.............

1. Approach to Peripheral Nerve
Disease
Dr N Anand

2. •History –Questions to be asked
•Examination-What are typical Signs that
implicate Peripheral Nerve from other causes
•Electrodiagnostic Studies
•Diagnosis and Treatment

3. Symptoms
Early features
Distal numbness and tingling
Distal neuropathic pain
Gait imbalance
Toe weakness
Latter features
Progression of numbness and tingling to proximal body parts
Prominent neuropathic pain
Tripping easily
Worsening of gait
frequent falls
Complaints

4. Motor Symptoms
Positive Muscle Cramps,Fasciculations,Myokymia(or Tremors)
Negative Weakness, Atrophy, Walking Difficulty
Difficulty in turning keys in locks, unfasten button and opening
bottles and jars
Sensory Symptoms
Positive Paresthesia, Band-like sensation on feet or trunk,Stumbling, Tingling
Pain- Prickling, Searing, Burning,Pins and Needles
Neuropathic Pain
Allodynia, Hyperalgesia
Negative Numbness,
Lack of feeling/Loss of sensation,
Walking on cotton wool

5. Autonomic Symptoms
• Anhidrosis
• Orthostatic Hypotension
• Intolerance to light
• Lack of tear and saliva
• Sexual impotence
• Bladder and Bowel dysfunction
• Gastroparesis
• Heat Intolerance

6. Temporal evolution?

7. Onset, Duration
and Evolution of
symptoms
Acute(days to 4 weeks) GBS,Vasculitis,Radiclupathies,Toxic
neuropathies,Acute intermittent
Porphyria)
Subacute (4-8 weeks)
Chronic(>8 weeks) Most Neuropathies
(Diabetes,CRF,CIDP,Paraneoplastic,
Hereditary motor sensory
neuropathies)
Course Monophasic
Progressive
Relapsing CIDP,Porphyria,Toxic,HIV/AIDS,

8. Relevant History

9. Clues to diagnosis
• Viral illnesses
• lifestyle, and work and occupational exposure
• Alcohol abuse, vitamin deficiencies, and dietary habits
• Use of over-the-counter drugs, Vitamin B6 and zinc consumption
• Gastric bypass surgery(Copper Deficiency)
• Medications prescribed in the past
• HIV infection
• Diabetes

10. • Previous Diseases- amyloidosis, a history of thyroid disease, chronic renal
and liver disease,
• Malignancy, previous treatment with chemotherapeutic agents
• Connective tissue disorders
• recreational use of substances, and exposure to heavy metals, industrial
agents, herbicides, and pesticides
• foreign travel(leprosy)
• A detailed family history for presence of hammer toes, high arches, weak
ankles, gait abnormalities or “muscular dystrophy,” suggesting a longstanding
or hereditary neuropathy.
• possibility of a tick bite (Lyme disease)
• it is not uncommon to find more than one in the same patient, such as
diabetes, alcohol abuse, and vitamin b 12 deficiency

11. Drugs causing Neuropathies
Axonal Demyelinating
Vincristine
Paclitaxel
Nitrous oxide
Colchicine (Probenecid, Col-
Probenecid)
Isoniazid
Hydralazine Metronidazole
Pyridoxine
Didanosine
Lithium
Alfa interferon
Dapsone
Phenytoin
Cimetidine
Disulfiram
Chloroquine
Ethambutol Amitriptyline
Amiodarone
Chloroquine and Hydroxychloroquine

12. Examination

13. Examination
• Abnormal Sensation especially Distal
• Weakness(typically Distal,but may be proximal/both)
• Normal Muscle Tone-No Spasticity
• Absent Tendon Reflexes
• Abnormal Gait
• Is there a evidence of UMN involvement- Consider combined system
degeneration with neuropathy-Vitamin B 12 deficiency,copper
deficiency,HIV,Severe Hepatic Disease,adrenomyeloneuropathy)

