1. ALDY S. RAMBE DEPARTEMEN NEUROLOGI FK USU/ RSUP H. ADAM MALIK MEDAN NEUROPATHY

2. DEFINITION Neuropathy is defined as a disease or injury of the peripheral sensory, motor, or autonomic nerves. Can be :- pure motor - pure sensory - mixed sensorimotor - autonomic

3. Category Usually categorized separately : Neuronopathy : selective injury to the cell body of the axon Radiculopathy : selective injury to the nerve roots distal to their origin Plexopathy : injury to the brachial or lumbosacral plexus

4. CLASSIFICATION 1. BASED ON THE ONSET OF NEUROPATHY: ACUTE NEUROPATHY eg. : ACUTE IDIOPATHIC POLYNEUROPATHY CHRONIC NEUROPTHY eg. : BERI BERI DIABETES MELLITUS LEPROSY

5. 2. BASED ON SEVERITY 1.MILD NEUROPATHY : SENSORY ONLY 2.MODERATE NEUROPATHY : SENSORY, MOTOR, AND DECREASE OF TENDON REFLEXES 3.SEVERE NEUROPATHY : SENSORY, MOTOR, DECREASE OF TENDON REFLEXES, MUSCLE ATROPHY

6. 3. BASED ON THE NUMBER OF NERVES INVOLVED 1. MONONEUROPATHY SIMPLEX : ONLY ONE PHERIPHERAL NERVE INVOLVED. 2. MONONEUROPATHY MULTIPLEX (MULTIFOCAL NEURPATHY) : MULTIPE, SCATTERED NERVES IN AN IRREGULAR DISTRIBUTION 3. POLYNEUROPATHY : SEVERAL NERVES INVOLVED, SYMMETRICAL, SAME ONSET AND DISTAL PREDOMINANT.

7. 4. BASED ON LESION SITE 1 DISTAL AXONOPATHY : AXONAL LESION 2. MYELINOPATHY : DISORDER OF MYELIN SHEATH. 3. NEUROPATHY : DISORDER OF CELL BODY AT ANTERIOR HORN CELLS, SPINAL CORD OR DORSAL ROOT GANGLION.

8. ETIOLOGY 1. IDIOPATHIC INFLAMMATORY NEUROPATHIES - ACUTE IDIOPATHIC POLYNEUROPATHY (GUILLAIN BARRE SYNDROME) -CHRONIC INFLAMMATORY DEMYELINATING POLYNEUROPATHY 2. METABOLIC AND NUTRITIONAL NEUROPATHIES -DIABETES, HYPOTHYROIDI, ACROMEGALY -UREMIA -LIVER DISEASES -VIT B1, OR VIT B12 DEFICIENCY

9. ETIOLOGY 3. INFECTIVE AND GRANULOMATOUS NEUROPATHIES: AIDS, LEPROSY. DIPHTHERY, SARCOIDOSIS 4. VASCULITIS NEUROPATHIES: - POLYARTERITIS NODOSA - RHEUMATOID ARTHRITIS - SYSTEMIC LUPUS ERYTHEMATOSUS

10. ETIOLOGY 5. NEOPLASTIC AND PARAPROTEINEMIC NEUROPATHIES: - COMPRESSION AND IRITATION BY TUMOR - PARANEOPLASTIC SYNDROME - PARAPROTEINEMIAS - AMYLOIDOSIS

11. ETIOLOGY 6. DRUGS INDUCED AND TOXIC NEUROPATHIES -DAPSONE, ISONIAZIDE, PHENYTOIN, PIRIDOXYNE, VINCRISTIN, HIDRALAZINE. - ALCOHOL - TOXINS :ORGANOPHOSPHAT ARSENIC LEAD THALIUM GOLD

12. ETIOLOGY (cont.d) 7. HEREDITARY NEUROPATHIES - IDIOPATHIC HEREDITARY MOTOR AND SENSORY NEUROPATHIES HEREDITARY SENSORY NEUROPATHIES FAMILIAL AMYLOIDOSIS - METABOLIC PORPHYRIA METACHROMATIC LEUCODYSTROPHY ABETALIPOPROTEINEMIA

13. ETIOLOGY 8. ENTRAPMENT NEUROPATHIES - UPPER LIMBS MEDIAN NERVE (CARPAL TUNNEL SYNDROME) ULNAR NERVE RADIAL NERVE - LOWER LIMBS PERONEAL NERVE FEMORAL NERVE OBTURATOR NERVE

14. PATHOGENESIS Can be divided into 4 major categories : 1.Neuronal degeneration : results from damage to the motor or sensory nerve cell bodies, with subsequent degeneration 2.Wallerian degeneration : results from damage to the axon at a specific point below the cell body, with degeneration distal to the injury. 3.Axonal degeneration : results from diffuse axonal damage. The distal portion undergoes the earliest and most severe change followed by gradual proximal ascent with continued injury (dying back phenomenon) 4.Segmental demyelination : results from injury to the myelin sheath without injury to the axon

