Harnessing Real-World Data to Inform Decision-Making: Multiple Sclerosis Partners Advancing Technology and Health Solutions (MS PATHS).

Background: Multiple Sclerosis Partners Advancing Technology and Health Solutions (MS PATHS) is the first example of a learning health system in multiple sclerosis (MS). This paper describes the initial implementation of MS PATHS and initial patient characteristics. Methods: MS PATHS is an ongoing initiative conducted in 10 healthcare institutions in three countries, each contributing standardized information acquired during routine care. Institutional participation required the following: active MS patient census of ≥500, at least one Siemens 3T magnetic resonance imaging scanner, and willingness to standardize patient assessments, share standardized data for research, and offer universal enrolment to capture a representative sample. The eligible participants have diagnosis of MS, including clinically isolated syndrome, and consent for sharing pseudonymized data for research. MS PATHS incorporates a self-administered patient assessment tool, the Multiple Sclerosis Performance Test, to collect a structured history, patient-reported outcomes, and quantitative testing of cognition, vision, dexterity, and walking speed. Brain magnetic resonance imaging is acquired using standardized acquisition sequences on Siemens 3T scanners. Quantitative measures of brain volume and lesion load are obtained. Using a separate consent, the patients contribute DNA, RNA, and serum for future research. The clinicians retain complete autonomy in using MS PATHS data in patient care. A shared governance model ensures transparent data and sample access for research. Results: As of August 5, 2019, MS PATHS enrolment included participants (n = 16,568) with broad ranges of disease subtypes, duration, and severity. Overall, 14,643 (88.4%) participants contributed data at one or more time points. The average patient contributed 15.6 person-months of follow-up (95% CI: 15.5-15.8); overall, 166,158 person-months of follow-up have been accumulated. Those with relapsing-remitting MS demonstrated more demographic heterogeneity than the participants in six randomized phase 3 MS treatment trials. Across sites, a significant variation was observed in the follow-up frequency and the patterns of disease-modifying therapy use. Conclusions: Through digital health technology, it is feasible to collect standardized, quantitative, and interpretable data from each patient in busy MS practices, facilitating the merger of research and patient care. This approach holds promise for data-driven clinical decisions and accelerated systematic learning.

MRI differences between MOG antibody disease and AQP4 NMOSD.

BACKGROUND: MOG antibody and AQP4 antibody seropositive diseases are immunologically distinct subtypes of neuromyelitis optica spectrum disorders (NMOSD) with similar clinical presentations. MRI findings can be instrumental in distinguishing MOG antibody disease from AQP4 antibody NMOSD. OBJECTIVES: The aim of this study is to characterize the neuroradiological differences between MOG antibody disease and AQP4 antibody NMOSD with the aim to distinguish between the two entities. METHODS: This is a retrospective study of 26 MOG and 25 AQP4 seropositive patients in which MRI features of the brain, spinal cord, and orbit were compared. RESULTS: The majority of the abnormal findings in the MOG cohort were located on orbital MRIs, while spinal cord magnetic resonance (MR) abnormalities were more common in the AQP4 cohort. Brain abnormalities showed some overlap, but cortical gray/juxtacortical white matter involvement was distinct to MOG patients, while area postrema involvement was a rare feature. CONCLUSION: Cortical gray/juxtacortical white matter lesions on brain MRI might help distinguish MOG antibody disease from AQP4-positive NMOSD. These findings could be of value in distinguishing the two entities as early as the first presentation.

No association between cortical lesions and leptomeningeal enhancement on 7-Tesla MRI in multiple sclerosis.

BACKGROUND: Autopsy data suggest a causative link between meningeal inflammation and cortical lesions (CLs) in multiple sclerosis (MS). OBJECTIVE: To use leptomeningeal enhancement (LME) and CLs on 7-Tesla (7T) magnetic resonance imaging (MRI) to investigate associations between meningeal inflammation and cortical pathology. METHODS: Forty-one participants with MS underwent 7T MRI of the brain. CLs and foci of LME were quantified. RESULTS: All MS participants had CLs; 27 (65.8%) had >1 focus of LME. Except for hippocampal CL count (ρ = 0.32 with spread/fill-sulcal pattern LME, p = 0.042), no significant correlations were seen between LME and CLs. Mean cortical thickness correlated with the number of LME foci (ρ = -0.43, p = 0.005). Participants with relapsing-remitting multiple sclerosis (RRMS) showed no correlation with neocortical CLs, but significant correlations were seen between LME and hippocampal lesion count (ρ = 0.39, p = 0.030), normalized cortical gray matter (GM) volume (ρ = -0.49, p = 0.005), and mean cortical thickness (ρ = -0.59, p < 0.001). CONCLUSION: This study supports a relationship between LME and cortical GM atrophy but does not support an association of LME and neocortical CLs. This may indicate that meningeal inflammation is involved with neurodegenerative inflammatory processes, rather than focal lesion development.