14. Signs
Early Signs
Distal sensory loss to cold, pinprick, and/or vibration
Reduced or lost ankle reflex
Romberg sign
Impaired tandem walking
Toe extensor weakness
Latter features
Distal loss of cold, pinprick, vibration, and joint position sense
Areflexia at ankles and knees
Footdrop
Inability to toe-and-heel walk

15. Cranial Nerve Involvement

16. Cranial Nerve Involvement
• External ophthalmoplegia - Miller Fisher syndrome
• Trigeminal sensory loss - Sjogren's syndrome
• Lower cranial nerve palsy with gynecomastia-Kennedy's syndrome
• Facial nerve palsy –GBS, Leprosy, Lyme Disease, Sarcoidosis, HIV

17. Distribution-Focal or multifocal

18. • Mononeuropathy, the neurological deficit follows the distribution of
a single nerve. Eg- foot drop due to a common fibular (peroneal)
nerve lesion(sensory loss is restricted to the lower two-thirds of
thelateral leg and dorsum of the foot) Causes-Leprosy,Entrapment
neuropathy,trauma
• Multiple mononeuropathies (mononeuropathy multiplex), the
neurological findings should point to simultaneous or sequential
damage to two or more noncontiguous peripheral Nerves. Eg-
Diabetes,Vasculitis

19. Causes of Multiple Mononeuropathies
Axonal injury Demyelination
Vasculitis (systemic, nonsystemic)
Diabetes mellitus
Sarcoidosis
Hansen disease (leprosy)
Human immunodeficiency virus 1
infection
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

20. Motor or Sensory
Symmetric or Asymmetric
Proximal or Distal

21. Distribution of Motor and Sensory Involvement
• Predominant Motor
Guillain-Barré syndrome
Chronic inflammatory demyelinating polyradiculoneuropathy
Neuropathy with osteosclerotic myeloma
Diabetic lumbar radiculoplexopathy(Amyotrophy)
Hereditary motor sensory neuropathies (Charcot-Marie-Tooth
disease)
Porphyria
Lead intoxication
Multifocal motor neuropathy
Paraneoplastic
Acute motor axonal neuropathy

22. Asymmetric Weakness Without Sensory Loss
• -a motor neuronopathy such as motor neuron disease or multifocal
motor neuropathy.
Symmetric Weakness without sensory loss
• Proximal and Distal- Spinal Muscular Atrophy
• Distal-Hereditary Motor Neuropathy
Symmetric with predominant Motor(Both Proximal and Distal)
• AIDP
• CIDP

23. Predominant Sensory Loss
• Leprosy
• Drugs(Vincristine,NFT,INH)
• Diabetes Mellitus
• Amyloidosis
• Alcohol
• Vitamin B12
• Sjogrens Syndrome

24. Sensory Involvement
Symmetric sensory Loss(with/without distal weakness)
• Diabetes, carcinoma, Sjögren syndrome, dysproteinemia, acquired
immunodeficiency syndrome (AIDS), Vitamin B 12 deficiency, celiac
disease
• Inherited and idiopathic sensory neuropathies(CSPN)
• Intoxications-Cisplatin, thalidomide, or pyridoxine.

25. Asymmetric Sensory Loss with Distal Weakness
Involvement of Multiple
Nerves -
Mulitifocal CIDP, Vasculitis, Cryglobulinemia,
Amyloidoisis,Sarcoid
Infectious (leprosy, Lyme, hepatitis B, C, or E, HIV,
CMV)
Tumor infiltration
Hereditary Neuropathy with liability to pressure
palsies
Involvement of single
Nerves/Region
Compressive mononeuropathy, plexopathy, or
radiculopathy

