A Case of Multiple Sclerosis Presenting as Eight and Half Syndrome.

Multiple sclerosis (MS) is a chronic disease characterized by inflammation, demyelination, gliosis (scarring), and neuronal loss; the course can be relapsing-remitting or progressive. Manifestations of MS vary from a benign illness to a rapidly evolving and incapacitating disease requiring profound lifestyle adjustments. We report a 24 year old female who presented with right internuclear ophthalmoplegia with right lower motor neuron facial nerve palsy which is called eight and half syndrome. The etiology in our patient was multiple sclerosis which was confirmed by radio-imaging studies. Patient improved on pulse therapy of methyl prednisolone and tapering dose of steroids

Hirayama Disease - A Variant of Motor Neuron Disease and Role of Flexion MRI in Diagnosis

Hirayama disease is a monomyelic variant of motor neuron disease (MND) and has distinctive features of male predominance, asymmetric involvement of upper extremities with a self limiting course. Flexion MRI (magnetic resonance imaging) forms the main stay for diagnosis of this condition. Here we report such an unusual case of Hirayama disease in a male patient of 20 years who presented with weakness and atrophy in right upper limb. Careful clinical examination will help to use the flexion MRI studies for the diagnosis of this condition as done in our case

Minimal clinically important difference of the EORTC QLQ-CIPN20 for worsening peripheral neuropathy in patients receiving neurotoxic chemotherapy.

Context/objectivesThis is the first study to determine the minimal clinically important difference (MCID) of the European Organisation of Research and Treatment of Cancer Quality of Life Questionnaire-CIPN twenty-item scale (EORTC QLQ-CIPN20), a validated instrument designed to elicit cancer patients' experience of symptoms and functional limitations related to chemotherapy-induced peripheral neuropathy.MethodsCancer patients receiving neurotoxic chemotherapy completed EORTC QLQ-CIPN20 and the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity [FACT/GOG-NTX] at baseline, second cycle of chemotherapy (T2, n = 287), and 12 months after chemotherapy (T3, n = 191). Anchor-based approach used the validated FACT/GOG-NTX neurotoxicity (Ntx) subscale to identify optimal MCID cutoff for deterioration. Distribution-based approach used one-third standard deviation (SD), half SD, and one standard error of measurement of the total EORTC QLQ-CIPN20 score.ResultsThere was a moderate correlation between the change scores of the Ntx subscale and sensory and motor subscales of QLQ-CIPN20 (T2: r = - 0.722, p < 0.001 and r = - 0.518, p < 0.001, respectively; T3: r = - 0.699; p < 0.001 and r = - 0.523, p < 0.001, respectively). The correlation between the change scores of the Ntx subscale and the QLQ-CIPN20 autonomic subscale was poor (T2: r = - 0.354, p < 0.001; T3: r = 0.286, p < 0.001). Based on the MCID derived using distribution-based method, the MCID for the QLQ-CIPN20 sensory subscale was 2.5-5.9 (6.9% to 16.4% of the subdomain score) and for motor subscale was 2.6-5.0 (8.1%-15.6% of the subdomain score).ConclusionThe MCID for the EORTC QLQ-CIPN20 established using distribution-based approaches was 2.5-5.9 for the sensory subscale and 2.6-5.0 for the motor subscale. When noted in assessments even with small change in scores, clinicians can be alerted for appropriate intervention

SARS-CoV-2 B.1.617.2 Delta variant replication and immune evasion

The B.1.617.2 (Delta) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first identified in the state of Maharashtra in late 2020 and spread throughout India, outcompeting pre-existing lineages including B.1.617.1 (Kappa) and B.1.1.7 (Alpha)1. In vitro, B.1.617.2 is sixfold less sensitive to serum neutralizing antibodies from recovered individuals, and eightfold less sensitive to vaccine-elicited antibodies, compared with wild-type Wuhan-1 bearing D614G. Serum neutralizing titres against B.1.617.2 were lower in ChAdOx1 vaccinees than in BNT162b2 vaccinees. B.1.617.2 spike pseudotyped viruses exhibited compromised sensitivity to monoclonal antibodies to the receptor-binding domain and the amino-terminal domain. B.1.617.2 demonstrated higher replication efficiency than B.1.1.7 in both airway organoid and human airway epithelial systems, associated with B.1.617.2 spike being in a predominantly cleaved state compared with B.1.1.7 spike. The B.1.617.2 spike protein was able to mediate highly efficient syncytium formation that was less sensitive to inhibition by neutralizing antibody, compared with that of wild-type spike. We also observed that B.1.617.2 had higher replication and spike-mediated entry than B.1.617.1, potentially explaining the B.1.617.2 dominance. In an analysis of more than 130 SARS-CoV-2-infected health care workers across three centres in India during a period of mixed lineage circulation, we observed reduced ChAdOx1 vaccine effectiveness against B.1.617.2 relative to non-B.1.617.2, with the caveat of possible residual confounding. Compromised vaccine efficacy against the highly fit and immune-evasive B.1.617.2 Delta variant warrants continued infection control measures in the post-vaccination era

