Neuromuscular disorders
FM Brett MD., FRCPath
At the end of this lecture you should be able to:
1. Distinguish between UMN and LMN lesions
2. Understand the differences between a neuropathy and
a myopathy
3. Know how MND presents
3. Know the common causes of a peripheral neuropathy
4. Know the importance of clinical history, f/x and
examination in understanding muscle disease.
Sites of lesions producing neuromuscular pathology
Either the upper (1,2,3)
or lower motor neurone
pathway (4,5),
N-M-J (6) or muscle (7)
may be responsible
Sites of lesions producing neuromuscular pathology
Commonest causes trauma or vascular
accidents (1,2) or demyelination (2,3,4,5)
neuronal degeneration (4), transmission
defects (6) and membrane, fibrillary or
metabolic lesions (7).
The motor unit
Neurone
Axon
NMJ
M
Diseases of
motor neurones
Peripheral
neuropathies
Diseases of neuromuscular
transmission
Primary muscle
disease: myopathies
MND ALS
~ generalised wasting & fasiculation
~ Bulbar muscle involvement common
~ Associated upper motor neurone symptoms and signs
~ No sensory symptoms
~ Steadily progressive and fatal
Clinical presentation of MND
• Selective loss of LMN from pons, medulla and
spinal cord, together with loss of UMN from the brain
• Clinical picture varies depending on
whether :
a) upper or lower motor neurones are predominantly
involved
a) Which muscles are most affected
b) The rate of cell loss
Aetiology of ALS
~ cause unknown
~ 5-10% AD and in familial cases usually starts 10 years
earlier than sporadic cases
~ Mutations in the Cu/Zn superoxide dismutase gene on Ch 21q
accounts for 25% of all familial cases
~ Mutations of the neurofilament heavy
~ Tunisian ALS uncommon AR disease linked to 2q33-q35
Macroscopic examination reveals
the anterior spinal nerve roots to
be shrunken and grey in appearance
Pathology
~ Loss of motor neurones and astrocytosis in spinal cord, brain stem
and motor cortex
~ Motor neurones in the pons and medulla are often involved
in the disease process
The motor unit
Neurone
Axon
NMJ
M
Diseases of
motor neurones
Diseases of neuromuscular
Peripheral transmission
neuropathies
Primary muscle
disease|: myopathies
Peripheral neuropathy
~ Axonal or demyelinating
~ Neurotransmission most impaired in long nerves
because nerve impulse confronted by a greater number
of demyelinated segments
~ Therefore symptoms distal in distribution
~ Affects legs and feet more than arm and hand
Spinal cord
M
Peripheral nerve
myelin
axon
Node of ranvier
Common causes of peripheral neuropathy
1. Deficiency – Vit B1 alcoholic
Vit B6 in pts taking isoniazid
Vit B12 in patients with PA and bowel disease
2. Toxic
Alcohol
Drugs – isoniazid, vincristine
3. Metabolic – DM, CRF
4. Post-infectious – Guillain- Barre syndrome
5. Collagen vascular – RA, SLE, PA
6. Hereditary – Charcot- Marie – Tooth disease
7. Idiopathic – Perhaps up to 50% cases
Guillane-Barree syndrome
~
~
~
~
Rapid evolution over several days
Life threatening weakness
Affects nerve roots as well as peripheral nerves
Occurs within 2 weeks of an infection usually
campylobacter, cytomegalo, EBV
~ Auto-immune response
~ Weakness and sensory symptoms which worsen
daily for 1-2 weeks
~ Demyelinating polyneuropathy and
polyradiculopathy
Myasthenia Gravis
UMN
~
~
~
~
LMN
Muscle weakness without wasting
Fatiguability
Ocular and bulbar muscles commonly involved
Responds well to treatment
NMJ
M
Muscle disease
UMN
LMN
NMJ
M
~ Muscle weakness and wasting – the distribution of which depends
on the type of disease but strong tendency to involve proximal muscles
i.e trunk and limb girdles
~ Various causes
Classification
Inherited
• Muscular dystrophies
• Myotonic dystrophy
• Congenital myopathis
• Metabolic myopathies
• Channelopathies
Acquired
Endocrinopathies
Drug induced
Idiopathic
inflammatory
myopathy
Metabolic myopathy
Myasthenia Gravis
/LEMS
Aim of the history and
examination
• To identify mode of inheritance
• Accompanying features
• Key pattern of muscle involvement
• Functional status
• Minimum tests to establish a diagnosis
Diagnostic Consultation
• F/x tree
• Personal and f/x h/x
• Observation
• Functional assessment
Pattern of muscle involvement:
• Specific in familial muscular dystrophies
e.g fascioscapuloperoneal
•Proximal weakness in the limbs in acquired
diseases of muscle such as polymyositis
Distribution of onset of muscle
weakness
A. Typical proximal (limb-girdle)
distribution of a myopathic disorder
(DMD)
B. More distal (glove and stocking)
distribution of a neurogenic disorder (SMA)
C. FSH –own distribution
D. SP - own distribution
Investigations of patients with generalised muscle
weakness and wasting
MND
Peripheral
neuropathy
CPK
N
N
EMG
Neuropathic
Neuropathic
Myopathic
Histology
Denervation
Denervation
Primary
muscle
disease
TEST
Muscle
disease
CONCLUSIONS
• UMN – lesions involving the corticospinal tract
• LMN – lesions involving brain stem and spinal cord
• MND – may present with UMN and LMN signs
• Peripheral neuropathy may be axonal or demyelinating
• Muscle disease may be inherited or acquired