Lecture by Prof. Osama Shukir Muhammed Amin FRCP(Edin), FRCP(Glasg), FRCP(Ire), FRCP(Lond), FACP, FAHA, to consolidate information pre-Task Based Learning about Limb Weakness. This lecture addresses lower motor neurons lesions and signs, their localization, and rationale for choosing diagnostic investigations. The next lecture will be about lower motor neuron lesions.

1. “Limb Weakness”
Part II
Osama Shukir Muhammed Amin
MBChB, MD, MRCP, FACP, FAHA, FCCP(USA),
FRCP(Edin), FRCP(Glasg), FRCP(Ire), FRCP(Lond)
Associate Professor of Neurology
School of Medicine, International Medical University,
Malaysia

3. In the previous lecture, we discussed
upper motor neuron lesions and
signs and their diagnostic approach.

4. Lower Motor Neurons?
• The cell bodies of “alpha motor neurons” reside within the
anterior (ventral) horns of the spinal cord.
• We have two normal areas of enlargements in the spinal
cord:
- Cervical: From C4 to T1, where the brachial plexus
originates to innervate the upper limbs. The
corresponding vertebrae lie roughly at the same level.
- Lumbosacral: From L2 to S3, where the lumbosacral
plexus originates to innervates the lower limbs. This area
lie within T9 to T12 vertebrae.

5. Journey?
Alpha motor neurons are in the spinal cord (i.e., within the
CNS).
Their axons exit the spinal cord through the anterior rami
and then pass through the peripheral nerves to innervate
skeletal muscles.
Therefore, these neurons are part of the “somatic/voluntary
nervous system”; the latter is part of the peripheral nervous
system.
Function: control of volitional muscle activity.
NB: Alpha motor neurons innervating skeletal muscles of the
head/part of the neck are found in the brainstem.

6. Motor Unit?
• Motor neuron + its axons which innervate skeletal muscle(s)
through motor-end-plates (neuromuscular junctions).
• Usually, many motor units cooperate and work together to
control the contraction of a “single” muscle; this is a “motor
pool”.
• Each muscle fiber is innervated by a single motor neuron.
• A single motor neuron can innervate many muscle fibers.
Examples:
- The biceps is innervated by approximately 400 motor
neurons.
- The tongue is innervated by approximately 8000 neurons.

7. Arrangement/Distribution of Ventral Horns’
Motor Neurons?
• Not haphazardly!
• The ventral grey horns’ alpha motor neurons are
clustered into “medial” and “lateral” groups. Each of
these groups in turn, subdivides into subgroups (e.g.,
ventromedial, centrodorsal, etc.).
• Each group/subgroup innervates a specific group of
muscles, e.g., large proximal muscles, paraspinal
muscles, extensors, distal small muscles, etc.
• In addition, certain neurons innervates specific
muscles, e.g., biceps.

9. Brachial Plexus?
• Formed by the anterior rami of C5 to T1.
• The plexus is divided into:
5 roots, 3 trunks, 6 divisions, 3 cords, and 5 branches.
• It has 5 terminal branches (musculoskeletal nerve, axillary nerve, radial nerve,
ulnar nerve, and median nerve) and many collateral branches (e.g., subscapular
nerve).
• Journey: after exiting through the intervertebral foramina, these nerve fibers will
pass through cervico-axillary canal, over the 1st rib, and then into the axilla.
• Function:
Motor (as well as sensory and vasomotor) innervation of the entire upper
limb, except trapezius (and small skin area in the axilla).

10. Cauda Equina?
• Pairs of the lumber, sacral, and coccygeal spinal roots.
• Surrounding the lower spinal cord (lumber enlargement and
conus medullaris) in a horse tail-like pattern.
• Lies within the lumber subarachnoid cistern at the lower
spine.
• Motor innervation of the entire lower limbs ( in addition to
sensory and visceral autonomic functions).
• Their anterior rami fibers after exiting the spinal canal will be
re-arranged to form the lumbosacral plexus.

11. Lumbosacral Plexus?
• Unlike the brachial plexus, in which the anatomy is clearly
delineated (trunks, divisions, cords,…etc.), it is roughly
divided in to lumber and sacral plexuses:
Lumber plexus: L1 to L5 roots.
Sacral plexus: S1 to S4 roots.
• The plexuses innervate the pelvic organs (and other viscera)
and the entire lower limbs (sensory, motor, vasomotor).
• The motor innervation of the lower limbs involves the pelvic
girdle muscles and muscles distal to the girdle.

12. Motor End-Plates (Neuromuscular Junction or
Myoneural Junction)?
• Represents a chemical synapse between the motor nerve
(presynaptic) terminals and the muscle fiber (postsynaptic
side).
• The released acetylcholine from the nerve terminals will bind
nicotinic receptors on the surface of the sarcolemma.
• The end-result of this binding is action potential, which may
culminate in a muscle contraction.
• The nerve impulses are important to keep the tone of the
muscle and to prevent atrophy.

13. Skeletal Muscles of the Limbs?
• Each muscle is composed of large number of myofibrils.
• Each myofibril is composed of long chains of sarcomeres (the
contractile unit of the muscle).
• Human skeletal muscles are composed of 2 types of fiber
“groups”: Type I and Type II (each displays distinct metabolic,
contractile, and motor-unit properties).
• Each muscle contains a combination of these 2 fiber types;
the percentage of each is variable depending on the muscle
itself and its function.

