W9 - Polyneuropathy (GBS & CMT) Flashcards
Briefly define the term “Guillain-Barré Syndrome (GBS)”.
GBS is a collection of post-infectious polyradiculoneuropathic clinical syndromes which are acute in onset, rapidly progressing, inflammatory and demyelinating.
List the factors that predispose to GBS.
Viral illness of infections (50% of cases)
- Campylobacter enteritis (most common cause)
- Cytomegalovirus (CMV)
- Mycoplasma pneumoniae
- Epsteinn-Barr virus (EBV)
Other causes:
- Autoimmune disease (eg RA, SLE)
- Immunisations (eg swine flu)
- Malignancy (Hodgkin’s disease)
- Trauma (eg surgery)
*Many illnesses and events trigger GBS, but reason it affects specific patients still unknown. Regardless of triggering events, the nerves of GBS patients are attacked by the body’s immune system (antibodies and leucocytes).
Molecular mimicry thought to play a major role in genetically susceptible people:
- Virus/bacteria enters body
- Macrophages phagocytose pathogen and present antigen on surface (aka antigen presenting cell - APC)
- T-lymphocytes recognise antigen on surface of APC, release substances and differentiate into cytotoxic T cells and signal B cells to differentiate and proliferate into memory and plasma cells
- Plasma cells release antibodies (Ab’s) that detect and destroy antigen
- Cytotoxic T-cells and Ab’s incorrectly recognise “self” cells as foreign (viral/bacterial) and destroy them (auto-reactive)
* In the case of GBS, the auto-reactive T-cells and Ab’s attack host’s nerve cells.
Describe the clinical manifestations of GBS.
Motor neuropathy
- Muscle weakness - May present as foot drop, fatigue upon climbing stairs. Progresses distally -> proximally
- Evolves over 3-21 days
- May be generalised
- Proximal, or commences distally and ascends
- DTRs lost (but plantar response remains flexor/normal)
- Severe cases - Respiratory and bulbar involvement
Early Ssx
- Pain suggestive of nerve root irritation
- Paraesthesia in legs and feet
- Back pain (occasionally initial presentation)
- CN lesions - especially CN VII (Facial weakness may precede other neuro ssx, often unilateral). CN I & VIII not affected
Sensory neuropathy
Pain
Autonomic manifestations
- Fluctuating BP (generally hypotension)
- Tachycardia
- Urinary retention
Describe the clinical course of GBS
Rapidly progresses over days to <4wks
Typically begins with progressive, ascending weakness
Reflexes diminished in the early stages and are quickly lost
Motor symptoms predominate (they gradually stabilize → remain constant → begin to recede)
Sensation and autonomic function can be affected
Respiratory failure requires support (mechanical ventilation is required in about 25% of patients)
Ssx severity reflects amount of Ab’s present in host to fight infection (infection → acute inflammation = lots of Ab’s → stabilizes and recedes as chronic inflammation ensues and recedes = less Ab’s)
Discuss the diagnosis of GBS.
GBS Ssx are quite varied, making early diagnosis difficult. Diagnosis relies on pattern recognition and a careful and detailed Hx usually required. Important points:
- GBS symptoms usually bilateral
- Ssx develop very rapidly; in other disorders, muscle weakness may progress over months rather than days or weeks
- In GBS, reflexes such as patella reflexes are usually lost
Lab tests cannot specifically diagnose GBS but can be used to exclude other neurological diseases.
- CSF – Increased protein (after 2nd/3rd week of illness), increased γ globulin, increased cells (raised monocytes in 20% of cases)
- Nerve conduction studies – Prolonged conduction velocities (late phenomenon)
- Virology – Rising titres to specific viruses may be found
- Serology – Campylobacter serology should be performed (positive titres identify patients with poorer prognosis)
- Forced vital capacity – Assess disease progression and predict need for respiratory support
- Electromyography – Rule out other conditions
- Other blood tests – Rule out other conditions
Discuss the treatment of GBS.
Treatment is supportive:
- Tracheostomy (progressive bulbar and respiratory weakness)
- Pressor drugs (severe hypotension due to ANS disturbance)
- Plasmapheresis and IV immunoglobulin (beneficial in severe and progressive cases when given early)
Discuss the prognosis and complications of GBS.
Prognosis:
- Most favourable cases – Patient likely to recover <3 months
- Recovery usually occurs over 6 months – 2 years or longer
- Median time to complete functional recovery = 9 months
- 33% have not recovered after 12 months
- Mortality <5%
- Those with respiratory failure – 30% disabled (20% severely disabled)
- 5% develop chronic relapsing course
- 45% have variable degree of long term disability (eg waddling gait)
- Physical signs such as areflexia may persist in spite of a return to normal function
Complications:
- Headaches
- Death
- Briefly define the term “Charcot-Marie-Tooth disease (CMT)”.
A group of hereditary sensorimotor neuropathies that affects motor and sensory nerves of the lower legs that results in lower limb weakness and atrophy.
Discuss the epidemiology and classification of CMT.
Epidemiology:
- Most common hereditary neuropathy
- Affects 1/2500 people
Classification, pathology and aetiology:
2 main subtypes (based on pathological process):
- CMT1 - Myelin sheath (demyelinating) peripheral polyneuropathy
- CMT2 - Axonal (non-demyelinating) peripheral polyneuropathy
* >50 subtypes, most of which are inherited as an autosomal dominant trait
Discuss the clinical picture of Type 1 CMT (CMT1).
Early:
Weakness begins in lower legs
- Inability to flex foot (footdrop)
- Calf muscle atrophy (stork leg deformity)
Later:
- Atrophy of hand muscles
- Centripedal loss of vibration, pain and temp sense in hands and feet
Disease progresses slowly and does not affect life span.
In milder subtypes of Type 1 CMT, high arches and hammer toes may be the only symptoms.
How is CMT diagnosed?
Diagnosis based on: Clinical presentation - Distribution of weakness - Age of onset - Presence of foot deformities (high arches and hammer toes) Family history Nerve conduction studies Genetic testing