26. Course of sensory and motor dysfunction in Polyneuropathies
• Distal gradient sensory loss from the toes to proximal legs. This stocking-
and-glove pattern is characteristic of axonal neuropathy(length dependent).
By the time sensory disturbance reaches the shin, dysesthesias develop in
fingers.
• They are relatively symmetric.
• Strength is lost in a similar pattern to the sensory loss but usually arises
later in the evolution of the illness.
• Usually affects the extensor muscles of the toes more than the flexor
muscles.
• In early motor involvement, the examiner may not find objective weakness,
and the patient’s only symptom may be the inability to walk on his heels or
slapping of feet suggestive of early ankle dorsiflexion weakness.
• Unsteadiness of gait may be out of proportion to the muscle weakness
because of proprioceptive loss

27. • As the disease advances, patients will often develop a foot drop from
weakness of the anterior tibial muscles.
• As the motor involvement progresses, patients develop hand
weakness. This often manifests as atrophy of the intrinsic hand
muscles and weakness of spreading and opposition of the fingers.
• Reflexes are diminished or lost progressing from distal to -proximal.
Ankle reflexes are lost first, followed by the knee, brachioradialis, and
lastly, the biceps brachii and triceps.
• In early neuropathy, ankle and knee reflexes are lost even with
preserved muscle bulk and strength.

28. Axonal Neuropathy Demyelinating Neuropathy
Usually Gradual and insidious Onset Usually Acute or subacute
Large and long long axons are affected early,
hence initially lower extremeties are affected
Diffuse process. Starts in lower limbs.But not
always distal
Stocking-glove sensory motor loss results in
symmetrical distal clinical signs in legs and arms
Generalized Weakness and mild sensory loss.
Distal involvement Proximal and distal involvement
Ankle jerk lost early and proximal tendon reflexes
preserved
All reflexes are lost early
Muscle wasting Common Relatively absent
CSF Proteins normal CSF Proteins elevated(since nerve roots are
involved
Slow Recovery Rapid Recovery
Residual deformity Common Residual deformity less common
Normal Conduction normal or slightly lowered Nerve Conduction is slowed

29. Modalities of sensation loss
• Loss of sensation in peripheral neuropathies often involves all sensory
modalities.
• The impairment may be restricted to selective sensory modalities
which correlates the type of sensory loss with the diameter size of
affected afferent fibers
• Pain and temperature sensation are mediated by unmyelinated and
small myelinated Aδ fibers,whereas vibratory sense, proprioception,
and the afferent limb of the tendon reflex are subserved by large
myelinated Aα and Aβ fibers.
• Light touch is mediated by both large and small myelinated fibers.
• Autonomic Functions are also small unmyelinated fibres

30. Type of Fiber Involved

31. Small Fiber Neuroathy
Diminished pain and temperature sensation predominate alongwith
spontaneous burning pain, painful dysesthesias, and autonomic dysfunction
with preservation of tendon reflexes, balance, and motor strength.
• Diabetes mellitus and impaired glucose tolerance
• Amyloid neuropathy (early familial and primary)
• Alcoholic Polyneuropathy
• HIV-associated distal sensory neuropathy
• Hereditary sensory and autonomic neuropathies
• Fabry disease
• Tangier disease
• Sjögren (sicca) syndrome
• Cryptogenic small-fiber neuropathy

32. Large-fiber sensory loss
• Sensory ataxia
• Loss of joint position and vibration sense
• Areflexia
• Romberg Positive
• Affected patients will note imbalance, especially in the dark
• Striking sensory ataxia, together with pseudoathetosis or asymmetrical
truncal or facial sensory loss, directs attention to a primary disorder of
sensory neurons or poly ganglionopathies
• A dramatic loss of proprioception with vibration loss and normal strength
points to a sensory neuronopathy/ganglionopathy. The loss is asymmetric
or affects the arms more than the legs, this pattern suggests a non-length-
dependent process.

