Unusual Localization of AIDS-Related Kaposi's Sarcoma in a Heterosexual Male during the COVID-19 Pandemic: A Case Report.

Kaposi's sarcoma is an AIDS-defining illness and remains the most frequent tumor arising in HIV-infected patients with multifactorial etiology. We present a case of a 30-year-old Caucasian male with an 18-year history of HIV infection. The patient was presented with a one-week history of fever, non-productive cough, and skin lesions. There was an associated weakness and weight loss in a duration of 6 months. Clinical examination showed fever, generalized lymphadenopathy, lower limb edema, ascites, and violaceous cutaneous eruption comprising patches, plaques, and nodules. He also had a red nodule on the left conjunctiva, as well as on his oral mucosa. His CD4+ count was below 10/mm3 and ARN-HIV viral load was above 100,000 c/mL, in relation to the antiretroviral failure after five drug regimens. The role of co-infections in oncogenesis and the course of Kaposi's sarcoma were considered in recent studies. Delayed diagnosis of Kaposi's sarcoma in the present case resulted in a negative impact for this patient during the COVID-19 pandemic.

Cognitive Dysfunction in Hospitalized Patient with Moderate-to-Severe COVID-19: A 1-Year Prospective Observational Study.

Purpose: To screen the neurocognitive impairment persistent post-COVID-19. Patients and Methods: We assessed the neuropsychiatric disorders associated with COVID-19 in a prospective study, by "Mini-Mental State Examination" (MMSE) and Montreal Cognitive Assessment (MoCA) questionnaires, applied in the discharge to COVID-19 hospitalized patients for moderate and severe forms of disease. They were followed-up in 6 and 12 months. Results: The tests were performed in the baseline and were reevaluated after 6 and 12 months. Baseline cognitive dysfunction was found in 12.4% of patients, according to the MMSE test and in 19.7% by the MoCA scores. Overall cognitive dysfunction in COVID-19 was returned to normal after 6 months, although some tasks are more severe and persistently impaired, such as attention, concentration, short memory, and execution skills. The male gender and the degree of hypoxia, related to the severity of COVID-19 infection, were related to cognitive dysfunction in the study group. Conclusion: Cognitive domain impairments related to COVID-19 could persist over 6 months post-acute infectious episode requiring systematic screening for early diagnosis of progressive brain pathologies and rehabilitation.

Neurological and Dermatological Manifestations of Tuberous Sclerosis Complex: Report from a Romanian Tertiary Hospital Cohort.

Tuberous sclerosis complex is a rare multisystem genetic disorder characterized by multiorgan involvement, frequently associated with intellectual impairment and epilepsy. The aim of our study was to describe the neurological and dermatological manifestations of TSC in 32 adult patients (of whom 19 were females) who attended the Neurology and Nephrology Clinics of Fundeni Clinical Institute in Romania from 2015 to 2020. Seventeen patients were diagnosed with epilepsy, nine patients had intellectual impairment, and complete neuroimaging was available for twenty-two patients. As expected, the most frequent dermatological lesions were cutaneous angiofibromas in 20 patients, but with a lower frequency than described in the current literature. Statistical analysis was performed considering the small number of patients. Cortical tubers in neuroimaging seemed to be associated with the diagnosis of epilepsy, while subependymal nodules represented a risk factor for intellectual impairment. Males showed a larger number of dermatological types of lesions, especially café -au-lait patches. Interestingly, we found a statistically significant positive association between epilepsy and the presence of cutaneous angiofibromas, as well as total dermatological involvement. Females had significantly higher Charlson comorbidity index scores, indicating a higher burden of disease. Everolimus seemed to be a well-tolerated treatment and showed promising results in controlling epileptic seizures alone in two patients. More studies, with the inclusion of a larger number of patients, are needed to confirm these results.

Ulceration and a White Lesion of the Tongue in a Male HIV Positive Patient: A Journey on the Avenue of Differential Diagnoses in Search of a Solution.

Oral lesions are early indicator of immunosuppression, leading to HIV new diagnoses. The type of oral lesions can reveal opportunistic diseases that are correlated with the severity of immune depletion. Highly active antiretroviral therapy decreases the incidence of opportunistic oral infections, whereas a large variety of lesions are frequently experienced in people with HIV. Overlapping pathogenic mechanisms and multiple contributing etiologies are related to unusual, atypical oral lesions that are challenging in the clinical practice. We present a rare case of eosinophilic granuloma of the tongue in an older male HIV patient with severe immunosuppression due to the failure of antiretroviral treatment. Differential diagnoses considered squamous carcinoma, lymphoma, viral, fungal or bacterial infections and autoimmune disorders, as well as the influence of HIV immune disfunctions or the influence of cannabidiol use. The histopathologic and immunohistochemistry examination clarified the inflammatory reactive benign substrate of the lesion, although future survey of the oral lesions is essential.

