Pharmacovigilance study of amphotericin B for mucormycosis in post-COVID and non-COVID patients at a tertiary care hospital in Eastern India.

BACKGROUND: Mucormycosis is a rare but serious fungal infection which has dramatically increased in post-COVID patients. There is a paucity of safety data on amphotericin B (amphoB) used for mucormycosis treatment. OBJECTIVES: The objective of this prospective, observational, active safety surveillance study was to evaluate the safety profile of amphoB in a cohort of hospitalized patients who were on the drug for suspected mucormycosis. MATERIALS AND METHODS: All suspected adverse drug reactions (ADRs) in hospitalized mucormycosis patients who had received amphoB were analyzed. The nature, severity, outcome of the ADRs were recorded and analyzed. RESULTS: Of the 77 patients enrolled, 70% had documented history of prior COVID-19 infection. 96% had comorbidities, the most common being diabetes. Majority received conventional amphotericin B deoxycholate formulation. 97% experienced at least one suspected ADR and the median ADR/patient was 3. Out of 214 ADRs, 91 were serious but there were no ADR-related deaths. The most common ADRs were hypokalemia (31.78%), infusion-related reactions (22.43%), and anemia (17.29%). Thirty-three patients had serum potassium <2.5 mEq/L, while 11 had serum magnesium <1.25 mg/dL. Doubling of pretreatment creatinine level was noted in 15 patients. Seventy percent ADRs were of "possible" category as per the World Health Organization Uppsala Monitoring Centre categorization. CONCLUSION: AmphoB deoxycholate use in mucormycosis patients was associated with a high incidence of electrolyte abnormalities and infusion-related reactions. All ADRs subsided with medical management and none were fatal. The safety data generated from this study may be useful in resource-limited settings where the far more expensive liposomal formulation is not being used.

The cognitive basis of psychosocial impact in COVID-19 pandemic. Does it encircle the default mode network of the brain? A pragmatic proposal.

Epigenetics, hypothalamic-pituitary axes, environmental and metabolic influences, and transgenerational plasticity govern social behavior. Cognitive research considers the brain's default mode network (DMN) as a central hub that integrates various cognitive and social processing domains responsible for emotion perception, empathy, theory of mind, and morality. Hence, DMN is regarded as the "social brain." Upsurge in social turmoil, social anxiety, panic, depression, post-traumatic stress, hoarding, herd behavior, substance and behavioral addictions, sexual abuse, and violence in the time of the COVID-19 pandemic are intricately related to personality traits resulting in disruptive social cognition and social behavior, conceptualized as the result of unsettling and disruption of the functional nexus of the DMN. Considering overt and conspicuous display of neuroticism during the current pandemic, its impact upon modulation of the DMN functional nexus and the DMN itself, and the potential to presage cognitive impairment in the future, the authors caution that an increase in the global burden of dementia may be one of the long-term ramifications of COVID-19. Social behavior, a functional derivative of the DMN, can strikingly affect the functional nexus of DMN and the DMN itself, in a centripetal way via the phenomenon called "Experience-Dependent Plasticity," with long-term consequences. In this review, we intend to 1) decipher the association between social cognition and social behavior with the DMN, in time of COVID-19; and to 2) discuss the prospective aftermath of disrupted social behavior during the pandemic on modulation/alteration of functional connectomes of DMN or the DMN itself in the time ahead.

Impact of COVID-19 pandemic in natural course of Moyamoya Angiopathy: an experience from tertiary-care-center in India.

BACKGROUND: COVID-19 mediated immune dysregulation and cytokine storm can precipitate and aggravate Moyamoya angiopathy (MMA), influencing its disease course. This index study was undertaken to prospectively evaluate the status of neurological symptoms of MMA in relation to COVID-19 affection. METHODOLOGY AND RESULTS: Follow-up MMA patients of institute's Stroke-clinic were telephonically interview from 24th March to 30th September, 2020. The first call familiarized them with COVID-19 symptoms and neurological manifestations of MMA, followed by monthly-calls with predesigned questionnaire. Patients with suggestion of COVID-19 underwent nasopharyngeal-swab-testing for COVID-19 Reverse transcription-polymerase chain reaction (RT-PCR) positive cases were subjected to antibody levels for COVID-19 Enzyme-linked immunoassay (ELISA) 8-12 weeks after recovery. During symptomatic phase till 14 days of asymptomatic, they were contacted daily/alternate day. Any new onset/worsening of neurological symptoms were noted. The baseline clinico-radiological details were obtained from stroke-clinic registery. Subsequently, all data were analyzed and compared using descriptive statistics. Seventy four of 104 MMA patients could be contacted and enrolled. The mean age, time since last follow-up and compliance to previously prescribed medication were 23.5 ± 16.1 years, 9.2 ± 1.7 months and 90.5% (n = 67), respectively. Aggravation/new onset neurological symptom were seen in 64.3% (n = 9) of COVID-19 positive MMA (n = 14), of which 8 were seen among the 11 pediatric COVID-19 positive MMA [(Transient ischemic attacks) TIA-4, TIA with headache-1, seizure-2, stroke causing mortality-1]. CONCLUSION: COVID-19 infection can potentiate MMA causing significant morbidity and mortality, especially in children. Providing optimal care for severe diseases (such as MMA) in developing countries during pandemic remains a challenge.

