Peripheral neuropathy

types of neuropathy
classification and management

1. Approach to peripheral neuropathy Dr. Anoop.K.R Dept of General Medicine

2. Generalized term including disorders of any cause affecting PNS May involve sensory nerves, motor nerves, or both May affect one nerve ( mononeuropathy ), several nerves together ( polyneuropathy ) or several nerves not contiguous ( Mononeuropathy multiplex ) 2 Definitions

3. Further classified into those that primarily affect the cell body (e.g., neuronopathy or ganglionopathy ), myelin ( myelinopathy ), and the axon ( axonopathy )

4. Most common causes Disease Diabetes 1 2 Paraproteinaemia 2 3 Alcohol misuse 1 Renal failure 1 Vitamin B-12 deficiency 1 HIV infection 1 Chronic idiopathic axonal neuropathy 4 Prevalence 11-41% (depending on duration, type,and control ) 9-10% 7% 4% 3.6 % 16% (depending on the population studied, usually much lower) 10-40% of different hospital series BMJ 2010:341:c6100

5. Loss of function “- symptoms” Disordered function “+ symptoms” Sensory “Large Fiber” ↓ Vibration ↓ Proprioception Hyporeflexia Sensory ataxia Paresthesias Sensory “Small Fiber” ↓ Pain ↓ Temperature Dysesthesias Allodynia The clinical response to sensory nerve injury

6. Loss of function “- symptoms” Disturbed function “+ symptoms” Motor nerves Large fibre Wasting Hypotonia Weakness Hyporeflexia Orthopedic deformity Fasciculation Cramps The clinical response to motor nerve injury

7. Loss of function “- symptoms” Disturbed function “+ symptoms” Autonomic nerves ↓ Sweating Hypotension Urinary retention Impotence Vascular color changes ↑ Sweating Hypertension The clinical response to autonomic nerve injury

8. Axonopathies By far the majority of the toxic, metabolic and endocrine causes NCVs: CMAPs ↓ 80% lower limit of normal w/o or min velocity or distal motor latency change. Legs>> arms. EMG: Signs of denervation (acute, chronic) and reinnervation

9. Myelinopathies Unusual by comparison with axonopathies Clues: hypertrophic nerves on exam global arreflexia weakness without wasting motor >> sensory deficits NCS can discriminate inherited from acquired NCS: Distal motor latency prolonged (>125% ULN) Conduction velocities slowed (<80% LLN) May have conduction block EMG: Reduced recruitment w/o much denervation

10. Causes of large fibre/ataxic NP SJOGREN’S SYNDROME VIT B12 NEUROPATHY CISPLATIN PYRIDOXINE NEUROTOXICITY FRIEDEREICH’S ATAXIA

11. SMALL FIBRE NEUROPATHY PAIN-burning,shock like,stabbing,prickling,shooting,lancinating Allodynia Decreased pinprick sensation Tight band like pressure Insensitive to heat and cold Diminished temperature sensation

12. Causes of small fibre neuropathy (painful NP&dissociated sensory loss) Heriditary sensory neuropathy Lepromatous leprosy Diabetes mellitus Amyloidosis(early familial&primary) Tangier disease Fabry’s disease-pain predomonates Dysautonomia-riley-day syndrome HIV & antiretroviral therapy neuropathy

13. SMALL & LARGE FIBRE NEUROPATHY Global sensory loss Carcinomatous sensory neuropathy Hereditary sensory neuropathy Diabetic sensory neuropathy Vacor intoxication Xanthomatous neuropathy of primary biliary cirrhosis

14. Motor predominant neuropathy Immune neuropathies Heriditary motor sensory neuropathies Acute intermittent porphyria Diphtheritic neuropathy Lead neuropathy Brachial neuritis Diabetic lumbosacralplexus neuropathy

15. Autonomic Acute-pandysautonomia -botulism -porphyria -GBS -Amiodarone -vincristine Chronic-amyloid,diabetes,sjogren’s,HSN 1&3,chagas,paraneoplastic

