Quantitative Susceptibility Mapping Changes Relate to Gait Issues in Parkinson's Disease.

BACKGROUND: Quantitative susceptibility mapping (QSM) demonstrates elevated iron content in Parkinson's disease (PD) patients within the basal ganglia, though it has infrequently been studied in relation to gait difficulties including freezing of gait (FOG). Our purpose was to relate QSM of basal ganglia and extra-basal ganglia structures with qualitative and quantitative gait measures in PD. METHODS: This case-control study included PD and cognitively unimpaired (CU) participants from the Comprehensive Assessment of Neurodegeneration and Dementia study. Whole brain QSM was acquired at 3T. Region of interests (ROIs) were drawn blinded manually in the caudate nucleus, putamen, globus pallidus, pulvinar nucleus of the thalamus, red nucleus, substantia nigra, and dentate nucleus. Susceptibilities of ROIs were compared between PD and CU. Items from the FOG questionnaire and quantitative gait measures from PD participants were compared to susceptibilities. RESULTS: Twenty-nine participants with PD and 27 CU participants were included. There was no difference in susceptibility values in any ROI when comparing CU versus PD (p > 0.05 for all). PD participants with gait impairment (n = 23) had significantly higher susceptibility in the putamen (p = 0.008), red nucleus (p = 0.01), and caudate nucleus (p = 0.03) compared to those without gait impairment (n = 6). PD participants with FOG (n = 12) had significantly higher susceptibility in the globus pallidus (p = 0.03) compared to those without FOG (n = 17). Among quantitative gait measures, only stride time variability was significantly different between those with and without FOG (p = 0.04). CONCLUSION: Susceptibilities in basal ganglia and extra-basal ganglia structures are related to qualitative measures of gait impairment and FOG in PD.

Oophorectomy in NMDA receptor encephalitis and negative pelvic imaging.

Ovarian teratomas are found in one-third of females presenting with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. When a teratoma is detected on imaging, its removal is first-line therapy. Even with multiple imaging modalities, occasionally, the teratoma is found only on subsequent imaging, long after initial presentation. Very rarely, patients have undergone oophorectomy despite negative imaging, with pathology demonstrating teratoma, and resulting clinical improvement. We present a patient in whom removal of a teratoma, not visible on conventional imaging, resulted in marked clinical improvement. Such cases present a major clinical challenge, needing to consider the risks of oophorectomy, including sterilisation and early menopause, versus the possibility of death in the absence of response to first-line (eg, corticosteroids, plasma exchange, intravenous immunoglobulin), second-line (eg, rituximab) and third-line (eg, bortezomib) immunosuppression. This decision is made more difficult as patients are usually females of childbearing age who at the time lack capacity to make medical decisions. This case also highlights the lack of consensus and guidelines for imaging modalities used to detect teratoma and when to pursue oophorectomy.

Sarcocystis myopathy in a patient with HIV-AIDS.

Sarcocystosis is a zoonotic infection that causes intestinal and muscular illnesses in humans. Sarcocystosis was until recently considered rare in humans. To complete their life cycle, Sarcocystis species require both a definitive and an intermediate host. Humans are the definitive host when infected by one of two species: Sarcocystis hominis (from eating undercooked beef) or Sarcocystis suihominis (from eating uncooked pork). Infection with either of these species results in intestinal sarcocystosis, causing a self-limited disease characterized by nausea, abdominal pain, and diarrhea. Humans act as the intermediate host when infected by Sarcocystis nesbitti, resulting in the markedly different clinical picture of muscular sarcocystosis. Most documented cases of muscular sarcocystosis were assumed to be acquired in Malaysia, in addition to other regions of Southeast Asia and India. Published cases of muscular sarcocystosis from the Middle East, Central and South America, and Africa are all rare. Although the clinical presentation of muscular sarcocystosis remains to be fully characterized, fever, myalgia, and headache are among the most common symptoms. Here, we report a patient from sub-Saharan Africa with chronic Sarcocystis myopathy and well-controlled HIV-AIDS.

Hypoxia and Inflammation-Induced Disruptions of the Blood-Brain and Blood-Cerebrospinal Fluid Barriers Assessed Using a Novel T1-Based MRI Method.