Post-COVID-19 Spondylodiscitis: A Case Study and Review of the Literature.

COVID-19 is currently a major health problem, leading to respiratory, cardiovascular and neurological complications, with additional morbidity and mortality. Spinal infections are rare, representing around 1% of all bone infections and comprising less than 2 per 10,000 of all hospitalizations in tertiary care centers. Spondylodiscitis is a complex disease, with challenging diagnosis and management. We report the case of a 45-year-old man, non-smoker hospitalized for severe COVID-19 disease with respiratory failure. Post-COVID-19, in the 8th week after discharge, he was diagnosed by magnetic resonance imaging with spondylodiscitis, but etiology was not confirmed by microbiological investigations. Antibiotics were used, considering the identification of MRSA from cultures of pleural fluid and nasal swab, but surgical intervention was not provided. Clinic, biologic and imagistic were improved, but rehabilitation and long term follow up are necessary. We concluded that spondylodiscitis with spinal abscess is a rare but severe complication post-COVID-19 disease, due to dysbalanced immune response related to the respiratory viral infection, endothelial lesions, hypercoagulation and bacterial superinfection.

Progressive slowing of clonic phase predicts postictal generalized EEG suppression.

OBJECTIVE: Postictal generalized electroencephalography (EEG) suppression (PGES) is a surrogate marker of sudden unexpected death in epilepsy (SUDEP). It is still unclear which ictal phenomena lead to prolonged PGES and increased risk of SUDEP. Semiology features of generalized convulsive seizure (GCS type 1) have been reported as a predictor of prolonged PGES. Progressive slowing of clonic phase (PSCP) has been observed in GCSs, with gradually increasing inhibitory periods interrupting the tonic contractions. We hypothesized that PSCP is associated with prolonged PGES. METHODS: We analyzed 90 bilateral convulsive seizures in 50 consecutive patients (21 female; age: 11-62 years, median: 31 years) recruited to video-EEG monitoring. Five raters, blinded to all other data, independently assessed the presence of PSCP. PGES and seizure semiology were evaluated independently. We determined inter-rater agreement (IRA) for the presence of PSCP, and we evaluated its association, as well as that of other ictal features, with the occurrence of PGES, prolonged PGES (≥20 s) and very prolonged PGES (≥50 s) using multivariate logistic regression analysis. RESULTS: We found substantial IRA for the presence of PSCP (percent agreement: 80%; beyond-chance agreement coefficient: .655). PSCP was an independent predictor of the occurrence of PGES and prolonged PGES (p < .001). All seizures with very prolonged PGES had PSCP. GCS type 1 was an independent predictor of occurrence of PGES (p = .02) and prolonged PGES (p = .03) but not of very prolonged PGES. Only half of the seizures with very prolonged PGES were GCS type 1. SIGNIFICANCE: PSCP predicts prolonged PGES, emphasizing the importance of gradually increasing inhibitory phenomena at the end of the seizures. Our findings shed more light on the ictal phenomena leading to increased risk of SUDEP. These phenomena may provide basis for algorithms implemented into wearable devices for identifying GCS with increased risk of SUDEP.

A Real-Life Action toward the End of HIV Pandemic: Surveillance of Mother-to-Child HIV Transmission in a Center from Southeast Romania.

Preventing mother-to-child HIV transmission is a strategy to eliminate new infections to move toward a world free of HIV/AIDS. The aim of this study is to assess the effectiveness of the perinatal infection prevention program in a single center from southeast Romania. Newborns of HIV-positive mothers from 2005 to 2020 were followed-up until the age of two in a retrospective study. The transmission rate from HIV-positive mothers to living children was zero, but neonatal mortality, preterm birth and birth defects were still high. The peculiarity of our study is the high proportion of mothers with a nosocomial pattern of HIV transmission. Intensifying the efforts for accurate implementing the interventions for the prevention of mother-to-child HIV transmission, a long time follow-up for HIV-exposed uninfected children and new research on related HIV pregnancies are necessary to reach the objective of a new generation free of HIV.

Therapeutic challenges of psoriasis in the HIV-infected patient: A case report.

