Peripheral neuropathies are common neurological disorders caused by dysfunction of peripheral nerves. A systematic diagnostic approach involving detailed history, physical exam, electrodiagnostic studies, and possibly additional testing is recommended to determine the nature and location of nerve lesions. Diagnostic tests should not be ordered without understanding their significance. Biopsy may be needed in some cases to confirm diagnoses like vasculitis or amyloidosis. Treatment involves managing underlying causes, IVIG or immunomodulators for rapidly progressive neuropathies, and symptomatic treatments like antidepressants, antiepileptics, and topical agents.

1. DR VINAYAK RODGE

2.  Peripheral nerve disorders are common
neurological problems caused by dysfunction of
peripheral motor, sensory, or autonomic nerves.
 The “shotgun” approach of ordering several panels
of diagnostic tests without an adequate
understanding of their significance and usefulness
should be avoided.
 A systematic diagnostic approach consists of a
detailed history, comprehensive physical and
neurological examinations, detailed
electrodiagnostic (EDX) studies, and possibly
additional testing (such as autonomic testing, skin
biopsy and nerve biopsy).

3.  The peripheral nerve is a cable-like structure containing
bundles of both unmyelinated and myelinated fibers and their
supporting elements.
 The unmyelinated axons are surrounded only by the plasma
membrane of a Schwann cell.
 The myelinated axons are surrounded completely by myelin
and Schwann cells except at regular gaps called the nodes of
Ranvier, which measure approximately 1 μm in adults.
 The propagation of action potentials from one node of
Ranvier to the next (saltatory conduction) is maintained by a
thick myelin sheath with low capacitance and high resistance
to electric current and by a high concentration of voltage-
gated sodium channels at the nodes of Ranvier.

5. 1. Peripheral neuropathies
(usually sensory motor):
.Myelinopathies,
.Axonopathies
2. Neuronopathies
(pure sensory or pure motor)
.Sensory neuronopathies (ganglionopathies)
.Motor neuronopathies ( MND )

6. Clues:
 global arreflexia, proximal and distal involvement .
 Weakness>>wasting, large fibre involvement, good
recovery.
 motor >> sensory deficits
 NCS -Can discriminate inherited from acquired
-Distal motor latency prolonged (>125% ULN)
-Conduction velocities slowed (<80% LLN)
- May have conduction block
 EMG: Reduced recruitment w/o much denervation

8. . Clues
Legs>> arms. Distal >>prox,
DTRs preserve till last, wasting more. Small
fiber involvement, poor recovery .
NCVs: CMAPs ↓ 80% lower limit of normal
w/o or minimal velocity or distal motor
latency change
 EMG: Signs of denervation (acute, chronic)
and reinnervation
 Causes; toxic, metabolic and endocrine

10. 1. Sensory neuronopathies (polyganglionopathies)
 Paraneoplastic sensory neuronopathy (malignant
inflammatory sensory polyganglionopathy):
 Sjögren syndrome, Sarcoidosis, HIV.
 Idiopathic
 Toxic (cisplatin , vitamin B6 excess)
2. Chronic immune sensory polyradiculopathy
3. Demyelinating polyradiculoneuropathies:
 Guillain–Barré syndrome (Miller Fisher variant)
 Immunoglobulin M monoclonal gammopathy of
undetermined significance
4. CANOMAD*
5. Tabes dorsalis
*Chronic ataxic neuropathy with ophthalmoplegia, IgM
paraprotein, cold agglutinins and anti-GD1b disialosyl antibodies.

12.  Mononeuropathies;-
..At Entrapment site(median, ulnar, commen
peroneal nerve ) leprosy, DM, pregnency,
myxedema, acromegaly, RA, or
..as a part of more generalized disorder like (
HNPP, Amyloidosis )
 Multiple mononeuropathy (mononeuritis
multiplex)-
..if two or more isolated nerves in separate areas
of the body are affected pattern is called as
mononeuritic multiplex.

13. 1.AXONAL INJURY
 Vasculitis
 Diabetes mellitus
 Sarcoidosis
 Hansen disease (leprosy)
 Human immunodeficiency virus 1 infection
2. DEMYELINATION
 Multifocal motor neuropathy
 Multifocal acquired demyelinating sensory and motor
neuropathy (Lewis-Sumner syndrome)
 Multiple compression neuropathies (hypothyroidism,
diabetes)
 Hereditary neuropathy with liability to pressure palsies

14.  Polyneuropathy; ( length dependent manner with
longest nerves first, Dying-back (distal symmetric
axonal) neuropathies
..initially involve the tips of the toes and progress
proximally in a stocking-glove distribution
(DM, TOXINS, DRUGS, METABOLIC,HERIDIETARY)
Symmetrical polyneuropathy
Asymmetrical polyneuropathy
..Peripheral neuropathy can present as restless leg
syndrome
 Polyradiculoneuropathy (both distal and proximal )
(AIDP, CIDP,VASCULITIS)