16. Distribution of neuropathy ?MONONEUROPATHY Focal involvement of a single nerve Weakness & sensory loss in the territory of a single peripheral nerve Pain along the pathway of the nerve Direct trauma compression entrapment Vascular lesions neoplasms

17. ?MONONEUROPATHY MULTIPEX Random pattern of nerve involvement In distribution of separate nerves,asymmetric May/may not be painful Not length dependent Isolated reflex loss CAUSES —inflammatory-leprosy,sarcoid Vascular-Diabetes Pressure,Trauma,Infiltration Vasculitis-PAN,SLE,RA,scleroderma Immune-vaccination

18. ?POLYNEUROPATHY MC type –Distal symmetric polyneurpathy Burning sensation,tingling,numbness Length dependent pattern Starts in feet,distal stocking glove pattern Fairly symmetric Symmetrically decreased reflexes Sensory>motor

19. CAUSES Diabetes mellitus Alcohol Vit B12 deficiency HIV Although more than one nerve involved one will be prominant

20. DDs of distal symmetricNP Lumbosacral polyradiculopathy/stenosis Myelopathy-structural -nonstructural Vascular insufficiency-exercise related cramps,aching pain>numbness Orthopedics –stress #,plantar fascitis

21. ?POLYRADICULOPATHY Disease of multiple peripheral nerve roots Asymmetric with erratic distribution-proximal in one,distal in another Pain is a common feature ?MONORADICULOPATHY Root disease by disease of spinal column Changes in distribution of spinal nerve root

22. ?SENSORY NEURONOPATHY Ganglion cells predominantly affected Both proximal & distal involvement Sensory ataxia is common No weakness But awkward movement d/t sensory disturbances ?MOTOR NEURONOPATHY Disorder of ant horn cells Weakness,fasciculation,atrophy Not properly a process of peripheral NP

23. ?PLEXOPATHY Asymmetric Painful onset Multiple nerves in a single limb Rapid onset of weakness,atrophy Isolated reflex loss

24. ?polyneuritis cranialis a/c idiopathic polyneuritis Peripheral nerve+cranial nerve involvement Self limiting painful ophthalmoplegia CAUSES-TB meningitis osteomyelitis skull otitis media syphilitic meningitis sarcoidosis carcinomatous meningitis

25. COURSE OF DISEASE 1.syndrome of a/c ascending motor paralysis a.acute idiopathic polyneuritis b.IMN with polyneuritis c.diphtheria d.hepatitis with polyneuritis e.porphyria f.TOCP poisoning g.paraneoplastic h.post vaccinial

26. 2.syndome of subacute sensorymotor NP A.Deficiency=alcoholic beriberi pellagra vit B12 B.Toxins=arsenic,lead,Hg,Pb C.Drugs=nitrofurantoin,INH dapsone,disulfiram clioquinol D.Uremic E.DM,PAN,sarcoidosis A,B,C,D====SYMMETRIC

27. 3.C/C sensorimotor polyneuropathy syndrome GENETIC ACQUIRED Peronealmuscle atrophy/CMT leprosy Dejerine sottas disease Diabetes mellitus Hereditary sensory NP uremia Portugeseamyloidosis/ andrade’s disease carcinoma Refsum’s disease myeloma A beta lipoproteinemia paraproteinemia Tangier’s disease amyloidosis Metachromaticleucodystrophy

28. RECURRENT POLYNEUROPATHY Relapsing CIDP Porphyria Refsum’s disease HNPP GBS Beriberi Toxic neuropathy

29. SENSORY ATAXIC NEUROPATHY Sensory NP(polyganglionopathy) Paraneoplastic sensory NP=sjogren’s =idiopathic Toxic=cisplatin =vit B6 excess Demyelinating polyradiculopathy=MGUS =Millerfisher

30. Clues for diagnosis

31. Constitutional symptoms DM hypothyroidism chronic renal failure liver disease intestinal malabsorption malignancy connective tissue diseases [HIV] drug use Vitamin B6 toxicity alcohol and dietary habits Weight loss, malaise, and anorexia.

