Cerebral microbleeds and Fazekas scale in brain magnetic resonance imaging after critical COVID-19: A prospective cohort study

Background: We aimed to report long-term brain magnetic resonance imaging (MRI) findings in survivors of ICU-treated COVID-19 compared to other groups. Material(s) and Method(s): In this prospective cohort study 70 ICU-treated, 46 ward-treated and 46 home-isolated patients, diagnosed with COVID-19 in 2020, underwent brain MRI 6 months after the acute phase to determine the presence of cerebral microbleeds (CMB) and Fazekas scale. Result(s): CMBs existed in 27 (38.6%) ICU-treated, 13 (28.3%) ward-treated, 8 (17.4%) home-isolated COVID-19 patients, and in 12 (22.6%) non-COVID controls (Figure 1). The number of CMBs in COVID-19 patients and controls was median 2 (IQR 1-4) and 1 (IQR 1-2), respectively. Patients with CMBs differed from those without, regarding age (median 62 vs. 52 years, p < 0.001), history of arterial hypertension (50% vs. 31%, p = 0.03), need of ICU (56% vs. 38%, p = 0.03) and ventilator treatment (42% vs. 22%, p = 0.01), length of hospital stay (median 21 vs. 12 days, p < 0.001), and supplementary oxygen therapy (median 18 vs. 10 days, p = 0.008), respectively. Within the ICU group, patients with and without CMBs differed regarding the duration of ICU stay (median 17 vs. 9 days, p = 0.006), and mechanical ventilation (median 14 vs. 6 days, p = 0.002). In multivariable analysis, only age was associated with CMBs (OR 1.06, 95% CI 1.02-1.09). The majority of subjects in all groups had Fazekas scale one for white matter hyperintensities (Figure 1). Conclusion(s): Although the severity of respiratory failure and history of arterial hypertension were associated with the presence of CMBs, only age was an independent predictor of CMBs.

Depression in patients with cerebral microangiopathy.

Cerebral microangiopathy (CMA) is one of the significant causes of depression in the elderly. Close associations of the risk of developing depression with white matter hyperintensity, the presence of lacunar infarcts, and other markers of vascular disease are shown. The available data suggest that various vascular mechanisms, in particular, involvement of small vessels of the brain, generalized microvascular and endothelial dysfunction, metabolic risk factors, - are risk factors for the development of depression. Pathogenetic mechanisms include cerebral hypoperfusion and immune dysregulation. Depression is also a common complication of coronavirus infection, occurring both in the acute and post-COVID periods. The same mechanisms as in vascular depression are involved in the pathogenesis of the development of post-COVID depressive disorders. Given the complexity of the mechanisms of development of depressive disorders in patients with CMA, the presence of severe comorbid vascular pathology, antidepressants with an optimal ratio of efficacy and safety should be preferred. Agomelatine (Valdoxan) is one of such drugs.Copyright © 2023 Ima-Press Publishing House. All rights reserved.

Cerebral blood flow in patients recovered from mild COVID-19.

BACKGROUND AND PURPOSE: Cerebral hypoperfusion has been described in both severe and mild forms of symptomatic Coronavirus Disease 2019 (COVID-19) infection. The purpose of this study was to investigate global and regional cerebral blood flow (CBF) in asymptomatic COVID-19 patients. METHODS: Cases with mild COVID-19 infection and age-, sex-, and race-matched healthy controls were drawn from the Aging Brain Consortium at The University of South Carolina data repository. Demographics, risk factors, and data from the Montreal Cognitive Assessment were collected. Mean CBF values for gray matter (GM), white matter (WM), and the whole brain were calculated by averaging CBF values of standard space-normalized CBF image values falling within GM and WM masks. Whole brain region of interest-based analyses were used to create standardized CBF maps and explore differences between groups. RESULTS: Twenty-eight cases with prior mild COVID-19 infection were compared with 28 controls. Whole-brain CBF (46.7 ± 5.6 vs. 49.3 ± 3.7, p = .05) and WM CBF (29.3 ± 2.6 vs. 31.0 ± 1.6, p = .03) were noted to be significantly lower in COVID-19 cases as compared to controls. Predictive models based on these data predicted COVID-19 group membership with a high degree of accuracy (85.2%, p < .001), suggesting CBF patterns are an imaging marker of mild COVID-19 infection. CONCLUSION: In this study, lower WM CBF, as well as widespread regional CBF changes identified using quantitative MRI, was found in mild COVID-19 patients. Further studies are needed to determine the reliability of this newly identified COVID-19 brain imaging marker and determine what drives these CBF changes.