16. Nociceptive pain
 caused by damage to body tissue and usually
described as a sharp, aching, or throbbing pain.
This can be due to benign pathology; or by tumors
or cancer cells that are growing larger and
crowding other body parts near the cancer site
Neuropathic pain -
 when there is actual nerve damage. Nutritional
imbalance, alcoholism, toxins, infections or auto-
immunity. A pain can be burning or heavy
sensation, or numbness along the path of the
affected nerve.
 Neuropathic pain can be dull and poorly localized (C
fibre ) (protopathic pain), or sharp and lancinating (A
delta fiber )(epicritic pain).

17.  Diabetes and Pre-Diabetes
 Guillain-Barré syndrome
 Vitamin B12 deficiency
 Alcohol neuropathy
 Heavy metals poisoning
 Chemotherapy
 Vasculitis and Connective Tissue Diseases
 HIV
 Amyloidosis
 Porphyria

19.  Paresthesias -spontaneous pins and needles
sensation.
 Dysesthesias -inappropriate sensation to
stimulus.
 Allodynia- perception of nonpainful stimuli as a
painful.

21.  Multifocal motor neuropathy*
 Acute motor axonal neuropathy*
 Guillain–Barré syndrome
 Chronic inflammatory demyelinating
polyradiculoneuropathy
 Neuropathy with osteosclerotic myeloma
 Diabetic lumbar radiculoplexopathy
 Hereditary motor sensory neuropathies (Charcot–Marie–
Tooth disease)
 Lead intoxication
*Pure motor syndromes with normal sensory nerve action
potentials.

23. ACUTE
 Paraneoplastic autonomic neuropathy
 Guillain–Barré syndrome
 Porphyria
 Toxic: vincristine.
CHRONIC
 Diabetes mellitus
 Amyloid neuropathy
 Paraneoplastic sensory neuronopathy (malignant
inflammatory sensory polyganglionopathy)
 Human immunodeficiency virus-related autonomic
neuropathy
 Hereditary sensory and autonomic neuropathy

25.  DM, hypothyroidism
 Metabolic- chronic renal failure , liver disease
 Nutritional- malabsorption, gastric surgery,
pancreatitis.
 Drug use
 HIV risk factors
 Diet (nutrition), alcohol, vitamin use (especially B6)
 Tick bite (Lyme disease)
 Constitutional symtoms (malignancy)
 Leprosy (hypo/hyperpigmeted anesthetic patches over
the body)
 Autoimmune (CTD, vasculitis )- joint pain , rash
 Toxin exposure- OP, lead, arsenic, thallium)
 Denctures –fixaives contain zinc lead to copper
deficiency.

26.  Axonal
 Vincristine, Paclitaxel, Nitrous oxide, Colchicine
Probenecid, Isoniazid, Hydralazine,
Metronidazole, Pyridoxine, Didanosine, Lithium,
Alfa-interferon, Dapsone, Phenytoin, Cimetidine,
Disulfiram, Chloroquine, Ethambutol,
Amitriptyline.
 Demyelinating
 Amiodarone, Chloroquine, Gold
 Neuronopathy
 Thalidomide, Cisplatin, Pyridoxine

27.  Pallor- B12 deficincy,
 clubbing-paraneoplastic ,HTN- AIDP, poephyria ,PAN,
CKD,
 Knuckle hyperpigmentation- b12 deficiency
 Mees line , rain drop pigmentation- arsenic poisoning
 Bartolin lines over gum s- lead exposure
 Scoliosis, high arched feet, hammer toes , inverted
champagne bottle appearance –HSMN
 Diarrhea /steatorrhea –gluten ataxia , celiac disease
,abetalipoproteinemia .
 h/o stroke- fabry disease (painful paresthesia, small
fibre neuropathy ,angiokeratoma aroung ambilicus )

28.  Mental retardation- CMTX2,CMTX4
 DEAFNESS-CMT2A, CMTX4, mitocondrial , refsums
 Painless ulcers- leprosy, CMT2B ( SEVERE SENSORY LOSS, SEVERE
FOOT ULCERS , HYPERKERATOSIS)
 UPPER LIMB PREDOMINENT –CMT2D
 Seizures- mitocindrial diseaSES
 ORANGE TONSIL –TANGIERS DISEASE
 Cranial nerve (3,4 & 6)-miller fisher, botulism, mitochondrial
neuropathies .
 Funduscopic examination may show abnormalities such as optic
pallor, which can be present in vitamin B12 deficiency, alcohol,
cisplatin, ethambutol and heridietary .

