Alzheimer's Disease: Treatment Today and Tomorrow.

Background and Aims: The scope of treatment in Alzheimer's Disease has widened in recent times with FDA approval of new drugs. This review looks at established treatments in AD as well as critically analyses the newer drugs available. Methods: Data in this review was gathered from PubMed; Google Scholar and MEDLINE from January-March 2023. Search words used were 'Alzheimer's Disease treatment' and 'Dementia treatment'. Results: Older time tested drugs like Acetyl Choline Receptor Inhibitors and NMDA Receptor antagonists remain the mainstay of pharmacological treatment in AD. Despite a lot of excitement about newer FDA approved drugs; we have to be cautious in their use. Aducanumab showed good reduction in CSF amyloid levels (biomarker of AD); but this did not necessarily translate into better clinical outcomes of patients. Conclusion: Despite the recent advances and approval of drugs in treatment of AD, we have to exhibit caution while prescribing these drugs. Even with a sound mechanism of action, these drugs do not always show improvement in clinical outcomes. More clinical trials are required for development of drugs in treatment of AD which explore various different mechanisms of action.

Rhino-Orbito-Cerebral Mycosis and COVID-19: From Bad to Worse?

Background: There has been an increase an alarming rise in invasive mycoses during COVID-19 pandemic, especially during the second wave. Aims: Compare the incidence of invasive mycoses in the last three years and study the risk factors, manifestations and outcomes of mycoses in the COVID era. Methodology: Multicentric study was conducted across 21 centres in a state of western India over 12-months. The clinico-radiological, laboratory and microbiological features, treatment and outcomes of patients were studied. We also analysed yearly incidence of rhino-orbito-cerebral mycosis. Results: There was more than five-times rise in the incidence of invasive mycoses compared to previous two-years. Of the 122 patients analysed, mucor, aspergillus and dual infection were seen in 86.9%, 4.1%, and 7.4% respectively. Fifty-nine percent had simultaneous mycosis and COVID-19 while rest had sequential infection. Common presenting features were headache (91%), facial pain (78.7%), diplopia (66.4%) and vison loss (56.6%). Rhino-orbito-sinusitis was present in 96.7%, meningitis in 6.6%, intracranial mass lesions in 15.6% and strokes in 14.8%. A total of 91.8% patients were diabetic, while 90.2% were treated with steroids during COVID-19 treatment. Mortality was 34.4%. Conclusion: Invasive fungal infections having high mortality and morbidity have increased burden on already overburdened healthcare system. Past illnesses, COVID-19 itself and its treatment and environmental factors seem responsible for the rise of fungal infection. Awareness and preventive strategies are the need of hours and larger studies are needed for better understanding of this deadly disease.

Neurological Manifestations in COVID-19 in Three Waves of the Pandemic: An Inpatient Study from India.

Background: Though severe acute respiratory syndrome coronavirus 2 (SARS CoV 2) virus primarily affects respiratory system, neurological involvement is well known. Aims: To describe the neurological manifestations of coronavirus disease 2019 (COVID-19) during three waves of the pandemic. Methodology: This was an ambispective observational single-centre study to describe the neurological manifestations of COVID-19 infection among inpatients from a tertiary care referral centre in Western India from March 2020 to January 2022. Results: Out of 14,822 patients admitted with COVID-19, 307 (2.07%) had neurological manifestations. Neurological manifestations were seen in 1.87% in first wave (onset to 10 Feb 21); 2.37% in second wave (Feb 11, 2021 to Dec 31, 2021) and 6.26% in third wave (Jan 1, 2022 to Jan 31, 2022). The most common neurological manifestations were encephalopathy (34.5%), ischemic stroke (32.1%), and acute symptomatic seizures (8.8%). Encephalopathy (p = 0.028) was more common in first wave while seizures were more common in third wave (p = 0.001). In patients with encephalopathy, hypoxia (p = 0.0001), shock (p = 0.001), renal involvement (p = 0.002), and sepsis (p = 0.033) were associated with higher mortality; while those with no systemic involvement had better survival (p = 0.0001). Among patients with ischemic stroke, 32.1% did not have any traditional vascular risk factors. These patients were 9 years younger and required 6 days less hospitalization than patients of stroke with vascular risk factors. Conclusion: SARS-CoV-2 produces many central and peripheral nervous system manifestations. Encephalopathy was more common in first wave while acute symptomatic seizures were more common in third wave. Encephalopathy was most common neurological manifestation with progressively higher mortality with increased number of systemic comorbidities. Ischemic stroke was seen in patients who had vascular risk factors as well as in patients without them.

Cerebrovascular Involvement in Mucormycosis in COVID-19 Pandemic.