Psoriasis can be paradoxically associated with human immunodeficiency virus (HIV) infection, having a prevalence similar to the general population but with a more severe evolution. In the genetically predisposed patients with the CW*0602 haplotype, HIV infection can be a triggering factor and a first sign of infection, and lesions can spontaneously remit with immune reconstruction after antiretroviral therapy. Our patient is a 34 year-old male with recent HIV infection, in spite of being for over 10 years the partner of an HIV-positive patient with whom the patient has two HIV-positive children. The patient was diagnosed with psoriasis 7 years ago and was treated topically. The physical examination at HIV diagnosis was overall favorable, with skin findings compatible with disseminated vulgar psoriasis. Following antiretroviral treatment with Triumeq the patient had a favorable viral response, with complete viral suppression after 12 weeks, but the pre-existent psoriasis lesions worsened. Methotrexate (MTX) treatment followed for 12 weeks, with partial improvement of psoriatic dermatitis. This medication was continued for 1 year, but the lesions reappeared, possibly due to treatment resistance. MTX treatment for psoriasis in the HIV-infected patient was beneficial, but limited to one year, leaving biologics as possible treatment following therapy under strict monitoring for adverse effects, T-lymphocyte CD4+ and viral levels.

Diagnostic and Treatment Challenges of Emergent COVID-Associated-Mucormycosis: A Case Report and Review of the Literature.

Mucormycosis is a rare fungal infection, with high mortality, commonly associated with diabetes, malignancies, immunosuppressive therapy, and other immunodeficiency conditions. The emergence of mucormycosis cases has been advanced by the COVID-19 pandemic. Clinical presentation is variable, from asymptomatic to persistent fever or localized infections. We present a case of a Romanian old man, without diabetes or other immunodepression, with COVID-19 who developed severe rhino-orbital mucormycosis and bacterial superinfections, with Pseudomonas aeruginosa and Klebsiella pneumoniae. The late diagnostic and antifungal treatment was related to extensive lesions, bone and tissue loss, and required complex reconstruction procedures. We review the relationships between mucormycosis, COVID-19, and bacterial associated infections. The suspicion index of mucormycosis should be increased in medical practice. The diagnostic and treatment of COVID-19-Associated-Mucormycosis is currently challenging, calling for multidisciplinary collaboration.

AIDS Related Kaposi's Sarcoma: A 20-Year Experience in a Clinic from the South-East of Romania.

Kaposi's sarcoma (KS) was peculiarly described in the first notified cases of the acquired immunodeficiency syndrome as an opportunistic condition. However, the medical progress and the development of active antiretroviral therapy allowed the control of the HIV/AIDS epidemic, although the features of KS have changed throughout the past decades. The purpose of our study is to assess the epidemiological and clinical features of AIDS related KS in Romanian patients. A retrospective follow-up study was achieved in a single infectious diseases' clinic from Galati-Romania, between 2001 and 2021. Referring to 290 new HIV diagnosed cases from our clinic retained in care, the prevalence of KS was 3.4%. The main characteristics of patients with KS are a median age of 33, a predominance of males, prevalent severe systemic forms of diseases, frequent association of past or concomitant tuberculosis, and context of immune reconstruction syndrome. The mortality rate was 70%. KS has occurred in patients with delayed HIV diagnoses and inadequate adherence to therapy. Early recognition of both infections, the close monitoring of latent or symptomatic tuberculosis, improving the antiretroviral adherence and raising the access to oncologic procedures in Romanian HIV patients could improve their prognosis related to KS.

Epidemiologic and Clinic Characteristics of the First Wave of the COVID-19 Pandemic in Hospitalized Patients from Galați County.

The first cases of COVID-19 were reported in Wuhan Province, in China, in December 2019, spreading rapidly around the world. The World Health Organization (WHO) declared this pandemic at the beginning of March 2020 and, at the same time, the first patient in Galați County was confirmed. Both the global and the regional epidemiological evolutions have taken place with variations in incidence, which have been graphically recorded in several "waves". We conducted a retrospective study on cases of COVID-19 infection, hospitalized between March and June 2020 in an infectious diseases clinic from Galati, in the south-east of Romania. The present paper describes the "first-wave" regional epidemiological and clinical-biological features and the evolution of the COVID-19 pandemic. A poor outcome was related to late presentation to hospital, old age, and over six comorbid conditions including Alzheimer's disease. The high death rate among people from long-term care institutions is the consequence of the cumulative risk factors associated with immune senescence and inflammation, while COVID-19 is more likely a contributing factor to lower life expectancy.

Tuberous sclerosis with negative genetic testing and multiple cerebral cavernomas: A new association (Case report).