29.  Guillain–Barré syndrome
 Lyme disease
 Sarcoidosis
 Chronic inflammatory demyelinating
polyradiculoneuropathy (rare)
 Human immunodeficiency virus 1 infection

31.  Hypertrophy of a single nerve trunk
1. Neoplastic process (e.g., neurofibroma,
schwannoma, malignant nerve sheath tumor) or
Localized perineurial hypertrophic neuropathy.
 Generalized or multifocal nerve hypertrophy
1. leprosy,
2. Neurofibromatosis,
3. Charcot–Marie–Tooth disease -types 1 and 3,
4. Acromegaly,
5. Refsum disease, and rarely CIDP

32.  Multifocal motor neuropathy
 Lewis-Sumner variant of CIDP
 Lead neuropathy*
 Porphyria
 Tangier disease
 Familial amyloid neuropathy type 2
 Hereditary neuropathy ( CMT1 ,CMT 2D )
*Frequently presents with wrist drop.

33.  Screening laboratory tests.
Tests with the highest yield of abnormality:
 1. blood glucose (fasting)
 2. serum B12 level
 3. SPEP (serum protein electrophoresis).

34.  ANA, RF, Anti-dsDNA, Anti-Ro, Anti-La,
 ANCA screen, cryoglobulins
 Urine for heavy metals, porphyrins
 IFE/urine IFE/ plasma light chain analysis
 CBC, ESR, HIV, HBsAg, and Anti HCV .
 Csf study-
..Csf protein raised (albuminocytological
dissociation) –AIDP,CIDP
..Significant pleocytosis-HIV, Borrelia, sarcoidosis

35.  (1) Confirming the presence of neuropathy,
 (2) Locating focal nerve lesions,
 (3) Nature of the underlying nerve pathology

37.  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.

38.  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

40.  Nerve to be biopsied
- it should be distal (most neuropathies affect
longest fibre first ), accessible to conduaction
study, constant anatomic course,
 Sural nerve is selected most commonly.
 Radial cutaneous and superficial peroneal nerve –
alternative;
 Allowing simultaneous biopsy of superficial
peroneal nerve and peroneus brevis muscle
through the same incision increases yield of
identifying suspected vasculitis

41. ESSENTIAL FOR DIAGNOSIS
 Vasculitis*
 Amyloidosis*
 Sarcoidosis*
 Hansen disease (leprosy)
 Giant axonal neuropathy
 Tumor infiltration
ONLY SUPPORTIVE OF DIAGNOSIS
 Charcot–Marie–Tooth disease types 1 and 3
 CIDP
 Paraproteinemic neuropathy .
*Consider combined distal nerve and muscle biopsies.

42.  Skin biopsy may be considered to diagnose SFSN
,when nerve conduction studies, are normal.
 The diagnosis of small-fiber neuropathy is best
accomplished when at least two abnormal results
are met, including positive clinical findings,
quantitative autonomic testing {deep breathing,
valsalva maneuver ,head up tilt and QSART-
Quantitative sudomotor axon reflex test } , and
skin biopsy examinations
 3 mm circular skin punch biopsy usually taken
from lower calf , distal thigh and proximal thigh
areas.
 Quantification of epidermal nerves done.

44.  DADS (distal acquired demyelination sensory
or sensory motor neuropathy) DADS varient
of CIDP- Anti –MAG( IgM )
 CIDP- P0, MYELIN P2 PROTEIN, PMP22
 Acute pharyngeal cervicobrachial neuropathy
APCBN – Anti GT1A
Battery for CMT (cover 65-70% of CMT)
 Demyelinating;-CMT 1A(PMP22), CMT1B (MPZ
DNA sequencing),CMTX1( CX32 )
 Axonal;-CMT 2A (MFN2 Mutation)

45.  3 Goals:: 1. Where the lesion is?
2. What is the cause of the lesion?
3. What is the possible therapy?
 In order to accomplish the goal of determining the site and
cause of the lesion, the clinician gathers information from the
history, the neurologic examination and various laboratory
studies.
 While gathering this information, six key questions are asked
and the patient is placed into 9 different phenotype patterns.
Therefore, it is the 3-6-9 step clinical approach to
neuropathy:
 3 goals – 6 key questions- 9 phenotypic patterns.

52.  Slow progression
Treat causative factors if possible
 If rapidly progressing
IVIG
Immunomodulating agents
Symptomatic

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

54.  Antiepileptic Drugs- Carbamazepine,
phenytoin,
 SSRI’s
 Opioid analgesics- Tramadol

55.  First line drugs
 • Tricyclic antidepressants
 • Gabapentin
 • Pregabalin p.o.
 • Duloxetine
 Second line
 • Carbamazepine
 • Phenytoin
 • Venlafaxine
 • Tramadol

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

57. THANKS