BACKGROUND: Many countries have seen an unprecedented rise of cases of coronavirus disease 2019 (COVID-19) associated mucormycosis (CAM). Cerebrovascular involvement in CAM has not been studied so far. We describe clinico-radiological manifestations of cerebrovascular complications observed in CAM. METHODS: In this multicentric retrospective observational study from India, patients with CAM who developed cerebrovascular involvement were studied. Their demographics, risk factors, clinical manifestations, imaging, laboratory profile and outcomes were noted. RESULTS: Out of 49 subjects with cerebrovascular involvement, 71.4% were males while average age was 52.9 years. Ischemic stroke was commonest (91.8%) followed by intracranial haemorrhage (6.1%) and subarachnoid haemorrhage (2%). The incidence of cerebrovascular complications in CAM was found to be 11.8% in one center. Cerebrovascular symptoms appeared a median of 8.3 days from the onset of mucormycosis. Commonest presentation of mucormycosis was rhino-orbito-cerebral syndrome in 98%. Diabetes mellitus was present in 81.7%. Forty percent developed stroke despite being on antiplatelet agent and/or heparin. Amongst subjects with ischemic strokes, location of stroke was unilateral anterior circulation (62.2%); bilateral anterior circulation (17.8%); posterior circulation (11.1%) and combined anterior and posterior circulation (8.9%). Vascular imaging revealed intracranial occlusion in 62.1%; extracranial occlusion in 3.4% and normal vessels in 34.5%. Mortality was 51% during hospital stay. CONCLUSIONS: Cerebrovascular involvement was seen in 11.8% patients of CAM. Angio-invasive nature of the fungus, prothrombotic state created by COVID-19, and diabetes were important causative factors. Subjects with CAM should be screened for involvement of the brain as well as its vessel. Antiplatelet agents/heparin did not seem to provide complete protection from this type of stroke.

Neurological Manifestations of Dengue Fever.

BACKGROUND: Dengue is a common endemic infection in India. Neurological complications involving various parts of the neuro-axis have been reported. We report neurological complications amongst dengue patients admitted to a tertiary hospital in Western India. MATERIALS AND METHODS: Patients admitted in a tertiary hospital in Western India with dengue infection and having neurological symptoms were included in this study. Their history, physical examination, laboratory investigations and imaging studies were obtained from the inpatient records and analysed. RESULTS: Between January 2014 to December 2019, a total of 5821 patients were diagnosed with dengue. Of these, 154 (2.64%) had neurological manifestations. Encephalopathy in a setting of multisystem involvement was seen in 31.2% patients, encephalitis with focal features, abnormal imaging and/or abnormal cerebrospinal fluid (CSF) examination was seen in 15.6%, syncope in 27.3% and acute symptomatic seizure in 11.0%. Less common presentations were intracranial haemorrhage (4.5%), Guillain-Barre syndrome (GBS) (3.2%), optic neuritis (1.9%), myositis (1.3%), hypokalemic paralysis (1.3%), ischemic stroke (0.6%), posterior reversible encephalopathy syndrome (PRES) (0.6%), myoclonus (0.6%) and brachial plexopathy (0.6%). CONCLUSIONS: In this study of patients admitted with dengue, neurological complications due to dengue were seen in 2.64%. Encephalopathy, encephalitis and syncope were the commonest manifestations, followed by acute symptomatic seizures, intracranial haemorrhage and GBS. The entire neuroaxis can be involved in dengue infection. To the best of our knowledge, this is the largest reported study of neurological complications of dengue.

Isoniazid and rifampicin concentrations in children with tuberculosis with either a daily or intermittent regimen: implications for the revised RNTCP 2012 doses in India.

Suboptimal plasma drug concentrations in antitubercular therapy (ATT) may lead to delayed treatment response and the emergence of acquired drug resistance. This study aimed (i) to determine and compare plasma concentrations of isoniazid (INH) and rifampicin (RIF) in children treated for tuberculosis receiving a daily or intermittent ATT regimen and (ii) to study the effect of INH and RIF exposure on clinical outcome at the end of therapy (EOT). A total of 41 children aged 2-16 years initiated on either a daily or three-times weekly (intermittent) ATT regimen were recruited into the study. Towards the end of the intensive phase, blood specimens were collected pre-dose and at 0.5, 1, 1.5, 2, 2.5, 4 and 6 h post-dose. Concentrations of INH and RIF were analysed using validated liquid chromatography-tandem mass spectrometry and high-performance liquid chromatography assays, respectively. The maximum plasma concentration (Cmax), the area under the concentration-time curve from 0-6 h (AUC0-6h) and treatment outcome were determined. Ninety-two percent of patients had an INH Cmax > 3 µg/mL. Seventy-seven percent of patients had a RIF Cmax < 8 µg/mL and 28% of patients had a RIF AUC0-24h < 13 mg ⋅ h/L. INH and RIF exposure did not differ between daily and intermittent ATT regimens on the day of administration. All children had a favourable outcome at EOT. Since 77% of children had low RIF exposure, we recommend routine use of therapeutic drug monitoring to prevent relapse and to support implementation of the revised RNTCP 2012 doses.