Subtle blood-brain barrier (BBB) disruption is involved in numerous neurological conditions. This disruption is found diffusely in the brain and requires quantitative methods for assessment. We propose a statistical method to identify individual voxels where the BBB is disrupted using T1-weighted MRI. We used models of severe and focal vs. mild and generalized disruption of the BBB to show proof of principle with the cold injury model, hypoxia, and a model of inflammation using low- and high-dose lipopolysaccharide (LPS) treatment. Using voxel-based analysis, we found that mild hypoxia resulted in diffuse disruption of the BBB, whereas more severe hypoxia and high-dose LPS treatment resulted in prominent leakage, particularly in the periventricular area, suggestive of blood-cerebrospinal fluid (CSF) barrier disruption. Our data suggest that the periventricular area may be compromised first in conditions of inflammation and hypoxia. Voxel-based analysis could be used in future studies assessing subtle blood-CSF or BBB disruption.

Using magnetic resonance imaging in animal models to guide drug development in multiple sclerosis.

Major advances are taking place in the development of therapeutics for multiple sclerosis (MS), with a move past traditional immunomodulatory/immunosuppressive therapies toward medications aimed at promoting remyelination or neuroprotection. With an increase in diversity of MS therapies comes the need to assess the effectiveness of such therapies. Magnetic resonance imaging (MRI) is one of the main tools used to evaluate the effectiveness of MS therapeutics in clinical trials. As all new therapeutics for MS are tested in animal models first, it is logical that MRI be incorporated into preclinical studies assessing therapeutics. Here, we review key papers showing how MR imaging has been combined with a range of animal models to evaluate potential therapeutics for MS. We also advise on how to maximize the potential for incorporating MRI into preclinical studies evaluating possible therapeutics for MS, which should improve the likelihood of discovering new medications for the condition.

A tale of two methods: combining near-infrared spectroscopy with MRI for studies of brain oxygenation and metabolism.

Combining magnetic resonance imaging (MRI) with near-infrared spectroscopy (NIRS) leads to excellent synergies which can improve the interpretation of either method and can provide novel data with respect to measuring brain oxygenation and metabolism. MRI has good spatial resolution, can detect a range of physiological parameters and is sensitive to changes in deoxyhemoglobin content. NIRS has lower spatial resolution, but can detect, and with specific technologies, quantify, deoxyhemoglobin, oxyhemoglobin, total hemoglobin and cytochrome oxidase. This paper reviews the application of both methods, as a multimodal technology, for assessing changes in brain oxygenation that may occur with changes in functional activation state or metabolic rate. Examples of hypoxia and ischemia are shown. Data support the concept of reduced metabolic rate resulting from hypoxia/ischemia and that metabolic rate in brain is not close to oxygen limitation during normoxia. We show that multimodal MRI and NIRS can provide novel information for studies of brain metabolism.

Imaging phenotypic differences in multiple sclerosis: at the crossroads of aging, sex, race, and ethnicity.

Clear sex differences are observed in clinical and imaging phenotypes of multiple sclerosis (MS), which evolve significantly over the age spectrum, and more specifically, during reproductive milestones such as pregnancy and menopause. With neuroimaging being an outcome measure and also a key subclinical biomarker of subsequent clinical phenotype in MS, this comprehensive review aims to provide an overview of sex and hormone differences in structural and functional imaging biomarkers of MS, including lesion burden and location, atrophy, white matter integrity, functional connectivity, and iron distribution. Furthermore, how therapies aimed at altering sex hormones can impact imaging of women and men with MS over the lifespan is discussed. This review also explores the key intersection between age, sex, and race/ethnicity in MS, and how this intersection may affect imaging biomarkers of MS.

Susceptibility-weighted imaging in the experimental autoimmune encephalomyelitis model of multiple sclerosis indicates elevated deoxyhemoglobin, iron deposition and demyelination.

BACKGROUND: Susceptibility-weighted imaging (SWI) is an iron-sensitive magnetic resonance imaging (MRI) method that has shown iron-related lesions in multiple sclerosis (MS) patients. The contribution of deoxyhemoglobin to the signals seen in SWI has not been well characterized in MS. OBJECTIVES: To determine if SWI lesions (seen as focal hypointensities) exist in the experimental autoimmune encephalomyelitis (EAE) animal model of MS, and to determine whether the lesions relate to iron deposits, inflammation, demyelination, and/or deoxyhemoglobin in the vasculature. METHODS: We performed SWI on the lumbar spinal cord and cerebellum of EAE and control mice (both complete Freund's adjuvant/pertussis toxin (CFA/PTX)-immunized and naive). We also performed SWI on mice before and after perfusion (to remove blood from vessels). SWI lesions were counted and their locations were compared to histology for iron, myelin and inflammation. RESULTS: SWI lesions were found to exist in the EAE model. Many lesions seen by SWI were not present after perfusion, especially at the grey/white matter boundary of the lumbar spinal cord and in the cerebellum, indicating that these lesion signals were associated with deoxyhemoglobin present in the lumen of vessels. We also observed SWI lesions in the white matter of the lumbar spinal cord that corresponded to iron deposition, inflammation and demyelination. In the cerebellum, SWI lesions were present in white matter tracts, where we found histological evidence of inflammatory perivascular cuffs. CONCLUSIONS: SWI lesions exist in EAE mice. Many lesions seen in SWI were a result of deoxyhemoglobin in the blood, and so may indicate areas of hypoxia. A smaller number of SWI lesions coincided with parenchymal iron, demyelination, and/or inflammation.

