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Toronto Notes 2019
Landmark Neurology Trials
Neurology N55
Table 25. Common Medications – Major Issues (continued)
Indications
Mild to Moderate Alzheimer's Disease or Dementia with Lewy Bodies
Multiple Sclerosis
Spasticity (i.e. MS)
Mechanism of Action/Class
Cholinesterase Inhibitor
MS Disease Modifying Therapy
MS Disease Modifying Therapy
MS Disease Modifying Therapy
MS Disease Modifying Therapy
Muscle Relaxant – Antispastic
Generic Name
donepezil
interferon-β-1b interferon-β-1a SC interferon-β-1a IM
glatiramer acetate natalizumab
fingolimod baclofen
Trade Name
Aricept®
Betaseron® Rebif® Avonex®
Copaxone® Tysabri®
Gilenya® Lioresal®
Dosing
5 mg PO OD, may increase to 10 mg PO OD after 4-6 wk
0.25 mg (8 MU) SC every other day
44 μg SC 3 times/wk
30 μg IM once weekly
20 mg SC OD
300 mg IV given over 1 h, every 4 wk
0.5 mg PO OD
5 mg PO tid, increase by 15 mg/d q3d
to max dose 80 mg/d in three divided doses
Contraindications
Hypersensitivity to donepezil or to piperidine derivatives
Pregnancy, hypersensitivity to natural or recombinant interferon-β
Hypersensitivity to glatiramer or mannitol
Hypersensitivity to natalizumab, progressive multifocal leukoencephalopathy (PML)
Not available Hypersensitivity to baclofen
Side Effects
Diarrhea, N/V, insomnia, muscle cramps, fatigue, anorexia, HTN, syncope, AV block
Injection site reactions, injection site necrosis, flu-like symptoms (fever, chills, myalgia; tend to decrease over time)
Injection site reactions, nausea, transient chest pain, vasodilation
Rash, nausea, arthralgia, H/A, infections, rare risk of PML and melanoma
Diarrhea, transaminitis, H/A, bradyarrhythmia, lymphopenia
Transient drowsiness, daytime sedation, dizziness, weakness, fatigue, convulsions, constipation, nausea
Landmark Neurology Trials
Trial
NASCET
Interferon-β Multiple Sclerosis Study Group Trial
NINDS rtPA SPARCL ECASS 3 PROFESS RELY ROCKET-AF ERS CREST
INTERACT2 MR CLEAN
Reference
NEJM 1991;7:445-53 Neurology 1993;43:655-61
NEJM 1995;333:1581-7 NEJM 2006;355:549-59 NEJM 2008;359:1317-29 NEJM 2008;359:1238-51 NEJM 2009;361:1139 NEJM 2011;365:883-891 NEJM 2011;365:981-992 NEJM 2010;363:11-23
NEJM 2013;368:2355-65 NEJM 2015;372:11-20
Results
Patients with symptomatic carotid stenosis of 70-99% benefited more from carotid endarterectomy than best medical therapy Interferon-β-1b reduces relapse rate and severity of relapses in RRMS
rtPA reduces mortality and long-term disability when administered within 3 h of acute stroke
The observed benefit of statins in cardiovascular disease is also extended to patients with a recent stroke or TIA
rtPA improved clinical outcomes when administered within 3 to 4.5 h of acute ischemic stroke
ASA + dipyridamole and clopidogrel showed similar benefits in secondary stroke prevention
Dabigatran superior to warfarin for stroke prevention in patients with AF
Rivaroxaban noninferior to warfarin stroke prevention in patients with AF
Apixaban superior to warfarin for stroke prevention in patients with AFT
Carotid stenting and endarterectomy had similar benefits in reduction of stroke, MI, and death in carotid stenosis, but in the periprocedural period, stenting had a higher rate of stroke, while endarterectomy had a higher rate of MI
Intensive lowering of blood pressure (sBP<140) in spontaneous intracerebral hemorrhage did not improve mortality or severe disability but improved functional outcomes (odds ratio for greater disability, 0.87; 95% CI, 0.77 to 1.00; P=0.04)
Intra-arterial treatment (intra-arterial thrombolysis, mechanical treatment, or both) for emergency revascularization administered within 6 h after stroke onset was effective and safe for acute ischemic stroke caused by proximal intracranial occlusion of the anterior circulation
References
Coma
Bhidayasiri R, Waters MF, Giza CC. Neurological differential diagnosis: a prioritized approach. Massachusetts: Blackwell Publishing, 2005. 71-72.
Kasper DL, Braunwald E, Fauci AS, et al. (editors). Harrison’s principles of internal medicine, 16th ed. Toronto: McGraw-Hill Companies, 2005. 1629-1630.
Common Presenting Complaints
Bhidayasiri R, Waters MF, Giza CC. Neurological differential diagnosis: a prioritized approach. Massachusetts: Blackwell Publishing, 2005. 12-13, 305-314.
Drug Information
Compendium of Pharmaceuticals and Specialties 2010. Ottawa: Canadian Pharmacists Association, 2010. Lexi-Comp OnlineTM. Hudson: Lexi-Comp, 2011.
Epilepsy
Ambati BK, Smith WT, Azer-Bentsianov MT. Residents’ manual of medicine. Hamilton: BC Decker, 2001. 203-205. Ferri FF. Practical guide to the care of the medical patient. St. Louis: Mobsy, 2001. 617-619.
Lowenstein DH, Alldredge BK. Status epilepticus. NEJM 1998;338:970-976.
General
Aminoff MJ, Greenberg DA, Simon RP. Lange: clinical neurology, 6th ed. Toronto: McGraw-Hill, 2009.
Ettinger AB, Weisbrot DM. Neurologic differential diagnosis: a case-based approach. Cambridge: Cambridge University Press, 2014. Mumenthaler M, Mattle H. Fundamentals of neurology. Stuttgart and New York: Thieme, 2006.
Scherokman B, Selwa L, Alguire PC. Approach to common neurological symptoms in internal medicine: AAN core curricula. 2011. Yamada KA, Awadalla S. The Washington manual of medical therapeutics, 31st ed. New York: Lippincott Williams & Wilkins. 531-534.