6/20/2019 Relevant Disclosures None “What’s New in Neurology?” MEGAN RICHIE, MD ASSISTANT PROFESSOR OF NEUROLOGY Outline Acute stroke Stroke Potpourri DAWN Trial ◦ Acute treatment ◦ Neuropathic pain Inclusion criteria ◦ Prophylaxis ◦ Parkinson’s disease ◦ ICA or proximal MCA occlusion ◦ Intracranial hemorrhage ◦ Cognitive decline ◦ Last known well 6 – 24 hours earlier ◦ Lyme disease Epilepsy ◦ Mismatch between clinical exam and infarct volume ◦ First-line medications Randomized Intervention ◦ Epilepsy surgery ◦ Thrombectomy + standard care Multiple sclerosis ◦ Standard care alone ◦ New treatment options Results ◦ Avoiding progression ◦ Terminated early due to efficacy ◦ Less disability and higher independence with thrombectomy 1
6/20/2019 Acute stroke Acute stroke WAKE-UP Trial DEFUSE-3 Trial Inclusion criteria Inclusion criteria ◦ Unknown time of onset ◦ ICA or proximal MCA occlusion ◦ Particular MRI appearance ◦ Last known well 6 – 16 hours earlier ◦ Ischemic lesion on diffusion without T2 hyperintensity ◦ Perfusion: Small infarct size, high adjacent at-risk territory Randomized intervention Randomized Intervention ◦ Intravenous alteplase ◦ Placebo ◦ Thrombectomy + standard care ◦ Standard care alone Results ◦ Terminated early due to cessation of funding Results ◦ More favorable outcomes and lower disability with alteplase ◦ Terminated early due to efficacy ◦ More hemorrhage with alteplase ◦ Lower mortality, less disability and higher independence with thrombectomy After the Stroke: Acute stroke: Take-homes Prophylaxis More options available > 6 hours into symptoms POINT trial Inclusion criteria ◦ Minor ischemic stroke or high-risk TIA Randomized intervention Send patients for emergent evaluation if < 24 hours ◦ Clopidogrel + Aspirin ◦ Aspirin alone Results Educate patients & families regarding symptoms of acute ◦ Terminated early due to efficacy stroke and importance of emergent care ◦ Dual antiplatelet therapy (DAPT) with lower ischemic events and higher hemorrhage ◦ Meta-analysis of RCTs suggested DAPT within 24 hours reduced risk of recurrent stroke primarily within the first 21 days 2
6/20/2019 After the Stroke: Risk factors After the Stroke: Take-homes Dual antiplatelet therapy after minor stroke/TIA for 21-30 Post Hoc analysis of IRIS trial days (POINT Trial) Inclusion criteria ◦ Prior stroke or TIA + insulin resistance (not diabetes) ◦ Prediabetes: Hgb A1c 5.7-6.4% or fasting BG 100-125 mg/dL Treat patients with prediabetes Randomized intervention Hgb a1c 5.7 – 6.4 or Fasting BG 100-125 ◦ Pioglitazone ◦ Pioglitazone is one – but perhaps not the only – option ◦ Placebo Results ◦ Reduced risk of stroke, MI, progression to diabetes ◦ Increase in bone fractures, weight, edema Hemorrhagic Stroke: Unruptured Hemorrhagic Stroke: aneurysms Unruptured aneurysms Management strategies for tiny incidental aneurysms Risk of unruptured aneurysm repair: Meta-analysis of 74 studies Decision model Endovascular therapy ◦ Comparing management strategies ◦ 30-day complications 4.96% ◦ Incidental ≤ 3mm aneurysms ◦ Fatality 0.3% Outcome ◦ Quality-adjusted life years (QALYs) Neurosurgical therapy Results ◦ 30-day complications 8.34% ◦ No follow-up was associated with highest number of QALYs ◦ Fatality 0.1% ◦ MRA every 5 years had second highest number of QALYs 3
6/20/2019 Hemorrhagic Strokes: Take- Hemorrhagic Stroke: DOAC reversal homes Small aneurysms have very low risk of growing and Inclusion criteria ◦ Acute major bleeding rupturing ◦ Factor Xa inhibitor within 18 hours ◦ Repair is not benign ◦ Preferred no follow-up, or at the most MRA every 5 years Intervention ◦ Bolus Infusion of Andexanet Results Direct Oral Anticoagulants now have an FDA-approved ◦ Intracranial (64%), gastrointestinal (26%) reversal agent: Andexanet ◦ Reductions in median anti-factor Xa activity ◦ Modestly predictive of hemostatic efficacy in patients with ICH ◦ Excellent or good hemostasis at 12 hours: 82% ◦ 30-day thrombotic events: 10% Epilepsy: History Epilepsy: History continued Prior to 2004, only 6 major antiepileptic drugs (AEDs) available for In 2004, AAN investigated 7 new AEDs for treatment of new-onset epilepsy treatment epilepsy, adding 4 options ◦ Carbamazepine ◦ Lamotrigine ◦ Phenytoin ◦ Gabapentin ◦ Valproic acid ◦ Oxcarbazepine ◦ Phenobarbital ◦ Topiramate ◦ Primidone Insufficient evidence to recommend ◦ Ethosuxamide (absence seizures) ◦ Levetiracetam Significant drawbacks associated with these AEDs ◦ Tiagabine ◦ Enzyme-inducers ◦ Zonisamide ◦ Side-effect ridden 4
