Pattern Recognition of Neuropathic Disorders Richard J Barohn

Pattern Recognition of Neuropathic Disorders Richard J. Barohn, M. D. 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 Neuropathic Disorders Pattern NP 1: • Symmetric Proximal and Distal Weakness with sensory loss • Consider: • GBS/CIDP Dimachkie MM, Barohn RJ, Katz J. Neurol Clin 2013; 31(2): 533 -555; Dimachkie MM, Barohn RJ. Neurol Clin 2013; 31(2): 491 -510.

Pattern Recognition of Neuropathic Disorders Pattern NP 2: • Symmetric Distal Sensory Loss With or Without Weakness • Consider: • cryptogenic sensory polyneuropathy (CSPN) • metabolic disorders ― diabetic (DSPN) + IGT • drugs/toxins • Sjogren’s, sarcoid • hereditary amyloid, Hereditary Sensory Neuropathy (HSN), Fabry’s, others (? Nav 1. 7) CMT – but usually weakness, + sensory signs, no sensory symptoms • If acute/subacute with pain/weakness – consider vasculitis • If slow NCS – consider DADS Pasnoor M, Dimachkie MM, Barohn RJ. Neurol Clin 2013; 31(2): 463 -476; Pasnoor M, Dimachkie MM, Kluding P, Barohn RJ. Neurol Clin 2013; 31(2): 425 -445. Pasnoor M, Dimachkie MM, Barohn RJ. Neurol Clin 2013; 31(2): 447 -462.

Pattern Recognition of Neuropathic Disorders Pattern NP 3: • Asymmetric Distal Weakness With Sensory Loss – Single Nerves/Roots, consider: • compressive mononeuropathy and radiculopathy – Multiple Nerves, Consider: • vasculitis • HNPP (hereditary neuropathy with pressure palsy) • infectious (leprosy, lyme, HIV, sarcoid, hepatitis) • Multifocal Acquired Demyelinating Sensory And Motor (MADSAM) Neuropathy/Lewis-Sumner

Pattern Recognition of Neuropathic Disorders Pattern NP 4: • Asymmetric Proximal and Distal Weakness With Sensory Loss ―Consider: § polyradiculopathy § plexopathy § radiculoplexopathy ― Due to: § diabetes: lumbosacral radiculoplexopathy (DLSRP “amyotrophy”) § Neoplasia direct invasion § idiopathic (? dysimmune) – Parsonage–Turner syndrome § hereditary (HNPP-PMP, HNA-Sept 1) Pasnoor M, Dimachkie MM, Barohn RJ. Neurol Clin 2013; 31(2): 447 -462

Pattern Recognition of Neuropathic Disorders Pattern NP 5: Asymmetric Distal Weakness Without Sensory Loss • Consider: A. With upper neuron findings 1. motor neuron disease/ALS 2. only UMN PLS B. Without upper motor neuron findings 1. Progressive muscular atrophy 2. 3. 4. 5. Multifocal motor neuropathy Multifocal acquired motor axonopathy (MAMA) Juvenile monomelic amyotrophy Polio/post-polio/polio-like • Brachial amyotrophic diplegia (BAD) • Leg amyotrophic diplegia (LAD) • West Nile virus • Enterovirus 68 Statland JM, Barohn RJ, Mc. Vey AL, Katz JS, Dimachkie MM. Neurol Clin 2015; 33(4): 735 -748; Liewluck T, Saperstein DS. Neurol Clin 2015; 33(4): 761 -773; Jawdat O, Statland JM, Barohn RJ, Katz JS, Dimachkie MM. Neurol Clin 2015; 33(4): 775 -785; Statland JM, Barohn RJ, Dimachkie MM, Floeter MK, Mitsumoto H. Neurol Clin 2015; 33(4): 749 -760