MOG antibody-associated encephalomyelitis/encephalitis.

Myelin oligodendrocyte glycoprotein (MOG) antibody disease is a rare autoimmune disorder with antibodies against the MOG predominantly involving the optic nerve and spinal cord leading to vision loss and paralysis. When MOG antibody disease involves the brain, the phenotype is similar to acute disseminated encephalomyelitis (ADEM). In this review, we discuss MOG-positive cases presenting with encephalitis, encephalopathy, or ADEM-like presentation based on recently published series.

Radiological characteristics of myelin oligodendrocyte glycoprotein antibody disease.

BACKGROUND: MOG antibody disease is an autoimmune disease of the central nervous system (CNS) characterized by the presence of a serological antibody against myelin oligodendrocyte glycoprotein (MOG). MRI is instrumental in distinguishing neuromyelitis optica spectrum disorder (NMOSD) from multiple sclerosis (MS), but MRI features of MOG disease appear to overlap with NMOSD and MS. OBJECTIVES: In this study we aim to characterize the radiological features of MOG antibody disease and compare the findings with those previously described. METHODS: This is a retrospective study of 26 MOG positive patients. We aim to describe their brain, spinal and orbital MRI features and compare our findings with those previously reported in the literature. RESULTS: The majority of the abnormal findings was located on orbital MRIs, with more involvement of the anterior structures and bilateral involvement of the optic nerves. Brain abnormalities were distinct from both NMOSD and MS lesions. Spinal cord was the least affected. CONCLUSIONS: This is a dedicated radiological study aiming to characterize the features of MOG antibody disease which might aid in the proper investigation of cases presenting with acquired demyelinating disorders.

Comparative quantitative clinical, neuroimaging, and functional profiles in children with acute flaccid myelitis at acute and convalescent stages of disease.

AIM: To quantify characteristics in acute flaccid myelitis (AFM) at acute and convalescent stages. METHOD: This was a retrospective case series of children with AFM evaluated at a single institution in the USA (2014-2017). Acute inflammatory/ischemic myelopathies were excluded. Neurological assessments and segmental quantitative analysis of signal abnormalities on magnetic resonance imaging (MRI) of the brain and spinal cord were performed. RESULTS: Sixteen patients (11 males, five females) were evaluated. Median age at onset was 4 years (interquartile range [IQR] 3-6y). All had parainfectious acute-onset limb weakness, lower motor neuron examination, and spinal fluid pleocytosis. On acute spinal cord MRI, longitudinally extensive T2 hyperintensities were identified throughout the spinal cord mostly within grey matter; five out of 12 patients had dorsal brainstem T2 hyperintensities. At a median of 2 months follow-up (IQR 2-3mo), spinal cord MRI improved in seven out of nine patients although focal T2 hyperintensities persisted in cervical and lumbar grey matter. At a median follow-up of 4 months (IQR 2-6mo), Medical Research Council sum score rose from a median of 29 to 32; distal muscle groups improved more than proximal ones; four out of 16 patients were ventilator-dependent; and two out of 16 patients were quadriplegic. INTERPRETATION: While patients may show marked improvement on neuroimaging from acute to convalescent stages, the majority of children with AFM have limited motor recovery and continued disability. Clinicians should consider the timing of clinical and neuroimaging exams when assessing diagnosis and prognosis. WHAT THIS PAPER ADDS: During the 2014 to 2017 acute flaccid myelitis outbreak in the USA, clinical recovery was better in distal than proximal muscle groups. Lumbar spinal cord showed more residual abnormalities at convalescence.

Prevalence, Patterns, and Clinical Relevance of Hypoxic-Ischemic Injuries in Children Exposed to Abusive Head Trauma.

