UCSF: Advances in Internal Medicine 2020: Whats New in Neurology? - PowerPoint PPT Presentation

UCSF: Advances in Internal Medicine 2020: “What’s New in Neurology?” Megan Richie, MD Assistant Professor of Neurology

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2019 Advances in Internal Medicine: Updates in Neurology Select Take-homes: Multiple Sclerosis  Expanding armamentarium for Relapsing-Remitting multiple sclerosis: B-cell therapies  New approved therapies exist for: - Primary progressive multiple sclerosis - Secondary progressive multiple sclerosis  Use (or escalate to) highly effective therapy early in disease to reduce progression to SPMS  Stem cell transplant: emerging, but not ready for prime time

2019 Advances in Internal Medicine: Updates in Neurology Select Take-homes: Epilepsy  The list of first-line AEDs is shorter than you think - Before 2004: Carbamazepine, Phenytoin, Valproic acid, Phenobarbital, Primidone, Ethosuxamide (absence seizures) - 2004: Oxcarbazepine, Topiramate - 2018: Lamotrigine - Levetiracetam, Zonisamide and Gabapentin are only “possibly effective”  Epilepsy surgery is effective in children and adults and should be considered in refractory epilepsy - Traditional definition: Therapeutic failure of 3 antiseizure drugs - Current definition: Therapeutic failure of 2 antiseizure drugs OR seizures uncontrolled at 12 months - Encourage epilepsy center evaluation

2019 Advances in Internal Medicine: Updates in Neurology Select Take-homes: Potpourri  No need for “Levodopa sparing” in Parkinson’s disease  Indications for deep brain stimulation slowly expanding  Increasing evidence for benefit of aerobic exercise in cognitive functioning  Prolonged antibiotics of no benefit in cognitive symptoms after Lyme disease  Gabapentinoids have few FDA-approved indications, significant side effects, and are not a panacea alternative to opioids

2020 Updates In Neurology: Outline  Cognitive Decline  Multiple sclerosis - Microvascular disease - Vitamin D - Hypertension - Smoking - Agitation - DMTs and malignancy - Pediatric  Potpourri  Epilepsy and EEG - Fibromyalgia - Dementia - Headache - SUDEP - Suicide - Delirium - Guillain Barre Syndrome - Checkpoint inhibitors - Telehealth

Cognitive Decline and White Matter Lesions  Inclusion criteria - Age 35 – 69 years without cardiovascular disease  Outcomes - MRI brain scans - INTERHEART risk score - Cognitive assessments (Digit Symbol Substitution Test, Montreal Cognitive Assessment)  Results - 7547 adults age 35 – 69 years - High INTERHEART risk score correlated with brain lesions (10.4% high-risk, 3.7% low-risk) - Increasing age, INTERHEART risk score, brain lesions on MRI, > 2 brain infarctions, lack of post-secondary education each associated with reduced cognitive function  Incidental brain lesions accounted for 10% of low cognitive test scores

Cognitive Decline and White Matter Lesions  Methods - 3 Prospective longitudinal cohort studies  Outcomes MRI brain scans at baseline  Small vessel disease (SVD) score - - Cognitive tests at follow up - Progression to dementia  Results - In 1842 participants, SVD score improved prediction of dementia compared to clinical risk factors alone (AUC 0.85)  Performance better in patients with more severe SVD  Prediction slightly stronger with vascular dementia but was unchanged with addition of other vascular risk factors to the model

Hypertension & Microvascular ischemic disease  Inclusion criteria - Hypertensive, age 50+ without diabetes or stroke  Randomized intervention - Goal SBP < 120 - Goal SBP < 140  Results - 670 participants, of whom 449 had follow-up MRI scans - Goal SBP < 120: Less of an increase in white matter microvascular disease burden on MRI after median of 3.97 years of follow up (0.53 cm 3 difference)

Hypertension & Cognitive decline  Method - Cross-sectional pooled cohort study - 20,000 patients from 5 major US cardiovascular risk studies, all without previous stroke or dementia  Outcomes - Mean SBP - Change in global cognition, memory and executive function  Results - Cumulative mean SBP for Black patients was 4mm higher - Cumulative SBP associated with cognitive decline in both groups  Black patients with earlier onset of cognitive loss (2.4 – 4 years sooner) with steeper decline  Cognitive differences no longer statistically significant after adjusting for mean SBP