16. PATHOPHYSIOLOGY 1. NEUROPRAXIS : - the mildest form - conduction disruption only - intact nerve continuity - recovery in minutes or weeks

17. PATHOPHYSIOLOGY 2. AXONOTMESIS: - AXONAL DAMAGE FOLLOWED BY DEGENERATION - ENDONEURAL SHEATH REMAINS INTACT - POSSIBLE REGENERATION

18. PATHOPHYSIOLOGY 3. NEUROTMESIS: - PARTIAL OR TOTAL NERVE DAMAGE - SURGICAL INTERVENTION IS NEEDED - 50% RECOVER

19. CLINICAL SYMPTOMS 1. SENSORY SYMPTOMS : Involvement of sensory axons produces impairment of sensation with dysesthesias or paresthesias.

20. CLINICAL SYMPTOMS 2. MOTOR SYMPTOMS : Involvement of motor axons produces muscle wasting and weakness followed by atrophy and fasciculations - LMN TYPE MUSCLE WEAKNESS - FOOT DROP - WRIST DROP

21. CLINICAL SYMPTOMS 3.CHANGE OF TENDON REFLEXES The tendon reflexes supplied by the affected nerve are depressed or absent. decreased or absent of tendon reflexes

22. CLINICAL SYMPTOMS 4. AUTONOMIC : Involvement of axons supplying autonomic function produces loss of sweating, alteration in bladder fuction, constipation, and impotence in male

23. DIAGNOSIS 1. CLINICAL SYMPTOMS AND SIGNS 2. LABORATORY STUDIES 3. CHEST X-RAY 4. LP 5. ECG 6. BIOPSY : sural nerve or radial cutaneus nerve 7. ELECTROPHYSIOLOGY: EMG NCV

24. DIABETIC NEUROPATHY Neuropati diabetik : adanya gejala dan atau tanda disfungsi saraf perifer pd orang dgn diabetes setelah dieksklusikan penyebab lain. Prevalence : 10 - 20 % (symptomatic) Diabetic Neuropathy : ▫ 50% of diabetic patients ▫ type 1 than type 2 ▫ the most common : chronic sensorimotor ▫ 50% asymptomatic ▫ 10-20% needs specific treatment

25. PATHOGENESIS The etiology is uncertain. 4 hypothesis (not necessarily exclusive) : 1. Hyperglycemia-polyol-myoinositol hypothesis. 2. Microvascular hypothesis 3. Structural changes at the node of Ranvier. 4. Vasculitic neuropathy.

26. DIABETIC NEUROPATHIC SYNDROMES DISTAL SYMMETRIC NEUROPATHY : - large fiber sensory neuropathy  numbness, paresthesias, dysesthesias, hyperesthesias, ataxia. - sensorimotor neuropathy  any of the above plus distal weakness

27. DIABETIC NEUROPATHIC SYNDROMES Small Fiber Neuropathy : - “pure” small fiber neuropathy  numbness, paresthesias, painful dysesthesias, hyperesthesias. - Diabetic neuropathy cachexia  subacute, severe neuropathic pain, rapid weight loss - Autonomic neuropathy  erectile dysfunction, orthostasis, cardiac dysrhythmia, diarrhea, constipation

28. DIABETIC NEUROPATHIC SYNDROMES Ischemic Mononeuropathy. - cranial (eg. CNs III, VI,VII)  diplopia, pupil-sparing third nerve palsy, hemifacial weakness - Radicular (thoracic, lumbosacral)  pain, followed by numbness or weakness in a radicular distribution - Peripheral (eg. Femoral)  pain, followed by numbness, weakness or both in territory of a single nerve

29. DIABETIC NEUROPATHIC SYNDROMES Regional Neuropathic Syndromes. - Diabetic amyotrophy  subacute weakness and atrophy of proximal leg muscles - Diabetic thoracoabdominal neuropathy.  subacute weakness, numbness, and atrophy in thorax and abdomen

30. DIAGNOSIS

31. THERAPY Intensive diabetic therapy Maintain ideal body weight Adjuvant analgetics : TCA antidepressants carbamazepine gabapentin intravenous lidocaine, etc

32. Adjuvant Analgetics

33. CARPAL TUNNEL SYNDROME 80% in WOMEN, A COMMON TEMPORARY PHENOMENON DURING PREGNANCY PRESSURE TO THE NERVE WHEN PASSING BENEATH THE FLEXOR RETINACULUM  OBSTRUCTION OF VENOUS CIRCULATION AND EDEMA  ISCHEMIA  INCREASING PRESSURE ON THE NERVE  ISCHEMIC ATROPHY OF NERVE FIBERS

