This document provides an overview of peripheral neuropathy including: 1. It describes a typical case of diabetic peripheral neuropathy presenting with leg weakness, numb feet, and pain. 2. It asks questions to help classify the neuropathy including type of nerve fibers involved and diagnostic approach. 3. It outlines the lesson which will define neuropathy, discuss anatomy/physiology, classification, clinical features, investigations and management.

1. Peripheral neuropathy
Dr Prabha Adhikari
Professor and HOD Geriatric Medicine
Yenepoya Medical College
Yenepoya deemed to be university

2. Typical case
• Meet Mr Monappa who complains of leg weakness, ataxia,
numb feet and sharp sudden pain at nights which is shock
like pain since 2 years
• Romberg`s Positive
• He has wasting of interrossei and unable to grip chappals
,clawing of feet .
• His sensation for touch ,vibration are absent upto knee
• Pain and temperature decreased in feet
• His bed clothes also cause pain for him
• He is a diabetic for the last 15 years on OHA and refusing to
take insulin
• He begs for sedatives ………………….

3. Questions
• What is the diagnosis ?
• What type of neuropathy is it ?
• What types of nerve fibers are involved ?
• What are the 5 questions you need to ask to
make a complete diagnosis of neuropathy and
its type?

4. Lesson plan
• Open class with a case
• Over view on Anatomy and Physiology of peripheral nerve
to answer questions
• Defnition and 5 question approach
• Aetiology ,
• Clinical features ,importance of peripheral nerve thickening
Observe sural nerve biopsy
• Autonomic neuropathy
• Classify severity of diabetic neuropathy
• Investigations
• Value of NCV and nerve biopsy and findings

5. Source -Slide share

8. Peripheral neuropathy
• Definition –Diseases of the peripheral nerve
• 5 Question approach
1.Which are the fibers?
2.Where in the body –distribution
3.When did it start ?temporal
4.Any other features of primary disease ?
5.How did it happen –Pathology
.

10. 1-Which ?-Symmetrical neuropathies
• Sensory-large fiber /small fiber
A-alpha-proprioception-large ,A beta –touch ,A
delta –sharp pain and C-slow pain-small
• Symmetrical sensory motor
• Symmetrical demyelinating
polyneuropathy,predominantly motor –CIDP
to be excluded

11. Question 1 -Asymmetrical
• Entrapment neuropathies- Carpal tunnel
syndrome ,tarsal tunnel syndrome,meralgia
paraesthetica
• Mononeuropathy due to vascular
involvemet/compression
• Diabetic amyotrophy due to Femoral Neuropathy
–severe pain, asymmetrical quadriceps weakness,
absent knee jerk
• Thoracic or cervial radiculo neuropathy
• Lumbosacral radiculoplexopathy

12. Question 2 :Where in the body
1
• Distal only length lower limbs symmetrical –axonal
2
• Phenotye CIDP- proximal and distal motor with involvement of upper limbs
• Sensory only distal lower limb minimal
3
• Multifocal acquired demyelinating sensory motor neuropathy involving
multiple asymmetrical motor and sensory areas distally

15. Multi focal acquired demyelinating
sensory and motor neuropathy

16. When did it start ?
• Acute -4 weeks
• Subacute -4 weeks 8 weeks
• Chronic -8 weeks months or more
• Relapsing and recurring –Vasculitis
,hereditaray neuropathy with pressure palsy
Toxin exposure

17. What other -Clinical features of
Primary disease
• Diabetes related complications
• Vasculitis –rashes ,kidney involevment ,arthritis
,CNS, cardiac
• Refsum disease –family history ,deafness,
abnormal toes
• Inverted champagne bottle apearance of legs,
with pes cavus –CMT disease
• Sarcoidosis –features
• Leprosy –anaesthetic skin patches ,thickened
nerves

18. D/D for Peripheral neuropathy and
thickened nerves
• Leprosy
• CIDP
• Neurofibromatosis
• Amyloidosis
• Sarcoidosis
• Refsum disease
• Charcoat Marie Tooth disease