COVID-19 Pandemic, Personality and Geriatric Population: Proposed Pragmatism.

The elderly population is a sensitive and delicate cohort of society who is being compelled to bear the significant smoulders of disruptive social behavior of humankind amidst the COVID-19 pandemic. Our aim for this review was (1) to find out the root of disruption of societal integrity and self-centeredness by analyzing the spokes of HEXACO; (2) to delineate their possible relationships with the formation of Neuroticism and eventually Psychopathy, which have endangered human civilization the most in this pandemic; and (3) to search for the potential ways to get rid of these dark times. The constellation of different negative human behaviors probably originate from the negative deflection of components of the HEXACO model of personality towards the genesis of the dark triad. COVID-19 pandemic and upsurge of the dark triad in the form of Neuroticism, Narcissism and Machiavellianism potentially portend major mental health threats. Cultivation and practice of positive emotions and triumph of honesty, humility and humanity are imperative to save the mankind from the savagery of this pandemic.

MRI-negative myeloradiculoneuropathy following Covid-19 infection: An index case.

Covid-19 associated several neurological manifestation in the form of Post-infectious transverse myelitis(TM) and para-infectious TM has been reported. A 54 years old female patient presented to us with acute retention of urine and upper motor neuron type of bilateral lower limb weakness in shock stage, after 12 days of covid-19 infection. MRI (3T) brain and spine showed no abnormality and Nerve conduction study showed acquired motor axonal polyradiculoneuropathy in bilateral lower limbs. We herein present an index case of MRI-negative myeloradiculoneuropathy following covid-19 infection.

COVID-19 associated rhino-orbital-cerebral mucormycosis: An observational study from Eastern India, with special emphasis on neurological spectrum.

AIMS: 1: Describe the epidemiology and determine risk factors for COVID-19 associated mucormycosis. 2: Elaborate the clinical spectrum of Rhino-Orbital-Cerebral Mucormycosis (ROCM), pattern of neuroaxis involvement and it's radiological correlates. METHODS: Observational study. Consecutive, confirmed cases of mucormycosis (N = 55) were included. A case of mucormycosis was defined as one who had clinical and radiological features consistent with mucormycosis along with demonstration of the fungus in tissue via KOH mount/culture/histopathological examination (HPE). Data pertaining to epidemiology, risk factors, clinico-radiological features were analysed using percentage of total cases. RESULTS: Middle aged, diabetic males with recent COVID-19 infection were most affected. New onset upper jaw toothache was a striking observation in several cases. Among neurological manifestations headache, proptosis, vision loss, extraocular movement restriction; cavernous sinus, meningeal and parenchymal involvement were common. Stroke in ROCM followed a definitive pattern with watershed infarction. CONCLUSIONS: New onset upper jaw toothache and loosening of teeth should prompt an immediate search for mucormycosis in backdrop of diabetic patients with recent COVID-19 disease, aiding earlier diagnosis and treatment initiation. Neuroaxis involvement was characterized by a multitude of features pertaining to involvement of optic nerve, extraocular muscles, meninges, brain parenchyma and internal carotid artery.

Treatment related fluctuation and response to intravenous immunoglobulin therapy in post COVID-19 Guillain-Barre syndrome.

Treatment related fluctuation (TRF) poses a special challenge in the treatment of Guillain-Barre syndrome (GBS). Many cases of GBS following COVID-19 infection have been reported in literature till date, but treatment related fluctuation (TRF) in post COVID-19 GBS has not been reported till date. We report a 35-year-old male patient who developed GBS following COVID-19 infection and had TRF after intravenous immunoglobulin (IV-IG) therapy. He required ventilator support but repeat IV-IG therapy led to complete recovery. Significant proximal muscle involvement, cranial nerve palsy, no antecedent diarrhea and absence of anti-GM1 antibodies are important predictors of TRF in GBS and need to be recognized early in the course of this illness. Early recognition of TRF and differentiating it from other forms of immune mediated neuropathy such as acute onset chronic inflammatory demyelinating polyradiculoneuropathy (A-CIDP) are important for prognostication and management.

Cerebral venous thrombosis in COVID-19.