Cognitive, Motor, & Negative Valence Systems in Neurologic Pasc: A Preliminary Study

Background: Nervous system post-acute sequelae of COVID-19 (NS-PASC) include cognitive and mental health symptoms. To further define these, we applied a Research Domain Criteria (RDoC) approach to examine motor, positive valence (PV) and negative valence (NV) systems, and social processing data in The COVID Mind Study of NS-PASC. Method(s): NS-PASC participants (>3 months after COVID-19) referred from a NeuroCOVID Clinic and non-COVID controls from New Haven, CT and Baltimore, MD completed an RDoC test battery for cognition (language, declarative and working memory, cognitive control, perception), motor, PV, NV, and social processes. To date, 3T MRI with diffusion tensor imaging was performed in 11 NS-PASC to assess white matter integrity (global white matter fractional anisotropy [FA]) as a contributor to alterations identified on the RDoC tests. Analysis of Covariance examined group differences after adjusting for sex, race, ethnicity, age, and years of education. Result(s): 25 NS-PASC participants (age 43.4+/-11.3 yrs, 76% female, 402 days after COVID-19 symptom onset) and 29 controls (age 46.2.6+/-13.1 yrs, 66% female) completed the battery. Controls were more racially diverse and less educated than NS-PASC (43% vs. 12% Black, p=0.005;14.5 vs. 16.1 yrs of education, p< 0.05). Means and statistics for RDoC between NS-PASC and controls are shown in Table. NS-PASC performed worse in language, verbal working and declarative memory, and perception and reported greater cognitive control difficulties (e.g., behavioral inhibition, set shifting) without issues on performance-based metrics (Stroop, Trail Making Test-Part B), and had slower motor function. NS-PASC reported more NV issues including greater symptoms of depression, rumination in response to depressive mood, apathy, childhood trauma, anxiety, and perceived stress. There were no differences in PV and social processing. In a subset of NS-PASC participants who underwent MRI, there was a dynamic range of FA values with a mean of 0.509 (IQR 0.481 - 0.536). Conclusion(s): Our findings extend previous PASC studies characterizing cognitive and mental health alterations, indicating that additional RDoC assessments warrant focus, including alterations in motor and the negative valence system. In future analyses, we will examine white matter integrity as a pathophysiologic contributor to these RDoC systems.

Multiple Cerebral Infarcts Triggered by Sars-Cov-2 Virus in an Asymptomatic Cadasil Patient: Case Report

During the coronavirus pandemic, increasing evidence has confirmed that the SARS-CoV-2 virus is susceptible to increased risk of stroke. On the other hand, the relationship between the SARS-CoV-2 virus and CADASIL was among the topics discussed in the literature with a small number of cases. In this case report, we present multiple cerebral infarcts in an asymptomatic CADASIL patient and we aim to shed light on the complex nature of cerebrovascular manifestations of the SARS-CoV-2 virus. A 50-year-old man with an unremarkable past medical history was admitted to our department with fever and neurologic manifestations on the 6th day of self-isolation due to positive reverse-transcriptase-polymerasechain-reaction assay in a nasopharyngeal sample for SARS-CoV-2. Neurological deficits were related to the acute vascular lesions located in the border-zone areas of both hemispheres, corpus callosum, and cerebellar peduncles on brain MRI. Lesions in chronic nature in the bilateral subcortical white matter predominantly involving the external capsule and temporal poles were also challenging. As a result of a comprehensive study that could explain the neurological status and imaging findings, the CADASIL diagnosis is reached by genetic testing for NOTCH-3. The experience, in this case, suggests considering patients with suspicious MRI findings for CADASIL diagnosis during the coronavirus pandemic. Further studies are needed to explain the underlying pathophysiological mechanisms related to cerebrovascular manifestations of SARS-CoV-2.Copyright © 2022 by Turkish Cerebrovascular Diseases Society.