19. What is the pathology -Mechanisms of
Damage
1.Myelin degeneration :GBS,Post Diphtheria
Hereditary sensory motor neuropathy
2.Axonal Degeneration:DM,GB,Toxic neuropathy
3.Wallerian Degeneration :trauma
4.Compression-Entrapment –Focal
demyelination
5.Infarction:vascultis ,diabetes microangiopathy
6.Infiltration:Amyloidosis,sarcoidosis,Leprosy

20. Find - Broad aetiolgical classification-
genetic,drugs,toxins,vitamin Deficiencies,
Infections,Inflammatory ,metabolic ,infiltrative diseases
critical illness
• Diabetes –Most common
• Metabolic –Uremia.Hypoxia,Thyroid dysfucntion
• Toxic-Alcohol,Heavy metals leead, arsenic
,organophosphate
• Nutritional-B1,B12,,Folic acid def B6 excess ,
• Vasculitis-Churg Strauss,PAN
• Malignancy-paraproteinemia ,paraneoplastic
• Drugs-ART,INH,amiodarone,
• Hereditary-Charcot Marie Tooth,Refsum disease
• Infections –Leprosy,HIV
• Connective tissue disease-SLE,Rheumatoid
• Infiltrative –sarcoid ,Amyloid

21. Diabetic neuropathy types
1.Symmetrical
a.Sensory neuropathy
b.Sensory motor neuropathy
c.Proximal symmetric predominant motor demyelinating neuropathy –GB
type or CIDP type
2..Asymmetrical
a.Amyotrophy –Motor neuropathy-Femoral Neuropathy
b.Entrapment Neuropathy –carpal and tarsal tunnel syndrome ,meralgia
paraesthetica
c.Cranial neuropathy
d.Plexopathy /radiculopathy
3.Autonomic neuropathy

22. Diabetic Neuropathy -Thomson
system classification (Modified )
1.Hyperglycemic neuropathy
2.Generalized symmetrical polyneuropathies
3.Sensory neuropathy
4.Sensorimotor neuropathy
5.Autonomic neuropathy
6.Focal and multifocal neuropathies-cranial and
mononeuritis /mononeuritis multiplex
7.Superimposed chronic inflammatory
demyelinating polyneuropathy

23. Clinical features
• Burning or tingling numbness,lancinating pain
• Loss of vibration,touch ,pain,temperature
• Loss of ankle jerk
• Weakness of Interossei
• Claw feet
• Collapse of arches
• Callosity ,ulcers
• Charcot`s joints
• Ataxia,Romberg`spositive

24. Painful sensory symptoms
• prickling, searing, burning, and tight band like
sensations.
• Paresthesia: Unpleasant sensations arising
spontaneously without apparent stimulus
• Allodynia: perception of nonpainful stimuli as painful.
• Hyperalgesia: Painful hypersensitivity to noxious
stimuli
• Neuropathic pain: cardinal feature of many
neuropathies.

25. Motor
• Positive :
Muscle cramps, fasciculations, myokymia, or
tremor
• Negative :
early distal toe and ankle extensor weakness,
resulting in tripping on rugs or uneven ground

26. Autonomic neuropathy
1,2
• Cardiovascular –Postural hypotension ,resting tachycardia
and Poor HRV
• Genito urinary –ED,Incontinence ,due to atonic bladder
3,4
• Gastro intestinal –Nocturnal diarrhoea ,Gastroparesis
,constipation
• Sudomotor –Nocturnal sweating
5,6
• Cold clammy skin
• Pupillary-ARP Pupils

27. Mono Neuropathy
• Focal involvement of a single nerve and
implies a local process:
• Direct trauma
• Compression or
• Entrapment
• Vascular lesions
• Neoplastic compression
• Infiltration

28. Mononeuropathy multiplex
• Simultaneous /sequential damage to multiple
noncontiguous nerves.
• Hansen's disease (leprosy)
• Ischemia caused by vasculitis
• Microangiopathy in diabetes mellitus
• Inflitration : Infectious, granulomatous,
leukemic, or neoplastic infiltration and
sarcoidosis.