6/20/2019 Epilepsy: First-line update Epilepsy: First-line take-homes Established options Carbamazepine prior to ‘04 New 2018 AAN guidelines Phenytoin prior to ‘04 ◦ Lamotrigine Probably effective Valproic acid prior to ‘04 ◦ Including in patients aged > 60 years Oxcarbazepine in 2004 ◦ Levetiracetam Possibly effective Topiramate in 2004 ◦ Zonisamide Possibly effective (Phenobarbital) (prior to ’04) ◦ Gabapentin Possibly effective age > 60 years 2018: New option No change Lamotrigine ◦ Oxcarbazepine: Established as effective Less certain options include Levetiracetam Zonisamide Gabapentin Epilepsy surgery: Epilepsy surgery: Works in children Works in adults Inclusion criteria Inclusion criteria ◦ Anterior temporal lobectomy ◦ < 18 years ◦ 5 years of follow up ◦ Drug-resistant epilepsy Intervention Randomized Intervention ◦ Epilepsy surgery ◦ Antiepileptic drug (AED) withdrawal ◦ Medical therapy Results Results ◦ 84.9% attempted to withdrew at least one AED ◦ 72.8% of these remained seizure free ◦ Seizure freedom higher in surgical group ◦ After recurrence, 86% of these later achieved seizure freedom ◦ Better scores in behavior and quality of life in surgical group ◦ AED-free, seizure-free in 54% of the entire population 5
6/20/2019 Multiple Sclerosis: Quick Epilepsy surgery: When to refer reminder Medically refractory epilepsy: Traditional ◦ Therapeutic failure of 3 antiseizure drugs Relapsing-remitting Secondary progressive Medically refractory epilepsy: Currently ◦ Therapeutic failure of 2 antiseizure drugs ◦ Seizures uncontrolled at 12 months Primary progressive Encourage epilepsy center evaluation Relapsing-Remitting Multiple Sclerosis: Primary progressive Disease-modifying therapy (DMTs) Multiple sclerosis Class of DMT Advantages Disadvantages Risks ORATORIO Trial Injectable Established Less effective Flu-like symptoms Inclusion criteria • Glatiramer Safety profile Injection route Injection site necrosis acetate ◦ Primary progressive multiple sclerosis patients Leukopenia • Interferons Transaminitis Randomized Intervention Oral Self-administered *Safety Dimethyl fumarate : GI symptoms, ◦ Ocrelizumab • Dimethyl *Highly effective lymphopenia, LFTs ◦ Placebo fumarate Teriflunomide : Teratogen, hair loss, GI • Teriflunomide* symptoms, LFTs Results • Fingolimod* Fingolimod : Arrhythmia, macular edema, skin ◦ Reduced disability progression at 12 and 24 weeks cancer, LFTs, PML, other infections ◦ Reduced brain lesions and volume loss on MRI ◦ More infusion reactions, URIs, oral herpes infections Infusion *Highly effective Safety Natalizumab : PML, sx rebound • Natalizumab * New Ocrelizumab : HBV activation • Ocrelizumab * Alemtuzumab : Infections, autoimmune • Alemtuzumab * disease • Rituximab Rituximab : PML? 6
6/20/2019 Secondary progressive Avoiding Secondary Multiple sclerosis Progression EXPAND Trial Inclusion criteria ◦ Relapsing-remitting MS patient Inclusion criteria ◦ Beginning disease-modifying therapy ◦ Secondary progressive multiple sclerosis patients ◦ 4+ years of followup Randomized Intervention Exposures ◦ Simponimod ◦ Interferon beta Injectable ◦ Placebo ◦ Glatiramer acetate ◦ Fingolimod Results ◦ Natalizumab Highly-effective ◦ Reduced risk of disability progression ◦ Alemtuzumab ◦ More lymphopenia, transaminase elevation, bradycardia, bradyarrhythmia, Results macular edema, hypertension, varicella zoster reactivation, convulsions ◦ Conversion to SPMS lower with early highly-effective therapy New MS therapies: Multiple Sclerosis: Take-homes Stem Cell Transplant Expanding armamentarium for Relapsing-Remitting Inclusion criteria multiple sclerosis ◦ Relapsing remitting MS ◦ B-cell therapies are promising ◦ At least 2 relapses on DMT ◦ Disability score 2-6 New approved therapies exist for: Randomized Intervention ◦ Primary progressive multiple sclerosis ◦ Secondary progressive multiple sclerosis ◦ Stem cell transplant + cyclophosphamide + ATG ◦ DMT of higher efficacy or different mechanism than prior Use (or escalate to) highly effective therapy early in disease to reduce progression to SPMS Results ◦ Dramatically reduced disease progression in SCT Stem cell transplant: emerging therapy but not ready for ◦ More short-term infections in SCT prime time 7
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