Post-Covid Cognitive Impairment Mri Brain Scan Abnormalities: A Potential Biomarker

Background: Post-acute sequelae of SARS-COV-2 infection (PASC) is associated with cognitive impairment (CI) with unclear pathogenesis though blood brain barrier (BBB) impairment and excitotoxic injury appear significant. Post-acute sequelae of SARS-COV-2 infection (PASC) is associated with cognitive impairment (CI) with unclear pathogenesis though blood brain barrier (BBB) impairment and excitotoxic injury appear significant. We hypothesized that PASC CI patients would have brain inflammation and BBB disruption using advanced MR imaging. Method(s): In this prospective longitudinal study, 14 patients with PASC CI (mild and non-hospitalised) were enrolled (mean age of 45;10 F and 4 M) and 10 sex and age matched healthy controls. 13 had a follow up MR at 9-12 months (mean 10 months). All participants underwent DCE perfusion (an index of BBB integrity with Ktrans as the measurement), Diffusion Tensor Imaging (DTI) and single voxel MR spectroscopy (MRS) of the frontal cortex/white matter and the brainstem in addition to brain anatomical MRI. Between group analyses were used to determine which MRI outcomes were significantly different from controls in patients with PASC CI. Result(s): The PASCI CI group showed significantly increased (ie BBB impairment) Ktrans, and increased region (Frontal white matter and Brain Stem)-specific areas in the brain (p=< 0.005), reduction in NAA (ie neuronal injury) and mild reduction of Glx (ie excitotoxicity) in the frontal white matter and brain stem (p=0.004), and reduction in white matter integrity (increased diffusivity -greater radial and mean diffusivity). Increased Ktrans was correlated with increased both radial and mean diffusivity (r=0.9) in all tested brain regions. Ktrans significantly improved in the follow up MR (p= 002596 Z=-2.794872) with no difference between subjects and controls indicating BBB normalisation (p= 0.442418, z= -0.144841). White matter integrity also improved especially in the fractional anisotropy values in the executive networks (p=< 0.00045). MRS showed significant improvement in the NAA in the frontal white matter but Glx remain high as compared to the controls (p=0.0006). Conclusion(s): PASC CI was characterised by reversible diffuse BBB impairment, neuronal/axonal and excitotoxic injury. BBB impairment was associated with white matter disruption. These are suggestive biomarkers for the presence, severity and prognosis of PASC CI. Such biomarkers could underpin appropriate trial design and timing of intervention.

Reduced tissue creatine levels in patients with long COVID-19: A cross-sectional study.

Total creatine concentration in the skeletal muscle and brain of long COVID patients were significantly lower when compared to the reference values for the general population, as measured with proton magnetic resonance spectroscopy at 1.5-T in vastus medialis muscle, thalamus, and three bilateral cerebral locations across the white and gray matter.

Feasibility of diffusion-tensor and correlated diffusion imaging for studying white-matter microstructural abnormalities: Application in COVID-19.

There has been growing attention on the effect of COVID-19 on white-matter microstructure, especially among those that self-isolated after being infected. There is also immense scientific interest and potential clinical utility to evaluate the sensitivity of single-shell diffusion magnetic resonance imaging (MRI) methods for detecting such effects. In this work, the performances of three single-shell-compatible diffusion MRI modeling methods are compared for detecting the effect of COVID-19, including diffusion-tensor imaging, diffusion-tensor decomposition of orthogonal moments and correlated diffusion imaging. Imaging was performed on self-isolated patients at the study initiation and 3-month follow-up, along with age- and sex-matched controls. We demonstrate through simulations and experimental data that correlated diffusion imaging is associated with far greater sensitivity, being the only one of the three single-shell methods to demonstrate COVID-19-related brain effects. Results suggest less restricted diffusion in the frontal lobe in COVID-19 patients, but also more restricted diffusion in the cerebellar white matter, in agreement with several existing studies highlighting the vulnerability of the cerebellum to COVID-19 infection. These results, taken together with the simulation results, suggest that a significant proportion of COVID-19 related white-matter microstructural pathology manifests as a change in tissue diffusivity. Interestingly, different b-values also confer different sensitivities to the effects. No significant difference was observed in patients at the 3-month follow-up, likely due to the limited size of the follow-up cohort. To summarize, correlated diffusion imaging is shown to be a viable single-shell diffusion analysis approach that allows us to uncover opposing patterns of diffusion changes in the frontal and cerebellar regions of COVID-19 patients, suggesting the two regions react differently to viral infection.