32. Conditions Associated with Painful Peripheral Neuropathy Diabetes and Pre-Diabetes Alcohol neuropathy Chemotherapy Platinum-based Paraproteinemia Vasculitis and Connective Tissue Diseases Heavy metals and other toxins HIV Amyloidosis Porphyria

33. Medications Causing Neuropathies Axonal Vincristine Paclitaxel Nitrous oxide Colchicine Probenecid Isoniazid Hydralazine Metronidazole Pyridoxine Didanosine Lithium Alfa interferon Dapsone Axonal - continued.. Phenytoin Cimetidine Disulfiram Chloroquine Ethambutol Amitriptyline Demyelinating Amiodarone Chloroquine Suramin Gold Neuronopathy Thalidomide Cisplatin Pyridoxine

34. ETIOLOGICAL CLASSIFICATION 1. metabolic -DM,amyloidosis,porphyria 2. infections -leprosy,HIV,CMV,syphilis, diphtheria,lymedisease 3. immune - GBS,CIDN,MMN 4. hereditary -CMT 5 .Toxic -drugs,alcohol,heavymetals 6. vasculitis -PAN,CSS,cryoglobulinemia 7. paraneoplastic -lung 8. nutritional - B1,B6,B12

35. Proximal Symmetric Motor Polyneuropathies Guillain-Barré syndrome Chronic inflammatory demyelinating polyradiculoneuropathy Diabetes mellitus Porphyria Osteosclerotic myeloma Waldenstrom's macroglobulinemia Monoclonal gammopathy of undetermined significance Acute arsenic polyneuropathy Lymphoma Diphtheria HIV/AIDS Lyme disease Hypothyroidism Vincristine (Oncovin, Vincosar PFS) toxicity

36. History The temporal course of a neuropathy varies, based on the etiology. With trauma or ischemic infarction, the onset will be acute, with the most severe symptoms at onset. Inflammatory and some metabolic neuropathies have a subacute course extending over days to weeks. A chronic course over weeks to months is the hallmark of most toxic and metabolic neuropathies.

37. History A chronic, slowly progressive neuropathy over many years occurs with most hereditary neuropathies or with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Neuropathies with a relapsing and remitting course include CIDP, acute porphyria , Refsum's disease, hereditary neuropathy with liability to pressure palsies (HNPP), familial brachial plexus neuropathy, and repeated episodes of toxin exposure.

38. Ischemic neuropathies often have pain as a prominent feature. Small-fiber neuropathies often present with burning pain, lightning-like or lancinating pain, aching, or uncomfortable paresthesias (dysesthesias). History

39. Dying-back (distal symmetric axonal) neuropathies initially involve the tips of the toes and progress proximally in a stocking-glove distribution. History

40. Peripheral neuropathy can present as restless leg syndrome. Proximal involvement may result in difficulty climbing stairs, getting out of a chair, lifting and bulbar involvement can also be seen History

41. The clinical assessment should include: careful past medical history, looking for systemic diseases that can be associated with neuropathy, such as diabetes or hypothyroidism. History

42. All patients should be questioned regarding HIV risk factors diet (nutrition) vitamin use (especially B6) possibility of a tick bite (Lyme disease) Constitutional symtoms (malignancy) History

43. Differential Diagnosis of Neuropathies by Clinical Course Acute onset (within days) Subacute onset (weeks to months) Chronic course/ insidious onset Relapsing/ remitting course Guillain-Barré syndrome Maintained exposure to toxic agents/medications Hereditary motor sensory neuropathies Guillain-Barré syndrome Acute intermittent porphyria Persisting nutritional deficiency Dominantly inherited sensory neuropathy CIDP Critical illness polyneuropathy Abnormal metabolic state CIDP HIV/AIDS Diphtheric neuropathy Paraneoplastic syndrome Toxic Thallium toxicity CIDP Porphyria

44. Physical Examination A cranial nerve examination can provide evidence of mononeuropathies . Funduscopic examination may show abnormalities such as optic pallor, which can be present in leukodystrophies and vitamin B12 deficiency.