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder with multisystemic involvement usually resulting from mutations in the tuberous sclerosis 1 (TSC1) or TSC2 genes. However, 10 to 25% of patients do not exhibit these mutations. Cerebral cavernous malformations (CCMs) are capillary-venous malformations that can be asymptomatic or cause variable neurological manifestations, including seizures. Familial CCMs are recognized. In both conditions, specific dermatological lesions are associated. We present the case of a 31-year-old female with TSC diagnosed at the age of 18 years who presented with negative genetic testing. She was admitted to our department in 2019 for a sudden increased frequency of focal seizures. Patient examination revealed multiple facial and intraoral angiofibroma, diplopia, right hemihypoesthesia, brisk deep tendon reflexes, and distal leg paresthesia. VideoEEG indicated a frontal paramedian epileptogenic focus. Cerebral magnetic resonance imaging (MRI) and angioMRI identified multiple fronto-parietal cortical tubers, as well as multiple CCMs, with evidence of bleeding in one. Under antiepileptic drug (AED) and mTOR inhibitor treatment, the seizure frequency significantly improved in a short period of time. This is the first reported case of tuberous sclerosis with negative genetic testing associated with multiple cerebral cavernoma. Such complex patients require multidisciplinary management and detailed genetic testing for increasing knowledge on neuro-cutaneous disorders.

Cingulate cortex function and multi-modal connectivity mapped using intracranial stimulation.

The cingulate cortex is part of the limbic system. Its function and connectivity are organized in a rostro-caudal and ventral-dorsal manner which was addressed by various other studies using rather coarse cortical parcellations. In this study, we aim at describing its function and connectivity using invasive recordings from patients explored for focal drug-resistant epilepsy. We included patients that underwent stereo-electroencephalographic recordings using intracranial electrodes in the University Emergency Hospital Bucharest between 2012 and 2019. We reviewed all high frequency stimulations (50 â€‹Hz) performed for functional mapping of the cingulate cortex. We used two methods to characterize brain connectivity. Effective connectivity was inferred based on the analysis of cortico-cortical potentials (CCEPs) evoked by single pulse electrical stimulation (SPES) (15 â€‹s inter-pulse interval). Functional connectivity was estimated using the non-linear regression method applied to 60 â€‹s spontaneous electrical brain signal intervals. The effective (stimulation-evoked) and functional (non-evoked) connectivity analyses highlight brain networks in a different way. While non-evoked connectivity evidences areas having related activity, often in close proximity to each other, evoked connectivity highlights spatially extended networks. To highlight in a comprehensive way the cingulate cortex's network, we have performed a bi-modal connectivity analysis that combines the resting-state broadband h2 non-linear correlation with cortico-cortical evoked potentials. We co-registered the patient's anatomy with the fsaverage FreeSurfer template to perform the automatic labeling based on HCP-MMP parcellation. At a group level, connectivity was estimated by averaging responses over stimulated/recorded or recorded sites in each pair of parcels. Finally, for multiple regions that evoked a clinical response during high frequency stimulation, we combined the connectivity of individual pairs using maximum intensity projection. Connectivity was assessed by applying SPES on 2094 contact pairs and recording CCEPs on 3580 contacts out of 8582 contacts of 660 electrodes implanted in 47 patients. Clinical responses elicited by high frequency stimulations in 107 sites (pairs of contacts) located in the cingulate cortex were divided in 10 groups: affective, motor behavior, motor elementary, versive, speech, vestibular, autonomic, somatosensory, visual and changes in body perception. Anterior cingulate cortex was shown to be connected to the mesial temporal, orbitofrontal and prefrontal cortex. In the middle cingulate cortex, we located affective, motor behavior in the anterior region, and elementary motor and somatosensory in the posterior part. This region is connected to the prefrontal, premotor and primary motor network. Finally, the posterior cingulate was shown to be connected with the visual areas, mesial and lateral parietal and temporal cortex.

REM-sleep related hypermotor seizures: Video documentation and ictal source imaging.

INTRODUCTION: Rapid eye movement (REM) sleep has an inhibitory effect on epileptiform EEG discharges, and seizures occur extremely rarely in REM sleep. CASE STUDY: We present the case and video recordings of a 10-year-old boy, with sleep-related hypermotor seizures starting from REM sleep, identified from videoEEG recordings. The semiology comprised intense fear, tachycardia, tachypnea, followed by hypermotor manifestations. Further investigations included brain MRI and source localization of the EEG signals. Multiple antiepileptic drugs were tried, the patient obtaining a good control of the seizures in the last 2.5 years with eslicarbazepine. DISCUSSION AND CONCLUSION: The ictal EEG source imaging showed seizure onset in the anterior part of the right insula, with propagation to the orbitofrontal area, confirmed by the semiological sequence. Although rare, focal seizures can be triggered by REM sleep and our findings suggest that deficient maturation of brain areas involved in sleep modulation might induce insufficient desynchronization during REM sleep, thus allowing seizure emergence.

