approach to polyneuropathy

approach to polyneuropathy, demyelination, axonopathy, plexopathy, mononeuritis, ganglionopathy

1. APPROACH TO POLYNEUROPATHY STUDENT : Dr. Akhila GUIDE: Dr. Ram K.

2. INTRODUCTION Peripheral neuropathy is the term for damage to nerves of the peripheral nervous system, which may be caused either by diseases of the nerve or from the side-effects of systemic illness. CLASSIFICATION : MONONEUROPATHY MULTIPLE MONONEUROPATHY POLYNEUROPATHY

3. ANATOMICAL CLASSIFICATION OF PERIPHERAL NEUROPATHY Mononeuropathy Plexopathy- brachial, lumbar, sacral Radiculopathy- cervical, thoracic, lumbosacral Multiple mononeuropathy( mononeuropathy multiplex) Polyneuropathy- symmetrical/ asymmetrical polyradiculoneuropathy

4. ROLE OF NERVE FIBRES

5. ETIOLOGY OF POLYNEUROPATHY ETIOLOGY EXAMPLES 1.METABOLIC DIABETES MELLITUS, HYPOTHYROIDISM 2. TOXINS ALCOHOL, DRUGS (CHEMOTHERAPEUTIC), HEAVY METALS 3. VITAMIN DEFICIENCIES B1, B3, B6, B12, FOLATE 4. INFLAMMATORY GUILLIAN BARRE SYNDROME, VASCULITIS, CONNECTIVE TISSUE DISORDERS 5. INFECTIOUS VIRAL (HIV), BACTERIAL (LEPROSY, LYMES DISEASE) 6. HEREDITORY CHARCOT MARIE TOOTH DISEASE 7.NEOPLASTIC CARCINOMA, LYMPHOMA 8. IDIOPATHIC

6. PATHOPHYSIOLOGY MECHANISMS OF DAMAGE INCLUDE: DEMYELINATION ( myelinoathy ): GBS, Post diphtheric , HSMN AXONAL DEGENERATION ( axonopathy ) : Toxic neuropathies, systemic metabolic disorders, vasculitis . Wallerian degeneration : Nerve section – response to axonal interruption. Primary neuronal ( perikaryal ) degeneration ( neuronopathy )

7. AXONAL DEGENERATION

8. AXONAL DEGENERATION Usually chronic Sensory > motor in early disease Symmetric, length dependant (dying back) polyneuropathy- glove and stocking pattern Distal muscle weakness and atrophy, loss of distal limb reflexes. Examples : Diabetes, alcohol induced, vitamin deficiencies

9. DEMYELINATION

10. DEYELINATION Demyelination refers to injury to myelin sheath or Schwann cells with axonal sparing. Seen in acute/ chronic nerve entrapment, immune mediated demyelinating neuropathies , hereditary disorders of schwan cells. ` Clinically : Early generalised loss of reflexes disproportionately mild muscle atrophy Neuropathic tremor Palpably enlarged nerves

11. AXONAL DEMYELINATING DISTRIBUTION Length dependant Diffuse or patchy SENSATION Based on type of fibre involved Predominantly proprioception or vibration WEAKNESS Distal, symmetric Diffuse AUTONOMIC INVOLVEMENT Yes Only in GBS, autoimmune dysautonomia ELECTROPHYSIOLOGY CONDUCTION VELOCITY 2.CONDUCTION BLOCKS Normal or mild slowing NO Marked (<80% of lower limit)slowing YES CSF PROTEIN NORMAL ELEVATED RECOVERY RATE SLOW RAPID

12. Copyright ©2002 BMJ Publishing Group Ltd . Hughes, R. A C BMJ 2002;324:466-469 Using nerve conduction studies in polyneuropathy http://www.neuroanatomy.wisc.edu/SClinic/Weakness/Weakness.htm = Slow! = Low! = Slow!

13. 7 KEY POINTS Systems ( Fibers ) involved? Distribution? Nature of sensory involvement? Evidence of UMN involvement? Temporal evolution? Evidence for hereditary neuropathy? Associated medical conditions?

14. Loss of function “negative symptoms” Disturbed function “positive symptoms” Motor nerves W eakness Atrophy Walking difficulties Muscle cramp Fasciculation Tremor MOTOR SYSTEM

15. Loss of function “n e gati v e s y mpto m s” Disordered function “positive symptoms” Sensory “Large Fiber” ↓ Vibration ↓ Proprioception Hyporeflexia Sensory ataxia Paresthesias ( 60% in acquired & 17% in inherited PN) Sensory “Small Fiber” ↓ Pain ↓ Temperature H y peralgesia Allodynia TW Sensory neuropathy

16. Loss of function “- symptoms” Disturbed function “+ symptoms” Autonomic nerves ↓ Sweating Hypotension Urinary retention Impotence Vascular color changes ↑ Sweating Hypertension AUTONOMIC NEUROPATHY

17. Acute onset (days to 4 weeks) Subacute onset (4-8 weeks) Chronic course (>8 weeks) Relapsing/remitting course Guillain-Barré syndrome Acute intermittent porphyria Critical illness polyneuropathy Thallium toxicity Toxins or medications Nutritional deficiency Metabolic abnormality Paraneoplastic syndrome CIDP Hereditary motor and sensory neuropathy (HMSN) Inherited sensory neuropathy CIDP Guillain-Barré syndrome refsums disease CIDP Toxin (intermittent exposure) Porphyria TEMPORAL ASSOCIATION

