Peripheral neuropathy Anatomy, Physiology and Diseases

1. Dr Chandrashekar K
Assistant Professor
Dept of Medicine
KIMS, Hubballi

2. Definition
 Disorders of any cause affecting PNS m ay
involve sensory nerves, motor nerves, or
both.
 May affect one nerve (mononeuropathy),
several nerves together (polyneuropathy)
or several nerves not contiguous
(Mononeuropathy multiplex)

3. Pathology primarily affecting :
The cell body (Neuronopathy or
ganglionopathy)
Myelin (myelinopathy)
Axon (axonopathy)

4. Causes
 Diabetes
 Paraproteinaemia
 Alcohol misuse
 Renal failure
 Vitamin B-12 deficiency
 HIV infection
 Chronic idiopathic axonal neuropathy

7. Mononeuropathy
 Focal involvement of a single nerve
Implies a local process :
 Direct trauma
 Compression or entrapment
 Vascular lesions
 Neoplastic compression or infiltration

8. Mononeuropathy Multiplex
Simultaneous / sequential damage to multiple
noncontiguous nerves.
 Ischemia caused by vasculitis
 Microangiopathy in diabetes mellitus
 Less common causes : Granulomatous, leukemic, or
neoplastic infiltration, Hansen‘s disease (leprosy) and
sarcoidosis.

9. Polyneuropathy
 Symmetrical,
 Distal motor and sensory deficits
 Graded increase in severity distally
 Distal attenuation of reflexes
 Rarely predominantly proximal (acute intermittent
porphyria)
 Sensory deficits generally follow a lengthdependent
stocking-glove pattern

11. Axonopathy
 Toxic, metabolic and endocrine causes
 Legs>> arms
 EMG: Signs of denervation (acute, chronic) and
reinnervation

12. Myelinopathy
 Hypertrophic nerves on exam
 Global arreflexia
 Weakness without wasting
 Motor >> sensory deficits

13. NCS and EMG
NCS :
 Distal motor latency prolonged
 Conduction velocities slowed
 Rarely conduction block
EMG :
 Reduced recruitment w/o much denervation

16. Diagnostic clue
 Weight loss, malaise, and anorexia – constitutional symptoms
 DM
 Hypothyroidism
 Chronic renal failure
 Liver disease
 Intestinal mal absorption
 Malignancy
 Connective tissue diseases
 HIV
 Drug use
 Vitamin B6 toxicity
 Alcohol and dietary habits

17. Painful Peripheral Neuropathy
 Diabetes and Pre-Diabetes
 Alcohol neuropathy
 Chemotherapy : Platinum-based
 Paraproteinemia
 Vasculitis and Connective Tissue Diseases
 Heavy metals and other toxins
 HIV
 Amyloidosis
 Porphyria
 Tangier disease

18. Drugs causing neuropathy
Axonal Demyelinating Neuronopathy
Vincristine
Paclitaxel
Nitrous oxide
Colchicine
Probenecid
Isoniazid
Hydralazine
Metronidazole
Pyridoxine
Didanosine
Lithium
Alfa interferon
Dapsone
Amiodarone
Chloroquine
Suramin
Gold
Thalidomide
Cisplatin
Pyridoxine

19. Proximal Symmetric Motor
Neuropathy
 Guillain-Barré syndrome
 Chronic inflammatory demyelinating
polyradiculoneuropathy
 Diabetes mellitus
 Porphyria
 Acute arsenic polyneuropathy
 Lymphoma
 Diphtheria
 HIV/AIDS
 Lyme disease
 Hypothyroidism
 Vincristine toxicity

20. Large fibre / ataxic neuropathy
 Sjogren’s syndrome
 Vit B12 neuropathy
 Cisplatin
 Pyridoxine neurotoxicity
 Friedereich’s ataxia

21. Small and Large fibre neuropathy
 Global sensory loss
 Carcinomatous sensory neuropathy
 Hereditary sensory neuropathy
 Diabetic sensory neuropathy
 Vacor intoxication
 Xanthomatous neuropathy of primary biliary cirrhosis