45. Thickened nerves Physical examination

46. Assessing Autonomic Nervous System Cardiovagal Heart rate variability Adrenergic Valsalva maneuver Induces BP changes and monitors pulse reaction Postganglionic sudomotor function QSART

47. Recommendations for lab testing: Screening laboratory tests may be considered for all patients with DSP (Level C). Tests with the highest yield of abnormality: 1. blood glucose (fasting) 2. serum B12 with metabolites ( methylmalonic acid, homocysteine ) 3. SPEP(serum protein electrophoresis) (Level C).

48. Other laboratory studies ANA, RF, Anti- dsDNA , Anti-Ro, Anti-La, ANCA screen, cryoglobulins Urine for heavy metals, porphyrins IFE/urine IFE/ plasma light chain analysis

49. INVESTIGATIONS BLOOD TC,DC,ESR Urea,electrolytes,LFT RBS,HbA1C Serum protein electrophoresis Auto Ab=ANA,Antiganglioside,Antineuronal Vit B 12 level DNA analysis=chr 17 duplication-HMSN1&1A =chr 17 deletion -HLPP

50. URINE BJ protein Porphyr ia Heavy metals CSF ANALYSIS NERVE CONDUCTION STUDY Variation in axonal,demyelinating neuropathy Conduction block-CIDP,GBS,MMN EMG -muscle denervation changes Sensory threshold Thermal & vibration threshold

51. Neuropathies + Serum Autoantibodies Antibodies against Gangliosides GM 1 : Multifocal motor neuropathy GM 1 , GD1a : Guillain-Barré syndrome GQ1b : Miller Fisher variant Antibodies against Glycoproteins Myelin-associated glycoprotein : MGUS Antibodies against RNA-binding proteins Anti- Hu , antineuronal nuclear antibody 1: Malignant inflammatory polyganglionopathy

52. Electrodiagnostic studies (1) Confirming the presence of neuropathy, (2) Locating focal nerve lesions, (3) Nature of the underlying nerve pathology

53. Distal motor latency prolonged Nerve conduction velocity slow Reduced action potential

54. The limitations of EMG/NCS should be taken into account when interpreting the findings. There is no reliable means of studying proximal sensory nerves. NCS results can be normal in patients with small-fiber neuropathies Lower extremity sensory responses can be absent in normal elderly patients. EMG/NCS are not substitutes for a good clinical examination. Laboratory Evaluation

55. IMAGES CXR-sarcoidosis,malignancy Skeletal survey-multiple myeloma Screening for malignancy AUTONOMIC FUNCTION TESTS Diagnostic tests imp in Asymmetric,motor predominant,rapid onset,demyelinating neuropathy

56. NERVE BIOPSY-indications sural,sup peroneal&sup radialN VASCULITIS GIANT AXONAL NPthy AMYLOIDOSIS Infantile neuroaxonal dystrophy SARCOIDOSIS CMT 1&3 LEPROSY CIDPolyradiculoneuropathy KRABBE’S Paraprotein neuropathy METACHROMATIC LEUKODYSTROPY

57. Nerve biopsy In vasculitis , amyloid neuropathy, leprosy, CIDP, Inherited disorders of myelin, and rare axonopathies The Sural nerve is selected most commonly The superficial peroneal nerve – alternative; :advantage of allowing simultaneous biopsy of the peroneus brevis muscle through the same incision. This combined nerve and muscle biopsy procedure increases the yield of identifying suspected vasculitis

58. Skin biopsy “For symptomatic patients with suspected polyneuropathy, skin biopsy may be considered to diagnose the presence of a polyneuropathy, particularly SFSN.”

59. Slow progression Treat causative factors if possible If rapidly progressing IVIG Immunomodulating agents Symptom Management Treatment

60. Tricyclic antidepressants Amitryptilin , nortryptilin Calcium channel alpha-2-delta ligands Gabapentin , pregabalin SNRI’s Duloxetine , venlafaxine Topical Agents Lidocaine , Capsaicin Symptom Management

61. Antiepileptic Drugs Carbamazepine , phenytoin , lacosamide SSRI’s Opioid analgesics Tramadol Miscellaneous Botulinum toxin Mexiletine Alpha lipoic acid Symptom Management

62. Physical Therapy Gait and balance training Assistive devices Safe environment Footwear at all times Foot hygiene

63. Thanks