Population-level risks of alcohol consumption by amount, geography, age, sex, and year: a systematic analysis for the Global Burden of Disease Study 2020

Background The health risks associated with moderate alcohol consumption continue to be debated. Small amounts of alcohol might lower the risk of some health outcomes but increase the risk of others, suggesting that the overall risk depends, in part, on background disease rates, which vary by region, age, sex, and year. Methods For this analysis, we constructed burden-weighted dose–response relative risk curves across 22 health outcomes to estimate the theoretical minimum risk exposure level (TMREL) and non-drinker equivalence (NDE), the consumption level at which the health risk is equivalent to that of a non-drinker, using disease rates from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2020 for 21 regions, including 204 countries and territories, by 5-year age group, sex, and year for individuals aged 15–95 years and older from 1990 to 2020. Based on the NDE, we quantified the population consuming harmful amounts of alcohol. Findings The burden-weighted relative risk curves for alcohol use varied by region and age. Among individuals aged 15–39 years in 2020, the TMREL varied between 0 (95% uncertainty interval 0–0) and 0·603 (0·400–1·00) standard drinks per day, and the NDE varied between 0·002 (0–0) and 1·75 (0·698–4·30) standard drinks per day. Among individuals aged 40 years and older, the burden-weighted relative risk curve was J-shaped for all regions, with a 2020 TMREL that ranged from 0·114 (0–0·403) to 1·87 (0·500–3·30) standard drinks per day and an NDE that ranged between 0·193 (0–0·900) and 6·94 (3·40–8·30) standard drinks per day. Among individuals consuming harmful amounts of alcohol in 2020, 59·1% (54·3–65·4) were aged 15–39 years and 76·9% (73·0–81·3) were male. Interpretation There is strong evidence to support recommendations on alcohol consumption varying by age and location. Stronger interventions, particularly those tailored towards younger individuals, are needed to reduce the substantial global health loss attributable to alcohol. Funding Bill & Melinda Gates Foundation

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Are we mis-estimating chemotherapy-induced peripheral neuropathy? Analysis of assessment methodologies from a prospective, multinational, longitudinal cohort study of patients receiving neurotoxic chemotherapy.

BackgroundThere are inconsistencies in the literature regarding the prevalence and assessment of chemotherapy-induced peripheral neuropathy (CIPN). This study explored CIPN natural history and its characteristics in patients receiving taxane- and platinum-based chemotherapy.Patients and methodsMulti-country multisite prospective longitudinal observational study. Patients were assessed before commencing and three weekly during chemotherapy for up to six cycles, and at 6,9, and 12 months using clinician-based scales (NCI-CTCAE; WHO-CIPN criterion), objective assessments (cotton wool test;10 g monofilament); patient-reported outcome measures (FACT/GOG-Ntx; EORTC-CIPN20), and Nerve Conduction Studies.ResultsIn total, 343 patients were recruited in the cohort, providing 2399 observations. There was wide variation in CIPN prevalence rates using different assessments (14.2-53.4%). Prevalence of sensory neuropathy (and associated symptom profile) was also different in each type of chemotherapy, with paclitaxel (up to 63%) and oxaliplatin (up to 71.4%) showing the highest CIPN rates in most assessments and a more complex symptom profile. Peak prevalence was around the 6-month assessment (up to 71.4%). Motor neurotoxicity was common, particularly in the docetaxel subgroup (up to 22.1%; detected by NCI-CTCAE). There were relatively moderately-to-low correlations between scales (rs = 0.15,p < 0.05-rs = 0.48 p < 0.001), suggesting that they measure different neurotoxicity aspects from each other. Cumulative chemotherapy dose was not associated with onset and course of CIPN.ConclusionThe historical variation reported in CIPN incidence and prevalence is possibly confounded by disagreement between assessment modalities. Clinical practice should consider assessment of motor neuropathy for neurotoxic chemotherapy. Current scales may not be all appropriate to measure CIPN in a valid way, and a combination of scales are needed