22. Predominant Motor Neuropathy
 Immune neuropathies
 Heriditary motor sensory neuropathies
 Acute intermittent porphyria
 Diphtheritic neuropathy
 Lead neuropathy
 Brachial neuritis
 Diabetic lumbosacralplexus neuropathy

23. Autonomic Neuropathy
Acute- pandysautonomia
 Botulism
 Porphyria
 Gbs
 Amiodarone
 Vincristine
Chronic –
Amyloid, Diabetes, Sjogren’s, HSN 1&3, Chagas,
Paraneoplastic

24. Mononeuropathy Multiplex
 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

25. 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

26. Causes
 Diabetes mellitus
 Alcohol
 Vit B12 deficiency
 HIV
 Although more than one nerve involved one will
be prominant

27. POLYRADICULOPATHY and
MONORADICULOPATHY
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

28. 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 anterior horn cells
 Weakness,fasciculation,atrophy
 Not properly a process of peripheral NP

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

30. POLYNEURITIS CRANIALIS
Also known as IDIOPATHIC POLYNEURITIS
 Peripheral nerve+cranial nerve involvement
 Self limiting painful ophthalmoplegia
CAUSES-
 TB meningitis
 Osteomyelitis skull
 Otitis media
 Syphilitic meningitis
 Sarcoidosis
 Carcinomatous meningitis

31. Time of onset
 ACUTE ONSET : trauma or ischemic infarction with
most severe symptoms at onset.
 SUBACUTE COURSE : Inflammatory and some
metabolic neuropathies : extending over days to weeks
 CHRONIC COURSE : hallmark of most toxic and
metabolic neuropathies

32.  Hereditary neuropathies – over many years
Neuropathies with a relapsing and remitting
course :
 CIDP,
 Acute porphyria,
 Refsum's disease,
 Hereditary neuropathy with
 Liability to pressure palsies (HNPP),
 Familial brachial plexus neuropathy,
 Repeated episodes of toxin exposure
History

33. History
Small-fiber neuropathies present with :
 Burning pain,
 Lightning-like or lancinating pain,
 Aching, or
 Uncomfortable paresthesias
Dying-back (distal symmetric axonal) neuropathies :
 Involve the tips of the toes and
 Progress proximally
 Stocking glove distribution
 Can present as restless leg syndrome.

35. Examination
 A cranial nerve examination can provide evidence of
mononeuropathies.
 Funduscopic examination : leukodystrophies and
vitamin B12 deficiency.
 Thickened nerves
 Heart rate variability
 Valsalva maneuver : Induces BP changes and monitors
pulse reaction

36. Laboratory tests :
 Blood glucose (fasting)
 Serum B12 with metabolites (methylmalonic acid,
homocysteine)
 Serum protein electrophoresis
 ANA, RF, Anti-dsDNA, Anti-Ro, Anti-La,
 ANCA screen,
 Cryoglobulins
 Urine for heavy metals,
 Porphyrins
 IFE/urine IFE/ plasma light chain analysis

37. Serum Antibodies

38. NCV

40. Limitations
 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

41. Nerve Biopsy
 Vasculitis,
 Amyloid neuropathy,
 Leprosy,
 CIDP,
 Inherited disorders of myelin,
 Rare axonopathies
 Sural nerve is selected most commonly

42. 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.

43. Treatment
Treat causative factor :
 IVIG , Immunomodulating agents : if rapidly
progressive
Symptomatic management :
 Tricyclic antidepressants : Amitryptilin, nortryptilin
 Calcium channel alpha-2-delta ligands : Gabapentin,
pregabalin
 Calcium channel blocker : Prialt
 SNRI’s : Duloxetine, venlafaxine
 Topical Agents : Lidocaine, Capsaicin

44.  Antiepileptic Drugs : Carbamazepine, phenytoin,
lacosamide
 SSRI’s
 Opioid analgesics : Tramadol
 Miscellaneous : Botulinum toxin, Mexiletine, Alpha
lipoic acid