1. 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

2. Pattern Recognition of Neuropathic Disorders Pattern NP1: 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.

3. Pattern NP2: 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 (? Nav1.7) ̶CMT – but usually weakness, + sensory signs, no sensory symptoms If acute/subacute with pain/weakness – consider vasculitis If slow NCS – consider DADS Pattern Recognition of Neuropathic Disorders 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.

4. Pattern NP3: 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

5. Pattern NP4: 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-Sept1) Pattern Recognition of Neuropathic Disorders Pasnoor M, Dimachkie MM, Barohn RJ. Neurol Clin 2013;31(2):447-462

6. Pattern Recognition of Neuropathic Disorders 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 Brachial amyotrophic diplegia (BAD) Leg amyotrophic diplegia (LAD) 2.Multifocal motor neuropathy 3.Multifocal acquired motor axonopathy (MAMA) 4.Juvenile monomelic amyotrophy 5.Polio/post-polio/polio-like West Nile virus Enterovirus 68 Statland JM, Barohn RJ, McVey 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 NP5:

7. Pattern NP6: Symmetric Sensory Loss (With or Without Distal Weakness) and Upper Motor Neuron Signs – Consider causes of acquired combined system degeneration with neuropathy: B12 deficiency Copper deficiency End stage liver disease Inherited disorders ̶ Adrenomyeloneuropathy ̶ Metachromatic leukodystrophy ̶ Friedreich’s 2nd lesion, ex. Cervical spondylosis Pattern Recognition of Neuropathic Disorders Hammond N, Wang Y, Dimachkie MM, Barohn RJ. Neurol Clin 2013;31(2):477-489

8. Pattern NP7: 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 Pattern Recognition of Neuropathic Disorders Kolb SJ, Kissel JT. Neurol Clin 2015;33(4):831-846.

9. Pattern NP8 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

10. Pattern NP9: Asymmetric Proprioceptive Loss Without Weakness –Consider sensory neuronopathy due to:  cancer (paraneoplastic)  Sjögren’s syndrome  vitamin B6 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

11. Pattern NP10: 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 Pattern Recognition of Neuropathic Disorders

12. Clinical Patterns of Neuropathic Disorders Weakness PATTERN ProximalDistalAsymmSymmSensory Symptoms Severe Proprioceptive Loss UMN Signs Autonomic Symps/Signs Diagnosis NP1 - Symmetric prox & distal weakness w/sensory loss ++++GBS/CIDP NP2 - Distal sensory loss with/without weakness +++CSPN, metabolic, diabetes, drugs, hereditary, DADS NP3 - Asymmetric distal weakness with sensory loss +++Multiple – vasculitis, HNPP, MADSAM, infection Single - Mononeuropathy, radiculopathy NP4 - Asymmetric prox & distal weakness w/sensory loss ++++Polyradiculopathy, plexopathy, DLSRP, cancer, idiopathic, infection NP5 - Asymmetric distal weakness w/out sensory loss +++/-+ UMN – ALS/PLS - UMN – MMN NP6 – Symmetric sensory loss & upper motor neuron signs +++++B12/Copper defic; Friedreich’s, ALD NP7 - Symmetric weakness without sensory loss* +\-++Prox & Distal SMA Distal Hereditary motor neuropathy NP8 - Focal midline proximal symmetric weakness* + Neck/trunk extensor or + Bulbar + Diaphragm ++++ ++++ ALS ALS/PLS NP9 – Asymmetric proprioceptive loss w/out weakness +++Sensory neuronopathy (ganglionopathy) CISP NP10 – Autonomic dysfunction +Diabetes, GBS, amyloid, prophyria *Overlap patterns with myopathy and NMJ disorders Adapted from Barohn RJ, Amato AA,. Neurol Clin 2013;31(2):343-361