Multimodal neuroimaging in post-COVID syndrome and correlation with cognition.

Brain changes have been reported in the first weeks after SARS-CoV-2 infection. However, limited literature exists about brain alterations in post-COVID syndrome, a condition increasingly associated with cognitive impairment. The present study aimed to evaluate brain functional and structural alterations in patients with post-COVID syndrome, and assess whether these brain alterations were related to cognitive dysfunction. Eighty-six patients with post-COVID syndrome and 36 healthy controls were recruited and underwent neuroimaging acquisition and a comprehensive neuropsychological assessment. Cognitive and neuroimaging examinations were performed 11 months after the first symptoms of SARS-CoV-2. Whole-brain functional connectivity analysis was performed. Voxel-based morphometry was performed to evaluate grey matter volume, and diffusion tensor imaging was carried out to analyse white matter alterations. Correlations between cognition and brain changes were conducted and Bonferroni corrected. Post-COVID syndrome patients presented with functional connectivity changes, characterized by hypoconnectivity between left and right parahippocampal areas, and between bilateral orbitofrontal and cerebellar areas compared to controls. These alterations were accompanied by reduced grey matter volume in cortical, limbic and cerebellar areas, and alterations in white matter axial and mean diffusivity. Grey matter volume loss showed significant associations with cognitive dysfunction. These cognitive and brain alterations were more pronounced in hospitalized patients compared to non-hospitalized patients. No associations with vaccination status were found. The present study shows persistent structural and functional brain abnormalities 11 months after the acute infection. These changes are associated with cognitive dysfunction and contribute to a better understanding of the pathophysiology of the post-COVID syndrome.

An Astra-Nomical Headache

Introduction We present a case of myelin-oligodendrocyte glycoprotein antibody disease (MOGAD) requiring long-term immunosuppression triggered by a dose of the AstraZeneca COVID-19 vaccination. Relapsing MOGAD is thus far an unknown complication of COVID-19 vaccination. Case Description: A 58-year-old lady developed headache, nausea, dizziness, facial numbness, ataxia and slurred speech 8 days after the COVID-19 AstraZeneca vaccination. Her imaging showed acute disseminated encephalomyelitis (ADEM) with a white matter lesion in the left cerebellum and bilateral smaller lesions. Her cerebrospinal fluid showed 38 white cells and elevated protein. She initially responded well to steroids, however relapsed with optic neuritis 7 months later, requiring long-term immunosuppres- sion with mycophenolate mofetil. Discussion Although there have been some case reports of MOGAD following COVID-19 infection, to our knowledge this is only the second reported case of MOGAD following vaccination against COVID-19, and the first such case to require long-term immunosuppression. The other reported case also occurred following the COVID-19 AstraZeneca vaccine, and also presented with ADEM. This is in contrast to reported cases of MOGAD following COVID-19 infection, where adults mostly presented with optic neuritis. We wanted to highlight the possibility of this vaccine-related neurological complication occurring, particularly in the context of potentially frequent ongoing COVID-19 booster vaccinations.

