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.

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.

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.

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.

Susceptibility weighted imaging detects prominent veins that precede or coincide with maximal motor disability in a model of multiple sclerosis: A pilot study.

BACKGROUND: Susceptibility weighted imaging (SWI) has detected veins in the center of white matter lesions and alterations in veins themselves in multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE). However, the relationship between SWI-detected venous alterations and disease progression is unclear. The objective of this study was to assess alterations in the lumbar spinal cord veins in EAE mice over the disease course using serial SWI. METHODS: EAE mice (n = 8) underwent imaging for SWI using a 9.4T Bruker Avance console at baseline, 7 days (pre-motor dysfunction), 12 days (typical motor dysfunction onset), and 16-18 days (typical peak disease) post-immunization. Naïve controls were imaged alongside EAE mice (n = 3). SWI hypointensities were counted by two subjects and compared between time points. RESULTS: SWI hypointensities appeared before motor dysfunction onset in most EAE mice. The ratio of SWI hypointensities to baseline was highly variable for EAE mice (0.45-6.75) while less so for controls (0.80-1.31). The time point for the maximum number of SWI hypointensities always preceded or coincided with maximum motor disability. CONCLUSION: Venous alterations are detected before the onset of motor disability in some EAE mice using SWI which may relate to inflammation and/or tissue hypoxia.

Anti-N-methyl-d-aspartate receptor encephalitis: A primer for acute care healthcare professionals.

This primer summarizes the diagnosis, treatment, complications, and prognosis of anti-N-methyl-d-aspartate receptor encephalitis for healthcare professionals, especially those in acute care specialities. Anti-N-methyl-d-aspartate receptor encephalitis is an immune-mediated encephalitis that is classically paraneoplastic and associated with ovarian teratomas in young women. Other less common neoplastic triggers include testicular cancers, Hodgkin lymphoma, lung and breast cancers. It may also be triggered by infection, occurring as a para-infectious phenomenon, seen most commonly after herpes simplex-1 encephalitis. Presentation varies but typically consists of behavioural and cognitive manifestations, seizures, dysautonomia, movement disorders, central hypoventilation, and coma, necessitating intensive care unit admission. Diagnosis of anti-N-methyl-d-aspartate receptor encephalitis requires high clinical suspicion plus ancillary testing, the most sensitive being cerebrospinal fluid analysis for anti-N-methyl-d-aspartate receptor antibodies. Imaging in search of an ovarian teratoma should be exhaustive and tumours need to be surgically treated. Treatment should be expeditious with pulsed steroids and either plasma exchange or intravenous immunoglobulin. Second-line treatments include intravenous rituximab, cyclophosphamide, azathioprine, and intrathecal methotrexate. Most patients recover to be functionally independent, but the in-hospital course can be months long followed by extensive rehabilitation. Given the lengthy course of illness, we explain why education and debriefing are important for staff, and where families can obtain additional help.

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.

Lymphomatosis cerebri masquerading as the Marburg variant of multiple sclerosis.

Lymphomatosis cerebri (LC) is a rare variant of primary central nervous system lymphoma with few cases reported. Here, we describe the case of a patient with clinical presentation, imaging, and biopsy in keeping with aggressive multiple sclerosis (MS) such as that in Marburg variant. He deteriorated clinically over 9 months. Post-mortem examination yielded a diagnosis of LC with B-cell lymphoma. LC is notoriously difficult to diagnose, as it can present in various ways and biopsy of unaffected areas will be non-diagnostic. In our case, diagnosis was made more challenging by the patient's dramatic response to treatment with steroids and cyclophosphamide.

Proposed diagnostic and treatment paradigm for high-grade neurological complications of immune checkpoint inhibitors.

Immune checkpoint inhibitors such as antibodies to cytotoxic lymphocyte-associated protein 4 (ipilimumab) and programmed cell-death 1 (pembrolizumab, nivolumab) molecules have been used in non-small cell lung cancer, metastatic melanoma, and renal-cell carcinoma, among others. With these agents, immune-related adverse events (irAEs) can occur, including those affecting the neurological axis. In this review, high-grade neurological irAEs associated with immune checkpoint inhibitors including cases of Guillain-Barré syndrome (GBS) and myasthenia gravis (MG) are analyzed. Based on current literature and experience at our institution with 4 cases of high-grade neurological irAEs associated with immune checkpoint inhibitors (2 cases of GBS, 1 case of meningo-radiculitis, and 1 case of myelitis), we propose an algorithm for the investigation and treatment of high-grade neurological irAEs. Our algorithm incorporates both peripheral nervous system (meningo-radiculitis, GBS, MG) and central nervous system presentations (myelitis, encephalopathy). It is anticipated that our algorithm will be useful both to oncologists and neurologists who are likely to encounter neurological irAEs more frequently in the future as immune checkpoint inhibitors become more widely used.

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.