Tests for peripheral neuropathy

  • Electromyography
    • measures electrical impulses in muscle at rest & when contracting
    • Differentiates between muscle and nerve disorders
  • Nerve conduction velocity
    • assess the degree of damage in the larger nerve fibres due to myelin loss
    • Slow transmission –> myelin damage   
    • Decrease strength of impulse -> axonal degeneration
  • Nerve biopsy
    • invasive
    • sural nerves (unmyelinated nerve)
  • Skin biopsy
    • assess damage present in small fibres
    • nerve conduction tests cannot assess these

Approach to peripheral nerve diseases

Consider whether the pathology is:

  • Primary damage to Schwann cells/myelin
    • Acute inflammatory demyelinating polyradiculoneuropathy (GBS)
    • Chronic inflmamatory demyelinating polyradiculoneuropath
    • Paraprotein neuropathy
    • Charcot-Marie-Tooth type 1
  • Damage to neuron/axon
    • Damage affecting predominantly small unmyelinated fibres 
      • amyloid
      • diabetes mellitus
      • HIV
    • Affecting all axonal population
      • vasculitis
      • CMT type 2

Pathology of demyelination

  • Axon damaged
  • Neural bodies intact
  • Conduction block
    • conduction velocity decreases

Patterns of axonal pathology

  1. Wallerian degeneration
    • In transected axon
      • distal portion undergoes disintegration & degradation
    • Limited recovery & regeneration
    • Neuronal body
      • chromatolysis
        • activation of protein synthesis to help regenerate axon
    • Examples:
      • trauma
      • infarction
        • diabetic mononeuropathy
        • vasculitis
      • neoplastic infiltration
  2. Distal axonopathy
    • Degeneration of axon and myelin starts in the most distal part of the axon
    • Axon dies back (retrograde)
      • ‘stocking-glove’ sensory
      • motor deficit
    • Caused by neuronal body pathology
      • resulting in inability to sustain the metabolic needs of the axon
    • Examples
      • drugs
      • toxins
      • organophosphates
      • diabetic polyneuropathy*
      • alcohol
      • vitamin deficiency
      • uraemia
      • malignancy

Classification of peripheral neuropathy

By etiology

  1. Inflammatory neuropathies
    • Immune-mediated
    • Examples
      • Gullain-Barre Syndrome
      • chronic inflammatory demyelinating polyradiculoneuropathy
  2. Infectious
    • Examples
      • Leprosy (Hansen’s disease)
      • Diptheria
      • Varicella-zoster
  3. Hereditary
    • Examples
      • Charcot-Marie-Tooth 1,2 and X
  4. Acquired metabolic & toxic neuropathies
    • Examples
      • Diabetes mellitus
      • vitamin deficiency
      • liver disease
      • alcohol
      • malignancy
      • paraneoplastic

By site of pathology

  • Affecting Schwann cells/myelin
    • Acute inflammatory demyelinating polyradiculoneuropathy (GBS)
    • Chronic inflmamatory demyelinating polyradiculoneuropathy
    • Paraprotein neuropathy
    • Charcot-Marie-Tooth type 1
  • Affecting the neurons/axons
    • Damage affecting predominantly small unmyelinated fibres 
    • Example
      • Amyloid
      • Diabetes mellitus
      • HIV
  • Affecting all axonal population
    • Vasculitis
    • CMT type 2

_____________________________________________________________________

DEMYELINATING DISEASES

Acute inflammatory demyelinating polyradiculoneuropathy

  • General
    • Also known as: Guillain-Barre Syndrome
    • T-cell mediated immune response & humoral response
  • Clinical features
    • Rapidly evolving
      • Ascending symmetrical weakness
      • Areflexia
    • Variable autonomic dysfunction
    • Mild sensory sign
    • Mostly preceded by an acute flu-like illness
      • complication of influenzae infection
  • Important features
    • Ascending paralysis
    • Loss of deep tendon reflexes
    • Decreased nerve conduction
    • Increase in CSF protein
      • Little cell increase
  • Infectious agents implicated include
    • Campylobacter jejuni
    • CMV
    • EBV
    • Mycoplasma pneumoniae
    • Influenzae virus
  • Microscopic pathology picture:
    • Endoneurial lymphocytic inflammation
      • macrophage infiltration
      • MACROPHAGE mediated DEMYELINATION
    • More severe in the nerve roots
      • more subtle in the periphery
      • Axonal damage when disease is severe
    • Electron microscopy
      • macrophage penetrating basement membrane of Schwann cells
      • Stripping myelin sheath away
      • Remyelination can occur
  • Plasmapharesis is effective in some cases

image

Chronic inflmamatory demyelinating polyradiculoneuropathy

  • Classical Triad
    • Symmetrical proximal & distal weakness
      • for more than 2 months
    • Loss of large fibre modalities
    • Loss of deep tendon reflexes

  • Laboratory studies
    • Endoneurial inflammation
    • Onion-bulb formation in semithin sections
      • due to repeated demyelination & remyelination
  • Hereditary Sensory and Motor Neuropathy (HSMN)

