approach to polyneuropathy, demyelination, axonopathy, plexopathy, mononeuritis, ganglionopathy

1. APPROACH TO
POLYNEUROPATHY
STUDENT : Dr. Akhila
GUIDE: Dr. Ram K.

2. INTRODUCTION
• Peripheral neuropathy is the term for damage to
nerves of the peripheral nervous system, which
may be caused either by diseases of the nerve
or from the side-effects of systemic illness.
• CLASSIFICATION :
– MONONEUROPATHY
– MULTIPLE MONONEUROPATHY
– POLYNEUROPATHY

4. ANATOMICAL CLASSIFICATION OF
PERIPHERAL NEUROPATHY
1) Mononeuropathy
2) Plexopathy- brachial, lumbar, sacral
3) Radiculopathy- cervical, thoracic, lumbosacral
4) Multiple mononeuropathy( mononeuropathy multiplex)
5) Polyneuropathy- symmetrical/ asymmetrical
6) polyradiculoneuropathy

5. ROLE OF NERVE FIBRES

6. ETIOLOGY OF POLYNEUROPATHY
ETIOLOGY EXAMPLES
1.METABOLIC DIABETES MELLITUS, HYPOTHYROIDISM
2. TOXINS ALCOHOL, DRUGS (CHEMOTHERAPEUTIC),
HEAVY METALS
3. VITAMIN DEFICIENCIES B1, B3, B6, B12, FOLATE
4. INFLAMMATORY GUILLIAN BARRE SYNDROME, VASCULITIS,
CONNECTIVE TISSUE DISORDERS
5. INFECTIOUS VIRAL (HIV), BACTERIAL (LEPROSY, LYMES
DISEASE)
6. HEREDITORY CHARCOT MARIE TOOTH DISEASE
7.NEOPLASTIC CARCINOMA, LYMPHOMA
8. IDIOPATHIC

7. PATHOPHYSIOLOGY
MECHANISMS OF DAMAGE INCLUDE:
• DEMYELINATION (myelinoathy): GBS, Post
diphtheric, HSMN
• AXONAL DEGENERATION (axonopathy) : Toxic
neuropathies, systemic metabolic disorders,
vasculitis.
• Wallerian degeneration : Nerve section –
response to axonal interruption.
• Primary neuronal (perikaryal) degeneration
(neuronopathy)

8. AXONAL DEGENERATION

9. AXONAL DEGENERATION
• Usually chronic
• Sensory > motor in early
disease
• Symmetric, length
dependant (dying back)
polyneuropathy- glove and
stocking pattern
• Distal muscle weakness and
atrophy, loss of distal limb
reflexes.
• Examples : Diabetes, alcohol
induced, vitamin deficiencies

10. DEMYELINATION

11. DEYELINATION
• Demyelination refers to injury to myelin sheath or
Schwann cells with axonal sparing.
• Seen in acute/ chronic nerve entrapment,
immune mediated demyelinating neuropathies ,
hereditary disorders of schwan cells. `
• Clinically :
– Early generalised loss of reflexes
– disproportionately mild muscle atrophy
– Neuropathic tremor
– Palpably enlarged nerves

12. AXONAL DEMYELINATING
DISTRIBUTION Length dependant Diffuse or patchy
SENSATION Based on type of fibre
involved
Predominantly proprioception or
vibration
WEAKNESS Distal, symmetric Diffuse
AUTONOMIC
INVOLVEMENT
Yes Only in GBS, autoimmune
dysautonomia
ELECTROPHYSIOLOGY
1. CONDUCTION
VELOCITY
2. 2.CONDUCTION
BLOCKS
Normal or mild
slowing
NO
Marked (<80% of lower
limit)slowing
YES
CSF PROTEIN NORMAL ELEVATED
RECOVERY RATE SLOW RAPID

13. Copyright ©2002 BMJ Publishing Group Ltd.
Hughes, R. A C BMJ 2002;324:466-469
Using nerve conduction studies in
polyneuropathy
http://www.neuroanatomy.wisc.edu/SClinic/Weakness/Weakness.
htm
=
Slow!
=
Low!
=
Slow!

14. 7 KEY POINTS
1) Systems (Fibers) involved?
2) Distribution?
3) Nature of sensory involvement?
4) Evidence of UMN involvement?
5) Temporal evolution?
6) Evidence for hereditary neuropathy?
7) Associated medical conditions?

15. Loss of function
“negative symptoms”
Disturbed function
“positive symptoms”
Motor nerves Weakness
Atrophy
Walking difficulties
Muscle cramp
Fasciculation
Tremor
MOTOR SYSTEM

17. Loss of function
“negative symptoms”
Disordered function
“positive symptoms”
Sensory
“Large Fiber”
↓ Vibration
↓ Proprioception
Hyporeflexia
Sensory ataxia
Paresthesias ( 60%
in acquired & 17% in
inherited PN)
Sensory
“Small Fiber”
↓ Pain
↓ Temperature
Hyperalgesia
Allodynia
TWSensory neuropathy

18. Loss of function
“- symptoms”
Disturbed function
“+ symptoms”
Autonomic nerves ↓ Sweating
Hypotension
Urinary retention
Impotence
Vascular color changes
↑ Sweating
Hypertension
AUTONOMIC NEUROPATHY

19. Acute onset (days to 4 weeks)
Subacute onset (4-8 weeks)
Chronic course (>8 weeks)
Relapsing/remitting course
Guillain-Barré syndrome
Acute intermittent porphyria
Critical illness polyneuropathy
Thallium toxicity
Toxins or medications
Nutritional deficiency
Metabolic abnormality
Paraneoplastic syndrome
CIDP
Hereditary motor and sensory neuropathy
(HMSN)
Inherited sensory neuropathy
CIDP
Guillain-Barré syndrome
refsums disease
CIDP
Toxin (intermittent exposure)
Porphyria
TEMPORAL ASSOCIATION