BACKGROUND AND PURPOSE: Hypoxic-ischemic injuries (HIIs) are a scarcely investigated but important cause of morbidity and mortality in children who suffered abusive head trauma (AHT). The purpose of this study is to determine: (a) prevalence, types, and clinical relevance of cytotoxic edema compatible with HII in nonpenetrating AHT, (b) their relationship to other classic neuroimaging findings of AHT, and (c) their correlation with clinical outcomes. METHODS: Diffusion-weighted imaging sequences of magnetic resonance imagings performed on children under 5 years diagnosed with AHT were reviewed to detect the most common patterns of acute parenchymal damage. Patterns of cytotoxic edema were described, and HII-compatible ones divided in subtypes. Correlation between HII, fractures, and subdural hemorrhages (SDHs) and with clinical outcomes was determined using imaging and available follow-up data. RESULTS: Out of 57 patients, 36.8% showed lesions compatible with HII. A predominantly asymmetric cortical distribution was observed in 66.7% of cases, while 33.3% had diffused both cortical and deep gray/white matter distribution injury. Traumatic axonal injuries and focal contusions were less common. There was no significant correlation between the presence of SDH (P = .6) or skull fractures (P = .53) and HII. HII was the most severe form of parenchymal damage in terms of in-hospital mortality and morbidity at follow-up. CONCLUSIONS: HII is the most common type of parenchymal damage in children victim of AHT, being present in 1/3 of patients with this condition, and correlates with more severe outcomes. Its presence is independent from other classic traumatic findings such as SDH and fractures.

Acute progressive paraplegia in heroin-associated myelopathy.

As the opioid epidemic continues, understanding manifestations of abuse, including heroin-associated myelopathy remains essential. Here we describe a young man with a past medical history significant for polysubstance abuse who developed acute-onset, rapidly progressive myelopathy after resumption of intravenous heroin use. He had significant spinal cord involvement with findings suggestive of heroin-associated myelopathy. The salient features of this case include diffusion imaging of the spine and spinal angiography supporting a possible vasculopathy as the pathophysiologic mechanism underlying heroin-associated myelopathy. Additionally, CSF studies showed the transition from a neutrophilic pleocytosis to a lymphocytic pleocytosis suggesting an inflammatory component.

Magnetic resonance imaging of the spinal cord in the evaluation of 3 patients with sensory neuronopathies: Diagnostic assessment, indications of treatment response, and impact of autoimmunity: A case report.

RATIONALE: Sensory neuronopathy can be a devastating peripheral nervous system disorder. Profound loss in joint position is associated with sensory ataxia, and reflects degeneration of large-sized dorsal root ganglia. Prompt recognition of sensory neuronopathies may constitute a therapeutic window to intervene before there are irreversible deficits. However, nerve-conduction studies may be unrevealing early in the disease course. In such cases, the appearance of dorsal column lesions on spinal-cord MRI can help in the diagnosis. However, most studies have not defined whether such dorsal column lesions may occur within earlier as well as chronic stages of sensory neuronopathies, and whether serial MRI studies can be used to help assess treatment efficacy. In this case-series of three sensory neuronopathy patients, we report clinical characteristics, immunological markers, nerve-conduction and skin-biopsy studies, and neuroimaging features. PATIENT CONCERNS: All three patients presented with characteristic features of sensory neuronopathy with abnormal spinal-cord MRI studies. Radiographic findings included non-enhancing lesions in the dorsal columns that were longitudinally extensive (spanning ≥ 3 vertebral segments). DIAGNOSES: All patients had anti-Ro/SS-A and/or anti-La/SS-B antibodies, with patients one and two having Sjögren's syndrome. MRI findings were similar when performed in the earlier stages of a sensory neuronopathy (patient one, after four months) and chronic stages (patients two and three, after five and three years, respectively). INTERVENTIONS: Patient one was treated with rituximab combined with intravenous immunoglobulin therapy. OUTCOMES: Patient one was initially wheelchair-bound and had improved ambulation after treatment. In this patient, serial MRI studies revealed partial resolution of dorsal column lesions, associated with decreased sensory ataxia and improved nerve-conduction studies. LESSONS: In addition to vitamin B12 and copper deficiency, it is important to include sensory neuronopathies in the differential diagnosis of dorsal column lesions. MRI spinal-cord lesions have similar appearances in the earlier as well as chronic phases of a sensory neuronopathy, and therefore suggest that such dorsal column lesions may reflect inflammatory as well as a gliotic burden of injury. MRI may also be a useful longitudinal indicator of treatment response.

Cortical blindness and not optic neuritis as a cause of vision loss in a Sjögren's syndrome (SS) patient with the neuromyelitis optica spectrum disorder (NMOSD): Challenges of ascribing demyelinating syndromes to SS: a case report.