33. Small Fiber Neuropathy Large Fiber Neuropathy
Loss of Pain and Temperature Loss of touch,vibration and position
sense-Sensory ataxia
Preservation of touch,vibration and
pressure
Preservation of Pain and Temperature
Relative Preservation of Reflexes and
motor function
Reflexes lost early and motor functions
impaired
Spontaneous pain and Autonomic
Dysfunction
No Such phenomenon
Electrophysiologically silent
Quantitative sensory testing and skin
biopsy are used
Impaired nerve conduction velocity

34. Sensory Ataxic Neuropathies
Sensory neuropathies (polyganglionopathies)
• Paraneoplastic sensory neuronopathy (malignant inflamma-
• tory sensory polyganglionopathy):
• Sjögren syndrome
• Idiopathic
• Toxic (cisplatin and analogs, vitamin B 6 excess)
Chronic immune sensory polyradiculopathy
Demyelinating polyradiculoneuropathies:
Guillain-Barré syndrome (Miller Fisher variant)
Immunoglobulin M monoclonal gammopathy of undetermined significance
Tabes dorsalis produces severe ataxia with damage to the sensory
nerve fibers at the root entry zone of the dorsal roots.

35. Autonomic Involvement

36. Neuropathies with Autonomic Nervous System Involvement
Acute Guillain-Barré syndrome
Porphyria
Toxic: vincristine, Vacor (rodenticide)
Acute Pandysautonomic neuropathy(idiopathic,paraneoplastic)
Chronic Diabetes mellitus
Amyloid neuropathy (familial and primary)
HIV virus–related autonomic neuropathy
Paraneoplastic sensory neuropathy
Hereditary sensory and autonomic neuropathy

37. Other Findings

38. Nerve Thickening
Palpation of peripheral nerves for thickening
Hypertrophy of a single nerve trunk suggests either
• a neoplastic process (e.g., neurofibroma, schwannoma, malignant
nerve sheath tumor)
• localized perineurial hypertrophic neuropathy.
Generalized or multifocal nerve hypertrophy is found in a limited
number of peripheral nerve disorders including leprosy(radial and
greater auricular), Neurofibromatosis, Charcot-Marie-Tooth (CMT)
disease types 1 and 3, (ulnar,peroneal nerve), acromegaly, Refsum
disease, and rarely CIDP

39. Deformities and Trophic Changes
Hereditary
• Pes cavus and hammer toes in CMT disease
• Overriding toes and ichthyosis in Refsum disease
Chronic Childhood polyneuropathies leads to deformities
• Talipes Equinus,Claw Foot,Kyphoscoliosis
Anesthetic and immobile limb show tight and shinny skin,thickened
subcutaneous tissue,curved nails and diminished hair growth.
Distal Trophic Ulcers ,Thinning of Bone,Tinning of phallanges,
pathologic fractures or neuropathic arthropathy in long standing
neuropathies

40. Neuropathies with Skin, Nail, or Hair Manifestations
Vasculitis Purpura, livedo reticularis
Arsenic or thallium intoxication Mees lines
Thallium poisoning Alopecia
Cryoglobulinemia Purpura
Leprosy Skin hypopigmentation
Osteosclerotic myeloma (POEMS
syndrome)
Sskin hyperpigmentation or hypertrichosis
Fabry disease Angiokeratomas
Giant axonal neuropathy Curled hair

41. Investigations

42. Electrodiagnosis
Confirms diagnosis of neuropathy
Helps in differentiating
• Neuropathy vs myopathy
• Root/Plexus vs Distal Nerve trunk involvement
• UMN vs LMN weakness
• Axonal vs Demyelinating
Nature, activity and prognosis
Anatomy(which nerves are involved)
Characterization of disorder of neuromuscular junction
Identification of chronic partial denervation,fasciculations and myotonia
especially in muscles of normal bulk and strength

43. Evaluation of peripheral neuropathy,following
electrodiagnosis tests are performed
•Nerve conduction study of sensory and motor nerves
•Late responses (F response and H reflex)
•Needle electromyography (EMG)

44. Conduction block refers to a decline in the compound muscle action
potential exceeding 20% on proximal stimulation compared to that on
distal stimulation
Demyelinating neuropathy -
• Slowing of nerve conduction velocity,
• Prolongation of terminal latency,
• Temporal dispersion and
• Conduction block are consistent
Uniform demyelination favors inherited neuropathythy
Findings with difference between nerves and segments of the same
nerve are more in favor of acquired demyelination