Novel Framework for Neurocognitive Covid-19 Assessment

Background The neurotrophic effects of Covid-19 are becoming increasingly recognized, with altered mental state now being the second most common presenting complaint insert numbers. A key question is whether this has long term consequences. Cognitive problems are commonly reported in patients 3 months after acute infection as part of the so called Long-Covid syndrome. However, the underlying cause is not well understood. Candidate explanations include legacy from encephalitis and stroke;however, other complications such as the sequelae, delirium, remain underexplored. Furthermore, little consideration has been given to functional cognitive disorders and the cognitive consequences of depression, anxiety and fatigue. Aims We propose a structured approach to clinical assessment for clinicians reviewing late cognitive complaints after COVID 19. Methods We created our own unique framework for neurocognitive Covid assessment based upon a review of the literature. Results Covid status- Any positive test. If not review of core symptoms such as breathlessness, headache, anosmia, nasal obstruction, cough, myalgia, or gustatory dysfunction;duration, extent of exposure to Covid confirmed cases. Consider rapid antibody testing. Neuropsychiatric history- Part 1 symptoms at onset- in particular disruptions of consciousness and altered mental state. Acute memory impairment, anterograde/retrograde and with/ without a temporal gradient. neurocognitive function. ITU admission and oxygen requirements. Part 2 Current cognitive and mental state- in addition to standard history seek evidence of internal inconsistency of memory symptoms and attentional dysregulation. Has social cognition and meta-cognition been affected. Note attribution bias i.e. no Im not depressed, I cant enjoy anything because of my symptoms Background history- subtle suggestion of neurodegeneration and depression, anxiety and functional symptoms should be explored. MRI findings- signal changes in the medial temporal lobe, nonconfluent multifocal white matter hyperintense lesions, and isolated white matter microhemorrhages. Novel biomarkers IL-6, MCP-1, and IP-10. Conclusion Cognitive symptoms are common after confirmed and assumed COVID exposure. We propose a framework for neuropsychiatric assessment and the use of adjuvant imaging and potential biomarkers.

Covid-19-associated diffuse posthypoxic leukoencephalopathy and microhemorrhages - A case report

Background: Delayed post-hypoxic leukoencephalopathy (DPHL) with associated microbleeds is a clinical entity presenting with cognitive impairment days or weeks after an episode of acute hypoxic brain injury. Case report: We describe a 68-year-old male with SARS-CoV2 infection who had cardiac arrest, required sedation and mechanical ventilation for 17 days, and after sedation was discontinued, he became unresponsive. Brain MRI showed diffuse confluent hyperintense signals in the subcortical white matter and multiple subcortical white matter microhemorrhages. EEG revealed diffuse attenuation of brain electrical activity with isolated polymorphic delta waves in the frontal region without epileptiform activity. Conclusion(s): Clinicians need to be aware that patients with Covid-19 can develop delayed post-hypoxic leukoencephalopathy.Copyright © 2022 The Authors

Multifactorial White Matter Damage in the Acute Phase and Pre-Existing Conditions May Drive Cognitive Dysfunction after SARS-CoV-2 Infection: Neuropathology-Based Evidence.

BACKGROUND: There is an urgent need to better understand the mechanisms underlying acute and long-term neurological symptoms after COVID-19. Neuropathological studies can contribute to a better understanding of some of these mechanisms. METHODS: We conducted a detailed postmortem neuropathological analysis of 32 patients who died due to COVID-19 during 2020 and 2021 in Austria. RESULTS: All cases showed diffuse white matter damage with a diffuse microglial activation of a variable severity, including one case of hemorrhagic leukoencephalopathy. Some cases revealed mild inflammatory changes, including olfactory neuritis (25%), nodular brainstem encephalitis (31%), and cranial nerve neuritis (6%), which were similar to those observed in non-COVID-19 severely ill patients. One previously immunosuppressed patient developed acute herpes simplex encephalitis. Acute vascular pathologies (acute infarcts 22%, vascular thrombosis 12%, diffuse hypoxic-ischemic brain damage 40%) and pre-existing small vessel diseases (34%) were frequent findings. Moreover, silent neurodegenerative pathologies in elderly persons were common (AD neuropathologic changes 32%, age-related neuronal and glial tau pathologies 22%, Lewy bodies 9%, argyrophilic grain disease 12.5%, TDP43 pathology 6%). CONCLUSIONS: Our results support some previous neuropathological findings of apparently multifactorial and most likely indirect brain damage in the context of SARS-CoV-2 infection rather than virus-specific damage, and they are in line with the recent experimental data on SARS-CoV-2-related diffuse white matter damage, microglial activation, and cytokine release.