29. Causes of axonal Neuropathy-
polyneuropathy• Metabolic: DM, CRF
• Drugs & Toxins: Alcohol, Vincristine, Phenytoin, TOCP,
Organophosporus, Statins
• Infections: Leprosy, HIV, Borreliosis
• Connective tissue/Vasculitic: Sjogern’s syndrome;
SLE; MCTD, RA
• Paraneoplastic: CA lung,ovary
• Inherited: CMT 2; CMT-X
• Vitamin deficiency: B12, Folate; Cobalamin, Vit E
• Endocrine: Hypothyroidism
• Paraproteinemia; Waldenstrom’s macroglobulinemia;
MGUS; POEMS syndrome

30. Neuropathies with Facial Nerve
Involvement
• Guillain-Barré syndrome
• Chronic inflammatory demyelinating
Polyneuropathy
• Lyme disease
• Sarcoidosis
• HIV

31. Autonomic dysfunction
• Diabetes
• GBS
• Amyloid sensorimotorpolyneuropathy
• Sjogren’s related neuropathies,
• Paraneoplastic
• HSAN

32. Investigations
• FPG, Hemoglobin A1c
• Complete blood count and
haeatology
• RFT/LFT
• Vitamin B-12 and folate levels
• Thyroid function tests
• Erythrocyte sedimentation rate
• C-reactive protein
• ANA,Heavy metal screen
• Serum electrophoresis
• Anti-SSA and SSB antibodies
• Rheumatoid factor
• Paraneoplastic antibodies
• Genetic screens
• Electro physiology
• Nerve Biopsy
• Autoantibodies

33. Electrodiagnostic testing-needed
1.assists in characterizing the neuropathic process as
sensory, motor or sensorimotor (What?).
2, Electrodiagnostic testing helps characterize a
neuropathy as primarily demyelinating, primarily axonal,
or mixed demyelinating and axonal(pathology )
3.help localize the neuropathic process (the “where”-
symmetrical, asymmetrical, proximal, distal, localization
to roots, plexus, nerve, radiculoplexopathy,
radiculoneuropathy)
4.help gauge the severity of neuropathy; help assess
treatment response

34. Axonal degeneration
• Most common pathological reaction of peripheral
nerve
• Caused by :Systemic metabolic disorders, toxin
exposure, and some inherited neuropathies
• Also called dying-back or length-dependent
neuropathy:
• The myelin sheath breaks down along with the
axon in a process that starts at the most distal
part of the nerve fiber and progresses toward the
nerve cell body.

35. Demyelinating neuropathies
• Relative sparing of temperature and pinprick sensation +
• 1.Early generalized loss of reflexes (large fiber,
predominantly motor neuropathy; immune mediated;
acute-subacute)
• 2.Disproportionately mild muscle atrophy but DTRs affected
• 3.Presence of proximal and distal weakness (P>D/P=D;
universal DTRs involvement)
• 4.Neuropathic tremor (Anti MAG-IgM paraproteinemic
neuropathy- CIDP like)
• 5. Palpably enlarged nerves
• 6. CSF Albumino cytologic dissociation

36. Sensitivity and specificity of clinical
tests and biothesiometer
• Tuning fork: 87-99% (sensitivity); 1-19% (specificity)
• 10 G Coarse monofilament: 16% (sensitivity); 64%
(specificity)
• 1 G Fine monofilament: 73% (sensitivity); 87%
(specificity)
• Biothesiometer: 61-80% (sensitivity); 64-76%
(specificity)

37. 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

38. Neuropathies + Serum Autoantibodies
Antibodies against ganglioside
• GM1 : Multifocal motor
neuropathy
• GM1, GD1a : Guillain-Barré
syndrome
• GQ1b : Miller Fisher variant
• CIDP can also be positive for
many of these and many
more
Antibodies against Glycoproteins
1.Myelin-associated
glycoprotein : MGUS
2.Antibodies against RNA-
binding proteins
• Anti-Hu, antineuronal
nuclear antibody 1:
Malignant inflammatory
polyganglionopathy

39. Nerve Biopsy

40. Hereditary poly neuropathy

41. Vasculitis

42. Diabetic neuropathy defintion
• the presence of symptoms and/or signs of
peripheral nerve dysfunction in people with
diabetes after exclusion of other causes."