18. DISTRIBUTION OF WEAKNESS Distal or proximal and distal Focal/asymmetric or Symmetric Ex: Symmetric proximal and distal weakness – AIDP (GBS) / CIDP Asymmetric subacute / acute sensory and motor symptoms – radiculopathies/ mononeuropathies / mononeuritis multiplex

19. NEUROPATHIES WITH PREDOMINANT MOTOR INVOLVEMENT Multifocal motor neuropathy Acute motor axonal neuropathy Guillain – Barré syndrome Chronic inflammatory demyelinating polyradiculoneuropathy Neuropathy with osteosclerotic myeloma Hereditary motor sensory neuropathies (Charcot–Marie–Tooth disease) Lead intoxication

20. NEUROPATHIES WITH PREDOMINANT SENSORY INVOLVEMENT Neuropathies caused by: Diabetes Carcinoma Sjögren syndrome Dysproteinemia acquired immunodeficiency syndrome vitamin B12 deficiency celiac disease. Inherited and idiopathic sensory neuropathies intoxications with cisplatin , thalidomide, or pyridoxine.

21. In most of the polyneuropathies legs are more severely affected than the arms. However, notable exceptions include Multifocal motor neuropathy Lewis-Sumner variant of CIDP Lead neuropathy Porphyria Tangier disease Familial amyloid neuropathy type 2 Hereditary motor neuropathy (uncommon forms)

22. NATURE OF SENSORY INVOLVEMENT SMALL FIBRE NEUROPATHIES Diminished pain and temperature sensation predominate, along with spontaneous burning P ain , painful dysesthesias , and autonomic dysfunction. There is preservation of tendon reflexes, balance, and motor strength.

23. Seen in : Diabetes mellitus and impaired glucose tolerance Amyloid neuropathy (early familial and primary) HIV-associated distal sensory neuropathy Hereditary sensory and autonomic neuropathies Fabry disease Tangier disease Sjögren ( sicca ) syndrome Cryptogenic small- fiber neuropathy

24. LARGE-FIBER SENSORY NEUROPATHY Selective large- fiber sensory loss is characterized by Areflexia sensory ataxia Loss of joint position and vibration sense – May present as pseudoathetosis and/or Romberg sign

25. Sensory Ataxic Neuropathies Sensory neuronopathy Paraneoplastic sensory neuronopathy (malignant inflammatory Sjögren syndrome Toxic ( cisplatin and analogs , vitamin B6 excess ) Demyelinating polyradiculoneuropathies : Guillain–Barré syndrome (Miller Fisher variant) Immunoglobulin M monoclonal gammopathy of undetermined significance CANOMAD Tabes dorsalis

26. EVIDENCE OF UMN INVOLVEMENT Presents with symmetric distal sensory involvement with e/o symmetric UMN involvement ie combined system degeneration Examples include : Vit B12 deficiency Copper deficiency HIV infection Severe hepatic insufficiency

27. EVIDENCE OF HEREDITARY NEUROPATHY Slowly progressive distal weakness Negligible sensory symptoms, yet significant sensory deficits Example : Charcot Marie Tooth disease Variable course, slow in case of CMT 1A NCS: symmetric demyelinating neuropathy with no conduction block Disabilities correlate to secondary axonal degeneration

28. ASSOCIATED MEDICAL CONDITIONS Diabetes mellitus Preceding or concurrent infection – ex: diarrhoeal disease preceding GBS Surgeries: ex: gastric bypass and nutritional neuropathies Medications : toxic neuropathy Alcohol and dietary habits

29. Clues from general survey? Pulse & BP- orthostatic hypotension without tachycardia Anaemia- Vitamin B12 deficiency, CKD Goitre- Hypothyroidism Skin & skeletal changes- DM, Leprosy , Amyloid, Connective tissue diseases.

30. GENERAL SURVEY

31. CUES FROM GENERAL SURVEY

32. INVESTIGATIONS Complete Hemogram Renal function tests Liver function tests FBS, PPBS, HBA1C, Throid function tests Urine analysis Vit B12, Folate ESR

33. Specific investigations : Mononeuritis multiplex : vasculitis work up ANCA Cryoglobulins Hepatitis serology Western blot for Lymes disease HIV CMV tire

34. Lumbar puncture – High protein : AIDP (GBS), CIDP Pleocytosis : HIV , Lyme disease, Sarcoidosis , lymphomatous , leukemic infiltration. Nerve biopsy : Vasculitis Amyloidosis Sarcoidosis Hansen disease Giant axonal neuropathy Tumour infiltration

35. T r ea t m e n t General Subtype specific Diabetes mellitus Renal insufficiency Hypothyroidism Vitamin B12 deficiency Systemic vasculitis

36. Once an agent is selected , it is started at the lowest possible dose. Titrated gradually every 3 to 7 days until significant pain relief or intolerable side effects ensue. Combinations can be used when pain is not controlled by a maximally tolerated dose of one drug.

37. References Harrisons Principles of Internal Medicine 20 th edition Bradley’s Neurology in clinical practice 7 th edition Adams and Victors Principles of Neurology

38. THANK YOU