20. DISTRIBUTION OF WEAKNESS
• Distal or proximal and distal
• Focal/asymmetric or Symmetric
– Ex: Symmetric proximal and distal weakness –
AIDP (GBS) / CIDP
– Asymmetric subacute/ acute sensory and motor
symptoms – radiculopathies/ mononeuropathies/
mononeuritis multiplex

21. NEUROPATHIES WITH PREDOMINANT
MOTOR INVOLVEMENT
• Multifocal motor neuropathy
• Acute motor axonal neuropathy
• Guillain–Barré syndrome
• Chronic inflammatory demyelinating
polyradiculoneuropathy
• Neuropathy with osteosclerotic myeloma
• Hereditary motor sensory neuropathies
(Charcot–Marie–Tooth
• disease)
• Lead intoxication

22. NEUROPATHIES WITH PREDOMINANT
SENSORY INVOLVEMENT
Neuropathies caused by:
• Diabetes
• Carcinoma
• Sjögren syndrome
• Dysproteinemia
• acquired immunodeficiency syndrome
• vitamin B12 deficiency
• celiac disease.
• Inherited and idiopathic sensory neuropathies
• intoxications with cisplatin, thalidomide, or pyridoxine.

25. • In most of the polyneuropathies legs are more
severely affected than the arms.
• However, notable exceptions include
– Multifocal motor neuropathy
– Lewis-Sumner variant of CIDP
– Lead neuropathy
– Porphyria
– Tangier disease
– Familial amyloid neuropathy type 2
– Hereditary motor neuropathy (uncommon forms)

26. NATURE OF SENSORY INVOLVEMENT
SMALL FIBRE NEUROPATHIES
• Diminished pain and temperature sensation
predominate, along with spontaneous burning
• Pain, painful dysesthesias, and autonomic
dysfunction.
• There is preservation of tendon reflexes, balance,
and motor strength.

27. • Seen in :
– 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

28. LARGE-FIBER SENSORY NEUROPATHY
Selective large-fiber sensory loss is characterized
by
• Areflexia
• sensory ataxia
• Loss of joint position and vibration sense –
May present as pseudoathetosis and/or
Romberg sign

29. Sensory Ataxic Neuropathies
• Sensory neuronopathy
• Paraneoplastic sensory neuronopathy (malignant
inflammatory
• Sjögren syndrome
• Toxic (cisplatin and analogs, vitamin B6 excess)
• Demyelinating polyradiculoneuropathies:
– Guillain–Barré syndrome (Miller Fisher variant)
– Immunoglobulin M monoclonal gammopathy of
undetermined significance
• CANOMAD
• Tabes dorsalis

30. EVIDENCE OF UMN INVOLVEMENT
• Presents with symmetric distal sensory
involvement with e/o symmetric UMN
involvement ie combined system
degeneration
• Examples include :
– Vit B12 deficiency
– Copper deficiency
– HIV infection
– Severe hepatic insufficiency

31. EVIDENCE OF HEREDITARY
NEUROPATHY
• Slowly progressive distal weakness
• Negligible sensory symptoms, yet significant
sensory deficits
• Example : Charcot Marie Tooth disease
– Variable course, slow in case of CMT 1A
– NCS: symmetric demyelinating neuropathy with
no conduction block
– Disabilities correlate to secondary axonal
degeneration

33. ASSOCIATED MEDICAL CONDITIONS
• Diabetes mellitus
• Preceding or concurrent infection – ex:
diarrhoeal disease preceding GBS
• Surgeries: ex: gastric bypass and nutritional
neuropathies
• Medications : toxic neuropathy
• Alcohol and dietary habits

35. Clues from generalsurvey?
• Pulse & BP- orthostatic hypotension without tachycardia
• Anaemia- Vitamin B12 deficiency, CKD
• Goitre- Hypothyroidism
• Skin & skeletal changes- DM, Leprosy , Amyloid,
Connective tissue diseases.

36. GENERAL SURVEY

37. CUES FROM GENERAL SURVEY

40. INVESTIGATIONS
• Complete Hemogram
• Renal function tests
• Liver function tests
• FBS, PPBS, HBA1C,
• Throid function tests
• Urine analysis
• Vit B12, Folate
• ESR

41. • Specific investigations :
– Mononeuritis multiplex : vasculitis work up
• ANCA
• Cryoglobulins
• Hepatitis serology
• Western blot for Lymes disease
• HIV
• CMV tire

42. • Lumbar puncture –
– High protein : AIDP (GBS), CIDP
– Pleocytosis : HIV , Lyme disease, Sarcoidosis,
lymphomatous, leukemic infiltration.
• Nerve biopsy :
i. Vasculitis
ii. Amyloidosis
iii. Sarcoidosis
iv. Hansen disease
v. Giant axonal neuropathy
vi.Tumour infiltration

43. Treatment
• General
• Subtype specific
• Diabetes mellitus
• Renal insufficiency
• Hypothyroidism
• Vitamin B12 deficiency
• Systemic vasculitis

44. • Once an agent is selected , it is started at the
lowest possible dose.
• Titrated gradually every 3 to 7 days until
significant pain relief or intolerable side
effects ensue.
• Combinations can be used when pain is not
controlled by a maximally tolerated dose of
one drug.

46. References
• Harrisons Principles of Internal Medicine 20th
edition
• Bradley’s Neurology in clinical practice 7th
edition
• Adams and Victors Principles of Neurology

47. THANK YOU