This document provides an overview of peripheral neuropathy, including: 1. It describes the anatomy of peripheral nerves and different types of peripheral neuropathies such as mononeuropathy, mononeuropathy multiplex, polyneuropathy, polyradiculopathy, and plexopathy. 2. It outlines the various clinical presentations of peripheral neuropathy including sensory, motor, and autonomic symptoms as well as patterns of nerve fiber involvement. 3. It discusses the etiology, clinical course, investigations and management of different peripheral neuropathies.

1. APPROACH TO PERIPHERAL NEUROPATHY PROF.RUCKMANI REDDY’S UNIT M1

2. HUMAN NS-----CNS -----PNS EACH NEURON has 3 parts SOMA DENDRITES AXON

3. What forms peripheral nerve?

4. 1.DORSAL NERVE ROOT 2.VENTRAL NERVE ROOT 3.DORSAL ROOT GANGLIA 4.CRANIAL NERVES EXCEPT 1 $ 2 5.BRACHIAL & LUMBOSACRALPLEXUS 6.OTHER sensory,motor,autonomic nerves

5. Role of nerve fibres in peripheralneuropathy

6. HISTORY Onset –acute/subacute/c/c Part of body involved Sequence of involvement Symptoms -----sensory -----motor -----autonomic

7. Sensory symptoms Pain -pricking,burning type Allodynia Hyperalgesia Neuropathic pain Anaesthesia Tremors-action tremor-in a phase of PNP -slow tremor with clumsiness large fibres affected-AI,CIDP,antimyelinasso GP polyneuropathy

8. Paraesthesia marked in hands & feet objectory sensoryloss is lacking Spontaneous parasthesia -in acquired causes-60% -in inherited causes-17% Painful parasthesia –DM --ALCOHOLIC NPY --AMYLOID Why pain?loss of large touch pressure fibres Exception – FREDERICH’S ATAXIA --Purely sensory polyNP

9. Motor symptoms SPASMS DIIFFICULTY WITH FOOD INTAKE TREMOR WASTING OF MUSCLE MYOKYMIA DECREASED MANUAL DEXTERITY FASCICULATIONS WEAKNESS MUSCLE CRAMPS

10. Autonomic symptoms ANOREXIA,NAUSEA,VOMITING-GASTROPARESIS BLADDER,BOWEL,SEXUAL DYSFUNCTION HEAT INTOLERANCE SWEATING-INCREASED/DECREASED FAINTING SPELLS ORTHOSTATIC LIGHT HEADEDNESS

11. PANDYSAUTONOMIA- Amyloidosis Hereditary smallfibrePN DRUG H/O-cisplatin,nitrofurantoin,pyridoxinetoxicity FAMILY H/O-Repeated injury,c/c subcut&osteomyelitis infection PAST H/O recent infections viral diseases

12. GE-SKIN,HAIR,NAILS BULLOUS LESIONS VARIEGATE PORPHYRIA HYPERPIGMENTATION OSTEOSCLEROTIC MYELOMA-POEMS SKIN HYPERPIGMENTATION LEPROSY ANGIOKERATOMAS FABRY’S DISEASE PURPURA CRYOGLOBULINEMIA PURPURA,LIVEDORETICULARIS VASCULITIS

13. CURLED HAIR GIANT AXONAL NEURPATHY ALOPECIA THALLIUM POISONING MEE’S LINES ARSENIC/THALLIUM INTOXICATION ICTHYOSIS REFSUM’S DISEASE

14. NERVE THICKENING in NPthy LEPROSY DIABETES AMYLOIDOSIS NEUROFIBROMATOSIS REFSUM’S DISEASE DEJERINE SOTTAS DISEASE ROUSSY LEVY SYNDROME

15. DEFORMITY in NPthy Foot,hand,spine Talipes equinus Claw foot Pes cavus Kyphoscoliosis Burns Pressure sores

16. Cranial nerves Neuropathy with facial nerve damage GBS C/C inflammatory polyradiculonuropathy Lyme diasease Sarcoidosis HIV-1infection Gelsolin familial amyloid neuropathy Tangier’s disease

17. Look for-muscle wasting Strength of muscle REFLEXES –decreased/lost --sign of PNP except in spinal shock Incoordination of movements Gait abnormality-flinging/slapping gait ATAXIA CAUSE? proprioceptive deafferentiation spinocerebellar dysfunction ATAXIA WITHOUT WEAKNESS -tabesdorsalis DDs-DM,miller fisher variant,sensoryNPthy

18. Ataxia similar to cerebellar,but no nystagmus,dysarthria SENSATIONS- pin prick temperature vibration pressure position sense Proprioception assessment

19. Pattern of sensory loss Sensory loss of trunk,scalp,face d/t simultaneous damage of proximal&distal part of sensory nerve SENSORY GANGLIONOPATHY ESCUTCHEON pattern of sensory loss over abdomen and thorax SEVERE AXONAL NEUROPATHY Symmetrical,distal,legs>arms Can even progress to face POLY NEUROPATHY

20. NERVE FIBRE AFFECTED? Poor balance Diminished or absent reflexes tingling Decreased joint position sense Pin & needle sensation Decreased vibration sense numbness SIGNS SYMPTOMS LARGE FIBRE NEUROPATHY

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

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

23. 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

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

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

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

27. 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 neoplasms Vascular lesions entrapment compression Direct trauma

28. ?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

29. ?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

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

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

32. ?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

33. ?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

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

35. ?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

36. ANATOMIC PATTERN?

37. Proprioceptive weakness Distal & proximal weakness Distal weakness Vibration&proprioception>pain&temp Vibration&proprioception>pain&temp Pain&temp affected>vib,proprioception ataxia,paraesthesia Paraesthesia&weakness Dysesthesia&distal weakness rapid Acute/subacute Slow evolution Non length dependent UE,LE,face Proximal=distal Distal>proximal Length dependent NEURONAL DEMYELINATING AXONAL

38. Poor recovery Rapid recovery Slow recovery Axonal degeneration,no regeneration Demyelination&remyelination Axonal degeneration&regeneration Sensoryamplitudeaffected. radial>sural Velocity>amplitude Amplitude affected>velocity areflexia areflexia Distal areflexia NEURONAL DEMYELINATING AXONAL

39. Diabetes mellitus Diabetes mellitus MMN CMT pyridoxine CIDP HIV cisplatin diphtheria metabolic Sjogren’s GBS Toxic NEURONAL DEMYELINATING AXONAL

40. 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

41. 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

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

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

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

45. HOW TO DISTINGUISH VARIOUS LMN LESIONS?

46. Nl/dec normal absent dec/Nl DTR + absent Usually+ absent Sensoryloss absent Usually neg Can occur severe wasting absent absent Maybe+ve marked fasciculation Prox except SMA Extraoccular,bulbar distal distal Distribution of weakness ----- More in evening ------ ----- Fatigue,diurnalweakness variation Myopathy NMJ Neuropathy AHC

47. 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

48. 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

49. 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

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

51. 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

52. H/O & EXAMINATION Mononeuropathy EDx Axonal/demyeln? Any systemic disorder Entrapment/compression

53. MNPthy multiplex axonal Demyeln +focal condcn block Vasculitis/multifocal Nerve biopsy CIDP Paraprotein,HIV,lyme

54. polyNPthy axonal Sub a/c c/c Toxins/systemic disease family h/o,genetics

55. demyelination Uniform slowing,C/C Nonuniform slowing,condnblock paraprotein Family h/o,genetics c/c or suba/c-CIDP a/c-GBS

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