Pattern Recognition of Neuropathic Disorders Pattern NP 6: • Symmetric Sensory Loss (With or Without Distal Weakness) and Upper Motor Neuron Signs – Consider causes of acquired combined system degeneration with neuropathy: • B 12 deficiency • Copper deficiency • End stage liver disease • Inherited disorders Adrenomyeloneuropathy Metachromatic leukodystrophy Friedreich’s • 2 nd lesion, ex. Cervical spondylosis Hammond N, Wang Y, Dimachkie MM, Barohn RJ. Neurol Clin 2013; 31(2): 477 -489

Pattern Recognition of Neuropathic Disorders Pattern NP 7: • Symmetric Weakness Without Sensory Loss – Proximal and distal § Spinal Muscular Atrophy – Only distal § Hereditary Motor Neuropathy “Distal SMA” § CMT can present pure motor but sensory deficits on exam • Overlap pattern with myopathy/NMJ Kolb SJ, Kissel JT. Neurol Clin 2015; 33(4): 831 -846.

Pattern Recognition of Neuropathic Disorders Pattern NP 8 • Focal Midline Proximal Symmetric Weakness – Neck or trunk extensor weakness • ALS • Overlap pattern: MG, INEM, ITEM – Bulbar weakness • ALS/PLS • Isolated Bulbar ALS (IBALS) • Kennedy’s syndrome; X-linked, bulbospinal SMA • Grunseich C, Fischbeck KH. Neurol Clin 2015; 33(4): 847 -854 • Overlap pattern: MG, OPD – Diaphragm weakness (SOB) • ALS • Overlap pattern: MG, Pompe

Pattern Recognition of Neuropathic Disorders Pattern NP 9: • Asymmetric Proprioceptive Loss Without Weakness – Consider sensory neuronopathy due to: § § § § cancer (paraneoplastic) Sjögren’s syndrome vitamin B 6 toxicity cisplatinum HIV-related Idiopathic Vitamin E deficiency (probably nerve, not cell body) • Consider chronic immune sensory polyradiculopathy (CISP) (Neurology 2004; 63: 1662)

Pattern Recognition of Neuropathic Disorders Pattern NP 10: • Autonomic Dysfunction (ex. Orthostasis, impotence) – Consider: § § § § § diabetes mellitus amyloidosis (familial & acquired) Guillain-Barré syndrome acute autonomic ganglionopathy Sjögren’s syndrome Fabry’s porphyria HIV-related autonomic neuropathy idiopathic pandysautonomia o Nav 1. 7 mutation § paraneoplastic

Clinical Patterns of Neuropathic Disorders Weakness Proximal Distal + Asymm Sensory Symptoms + + + GBS/CIDP NP 2 - Distal sensory loss with/without weakness + + + CSPN, metabolic, diabetes, drugs, hereditary, DADS NP 3 - Asymmetric distal weakness with sensory loss + + + Multiple – vasculitis, HNPP, MADSAM, infection Single - Mononeuropathy, radiculopathy + + + Polyradiculopathy, plexopathy, DLSRP, cancer, idiopathic, infection NP 5 - Asymmetric distal weakness w/out sensory loss + + NP 6 – Symmetric sensory loss & upper motor neuron signs + + PATTERN NP 1 - Symmetric prox & distal weakness w/sensory loss NP 4 - Asymmetric prox & distal weakness w/sensory loss + NP 7 - Symmetric weakness without sensory loss* +- NP 8 - Focal midline proximal symmetric weakness* + Neck/trunk extensor or + Bulbar + Diaphragm NP 9 – Asymmetric proprioceptive loss w/out weakness NP 10 – Autonomic dysfunction *Overlap patterns with myopathy and NMJ disorders + + Severe Proprioceptive Loss + UMN Signs Autonomic Symps/Signs Diagnosis +/- + UMN – ALS/PLS - UMN – MMN + B 12/Copper defic; Friedreich’s, ALD Prox & Distal SMA Distal Hereditary motor neuropathy + + + ALS/PLS + Sensory neuronopathy (ganglionopathy) CISP + Diabetes, GBS, amyloid, prophyria Adapted from Barohn RJ, Amato AA, . Neurol Clin 2013; 31(2): 343 -361