BACKGROUND AND AIMS: Initially, novel severe acute respiratory syndrome coronavirus (SARS-CoV-2) was considered primarily a respiratory pathogen. However, with time it has behaved as a virus with the potential to cause multi-system involvement, including neurological manifestations. Cerebral venous sinus thrombosis (CVT) has increasingly been reported in association with coronavirus infectious disease of 2019 (COVID-19). Here, we have shed light upon CVT and its possible mechanisms in the backdrop of the ongoing COVID-19 pandemic. METHODS: In this review, data were collected from PubMed, EMBASE and Web of Science, until March 30, 2021, using pre-specified searching strategies. The search strategy consisted of a variation of keywords of relevant medical subject headings and keywords, including "COVID-19", "SARS-CoV-2", "coronavirus", and "cerebral venous sinus thrombosis". RESULTS: COVID-19 has a causal association with a plethora of neurological, neuropsychiatric and psychological effects. CVT has gained particular importance in this regard. The known hypercoagulable state in SARS-CoV-2 infection is thought to be the main mechanism in COVID-19 related CVT. Other plausible mechanisms may include vascular endothelial dysfunction and altered flow dynamics. CONCLUSIONS: Although there are no specific clinical characteristics, insidious or acute onset headache, seizures, stroke-like, or encephalopathy symptoms in a patient with, or who has suffered COVID-19, should prompt the attending physician to investigate for CVT. The treatment of COVID-19 associated CVT does not differ radically from the therapy of CVT without the infection, i.e. urgent initiation of parenteral unfractionated heparin or low molecular weight heparin followed by conventional or mostly newer oral anticoagulants.

Complex movement disorders in SARS-CoV-2 infection induced acute disseminated encephalomyelitis.

Movement disorders are extremely rare in acute disseminated encephalomyelitis (ADEM) and in the novel severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection. We herein report a 34-years-old previously healthy woman who presented with a febrile illness and a constellation of movement disorders (predominantly myoclonus) followed by encephalopathy. After exclusion of common infectious, autoimmune and paraneoplastic etiologies, she was diagnosed to have COVID-19 induced ADEM, which responded to intravenous methylprednisolone and intravenous immunoglobulin. Our case adds to the tally of cases of post-SARS-CoV-2 infection related movement disorders and to the exceedingly rare list of cases in which movement disorders preceded ADEM.

De Novo Movement Disorders and COVID-19: Exploring the Interface.

Background: Neurological manifestations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are being widely documented. However, movement disorders in the setting of 2019 coronavirus infectious disease (COVID-19) have been a strikingly less discussed topic. Objectives: To summarize available pieces of evidence documenting de novo movement disorders in COVID-19. Methods: We used the existing PRISMA consensus statement. Data were collected from PubMed, EMBASE, Web of Science, and Scopus databases up to the 29th January, 2021, using pre-specified searching strategies. Results: Twenty-two articles were selected for the qualitative synthesis. Among these, a total of 52 patients with de novo movement disorders were reported. Most of these had myoclonus, ataxia, tremor or a combination of these, while three had parkinsonism and one a functional disorder. In general, they were managed successfully by intravenous immunoglobulin or steroids. Some cases, primarily with myoclonus, could be ascribed to medication exposures, metabolic disturbances or severe hypoxia, meanwhile others to a post-or para-infectious immune-mediated mechanism. SARS-CoV-2 could also invade the central nervous system, through vascular or retrograde axonal pathways, and cause movement disorders by two primary mechanisms. Firstly, through the downregulation of angiotensin-converting enzyme 2 receptors, resulting in the imbalance of dopamine and norepinephrine; and secondly, the virus could cause cellular vacuolation, demyelination and gliosis, leading to encephalitis and associated movement disorders. Conclusion: De novo movement disorders are scantly reported in COVID-19. The links between SARS-CoV-2 and movement disorders are not yet established. However, we should closely monitor COVID-19 survivors for the possibility of post-COVID movement disorders.

SARS-CoV-2-Associated Acute Hemorrhagic, Necrotizing Encephalitis (AHNE) Presenting with Cognitive Impairment in a 44-Year-Old Woman without Comorbidities: A Case Report.

BACKGROUND Acute hemorrhagic necrotizing encephalitis (AHNE) is a rare manifestation of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. AHNE usually involves the subcortical white matter but not the cortical grey matter. This study describes the disruptive effects of AHNE associated with SARS-CoV-2 on cognitive function in a previously healthy and sound middle-aged woman resulting from alterations in cortical areas involved in the cognitive network. CASE REPORT A 44-year-old previously healthy woman with a history of inter-state travel developed a flu-like illness, followed by acute, steadily progressive cognitive impairment. She was admitted in a comatose state after a first tonic-clonic seizure. Blood tests were non-informative. Cerebral magnetic resonance imaging (MRI) was indicative of AHNE. Cerebrospinal fluid analysis showed mild lymphocytosis with normal protein and normal glucose but an elevated IgG index. After testing positive for SARS-CoV-2, she was administered steroids. Treatment was ineffective, and the patient died. CONCLUSIONS SARS-CoV-2 is a potential central nervous system (CNS) pathogen, which may manifest as AHNE. These patients may present with generalized tonic-clonic seizures and frontal dysexecutive syndrome, with cognitive impairment being the presenting feature of neuro-coronavirus disease-2019 (COVID-19). The patient described in this report is unique for acute-onset and isolated cognitive impairments due to SARS-CoV-2 infection in the absence of clinical or radiological respiratory manifestations. These findings may help in the early detection and diagnosis of neuro-COVID-19, especially among clinicians and neurologists working in areas of endemic SARS-CoV-2 infection.