via a posterior approach has had a variable degree of success reported in the literature with recurrence rates ranging between 8% and 45%. The purpose of this study was to review the results of posterior capsulorrhaphy in a consecutive series of patients with recurrent posterior instability. Seventeen consecutive patients underwent operative management for posterior glenohumeral instability. The dominant shoulder was involved in ten patients. All patients were male with an average age of 28.1 years (range: 16 to 54 years). Ten patients had sustained a specific injury which precipitated the instability. Six patients reported dislocations requiring formal closed reduction maneuvers; the remainder described episodes of recurrent subluxation with spontaneous reduction. All patients underwent a posterior capsulorrhaphy using an infraspinatus splitting approach. Eight shoulders required repair of a posterior capsulolabral detachment. In addition, one patient required augmentation with a posterior bone block for significant glenoid rim deficiency. Outcome was assessed by personal interview, clinical assessment, and standardized radiographs. At an average follow-up of 3.9 years (range: 1.8 to 10.8 years) patients estimated their overall shoulder function to be 81% of the contralateral unaffected shoulder. The subjective result was excellent for eight patients, good for five patients, fair in two patients, and poor in two patients. One of the poor outcomes was in a patient with glenohumeral degenerative changes at the index procedure which progressed and eventually required a total shoulder arthroplasty. The other poor result was in a patient found to have a full-thickness rotator cuff tear 10.6 years after the index procedure. Two patients (12%) had recurrence of their instability. Both of these patients sustained a significant re-injury which precipitated their symptoms. Five patients complained of occasional night pain at the time of their last follow-up examination. Only one patient (who was re-injured) had to change professions as a result of shoulder symptoms. Posterior capsulorrhaphy for treatment of isolated posterior glenohumeral instability yields satisfactory clinical results. Recurrent instability in this series was associated with a specific re-injury and did not appear to increase with longer follow-up.