Autoimmune encephalitis in glial fibrillary acidic protein astrocytopathy.

Autoimmune encephalitis due to glial fibrillar acidic protein (GFAP) astrocytopathy is a rare cause of subacute neuropsychiatric changes. In this case, a young patient presented with a viral prodrome and meningismus, followed by progressive encephalopathy and movement disorders over the span of 2 weeks. Due to his clinical trajectory, inflammatory cerebrospinal fluid (CSF) analysis, initial normal brain imaging and negative serum autoimmune encephalopathy panel, his initial diagnosis was presumed viral meningoencephalitis. The recurrence and progression of neuropsychiatric symptoms and myoclonus despite antiviral treatment prompted further investigation, inclusive of testing for CSF autoimmune encephalopathy autoantibodies, yielding a clinically meaningful, positive GFAP autoantibody. This case highlights the importance of appropriately testing both serum and CSF autoantibodies when an autoimmune encephalitic process is considered. Through this case, we review the clinical and radiographic manifestations of GFAP astrocytopathy, alongside notable pearls pertaining to this autoantibody syndrome and its management.

Intravascular Lymphoma as a Cause of Recurrent Strokes - Case Report and Review of the Literature.

Background: Intravascular lymphoma is an uncommon cause of ischemic strokes. Because of its rarity and atypical pattern, most diagnoses are made post-mortem. Case study: We present a case of a 68-year-old male with multiple cardiovascular risk factors and recent SARS-CoV-2 infection who presented with recurrent strokes. Because of his stroke risk factors, he was initially managed with a sequentially escalating antithrombotic regimen. A malignant process was low on the differential at this point given his lack of systemic symptoms. When he continued to have new strokes despite these measures, including a spinal cord infarct, a broad workup was sent including for hypercoagulable states, vasculitis, and intravascular lymphoma. Eventually, a skin biopsy of a cherry angioma returned positive for lymphoma cells. He was treated with methotrexate followed by chemotherapy and rituximab. Unfortunately, he did not improve and was made comfort measures only by his family. Conclusion: This case illustrates the importance of considering intravascular lymphoma as a potential etiology of recurrent strokes, as early diagnosis and treatment are important for preventing irreversible neurological damage.

Case report: Anti-neurexin-3α-associated autoimmune encephalitis secondary to contrast-induced encephalopathy.

A 54-year-old man complained of episodic stinging in his left eye along with weakness and numbness in his right upper and lower extremities for 1 month. The neurological examination was negative. MRI showed bilateral paraventricular demyelination. CTA showed significant stenosis of the left internal carotid (60%) and vertebral arteries (70%). He underwent left internal carotid stenting and was intubated during the procedure. After the procedure, he did not wake up from anesthesia, and he developed flexion and spasticity in the right arm immediately. Thereafter, he was sent to the neurocritical unit (NCU). Anti-seizure treatment was adopted due to recurrent general tonic-clonic seizures. Two days later (day 15 of hospitalization), brain edema and meningitis appeared in MRI, and contrast-induced encephalopathy (CIE) was mainly considered, with the support of CSF results. After 18 days (day 21 of hospitalization), serum anti-neurexin-3α IgG was detected at a dilution of 1:10. Anti-neurexin-3α-associated encephalitis was diagnosed. The patient was fully recovered 7 months after taking immunoglobulin, steroids, mortimycophenate, and cyclophosphamide. Meanwhile, anti-neurexin-3α antibody IgG was negative in both CSF and serum. MRI was also normal. Although scarce evidence clarified the relationship between CIE and anti-neurexin-3α-associated encephalitis, we inferred that the BBB damaged by CIE may result in the anti-neurexin-3α antibody entrance into the CSF from serum, which led to autoimmune encephalitis (AIE).

Pearls & Oy-sters: Diagnosis and Subtyping of Listeria Ventriculitis in an Immunocompetent Host.

Listeria monocytogenes is a Gram-positive food-borne pathogen that causes gastrointestinal symptoms and CNS infection in susceptible hosts. Two lineages of Listeria cause the majority of neurolisteriosis in humans. In this report, we discuss a case of a 23-year-old previously healthy woman who presented with acute-onset rapidly progressive altered mental status after eating undercooked meats at a local restaurant. Given her age and lack of comorbidities, bacterial meningitis was suspected, and she was treated with ceftriaxone, vancomycin, and steroids. MRI of the brain was consistent with meningitis and ventriculitis; CSF analysis also suggested bacterial meningitis. Despite mechanical ventilation, pressors, and ventricular drain placement, she quickly decompensated and died 12 hours after arrival. CSF culture later returned positive for Listeria monocytogenes We used whole-genome sequencing and near-source comparison to identify the Listeria subtype that led to her unexpected presentation. The results suggest that her CSF isolate was consistent with a lineage II Listeria serotype, which is known to exhibit greater genetic variation than the more commonly isolated lineage I serotypes. We conclude the discussion with diagnostic and treatment approaches to neurolisteriosis. In susceptible hosts, namely immunocompromised, pregnant, neonatal, or elderly patients, Listeria infection may result in CNS invasion, causing meningoencephalitis and, rarely, ventriculitis and rhombencephalitis. Although neurolisteriosis most commonly affects individuals with known risk factors, CNS infection is nevertheless possible in otherwise healthy young patients. Suspicion should be raised in patients with an exposure history who do not improve with empiric antibiotics.

Alterations in Cortical-Subcortical Metabolism in Temporal Lobe Epilepsy With Impaired Awareness Seizures.