RATIONALE: The conception that multiple sclerosis may be challenging to distinguish from demyelinating manifestations of Sjögren's syndrome (SS) was introduced more than 30 years ago. However, it is now recognized that the neuromyelitis optica spectrum disorder (NMOSD) may occur more frequently in SS as opposed to multiple sclerosis. Characteristic NMOSD features can include severe attacks of optic neuritis, myelitis which is frequently longitudinally-extensive (spanning at least three vertebral segments on magnetic resonance imaging [MRI]), and an association with anti-aquaporin-4 antibodies. In addition, whereas NMOSD was initially thought to spare the brain, it is now recognized that brain lesions occur in a majority of NMOSD patients. Therefore, it is important for the multi-disciplinary team of physicians who care for SS patients to understand this widening spectrum of NMOSD as encompassing brain lesions. In this case-report we describe clinical features, radiographic findings, and treatment of a SS NMOSD patient presenting with severely decreased visual acuity, visual hallucinations, and encephalopathy. PATIENT CONCERNS: The SS NMOSD patient presented with rapid, bilateral onset of severely decreased visual acuity and was therefore suspected as having bilateral optic neuritis. DIAGNOSIS: However, the patient lacked stigmata of optic neuritis, instead had visual hallucinations and encephalopathy suggestive of cortical blindness, and was noted to have occipital lobe lesions on brain MRI. Other radiographic findings included simultaneous enhancement of brainstem and periventricular lesions. INTERVENTIONS: The patient was initially treated with methylprednisolone with no change in her neurological deficits. She was then treated with plasma exchange therapy. OUTCOMES: The patient had resolution of decreased visual acuity, visual hallucinations, encephalopathy, and contrast-enhancing brain lesions in response to plasma exchange therapy. LESSON: We provide the first example of severely decreased visual acuity in a NMOSD patient due to cortical blindness and not bilateral optic neuritis. This finding expands the spectrum of central nervous system syndromes and brain lesions which may occur in NMOSD. The synchronous enhancement of a brainstem lesion (known to occur in NMOSD) with occipital lobe lesions also suggests that our patient's occipital lobe findings were due to NMOSD. All of our patient's findings had an excellent clinical and radiographic response to plasma exchange therapy.

Venous hypertensive encephalopathy secondary to venous sinus thrombosis and dural arteriovenous fistula.

A 52-year-old man with a history of factor V Leiden thrombophilia, persistent headaches and papilloedema presented with worsening vision and confusion. MRI and MR angiography of the brain at the time of this presentation showed findings concerning for transverse sinus thrombosis and an associated dural arteriovenous fistula. Dural venous sinus thrombosis can lead to the formation of a dural arteriovenous fistula, which must be considered in the differential diagnosis for intracranial hypertension in patients with thrombophilia.

Follow-Up of Emergency Department MRI Scans Suggesting New Diagnosis of CNS Demyelination.

OBJECTIVE: The literature has shown that new cases of multiple sclerosis (MS) can be missed in the emergency department (ED), causing unnecessary delays for patients. In 2012, an MRI scanner was introduced into the ED of our institution. This study examines the potential value of the radiologists' MRI reports for patients with previously undiagnosed MS who presented to the ED. MATERIALS AND METHODS: In this retrospective study, electronic medical records were reviewed for patients without a prior diagnosis of a demyelinating disorder, who underwent imaging on the ED's MRI scanner between March 1, 2014, and March 1, 2016, and for whom the radiologist reported a possible demyelinating disorder. RESULTS: Patient encounters of 61 women and 31 men (mean age, 41.2 years) met the inclusion criteria. In 48 of 92 (52.2%) cases where the radiology report suggested a demyelinating diagnosis, the patient was also given such a diagnosis as the final outcome. Where a demyelinating disorder was placed as the only, first, second, or third (or later) differential diagnosis, the final diagnosis was concordant with demyelination in 84.3% (43/51), 37.5% (3/8), 18.2% (2/11), and 0% (0/22) of cases, respectively (p < 0.01). CONCLUSION: Radiologist-suggested demyelinating disease as the top differential diagnosis after MRI showed a high concordance rate with demyelinating disease being the final diagnosis. Scans in the ED for neurologic deficits can lead to early guidance for a diagnosis of demyelination to be made. Downstream effects may include reduced admission rates, avoidance of unnecessary use of other procedures, and early commencement of disease-modifying therapy.

Leptomeningeal Enhancement at 7T in Multiple Sclerosis: Frequency, Morphology, and Relationship to Cortical Volume.