45. Axonal neuropathy-
• Mild slowing of nerve conduction due to a fall out of large-diameter axons,
whereas the remaining axons may have normal nerve conduction.
• Reduced CMAP amplitude
• Fibrillations on EMG.
Sensory nerve action potentials and sensory conduction velocities are
reduced in both axonal and demyelinating neuropathies
Routine sensory nerve conduction studies assess only large myelinated
fibers. It is entirely normal in selective small fiber neuropathies. Quantitative
sensory testing assessing cold and heat-pain thresholds, tests of sudomotor
function, and skin biopsy with analysis of intraepidermal nerve fibre density
may be helpful in confirming the unmyelinated nerve fibre abnormalities

46. F Waves
• F waves are used for evaluating conduction problems in the proximal
segments of nerves,plexus,nerve roots and spinal cord.
A strong electrical stimulus (is applied to the skin surface above the distal
portion of a nerve so that the impulse travels both distally (towards the
muscle fiber) and proximally (back to the motor neurons of the spinal cord).
• When the orthodromic stimulus reaches the muscle fiber, it elicits a strong
M-response indicative of muscle contraction.
• When the antidromic stimulus reaches the motor neuron cell bodies, a
small portion of the motor neurons backfire and orthodromic wave travels
back down the nerve towards the muscle. This reflected stimulus evokes
small proportion of the muscle fibers causing a small, second CMAP called
the F wave.

50. Laboratory Investigations
Blood-
• TC,DC,ESR,Urea,Electrolytes,LFT
• Blood Sugar
• Thyroid Function Tests
• Serum Protein electrophoresis
• Autoantibodies-ANA,Rhematoid Factor, Antigangliosisde antibodies,
Antineuronal Antibodies
• Vitamin B12 level and Folate Levels
• DNA analysis-Chromosome 17 duplication(HMSN1 and HMS1A)

51. CSF Analysis-
• GBS and CIDP,- elevated cerebral spinal fluid (CSF) protein with no
pleocytosis
• If cells are present,consider HIV infection, Lyme disease, sarcoidosis,
or lymphomatous or leukemic infiltration of nerve roots

52. • Urine-Bence Jones Protein,Porphyrins
• immunoelectrophoresis, or immunofixation -a monoclonal
gammopathy in amyloidosis.
• antineutrophil cytoplasmic antibodies (ANCA), cryoglobulins, hepatitis
serology,
• Western blot for Lyme disease,
• HIV
• Imaging-Xray chest for sarcoidosis and malignancy
• Skeletal survey for for multiple myeloma
• Screening for malignancy
• Autonomic Function tests

53. Nerve Biopsy
Primary indication - suspicion for amyloid neuropathy or
vasculitis,Leprosy,Sarcoidosis and leukodystrophies
The sural nerve is most commonly biopsied because it is a pure sensory
nerve.
Used to diagnose a small-fiber neuropathy where EMG/NCS are normal

54. Alcoholic Neuropathy
• Alcoholic neuropathy is defined to be neuropathy following regular
intake of more than 100 grams of ethanol daily for at least 10 years,
with normal thiamine levels.
• Insidious and slowly progressive.
• Muscle weakness begins distally and spreads to more proximal
muscles.
• Gait difficulty, weakness, and muscle cramps are common.
• Sensory loss and burning paresthesias starts distally.
• Distal muscle wasting, loss of tendon reflexes, and sensory loss of all
modalities in a stocking-glove distribution

55. • In advanced cases, sensory ataxia caused by loss of joint position
sense may coexist with alcoholic cerebellar ataxia.
• Autonomic dysfunction due to vagal nerve or sympathetic nerve
involvement may be present.
• EDX studies show an axonal sensorimotor polyneuropathy. Needle
EMG shows active denervation with chronic reinnervation in distal
muscles