Using DTI tractography to guide tDCS interventions in a complex acquired brain Injury neurorehabilitation protocol - a case report

51-year-old man (C.P.) had a diffuse-axonal-injury after falling from a 5-meter height, followed by a 22-minute anoxia due to a cardiac arrest. In the ICU, he tested positive to COVID-19, and needed intubation. After coronavirus infection, C.P. presented Guillain-Barre syndrome. 2months after discharge, he was admitted to rehabilitation. DTI tractography for evaluation of the structural integrity of white matter tracts revealed: i) Lesions in the basal ganglia;ii) Sequelary lesions in the right frontal, cortical, subcortical, temporal, parieto-occipital and cerebellar hemispheres;iii) Asymmetry of the corticospinal tracts - less fibers on the left;iv) Poor definition of the fibers of the right arcuate fasciculus;v)Asymmetrical thinning of the cortico-ponto-cerebellar tracts, worse on the left, and more discreetly in the spinocerebellar tracts. Based on this, C.P. underwent 4 different 30-session tDCS protocols consisting of twice-daily 20min 2mA sessions (10min interval), 5days/week (120sessions total), combined with physiotherapy, cognitive, swallowing and speech therapy. Montages: Pr1 (anode: Cz - 5x10cm;cathode: 10th Thoracic Vertebra - 5x7cm);Pr2 (1 - anode:C3;cathode:Fp2 / 2 - anode: Cerebellum;cathode:Fp2);Pr3 (anode:F3;cathode:Fp2) and Pr4 (anode:Cp5;cathode:Fp2). Except for Pr1, electrode size for all protocols were 5x7cm. We used the Coma Recovery Scale (CRS-R) and Rancho Los Amigos Scale (RLAS) for clinical assessments at the baseline and after every 10 sessions until the end of the intervention. At the baseline, C.P. presented a minimal responsive state of consciousness (CRS-R: 3;RLAS: Level 1) and tolerated well the tDCS interventions. CRS-R scores gradually improved in various domains during the treatment. At the end, RLAS score was level 5 and CRS-R, 19. Our preliminary results suggest DTI tractography may be a potential biomarker to guide more personalized tDCS interventions for complex cases of patients with acquired brain injuries. A second DTI tractography will be made in the future for comparison purposes. Research Category and Technology and Methods Clinical Research: 9. Transcranial Direct Current Stimulation (tDCS) Keywords: Acquired Brain Injury, Traumatic Brain Injury, COVID-19, Guillain Barre SyndromeCopyright © 2023

Transverse myelitis as a first event of multiple sclerosis precipitated by Pfizer-BioNTech COVID-19 vaccination

Background: Neurological complications from COVID-19 vaccines are rare Case Report: Herein, we present the case of a previously healthy woman who developed incomplete transverse myelitis (TM) immediately after receiving her first injection of the Pfizer-BioNTech COVID-19 vaccine. Conclusion(s): This case is an example of TM as a first clinical event in the diagnosis of multiple sclerosis triggered by COVID-19 vaccination. A review of the FDA's Vaccine Adverse Event Reporting System (VAERS) reveals similar instances of TM. Clinicians should be aware of this potential complication from COVID-19 vaccination.Copyright © 2022 The Authors