    • General
      • Also known as Charcot-Marie-Tooth type 1
    • Clinical features
      • Slowly progressive distal weakness
      • Usually begin in childhood
      • Muscle atrophy and sensory impairment
      • Dominance of distal lower extremities signs and symptom
      • Hammertoes
      • Pes caves
        • high arch
      • Nerve enlargement (hypertrophy)
        • If nerves palpable and tremors = CMT type 1
      • Very slow disease with normal longevity
    • Pathology
      • Decrease numbers of large & small myelinated fibres
      • Onion bulb formation
      • Increase in calibre of affected nerves
        • nerve hypertrophy
      • Axonal form (CMT2)
        • no onion bulb, but regenerative axonal clusters
      • Genetic mutation of myelin related proteins

    Paraprotein neuropathy

    image

    • Neuropathy associated with a monoclonal gammopathy
    • Incidence
      • > 50 yrs
      • male
    • Clinical features
      • Mild slowly progressive symmetrical distal weakness
      • Painful with severe sensory loss & paresthesia
    • Diagnosis
      • Monoclonal IgM with anti-MAG (myelin-associated glycoprotein activity)
    • Pathology
      • Non-specific myelin & axonal loss
      • POEMS syndrome
        • polyneuropathy
        • organomegaly
        • endocrinopathy
        • M protein
        • skin changes

    _____________________________________________________________________

    AXONAL DISEASES

    Amyloid neuropathy

    • General
      • Hereditary/acquired
    • Important features
      • Small fibre neuropathy
        • pain
        • temperature
        • autonomic dysfunction*
    • Clinical features
      • Painful dysesthesias
      • Bowel & bladder dysfunction
      • Impotence
      • Orthostasis
      • Cardiac & renal abnomalites
    • Pathology
      • Biopsy abdominal fatpad
        • Amyloid deposition in endomerium & vascular wall
        • Large myelinated fibres are preserved

    image

    Diabetic polyneuropathy

    • Cause
      • diabetes mellitus
    • Most common pattern
      • length-dependent axonal sensorimotor polyneuropathy
    • Manifest as
      • PAIN and PARESTHESIAS
    • Clincal features
      • Start in distal lower extremities
        • longest nerve fibres
      • Gait abnormality
      • Autonomic abnormality
        • ‘diabetic autonomic neuropathy
      • Sensory dysfunction distal extremity
        • glove & stocking numbness
      • weakness of distal lower extremity
    • Pathology
      • Axonal neuropathy
      • Loss of large, small & unmyelinated fibres
      • Entirely NON-SPECIFIC
    • Pathophysiology
      • Nerve ischaemia
        • due to diabetic microangiopathy
        • poor blood flow
        • may easily develop ulceration

    image 

    • Skin biopsy to assess small-nerve fibres
      • Easy to perform
      • Provides information on small nerve fibres
        • not possible with sural nerve biopsy
        • nor with routine neurophysiological testing
      • Can demonstrate subclinical neuropathy
        • eg. in diabetic patients

    image

    _____________________________________________________________________

    Hansen’s disease

    • Causal organism
      • Mycobacterium leprae
    • Pathology
      • In Lepromatous leprosy
        • Schwann cells are invaded by the mycobacteria
        • Increase in Th2 cytokines: IL3, IL5, IL10
        • Increase CD8 cells
      • In Tuberculoid leprosy
        • active cell mediated immune response
          • injures cutaneous nerves
          • including axons, schwann cells & myelin
        • Increase Th1 cytokines: IL2, IFNγ, TNFβ
        • Histology:
          • granulomatous inflammation, scanty bacilli
    • Clinical features
      • Pain fibres affected
        • loss of sensation

    Traumatic neuroma

    • Non-neoplastic
    • Occurs at proximal end of severed nerve
      • trauma
      • surgery
    • Clinical features
      • Firm nodule, painful or tender
        • Reactive proliferation of schwann cells, axons & fibrous ce
          lls

    Tumours of peripheral nerves

    Neurofibroma

    image

    image

    • Cutaneous/ in Peripheral nerve
    • Plexiform type
      • only seen in Neurofibromatosis Type1 (NF1)
    • Tumours in NF1 are more likely to become malignant
      • Malignant tumours are called
        • Malignant Peripheral Nerve Sheath tumours (MPNST)
    • Histology
      • Spindle shaped cells
      • Serpentine nuclei
      • Schwann cells, axons, fibroblastic cells and perineurial cells are present

    Schwannoma

    image

    • Arise from Schwann cells
    • Histology
      • True encapsulation
      • Antoni type A & Antoni type B areas
      • Verocay bodies
    • Multiple tumours seen in NF2
      • Benign
    • Malignant counterpart is MPNST

    terri

    Terri is obsessed with making medical school as painless as possible. She studies and compiles medical school notes in a concise, easy-to-understand format. She also enjoys reading contributions by others. She is an investor in sustainability projects. Her ideal weekend is wine tasting and experimenting on bread-making. She has yet to master the art of Sourdough baking.

    2 Comments

    Georgia M. · January 6, 2012 at 9:49 pm

    We just wrote a small tidbit (sourcing a Harvard study) about using ATP supplementation to lessen or prevent the symptoms of small fiber peripheral neuropathy: http://www.chrisbyrnes.com/2012/01/06/treating-small-fiber-neuropathy-symptoms-with-atp/

    Ali · June 3, 2013 at 8:15 pm

    Nice

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