43. Staging of diabeteic neuropathy
• NO - No neuropathy
• N1a - Signs but no symptoms of neuropathy
• N2a - Symptomatic mild diabetic polyneuropathy; sensory,
motor, or autonomic symptoms; patient is able to heel-walk
• N2b - Severe symptomatic diabetic polyneuropathy; patient
is unable to heel-walk)
• N3 - Disabling diabetic polyneuropathy

44. Complications of neuropathy
• Neuropathies cause pain and balance issues
severely decrease patients' quality of life
(QOL).
• the secondary complications (eg, falls, foot
ulcers, cardiac arrhythmias, and ileus) are
even more serious and can lead to fractures,
amputations, and even death in patients with
DM

45. Nerve conduction studies
• Conventional NCV testing includes
measurement of the speed of both motor and
sensory conduction. The amplitude of the
distal response is also measured. The proximal
component of conduction can be investigated
with H-reflex (S1 root) or F-wave (motor
pathways only) response.

46. EMG Indicated in
• distal muscles in cases of generalized
neuropathy and entrapment
• in the proximal limb muscles in amyotrophy
• limb muscles in suspected radiculopathy.

47. NCV-Distal sensorimotor neuropathy
• . have reduced or absent sensory nerve action
potentials, especially in the legs.
• With progression of neuropathy, compound
motor action potential amplitudes may also
be reduced
• Abnormalities may be observed in the hands.

48. NCV-Distal symmetrical neuropathy
• Conduction velocities are normal range or
• Only mildly slowed.
• If conduction velocities are less than 70% of
the lower limit of normal, or if conduction
block ,suspect demyelination and CIDP.
• Focal slowing of conduction velocity at
common sites of entrapment may diagnose
CTS, tarsal Tunnel S etc

49. Treatment-Glycemic Control
Symptoms
1.Pain
2.ED
3.Sweating
4.Gastroparesis
5.Diarrohoea
6.Incontinence
Treatment
• Anticonvulsants
,antedepressants ,capsasin
,and alpha lipoic acid
• Sildanafil,Injection of
prostagladin ,prosthesis
• Anticholinergics
• Domeperidone
• Loperamide,Octreotide,
antibiotics
• Anticholinergics,catheter

50. Treatment-Pain management
Anti convulsants Pregabalin 75mg -600 mg
Gabapentin
Sodium valproate
Anti depressant Duloxetine-60 mg -120 mg
Amytryptaline-25 mg -75 mg
Opiods Tramadoll
Oxy codone
Morphine
Other drugs Capsacin
Isosorbide dinitrate topical
Dextrometharphan
Non pharmacological TENS,nerve mobilisation

51. Treatment
• Control of diabetes with insulin
• Foot wear protection and foot care education
• Nerve blocks for shock like pains
• Counselling /psychosocial issues

52. Typical case
• Meet Mr Monappa who complains of leg weakness, ataxia,
numb feet and sharp sudden pain at nights which is shock
like pain-2 years
• Romberg`s Positive
• He has wasting of interrossei and unable to grip chappals
,clawing of feet .
• His sensation for touch ,vibration are absent upto knee
• Pain and temperature decreased in feet
• His bed clothes also cause pain for him
• He is a diabetic for the last 15 years on OHA and refusing to
take insulin
• He begs for sedatives ….

53. Final diagnosis
• Chronic diabetic polyneuropathy
• Symmetrical distal sensori motor
polyneuropathy
• Autonomic neuropathy
• Severe pain
• Axonal degeneration –large fiber.A- alpha,
beta and delta and C -small fiber neuropathy

54. Home work
• Observe a video of sural nerve biopsy
• Read all about CIDP and Hereditary poly
neuropathy types and clinical features

55. References
Davidson`s Principles and practice of medicine
23rd edition
Harrison`s text book of Medicine
UptoDate
E medicine –Medscape
Slide share –pictures

56. Thank You