Sleep modulates effective connectivity: A study using intracranial stimulation and recording.

OBJECTIVE: Sleep is an active process with an important role in memory. Epilepsy patients often display a disturbed sleep architecture, with consequences on cognition. We aimed to investigate the effect of sleep on cortical networks' organization. METHODS: We analyzed cortico-cortical evoked responses elicited by single pulse electrical stimulation (SPES) using intracranial depth electrodes in 25 patients with drug-resistant focal epilepsy explored using stereo-EEG. We applied the SPES protocol during wakefulness and NREM - N2 sleep. We analyzed 31,710 significant responses elicited by 799 stimulations covering most brain structures, epileptogenic or non-epileptogenic. We analyzed effective connectivity between structures using a graph-theory approach. RESULTS: Sleep increases excitability in the brain, regardless of epileptogenicity. Local and distant connections are differently modulated by sleep, depending on the tissue epileptogenicity. In non-epileptogenic areas, frontal lobe connectivity is enhanced during sleep. There is increased connectivity between the hippocampus and temporal neocortex, while perisylvian structures are disconnected from the temporal lobe. In epileptogenic areas, we found a clear interhemispheric difference, with decreased connectivity in the right hemisphere during sleep. CONCLUSIONS: Sleep modulates brain excitability and reconfigures functional brain networks, depending on tissue epileptogenicity. SIGNIFICANCE: We found specific patterns of information flow during sleep in physiologic and pathologic structures, with possible implications for cognition.

The localizing value of epileptic auras: pitfalls in semiology and involved networks.

A more complete understanding of the epileptic aura represents an important challenge for localizing the epileptogenic zone and understanding brain networks. This review re-visits the localizing value of the epileptic aura, focusing on clinical pitfalls in epileptogenic zone detection and the importance of defining functional connectivity. We review the role of network node activation or alteration and its relationship to hub activation.

Illusory own body perceptions mapped in the cingulate cortex-An intracranial stimulation study.

Body awareness is the result of sensory integration in the posterior parietal cortex; however, other brain structures are part of this process. Our goal is to determine how the cingulate cortex is involved in the representation of our body. We retrospectively selected patients with drug-resistant epilepsy, explored by stereo-electroencephalography, that had the cingulate cortex sampled outside the epileptogenic zone. The clinical effects of high-frequency electrical stimulation were reviewed and only those sites that elicited changes related to body perception were included. Connectivity of the cingulate cortex and other cortical structures was assessed using the h2 coefficient, following a nonlinear regression analysis of the broadband EEG signal. Poststimulation changes in connectivity were compared between two sets of stimulations eliciting or not eliciting symptoms related to body awareness (interest and control groups). We included 17 stimulations from 12 patients that reported different types of body perception changes such as sensation of being pushed toward right/left/up, one limb becoming heavier/lighter, illusory sensation of movement, sensation of pressure, sensation of floating or detachment of one hemi-body. High-frequency stimulation in the cingulate cortex (1 anterior, 15 middle, 1 posterior part) elicits body perception changes, associated with a decreased connectivity of the dominant posterior insula and increased coupling between other structures, located particularly in the nondominant hemisphere.

Parkinsonian Syndrome and Toxoplasmic Encephalitis.

Toxoplasmosis encephalitis in patients with human immunodeficiency virus may progress rapidly with a potentially fatal outcome. Less common neurological symptoms associated with this are Parkinsonism, focal dystonia, rubral tremor and hemichorea-hemiballismus syndrome. A 58 year old woman suddenly lost consciousness and was admitted to the emergency service. Her medical history was unremarkable, except for frequent headaches in the last year, recurrent herpes simplex skin lesions and an episode of urticaria. A computer tomography scan showed supra and infra-tentorial lesions on suggestive of cerebral toxoplasmosis. Both Toxoplasma gondii and HIV tests were positive. In the intensive care unit, antiparasitic and antiretroviral drugs were administered, and she recovered from the coma after six weeks but presented with tetraparesis, diplopia, and depression. The LCD4 count increased from 7 to 128/mm3. The neurological lesions slowly resolved over the next two months, although postural instability, rigidity, bradykinesia and predominantly left side tremor persisted. Mild improvement was achieved after the administration of levodopa. Associated Parkinsonian syndrome in HIV patients is a rare condition, explained by the location of the brain and basal ganglia lesions, and by the observed effect of Toxoplasma gondii which increases dopamine metabolism in neural cells. Early HIV diagnostic and treatment are necessary to prevent neurological disability.