Objective: The features of cerebral metabolism associated with loss of consciousness in patients with temporal lobe epilepsy (TLE) have not been fully elucidated. We aim to investigate the alterations in cortical-subcortical metabolism in temporal lobe epilepsy with impaired awareness seizures (IAS). Methods: Regional cerebral metabolism was measured using fluorine-18-fluorodeoxyglucose positron emission tomography (18F-FDG PET) in patients with TLE-IAS and healthy controls. All patients had a comprehensive evaluation to confirm their seizure origin and lateralization. Videos of all seizures were viewed and rated by at least two epileptologists to identify the state of consciousness when a seizure occurred. By synthesizing the seizure history, semeiology, and video EEG of all patients, as long as the patients had one seizure with impaired awareness, she/he will be included. 76 patients with TLE-IAS and 60 age-matched healthy controls were enrolled in this study. Regional cerebral metabolic patterns were analyzed for TLE-IAS and healthy control groups using statistical parametric mapping. Besides, we compared the MRI-negative patients and MRI-positive patients with healthy controls, respectively. Results: There were no significant differences in the age and sex of TLE-IAS patients and healthy control. TLE-IAS patients showed extensive bilateral hypermetabolism in the frontoparietal regions, cingulate gyrus, corpus callosum, occipital lobes, basal ganglia, thalamus, brainstem, and cerebellum. The region of metabolic change was more extensive in right TLE-IAS than that of the left, including extensive hypometabolism in the ipsilateral temporal, frontal, parietal, and insular lobes. And contralateral temporal lobe, bilateral frontoparietal regions, occipital lobes, the anterior and posterior regions of the cingulate gyrus, bilateral thalamus, bilateral basal ganglia, brainstem, and bilateral cerebellum showed hypermetabolism. The TLE patients with impaired awareness seizure showed hypermetabolism in the cortical-subcortical network including the arousal system. Additionally, 48 MRI-positive and 28 MRI-negative TLE-IAS patients were included in our study. TLE-IAS patients with MRI-negative and MRI-positive were both showed hypermetabolism in the cingulate gyrus. Hypometabolism in the bilateral temporal lobe was showed in the TLE-IAS with MRI-positive. Conclusion: These findings suggested that the repetitive consciousness impairing ictal events may have an accumulative effect on brain metabolism, resulting in abnormal interictal cortical-subcortical metabolic disturbance in TLE patients with impaired awareness seizure. Understanding these metabolic mechanisms may guide future clinical treatments to prevent seizure-related awareness deficits and improve quality of life in people with TLE.

Acute cerebral atrophy in autoimmune encephalitis complicated by haemophagocytic lymphohistiocytosis.

Autoimmune encephalitis is a disease characterised by neural-specific antibodies. This case report presents a 20-year-old young man with a recent history of suspected viral encephalitis who presented with recurrent fevers and episodes of confusion. He was found to have anti-N-methyl-D-aspartate receptor (NMDAR) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid 1 receptor (AMPAR1) positive autoantibodies and was diagnosed with autoimmune encephalitis. He subsequently developed global cerebral atrophy and was found to meet diagnostic criteria for haemophagocytic lymphohistiocytosis (HLH). This patient's presentation was consistent with existing literature showing that autoimmune encephalitis may develop after an initial viral meningoencephalitis. However, concurrent anti-NMDAR and anti-AMPAR1 positive autoimmune encephalitis has not been reported in literature to date, and this case report represents one instance of its presentation. We speculate that multiple antibodies against neural surface antigens may increase the risk for systemic immune activation leading to HLH and acute cerebral atrophy.

A Tale of Immune-Related Adverse Events With Sequential Trials of Checkpoint Inhibitors in a Patient With Metastatic Renal Cell Carcinoma.

Immune checkpoint inhibitor (CPI) therapy is approved for the treatment of many cancers. As its use becomes more prevalent, sequential trials with different CPIs as monotherapy or combination therapy will become more common. It is thought that the increased cumulative dose of CPIs over multiple trials increases the risk of immune-related adverse events (irAEs). However, it is not known if using one CPI combination increases the risk of developing irAEs during the subsequent trial of a different CPI combination. Here, we present a patient with multiple episodes of high-grade irAEs over the course of sequential trials of combination CPIs. A 65-year-old female patient with metastatic renal cell cancer received two trials of combination CPIs. During the first trial with durvalumab and tremelimumab, she had CPI-induced grade 2 skin rashes and primary hypothyroidism with a mild elevation in lipase, normal antithyroid antibody profile, and normal blood glucose. Due to progression after the first trial, her regimen was changed to ipilimumab and nivolumab combination therapy. She subsequently presented to the emergency room with diabetic ketoacidosis on the sixth week following treatment initiation and was diagnosed with new-onset insulin-dependent type 1 diabetes mellitus (DM) with a negative antibody profile for DM. Immune CPIs cause irAEs by increasing immune activity against self-antigens. Sequential trials of CPIs may increase the risk of irAEs by increasing the cumulative CPI dose, or by organ injury inflicted by the first set of CPIs which is tipped "over the edge" by subsequent trials. We believe that the latter mechanism could be responsible for our case. Sequential CPI therapy should be planned carefully with increased surveillance for the early diagnosis and treatment of irAEs.

Childhood acute lymphoblastic leukaemia relapse with atypical localised presentation mimicking ankle trauma in a 28-year-old man.

Acute lymphoblastic leukaemia (ALL) is a common paediatric cancer with a tendency to relapse, usually within 3 years of remission. Most patients present with hepatomegaly, splenomegaly, pallor, fever and bruising. Localised muskuloskeletal presentation is extremely rare. Here, we present a case of leukaemia relapse in the bone marrow of a 28-year-old man 9 years after achieving remission, presenting only with ankle pain and normal routine labs besides mild hypercalcemia, and no signs of disease in common bone marrow biopsy sites. This highly localised presentation is unusual and would hopefully inform clinicians to have a high index of suspicion for relapse in an adult patient who has had childhood ALL.