34. Etiology 1. Hereditary: HMSN type III 2. Traumatic: dislocation, fracture, hematoma, wrist sprain 3. Infection: tenosynovitis, tbc, sarcoidosis 4. Metabolic: amyloidosis, gout 5. Endocrine: acromegaly, DM, hypothyroidism, pregnancy 6. Neoplastic: ganglion cysts, lipoma, myeloma 7. Collagen vascular diseases : RA, polymyalgia rheumatica, SLE 8. Degenerative disease : OA 9. Iatrogenic: radial artery puncture, shunt for dialysis, anticoagulant therapy

35. Clinical Symptoms The earliest symptoms : numbness and paresthesias in the sensory distribution of the median nerve in the hand (thumb, index, middle and lateral half of the ring finger) Later on : pain, worst at night Late : inability to screw bottle caps or grip properly

36. SIMPLE CLINICAL TESTS FOR CTS PHALEN’S SIGN (PHALEN’S MANEUVRE): is present when tingling (paresthesia) is experienced in the distribution of the median nerve when the wrist is held in forced flexion (90 o for 30-60 seconds) TINEL’S SIGN (HOFFMANN-TINEL’S SIGN) : is present when tingling (paresthesia)is experienced when tapping lightly with a finger or a tendon hammer over a compressed or regenerating peripheral nerve. The tingling is present in the distribution of the damaged nerve.

37. Therapy Identified causes should be treated Corticosteroid injection around the median nerve in the carpal tunnel. Surgical division of the transverse ligament (flexor retinaculum) Endoscopic carpal tunnel release

38. GUILLAIN - BARRE SYNDROME (GBS) ESSENTIALS of DIAGNOSIS : Rapidly progressive paralysis, often ascending Areflexia Increased CSF protein without increased cell count (albuminocytologic dissociation) Evidence of demyelination on nerve conduction studies (may be delayed) A neurologic emergency that may rapidly progress to respiratory compromise

39. GBS : Subtypes and Clinical Findings Acute inflammatory demyelinating polyneuropathy (AIDP) : - ascending paralysis - minor sensory symptoms - nonspecific antibody (Ab) - EMG/NCV : demyelination on NCS, absent F waves

40. GBS : Subtypes and Clinical Findings Acute motor axonal neuropathy (AMAN) : - flaccid paralysis - often with Campylobacter jejuni infection - IgG anti-GM1, IgG anti-GD1a - EMG/NCV : reduced motor amplitudes normal sensory studies

41. GBS : Subtypes and Clinical Findings Acute motor sensory axonal neuropathy (AMSAN) : - acute (< 1 week) - profound quadriparesis - ventilation often required - IgG anti-GM1 -EMG/NCV : reduced or absent motor amplitudes reduced or absent sensory amplitudes axonal injury by EMG

42. GBS : Subtypes and Clinical Findings Miller Fisher syndrome : - ataxia - areflexia - opthalmoplegia - IgG anti-GQ1b - EMG/NCV : decreased sensory nerve AP motor conductions often normal

43. GBS : SYMPTOMS AND SIGNS AIDP often begins 1-3 weeks after an infection or inciting event such as surgery 70% cases initially have paresthesias or vague numbness in their hands and feet. Symmetric weakness appears a few days later and progress over days to a few weeks. Paralysis is maximal by about 2 weeks in> 50% cases, and by 1 month in > 90% cases. Ascending weakness beginning in the distal legs is typical, although descending paralysis with predominant proximal muscles weakness rarely appears.

44. GBS : SYMPTOMS AND SIGNS Facial weakness occurs in half of patients with AIDP and ophthalmoparesis and lower cranial nerves neuropathies can cause dysarthriaand dysphagia. ¼ AIDP require mechanical ventilation Weakness is symmetric, and ranges from mild to severe flaccid quadriparesis. Sensation is usually normal, despite sensory symptoms, although mild distal vibratory loss may be found Reflexes are diminished or absent Sphincter tone is normal

45. GBS : DIAGNOSTIC STUDIES Imaging studies of the spinal cord  to rule out myelopathic disease. LP (after spinal cord disease excluded) Evaluation for infection ECG Chest radiographs EMG/NCV

46. GBS : DIFFERENTIAL DIAGNOSIS Acute spinal cord disease (acute myelopathy, transverse myelitis) Brainstem ischemia Acute disorders of neuromuscular junction (myasthenia gravis, botulinum intoxication) Acute neuropathies (porphiric neuropathy, diphtheritic neuropathy, mononeuropathy multiplex, toxic neuropathy)

47. THERAPY PLASMAPHARESIS (5-6 exchanges over 1- 2 weeks) or IMMUNOGLOBULIN IV (0,4 g/kg/day for 5 days)  Equally effective when given within the first 2 weeks after onset  Combination of both – no additional benefit RCTs on oral or IV corticosteroid – failed to show benefit