56. Diabetic Neuropathy
• Distal symmetric sensory or sensorimotor polyneuropathy is the MC form
• Autonomic neuropathy,
• Mononeuropathies.
• Diabetic polyradiculopathy is a syndrome characterized by severe disabling
pain in the distribution of one or more nerve roots. It may be accompanied
by motor weakness.
• Involvement of the lumbar plexus or femoral nerve may cause severe pain
in the thigh or hip and may be associated with muscle weakness in the hip
flexors or extensors (diabetic amyotrophy). Usually self-limited and resolve
over 6–12 months

57. Entrapment Neuropathies
Mechanical distortion of the nerve fibers leads to focal demyelination or, in severe
cases, to wallerian degeneration.
Edx is diagnostic -short-segment conduction delay (i.e., focal slowing) or
conduction block across the site of entrapment
Common Sites
• Median Nerve in Carpal tunnel - Paresthesia, pain, thenar atrophy
• Ulnar nerve at the elbow - Clawing and sensory loss of 4th and 5th fingers
• Lateral cutaneous nerve of thigh at the inguinal ligament - Sensory loss in lateral
thigh
• Radial in the spiral groove - Wrist drop, sensory loss
• Peroneal Neuropathy - Foot drop, weak ankle eversion,sensory loss in dorsum of
foot

58. Cryptogenic(idiopathic) Sensory and Sensimotor
Polyneuropathy
• Diagnosis of exclusion
• Onset of CSPN is predominantly in the sixth and seventh decades
• Both large- and small-fiber loss
• Distal numbness, tingling, and often burning pain that begins in the
feet and may eventually involve the fingers and hands.
• Patients exhibit a distal sensory loss to pinprick, touch, and vibration
in the toes and feet, and occasionally in the fingers.

59. Hereditary Neuropathies
The inherited neuropathies can broadly be classified into two groups:
• Those in which the neuropathy is the sole or primary part of the
disease (e.g., Charcot-Marie-Tooth disease, CMT)
• Those in which the neuropathy is part of a more generalized
neurological or multisystem disorder.
• Charcot-Marie-Tooth Disease is the most coomon type.

60. Classification of the Inherited Neuropathies
Neuropathies in which the neuropathy is the sole or primary part of the disorder
Charcot-marie-tooth disease (CMT)
Hereditary neuropathy with liability to pressure palsies (HNPP)
Hereditary sensory and autonomic neuropathies/hereditary sensory neuropathies (HSAN/HSN)
Distal hereditary motor neuropathies (dHMN)
Hereditary neuralgic amyotrophy (HNA)
Neuropathies in which the neuropathy is part of a more widespread neurological or multisystem
disorder
Familial amyloid polyneuropathy (FAP)
Disturbances of lipid metabolism (e.g., adrenoleukodystrophy)
Porphyrias
Disorders with defective DNA (e.g., ataxia telangiectasia)
Neuropathies associated with mitochondrial diseases
Neuropathies associated with hereditary ataxias

61. Charcot Marie Tooth Disease
• MC type
• CMT 1 -demyelinating neuropathy,
• CMT 2 - the axonal neuropathy
• 1st and 2nd decade
• Slowly Progressive Distal Weakness
• Foot deformity and weakness
• Pes Cavus and Hammer toes
• Ankle Jerk absent mostly and total areflexia in 50%

62. HIV
1. Distal symmetric polyneuropathy
2. Inflammatory demyelinating polyneuropathy (including both GBS
and CIDP),
3. Multiple mononeuropathies (e.g., vasculitis, CMV-related),
4. Polyradiculopathy (usually CMV-related),
5. Autonomic neuropathy,
6. Sensory ganglionitis.

63. DSP is the most common form of peripheral neuropathy
• Usually seen in patients with AIDS
• It is characterized by numbness and painful paresthesias involving
the distal extremities.
AIDP and CIDP can occur as a complication of HIV infection.lymphocytic
pleocytosis is evident in the CSF

64. Thank You