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Peripheral Neuropathy

Common features of peripheral neuropathy.

  1. Paresthesia in gloves and stocking area.
  2. Diminish DTR.
  3. Decrease nerve conduction velocity.
  4. Proximal muscle weakness can occur.

Common causes of trophic/Neuropathic ulcers

Peripheral nerve involvement

Spinal Cord Involvement

1. Diabetic Neuropathy

2. Leprotic Neuropathy

3. Hereditary Sensory neuropathy

1. Syringomyelia

2. Tabes dorsalis

3. Transverse myelitis

4. Prolapsed intervertebral disc

5. Cervical spondylosis

6. Spinal cord trauma

Pathology of Neuropathy


Pathogenesis in neuropathy

  1. Axonal degeneration (In nerve conduction study, amplitude affected > velocity).         
  2. Demyelination. (In nerve conduction study, velocity affected > amplitude.)

  1. Axonal Degeneration (Retrograde) (Dying back Neuropathy)
    1. Retrograde Axonal Degeneration is one type of classical response of nerve to an insult and consists of degeneration of axon from distal to proximal (Referred to as 'Dying back neuropathy')
    2. This type of degeneration is most commonly seen after toxic and metabolic injuries
  2. Demyelination
    1. It is associated with a conduction block' which results from failure of nerve conduction across the demyelinated segment and results in a rapid onset type neuropathy (weakness)
    2. Neuropathies resulting from demyelination do not have a distal to proximal progression and may occur either distally or proximally depending on the location of the demyelinated site of the nerve
    3. Causes
      1. GBS
      2. Multiple sclerosis.

Neuropathy (Ref. Hari. 18th ed., Pg- 3452)

Extra Edge:

  1. Peripheral neuropathy is not a feature of TB, Osteoporosis.
  2. In hypothyroid peripheral neuropathy is very rare but entrapment neuropathy can occur.


Note: NCS-EMG, nerve conduction studies/electromyography; QSART, quantitative sudomotor axon reflex testing; QST, quantitative sensory test; LP, lumbar puncture.


Classification of neuropathy based on type of newer involved.





1. Sensory neuropathy Causes

Diabetes mellitus, Uremia, Alcohol abuse, Deficiencies of Vitamins B1' B6' B12' niacin HIV, Hereditary neuropathies, Amyloidosis, Leprosy, CIDP, Arsenic (Sensory > motor)

Drugs, Vinca alkaloids Cisplatin, Phenytoin,

2. Motor neuropathy Causes

Guillain-Barre syndrome Diabetes mellitus, Porphyria.
Lead intoxication

3. Autonomic neuropathy

Diabetes mellitus Amyloidosis,Guillain-Barre syndrome Porphyria, HIV. 

Causes of mononeuritis multiplex

  1. Classic polyarteritis nodosa
  2. Microscopic polyangiitis
  3. RA
  4. SLE
  5. Mixed connective tissue disease
  6. Churg Strauss
  7. Wagner’s granulomatosis
  8. Hypersensitivity angitis
  9. Sjögren syndrome
  10. Diabetes
  11. Leprosy
  12. Amyloidosis
  13. Mixed cryoglobulinemia
Important Points:

The common peroneal nerve is affected in ~75% of patients with vasculitic neuropathy; symptoms consist of a painful foot drop. The ulnar, median, and radial nerves may also be involved.


Extra Edge:

  1. Insulin neuritis describes a painful neuropathy seen with initiation of insulin treatment for diabetes. The clinical presentation is similar to the acute painful neuropathy of diabetes, and most patients improve.
  2. Pyridoxine toxicity (excess of pyridoxine) can cause peripheral neuropathy.
  3. The classical examples of sitting posture causing nerve palsy is Saturday night nerve palsy (Radial nerve is compressed) and Sciatic nerve palsy after a prolong sitting.   

Tabes dorsalis

  1. Tabes dorsalis is characterized by areflexia resulting from degeneration, demyelination of posterior nerve root (M./C & earliest feature) and ganglia.
  2. Tabes dorsalis is a parenchymatous manifestation of tertiary stage of syphilis.
  3. Characterized by demyelination and degeneration of posterior nerve roots and posterior column of cord.
  1. Associated with an atonic bladder
  2. Argyll Robertson pupil
    1. Loss of light reflex
    2. Accommodation reflex present (ARP)
    3. Pupil is small, irregular and does not respond to mydriatics

Extra Edge: Important causes of descending motor paralysis

  1. Botulinum    
  2. Diphtheria  
  3. Polio


  1. History of recent ingestion of home canned or smoked food or injection of drug.
  2. Symmetric descending paralysis with prominent bulbar palsy 4 'D' of Bulbar palsy:
    1. Diplopia (LQ 2012)
    2. Dysarthria
    3. Dysphonia
    4. Dysphagia
  3. 'Ptosis, cranial nerve palsies with impairment of extraocular muscles and fixed dilated pupils (LQ 2012) are characteristic signs'
  4. Normal sensory examination normal sensorium (not confused)
  5. Afebrile (Temperature remains normal)

(Because Botulism is not an 'infection' but on 'intoxication' manifestation are due to the effect of toxin. Patient remains without fever until secondary infection is acquired).