Progressive multifocal leukoencephalopathy, neuroradiology-neuropathology

Introduction: Progressive multifocal leukoencepha-lopathy (PmL) is an unfavorable demyelinating disease of the CNS caused by reactivation of JC virus (JCV). JCV is a double-stranded DNA human polyomavirus predominatingly acquired in childhood. Blood samples taken from healthy persons indicate that 50-90% of adults have been exposed to this virus. JCV is an opportunistic pathogen, with PmL manifesting primarily in patients with immunodefciency or taking immunomodulatory treatments or with lymphoproliferative diseases. We report a patient who developed PmL shortly after diagnosis of follicular lymphomma. Case presentation: A 70-year-old-woman admitted to the neurological departament with hemiparesis, psy-chomotor slowing down, balance problems, dizziness and in depressed mood. the patient underwent aorto-femoral transplant 12 years ago and for 10 years was under constant observation of a hematologist due to enlarged lymph nodes. Five years ago, the patient had planoepithelial cell carcinoma removed. the patient also sufered from COViD-19 infection and sufered from depression. elevated leukocytosis and D dimers, were the only abnormal results obtained in laboratory tests. However, pulmonary embolism was excluded in Ct angio. Cytometry of blood showed follicular lymphoma. Radiological fndings: mRi and Ct scans showed multiple asymmetrical pathological areas of hyperin-tense signal in t2-dependent images, hypointense in t1-dependent ones and Ct-hypodense regions which extended continuously in control examinations. they were located in the white matter of multiple lobes of both brain hemispheres subcortically and periventric-ullary. the subcortical U-fbers were involed. they did not show contrast enhancement and mass efect. they showed peripheral ring and patchy difusion restriction particularly at their leading edge. in spite of the used steroid therapy the patient's health deteriorated rapidly. the patient died of symptoms of cardio-respiratory failure 1 month after admission to hospital. Neuropathological features: the neuropathological examination revealed numerous foci of demyelination in the white matter of the frontal lobe, the parietal lobe in the pons and in the cerebellum. myelin losses were accompanied by damage to oligodendrocytes and proliferation of macrophages. the nuclei of the damaged oligodendrocytes were enlarged and hyperchromatic, and some had a "ground-glass" appearance typical of viral infection. the astrocytes were bizarre with lobulat-ed, hiperchromatic or hypochromatic nuclei and damage of cytoplasmic procesesses (clasmatodendrosis). Conclusion(s): the triad of neuropathological injuries: destruction of oligodendrocytes with intranuclear viral inclusions ("ground-glass" appearance), multifocal demyelination and bizarre astrocytes allowed for the diagnosis of late form of classical progressive multifo-cal leukoencephalopathy (cPmL), despite the short time since diagnosis of follicular lymphoma, but with many years of enlargement of the lymph nodes.

Possible autoimmune pediatric encephalitis following COVID-19 infection with focal cerebral dysfunction in a young female: A case report

Introduction: Post-COVID-19 autoimmune encephalitis is a rare manifestation following COVID-19. Most cases have not demonstrated solid evidence regarding their pathogenesis. Some believe it to be an immune process. Case presentation: In this case report, we present a case of a young female who presented to our emergency department with visual, auditory, and olfactory hallucinations after successfully treating COVID-19 two weeks prior to this visit. On examination, her vital signs were stable, but she was agitated, distressed, and hallucinating. Neurological examinations were normal. Laboratory investigations, including autoimmune profiles, were all negative. Magnetic resonance imaging of the brain showed non-specific changes in the bilateral frontal area. Electroencephalography (EEG) showed lateralized rhythmic delta activity (LRDA) arising more from the right occipital lobes. Autoimmune psychosis was suspected due to psychosis, abnormal imaging, and abnormal EEG findings. She was given corticosteroids and antipsychotic medication. Her symptoms improved within ten days. On follow-up, she remained well without any return of psychosis. Conclusion(s): Possible autoimmune pediatric encephalitis following COVID-19 is a rare entity that has scarcely been reported. The majority of the cases were reported to have been related to stress following the infection. To establish the correct diagnosis, an extensive workup, including an autoimmune profile, lumbar puncture, magnetic resonance imaging, and electroencephalography, is recommended.Copyright © 2022 The Author(s)

Immunotherapy-responsive recurrent extensive white matter disease without neuronal or glial surface antibodies: A case report

Background: Acute disseminated encephalomyelitis (ADEM) is classically considered as a monophasic immune-mediated demyelinating disorder. A relapse can occur in children but extremely rare in adults. Case-report: A 57-year-old man presented with fulminant ADEM-like episode without proceeding viral illness. Neurological deficits rapidly developed associated with extensive demyelinating brain lesions with vasogenic edema. After the initiation of aggressive immunotherapy, his symptoms resolved, but he relapsed twice during 26-month observation period;one was a mild episode characterized by rapidly evolving MRI lesions without development of symptoms, and the other was a fulminant ADEM-like episode similar to the first one. The second fulminant episode occurred only 2 days after getting a flu shot despite no clinical or radiological relapse when he received COVID-19 vaccinations. The patient's symptoms and extensive brain MRI lesions improved after the initiation of aggressive immunotherapy at the early stage. No autoantibodies against neuronal surface (such as GABA A receptor) or glial surface antigens (aquaporin 4, or myelin oligodendrocyte glycoprotein) were identified in either serum or CSF. Conclusion(s): Extensive white matter lesions can occur without neuronal or glial surface antibodies, recurrent fulminant ADEM-like episode can develop even in an adult patient, and flu shot may provoke fulminant ADEM-like episode.Copyright © 2022