Do magnetic resonance imaging features differ between persons with multiple sclerosis of various races and ethnicities?

Those of African American or Latin American descent have been demonstrated to have more severe clinical presentations of multiple sclerosis (MS) than non-Latin American White people with MS. Concurrently, radiological burden of disease on magnetic resonance imaging (MRI) in African Americans with MS has also been described as being more aggressive. Here, we review MRI studies in diverse racial and ethnic groups (adult and pediatric) investigating lesion burden, inflammation, neurodegeneration, and imaging response to disease modifying therapy. We also discuss why such disparities may exist beyond biology, and how future studies may provide greater insights into underlying differences.

Normocomplementemic urticarial vasculitis in a patient with multiple sclerosis on glatiramer acetate.

Glatiramer acetate is one of the oldest and safest disease modifying therapies used to treat relapsing-remitting multiple sclerosis. Urticarial vasculitis is a rare complication of treatment with glatiramer acetate, having been reported by only two others previously. Here, we describe a case of normocomplementemic urticarial vasculitis diagnosed on skin punch biopsy in a patient with multiple sclerosis treated with glatiramer acetate for five years. Upon treatment with steroids and an antihistamine along with discontinuation of glatiramer acetate, the urticaria resolved.

Recurrent Tumefactive Central Nervous System Lesions Due to BRIP1 -Related Fanconi Anemia.

INTRODUCTION: Fanconi anemia (FA) is an inherited condition associated with genetic mutations that affect DNA repair proteins. More than 20 genes involved in the FA/BRCA pathway have been implicated in FA, including BRIP1 . Tumefactive brain lesions are rare in FA. CASE REPORT: We describe a patient with FA and recurrent tumefactive brain lesions preceded by calcifications on head computed tomography. A biopsy revealed white-matter gliosis with severe vasculopathy. Whole-genome sequencing demonstrated a BRIP1 homozygous variant with a final diagnosis of recurrent tumefactive brain lesions due to BRIP1 -associated CNS vasculopathy. Immunosuppressive treatment was ineffective in the present case. CONCLUSIONS: Mechanistically, the specific role of BRIP1 mutation in CNS inflammation and vasculopathy is unclear. However, immunodeficiency disorders can lead to autoimmunity and/or immune dysregulation due to the possible loss or gain of function of components of the immune system.

Extreme Delta Brush in Anti-NMDAR Encephalitis Correlates With Poor Functional Outcome and Death.

Objective: To characterize EEG findings in anti-NMDAR encephalitis patients looking for the proportion of EEGs that were abnormal, presence of extreme delta brush (EDB), and to relate EEG findings to clinical outcomes (Glasgow Outcome Scale (GOS) at 6 months, need for ICU admission, and death). Methods: This retrospective cohort single center study included patients with anti-NMDAR encephalitis who had ≥1 EEGs obtained from 2014 to 2021. EEGs were retrospectively analyzed by 2 reviewers. Clinical outcomes of interest were extracted through hospital and clinic chart review. Results: Twenty-one patients with anti-NMDAR encephalitis were included. Sixty-four EEGs were analyzed. Four EEGs (6.3%) were within normal limits. Focal or generalized slowing (without EDB) was seen on 44 EEGs (68.8%). EDB was seen on 16 EEGs (25.0%) in 9 of 21 patients (42.9%). The presence of EDB was significantly associated with need for ICU admission (p = 0.02), poorer outcome at 6 months as per the GOS (p = 0.002), and with death (p=0.02). EDB was present on ≥1 EEG of every patient who died. Conclusions: The presence of EDB on EEG in anti-NMDAR encephalitis patients is associated with increased need for ICU admission, worse functional outcomes at 6 months, and risk of death.