Diphtheria Poliomyelitis, & Porphyria may all present with descending paralysis and bulbar palsy but fixed dilated pupils are characteristic of Botulism.

Guillain-Barre syndrome (Ref. Hari. 18th ed., Pg- 3473)
  1. Definition and etiology. A predominantly acute immune mediated inflammatory (LQ 2012), demyelinating (LQ 2012) motor polyneuropathy that usually occurs in otherwise healthy individuals. The illness can follow a nonspecific viral syndrome or be associated with HIV infection, Campylobacter jejuni (LQ 2012) infec­tion, hepatitis, infectious mononucleosis, Mycoplasma pneumoniae infection, vaccination, surgery, lymphoma, or SLE.
  2. Diagnosis
    Clinical signs
    1. Classically, patients present with progressive ascending weakness (LQ 2012) and areflexia.
    2. Generalized paralysis can develop gradually or relatively acutely, impeding respiratory function.
    3. Relatively minor sensory signs and symptoms occur. Patients may complain of painful extremities.
    4. The autonomic nervous system is often involved. Involvement of the autonomic nervous system can lead to early mortality as a result of cardiac arrhythmias and wide swings in blood pressure.

'Bladder dysfunction may occur in severe cases but is usually transient.' (Bladder is most often spared then it is involved)


'If bladder dysfunction is a prominent feature and comes early in the course possibilities other than GBS should be considered particularly spinal cord disease ………. (Ref. Hari. 18th ed., Pg- 3476)

Important Points:

GBS evolves as rapidly developing areflexic 'predominantly motor paralysis'. They may have a sensory component which is often subclinical. Usual pattern is an ascending paralysis.

Diagnostic studies

  1. Examination of the CSF shows an elevated protein and less than 50 mononuclear cells/mm3 (albuminocytologic dissociation).
  2. The motor nerve conduction velocities are typically slowed.
  3. Antiganglioside antibodies, most frequently to GM1, are common in GBS (20–50% of cases), particularly in those preceded by C. jejuni infection. (Ref. Hari. 18th ed., Pg- 3474)

Therapy (Ref. Hari. 18th ed., Pg- 3477)

  1. Plasmapheresis (LQ 2012)
  2. Intravenous immunoglobulin. (LQ 2012)

Extra Edge: Corticosteroid is not used in the treatment of acute GBS. (LQ 2012).


Extra edge: 

  1. Either high-dose intravenous immune globulin (IVIg) or plasmapheresis can be initiated, as they are equally effective for typical GBS. A combination of the two therapies is not significantly better than either alone.
  2. In GBS 85% of the patients achieve a full functional recovery within several months to years.
  3. Recovery is usually remarkable in GBS although all patients may not recover fully.


Table 385-1 Subtypes of Guillain-Barré Syndrome (GBS) (Ref. Hari. 18th ed., Pg- 3473)





Acute inflammatory demyelinating polyneuropathy (AIDP)

Adults affected more than children; 90% of cases in western world; recovery rapid; anti-GM1 antibodies (<50%)


First attack on Schwann cell surface; widespread myelin damage, macrophage activation, and lymphocytic infiltration; variable secondary axonal damage

Acute motor axonal neuropathy (AMAN)

Children and young adults; prevalent in China and Mexico; may be seasonal; recovery rapid; anti-GD1a antibodies


First attack at motor nodes of Ranvier; macrophage activation, few lymphocytes, frequent periaxonal macrophages; extent of axonal damage highly variable

Acute motor sensory axonal neuropathy (AMSAN)

Mostly adults; uncommon; recovery slow, often incomplete; closely related to AMAN


Same as AMAN, but also affects sensory nerves and roots; axonal damage usually severe

M. Fisher syndrome (MFS)

Adults and children; uncommon; ophthalmoplegia, ataxia, and areflexia; anti-GQ1b antibodies (90%)


Few cases examined; resembles AIDP


Extra Edge: Plasmapheresis

  1. Plasmapheresis is the removal, treatment, and return of (components of) blood plasma from blood circulation.
  2. It is thus an extracorporeal therapy.
  3. An important use of plasmapheresis is in the therapy of autoimmune disorders, where the rapid removal of disease-causing autoantibodies from the circulation is required
  4. Other uses are the removal of blood proteins where these are overly abundant and cause hyperviscosity syndrome.
  5. Diseases that can be treated with plasmapheresis:
    1. Guillain-Barré syndrome
    2. Chronic inflammatory demyelinating polyneuropathy
    3. Goodpasture's syndrome
    4. Hyperviscosity syndromes:
      1. Cryoglobulinemia
      2. Paraproteinemia
      3. Waldenström macroglobulinemia
    5. Myasthenia gravis
    6. TTP
    7. Wegener's granulomatosis
    8. Lambert-Eaton Syndrome
    9. Antiphospholipid Antibody Syndrome
    10. Microscopic polyangiitis
    11. Recurrent FSGC in the transplanted kidney
    12. HELLP syndrome
    13. Behcet syndrome
    14. HIV-related neuropathy
    15. Graves' disease in infants and neonates
    16. Pemphigus vulgaris
    17. Multiple sclerosis

Extra Edge: Plasmapheresis is not done in polymyositis.