Hypertension & Cognitive decline  Method - Meta-analysis of observational studies (1980-2019) containing > 2000 participants and at least 5 years’ of data  Outcomes - Blood pressure, use of antihypertensive medications, dementia events, mortality  Results - 6 prospective community-based studies, total N = 31,090 dementia-free adults > 55 yrs - 3728 incident cases of dementia, including 1741 Alzheimer’s disease - Those with HTN (15,537) treated with any antihypertensive medication had reduced risk of developing dementia (HR 0.88) and Alzheimer’s (HR 0.84) than those not on meds - Patients with normal BP had no association with dementia & use of antihypertensives

Aggression & Agitation in Dementia  Method - Systematic review of RCTs comparing interventions for treating aggression and agitation in adults with dementia  Results - 163 studies (N = 23,143 patients) - Multidisciplinary care (SMD -0.5), massage and touch therapy (SMD -0.75) both more efficacious than usual care - Recreational therapy statistically but not clinically more efficacious (SMD -0.29) - 46% of studies had missing outcome data

Cognitive Decline and Dementia: Take-homes  White matter disease on MRI is associated with cognitive decline  Hypertension is a modifiable risk factor for white matter disease and cognitive decline  May partially account for observed racial disparity in cognitive decline  Nonpharmacologic interventions are more efficacious than usual care in management of aggression and agitation in dementia

2020 Updates In Neurology: Outline  Cognitive Decline  Multiple sclerosis - Microvascular disease - Vitamin D - Hypertension - Smoking - Agitation - DMTs and malignancy - Pediatric  Potpourri  Epilepsy and EEG - Fibromyalgia - Dementia - Headache - SUDEP - Suicide - Delirium - Guillain Barre Syndrome - Checkpoint inhibitors - Telehealth

Dementia and Epilepsy  Method - Retrospective cohort study - Random sample of 1 million veterans age 55+ from 2001 - 2015  Exposures & Outcomes - Exposure: Late-onset unprovoked seizure of unknown etiology - Outcome: Incident dementia diagnosis  Results - 2166 veterans (0.7%) developed late-onset epilepsy - Veterans with late-onset epilepsy had greater risk of dementia (HR 1.89)

Epilepsy: Risk of Death  Inclusion criteria - North American SUDEP Registry Cases from 10/2011 – 6/2018  Methods - Retrospective review of 237 SUDEP cases (38% female)  Results - All types of epilepsy: Generalized or localized, recent or longstanding, severe or mild - High proportion (30%) were not on anti-seizure medications at time of death  Only 37% had taken their last dose of anti-seizure medications - 70% of cases occur in sleep, and of these, 69% were found prone - High frequency of GTCs not strongly associated with SUDEP

EEG: Delirium  Methods - Prospective cohort - EEG for altered mental status  Outcomes - 3-minute Diagnostic Interview for Confusion Assessment Method (3D-CAM) - EEGs interpreted by neurophysiologists - Clinical outcomes: Length of stay, Glasgow outcome scales, mortality  Results - 200 patients evaluated, of whom 121 met delirium criteria (60.5%) - EEG finding most strongly associated with delirium: generalized slowing (sensitive)  Correlated with severity of delirium and individual features on CAM  Correlated with longer hospitalizations, worse outcomes, increased mortality even after adjusting for delirium presence or severity - Most specific EEG findings: periodic discharges, triphasic waves, lateralized rhythmic delta, low voltage/generalized attenunation (all insensitive)

Epilepsy and EEG: Take-homes  New-onset epilepsy in older patients may herald incipient dementia  Sudden unexplained death in epilepsy (SUDEP) can occur in any patient, and the biggest risk factors are poor adherence to epileptics and poor seizure control  EEG is helpful in the evaluation and prognostication of delirium

2020 Updates In Neurology: Outline  Cognitive Decline  Multiple sclerosis - Microvascular disease - Vitamin D - Hypertension - Smoking - Agitation - DMTs and malignancy - Pediatric  Potpourri  Epilepsy and EEG - Fibromyalgia - Dementia - Headache - SUDEP - Suicide - Delirium - Guillain Barre Syndrome - Checkpoint inhibitors - Telehealth

Multiple Sclerosis: Smoking and Vitamin D  Inclusion criteria - Adults with clinically isolated syndrome  Outcomes - Neurofilament levels, cognitive function (PASAT), vitamin D levels, EBV IBNA-1 IgG, cotinine (nicotine metabolite) all measured at 6, 12, 24 months - Follow up data obtained at year 11  Results - 278 participants with 11 year follow-up data (of original 468) - Higher vitamin D levels predicted better cognitive performance - Smoking predicted worse cognitive performance - Anti-EBNA-1 did not predict cognitive performance - NFL levels corroborated results