Pattern Recognition of Myopathic Disorders www.rrnmf.com Richard J. Barohn, MD Chair, Department of Neurology Gertrude and Dewey Ziegler Professor of Neurology University Distinguished Professor Vice Chancellor for Research University of Kansas Medical Center Kansas City, KS

Pattern Recognition of Myopathic Disorders Pattern MP1: Proximal “limb-girdle” weakness Acute/subacute – acquired Inflammatory (PM/DM) - pain/rash/CTD Endocrine Toxic drugs Chronic/congenital/painless – hereditary Most dystrophies Congenital Mitochondrial Pompe’s disease Carnitine deficiency Neuromuscular junction Overlap with SMA

Pattern Recognition of Myopathic Disorders Pattern MP2: Distal weakness Distal muscular dystrophies: Late adult onset: Welander; Markesbery/Udd Early adult onset: Nonaka; Miyoshi; Laing Myofibrillar (Desmin) myopathy Myotonic dystrophy Congenital myopathies Other: NMJ disease - MG, congenital MG Overlap with CMT/hereditary motor neuropathy Barohn RJ et al. Autosomal recessive distal dystrophy. Neurology 1991;41:1365-1370 Dimachkie MM, Barohn RJ. Neurol Clin 2014;32(3):817-42

Pattern Recognition of Myopathic Disorders Pattern MP3: Proximal arm/distal leg weakness (Scapuloperoneal) Facioscapulohumeral dystrophy With facial weakness Scapuloperoneal myopathy Emery-Dreifuss humeroperoneal dystrophy Pompe’s disease Barohn et al. Adult acid maltase deficiency. Muscle Nerve 1993;16:672-676 Congenital myopathy From: Barohn et al. Adult acid maltase deficiency. Muscle Nerve 1993;16:672-676.

Pattern Recognition of Myopathic Disorders Pattern MP4: Distal arm/proximal leg weakness Inclusion body myositis Common presentation Finger & wrist flexor weakness Knee extensor weakness Asymmetric Occasionally myotonic dystrophy Amato AA, et al. Ann Neurol 1996;40(4):581-6.;Dimachkie MM, Barohn RJ. Neurol Clin 2014;32(3):817-42

Pattern Recognition of Myopathic Disorders Pattern MP5: Eyeball Pattern Ptosis / ophthalmoplegia Ptosis without ophthalmoplegia Myotonic dystrophy Congenital myopathies Ptosis with ophthalmoplegia Oculopharyngeal dystrophy Mitochondrial myopathy Centronuclear myopathy Neuromuscular junction disease: MG, LEMS, congenital MG, botulism* *Diplopia

Pattern Recognition of Myopathic Disorders Pattern MP6: Prominent neck and trunk extensor weakness Isolated neck extensor myopathy (INEM) Isolated trunk extensor myopathy (ITEM) Myasthenia gravis IBM / PM/ DM Myotonic dystrophy FSH dystrophy Congenital myopathy Carnitine deficiency Hyperparathyroidism Overlap pattern with ALS Katz JS, Wolfe GI, Bryan WW, Burns DK, Barohn RJ. Neurology 1996;47:917-21; Barohn RJ, Dimachkie MM, Jackson CE. Neurol Clin 2014;32(3):569-93

Pattern Recognition of Myopathic Disorders Pattern MP7: Bulbar weakness – tongue/pharyngeal/ diaphragm (dysarthria or dysphagia, SOB) MG, LEMS Oculopharyngeal dystrophy LGMD 1A myotilinopathy Myotonic dystrophy IBM Pompe (respiratory) Overlap pattern with: ALS, Kennedy’s

Pattern Recognition of Myopathic Disorders Pattern MP8: Episodic pain, weakness, myoglobinuria with trigger Related to exercise Glycogenoses (McArdle’s, etc) Lipid disorders (CPT def) Couch potatoes & exercise Not related to exercise Malignant hyperthermia Drugs/toxins Trauma (crush injury) Other: Neuroleptic malignant syndrome Epileptic status Sharp LJ, Haller RG. Neurol Clin 2014;32(3):777-99

Pattern Recognition of Myopathic Disorders Pattern MP9: Episodic weakness delayed or unrelated to exercise Myasthenia gravis Periodic paralysis Na+ channelopathies (hyperkalemic) Ca++ channelopathies (hypokalemic) Andersen’s syndrome Secondary PP (thyrotoxicosis) Matthews E, et al. Brain 2010;133(Pt 1):9-22.

Pattern Recognition of Myopathic Disorders Pattern MP10: Stiffness/decreased ability to relax Improves with exercise Myotonia – usually Cl- channelopathy Worsens with exercise/cold sensitivity Paramyotonia - Na+ channelopathy Brody’s disease With fixed weakness Myotonic dystrophy (DM 1) Proximal myotonic myopathy (DM 2) Becker’s disease (AR Cl- channelopathy) Other: rippling muscle, neuromyotonia, stiff-person Statland JM, et al. JAMA 2012;308:1357-1365; Trivedi JR, et al. Brain 2013;136(Pt 7):2189-2200; Statland J, Phillips L, Trivedi JR. Neurol Clin 2014;32(3):801-815

Clinical Patterns of Muscle Disorders Weakness PATTERN Proximal Distal Asymmetric Symmetric Episodic Trigger Diagnosis MP1 - Limb girdle + Most myopathies – hereditary and acquired MP2 – Distal* Distal myopathies (also neuropathies) MP3 - Proximal arm / distal leg “scapuloperoneal” Arm Leg (FSH) (others) FSH, Emery-Dreifuss, acid maltase, congenital scapuloperoneal MP4 - Distal arm / proximal leg IBM Myotonic dystrophy MP5 - Ptosis / Ophthalmoplegia (MG) OPD, MG, myotonic dystrophy, mitochondria MP6 - Neck – extensor* INEM, MG MP7 - Bulbar (tongue, pharyngeal, diaphragm)* MG, LEMS, OPD (also ALS) MP8 - Episodic weakness/ Pain/rhabdo + trigger McArdle’s, CPT, drugs, toxins MP9 - Episodic weakness Delayed or unrelated to exercise +/- Primary periodic paralysis Channelopathies: Na+ Ca++ Secondary periodic paralysis MP10 - Stiffness/ Inability to relax Myotonic dystrophy, channelopathies, PROMM, rippling (also stiff-person, neuromyotonia) *Overlap patterns with neuropathic disorders Adapted from Barohn RJ, Dimachkie MM, Jackson RJ. Neurol Clin 2014;32(3):569-593