BACKGROUND AND PURPOSE: Perform an investigation of the frequency and distribution of leptomeningeal enhancement on postgadolinium magnetization-prepared FLAIR (MPFLAIR) in multiple sclerosis (MS) on 7 Tesla (7T) MRI and to relate this finding to measures of brain structure and lesion volumes. METHODS: Twenty-nine participants with MS underwent 7T MRI of the brain. Three healthy volunteers (HVs) were scanned for comparison. Areas of postcontrast leptomeningeal enhancement were identified. Images were segmented for brain structure and lesion volumes. The relationship between leptomeningeal enhancement and clinical and volumetric data was explored. RESULTS: Two patterns of enhancement were found: "nodular" (discrete, spherical nodules at the pial surface or subarachnoid space) and "spread/fill" (appearance of contrast spread through the local subarachnoid space). Twenty-six of 29 (90%) MS participants had at least one focus of leptomeningeal enhancement. Nodular foci were present in 15 of 29 (51%) MS participants. Spread/fill foci were present in 22 of 29 (76%) MS participants. Two HVs had examples of nodular foci, but none had spread/fill enhancement. MS participants with spread/fill foci were older (48.9 years [SD 8.3]) than those without (33.3 years [SD 11.5], P = .005). MS participants with spread/fill foci had reduced cortical gray matter volume compared to those without (P = .020). CONCLUSIONS: Leptomeningeal enhancement on postcontrast 7T MPFLAIR is more prevalent than prior reports at 3T-occurring at frequencies closer to histopathologic data. Spread/fill foci are associated with reduced cortical gray matter volumes and may represent blood-meningeal barrier breakdown near sites of meningeal inflammation, whereas nodular foci may be a normal variant.

Supratentorial Tumors in Pediatric Patients.

The breadth of tumors that can arise in the supratentorial brain in children is extensive. With the exception of those that result in seizures and the highly malignant histologies, supratentorial tumors may come to medical attention later compared with infratentorial tumors, as they are less commonly associated with ventricular obstruction. This article presents an overview of the neuroimaging characteristics of these entities, with particular attention to relevant features that may aid in narrowing the differential diagnosis, including correlation with demographics and clinical presentation.

Case 236: Middle Interhemispheric Variant of Holoprosencephaly.

History A 13-year-old girl presented for evaluation and further management of spastic diplegia cerebral palsy. Absence of the corpus callosum was noted at screening prenatal head ultrasonography. She was born at full term via spontaneous vaginal delivery. Physical examination revealed decreased axial muscle tone and increased muscle tone in her extremities; the latter was more severe. She was nonambulatory. No midline craniofacial anomaly was seen. She had dysarthria but was able to speak in full sentences. She was in sixth grade with an individualized education program. She had mild behavioral problems, such as "acting out" in school. Brain magnetic resonance (MR) imaging, including three-dimensional T1- and T2-weighted sequences, was performed without intravenous administration of contrast material to evaluate the brain.

Bilateral temporal lobe disease: looking beyond herpes encephalitis.

UNLABELLED: The temporal lobes have unique architecture, and functionality that makes them vulnerable to certain disease processes. Patients presenting with bilateral temporal lobe disease are often confused and have altered consciousness, and are therefore unable to provide cogent histories. For these reasons, imaging plays an important role in their workup and management. Disease entities causing bilateral temporal lobe involvement can be infectious, metabolic, neoplastic, and degenerative aetiologies, as well as trauma and cerebrovascular events. We will first describe the structural and functional anatomy of the temporal lobes and explain the mechanisms that underlie bilateral temporal lobe disease, and then show and discuss the different disease entities and differential diagnosis. TEACHING POINTS: • Bilateral temporal lobe disease is a unique pattern with specific differential diagnosis. • Patients presenting with bilateral temporal lobe disease are often confused. • Radiologists should be familar with the variety of disease processes that cause bitemporal disease.

What do we know about brain contrast enhancement patterns in neuromyelitis optica?

Neuromyelitis optica (NMO) is an autoimmune disorder of the central nervous system that usually presents with acute myelitis and/or optic neuritis. Recently, some brain magnetic resonance imaging findings have been described in NMO that are important in the differential diagnosis. Pencil-thin, leptomeningeal, and cloud-like enhancement may be specific to NMO. These patterns are usually seen during relapses. Recognizing these lesions and enhancement patterns may expedite the diagnosis and allows early effective treatment. The purpose of this article is to review the latest knowledge and to share our experience with the contrast enhancement patterns of NMO brain lesions.