  1. Diabetic neuropathy.
    1. A predominantly sensory, distal, symmetric, small fiber polyneuropathy can be dyses­thetic and involve pain and temperature modalities more than vibration and position senses.
    2. A predominantly sensory, distal, symmetric, large-fiber polyneuropathy may occur, affecting vibration and position modalities.
    3. A sensorimotor neuropathy can develop.
    4. An autonomic neuropathy or a mononeuropathy or mononeuritis multiplex can occur.
    5. Proximal diabetic neuropathy represents injury to large nerves that causes weakness and pain; it commonly involves the lumbosacral plexus.


Demyelinating neuropathy

Axonal neuropathy

Primary pathology.

Dysfunction of Schwann cells or the myelin sheath.

Destruction of the axon with possible secondary disintegration of the myelin.


Usually segmental

Whole axon involved

Microscopic findings

Sequential episodes of demyelination and remyelination resulting in onion bulb appearance, new myelinated internodes shorter and thinner(seen best on teased nerve preparation.)

Wallerian degeneration:

Break down and phagocytosis of axon and its myelin sheath (myelin ovoids ), a regenerating cluster at the proximal stumps.             


i.    Guillain-Barre syndrome
ii.   lead toxicity
iii.  diphtheria neuropathy

Toxic, metabolic neuropathies many hereditary neuropathies.

Autonomic Neuropathy

Autonomic Testing (Ref. Hari. 18th ed., Pg- 3355

  1. Heart Rate Variation with Deep Breathing
    1. This is a test of the parasympathetic component of cardiovascular reflexes, via the vagus nerve.
    2. The lower limit of normal heart rate variation with deep breathing in persons <20 years is >15–20 beats/min, but for persons over age 60 it is 5–8 beats/min.
    3. Heart rate variation with deep breathing (respiratory sinus arrhythmia) is abolished by the muscarinic acetylcholine (ACh)-receptor antagonist atropine but is unaffected by sympathetic postganglionic blockade (e.g., propranolol).
  2. Valsalva Response
    1. This response assesses integrity of the baroreflex control of heart rate (parasympathetic) and BP (adrenergic).
    2. Under normal conditions, increases in BP at the carotid bulb trigger a reduction in heart rate (increased vagal tone), and decreases in BP trigger an increase in heart rate (reduced vagal tone).
    3. The Valsalva response is tested in the supine position.
    4. Autonomic function during the Valsalva maneuver can be measured using beat-to-beat blood pressure or heart rate changes.
    5. The Valsalva ratio is defined as the maximum phase II tachycardia divided by the minimum phase IV bradycardia.
    6. The ratio reflects the integrity of the entire baroreceptor reflex arc and of sympathetic efferents to blood vessels.3. Sudomotor Function.

Table 375-7 Normal Blood Pressure and Heart Rate Changes during the Valsalva Maneuver



Blood Pressure

Heart Rate



Forced expiration against a partially closed glottis

Rises; aortic compression from raised intrathoracic pressure



II early

Continued expiration

Falls; decreased venous return to the heart

Increases (reflex tachycardia)

Reduced vagal tone

II late

Continued expiration

Rises; reflex increase in peripheral vascular resistance

Increases at slower rate

Requires intact efferent sympathetic response


End of expiration

Falls; increased capacitance of pulmonary bed

Increases further




Rises; persistent vasoconstriction and increased cardiac output

Compensatory bradycardia

Requires intact efferent sympathetic response

  1. Sudomotor Function
    1. Sweating is induced by release of ACh from sympathetic postganglionic fibers.
    2. The quantitative sudomotor axon reflex test (QSART) is a measure of regional autonomic function mediated by ACh-induced sweating.
  2. Orthostatic BP Recordings
    1. Beat-to-beat BP measurements determined in supine, 70° tilt, and tilt-back positions are useful to quantitate orthostatic failure of BP control.
    2. Allow a 20-min period of rest in the supine position before assessing changes in BP during tilting.
    3. The BP change combined with heart rate monitoring is useful for the evaluation of patients with suspected OH or unexplained syncope.
  3. Tilt Table Testing for Syncope
    The great majority of patients with syncope do not have autonomic failure. Tilt table testing can be used to make the diagnosis of vasovagal syncope with sensitivity, specificity, and reproducibility.

Table 375-8 Neural Pathways Underlying Some Standardized Autonomic Tests

Test Evaluated


Autonomic Function


6 deep breaths/min

Cardiovagal function

Valsalva ratio

Expiratory pressure, 40 mm Hg for 10-15s

Cardiovagal function


Axon-reflex test 4 limb sites

Postganglionic sudomotor function


BPBB response to VM

Adrenergic function: baroreflex adrenergic control of vagal and vasomotor function


BPBB and heart rate response to HUT

Adrenergic and cardiovagal responses to HUT

 BPBB, beat-to-beat blood pressure; HRDB, heart rate response to deep breathing; HUT, head-up tilt; QSART, quantitative sudomotor axon-reflex test; VM, Valsalva maneuver.

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