15. Lower Motor Neuron Lesions and Signs?
• Any lesion from the spinal cord’s ventral horn neurons down
to the muscle fibers (a long pathway).
• The classical signs are:
Weakness or complete paralysis.
Hypotonia (flaccidity).
Hyporeflexia or areflexia.
Fasciculation (involuntary rippling muscle movements).
Early and prominent atrophy.

16. Clinical Presentation?
•Depends on the etiology, site of the lesion,
multiplicity of the lesion, onset, and progression.
•And, if there is any coexistent central nervous
system damage.

17. Spinal ventral horn cells damage?
• Depends on the spinal segment?
• Accordingly, which muscle or group of muscles that segment
innervates.
• The lesion can be unilateral or bilateral, symmetrical or
asymmetrical.
• Any associated long tracts lesions?
For example, poliomyelitis affecting the right ventral grey horn
of the lower cervical segments resulting in lower motor
neuron signs in the right distal arm.

18. Root Lesion (radiculopathy)?
• Single or multiple (polyradiculopathy).
• Right and/or left, symmetrical or asymmetrical lesions.
• Accompanying sensory signs and symptoms?
• Level?
• Examples:
Left C5-C8 spondylolytic (compressive) radiculopathy:
biceps, brachioradialis, and triceps hyporelfexia with
corresponding dermatomal sensory changes.
Wide-spread and demyelinative, as in Guillain-Barre
syndrome: flaccid areflexic ascending pure motor weakness.

19. Cauda Equina Lesions?
• Depends on the level of the lesion, bilaterality, symmetry, and whether the
conus medullaris (upper motor neurons) is also damaged or not?
• Usually damaged by tumors or spinal compression (e.g., severe
spondylolytic spinal stenosis or tumors).
• The resulting clinical picture is a combination of bilateral asymmetrical and
“bizarre” motor, sensory, and sphincter disturbances, e.g., weakness of left
knee flexion and right ankle plantar flexion as well as perineal numbness,
urinary retention and over flow incontinence.
• Any conus medullaris involvement will add upper motor neuron lesions’
signs, e.g. ,bilateral Babinski to the above example.

20. Plexopathy?
• Beyond undergraduates!

21. Peripheral Nerves’ Damage?
• Peripheral nerves may convey pure motor, pure sensory, or
sensori-motor fibers (which may be predominantly motor or
predominately sensory).
• Therefore, the resulting clinical picture depends on the
damaged nerve itself and “where” it is damaged (e.g.,
proximally versus distally).
• A lesion in a single peripheral nerve never results in a “whole
limb weakness”.
• Rather, such a single nerve lesion results in a predictable
weakness (distribution) in a muscle or group of muscles
innervated by that nerve.

22. Etiologies?
• Long list (refer to textbooks)!

23. Distribution?
• Mononeuropathy: focal involvement of a single nerve
(usually by local causes).
• Polyneuropathy: generalized, relatively “homogeneous”
process affecting many peripheral nerves, with the “distal
nerves” usually affected most prominently.
• Mononeuritis multiplex: simultaneous or sequential
involvement of noncontiguous nerve trunks (usually the
term is reserved for nerves infarction from vasculitis).

24. The lesion:
Can attack the axons only (axopathy), myelin sheaths
(demyelinative), or a combination of both
(demyelinative-axonal; simultaneously or
sequentially).
Can be acute, subacute, or chronic.
May also affect skeletal muscles and/or the autonomic
nervous system.

25. Motor-End Plates?
• The classical example is myasthenia gravis.
• In which the pathology targets the “presynaptic membrane” of
the motor endplates of skeletal muscles, reducing acetylcholine
release.
• The cardinal feature is “painless fluctuating fatigability” of
muscles (worse at the end of the day and after sustained motor
activity).
• Because both the nerves and muscles are spared, no changes in
deep tendon reflexes occur. Sensation and sphincters are intact,
likewise.

26. Lambert-Eaton?
• Paraneoplastic.
• Post-synaptic.
• Autonomic involvement (dry mouth, orthostasis,
constipation,…etc.).
• The weakness improves after sustained activity or
exercise.
• The weakness is usually proximal, more in the lower
limbs, occasionally painful and tender.
• May be associated with peripheral neuropathy.

27. Myopathy?
• The first step is to differentiate true weakness of myopathy from
apparent weakness due to asthenia, motor impairment due to
pain or join dysfunction, etc.
• True muscle weakness patients complain of weakness upon
doing specific tasks, e.g., standing from a low chair, combing
their hair, or climbing stairs.
• Patients with severe anemia, cardiopulmonary diseases, wide-
spread joint diseases, cachexia, chronic infections, organ failure,
depression, etc usually express themselves as being “weak”.
 Those patients are actually functionally-limited but not
truly weak.

28. Etiologies of myopathies?
• Long list (refer to textbooks)!
• Remember that many systemic diseases and
medications/drugs can result in both
myopathy/myositis and polyneuropathy.

29. Myopathy?
• Painful and tender myositis.
• Muscle pain is relatively uncommon in patients with
many types of myopathy and true weakness, but is
often a problem for patients with overexertion,
cramps, or fibromyalgia.
• The cardinal feature of myopathy is the bilateral
symmetrical involvement.

30. Pattern: proximal, distal, or a “specific pattern”.
Proximal Weakness:
• Shoulder (deltoids; abductors) and pelvic girdles (quadriceps; hip
flexors).
• Combing hair, rising from a seated position without using their upper
limbs.
• Usually, those patients display inability to perform a “deep knee
bend”. Therefore, may suddenly drop into the chair when trying to sit
down slowly!
• Sometimes, patients “climb up their legs with their hands”, i.e.,
Gower’s sign (classically seen in Duchenne muscular dystrophy).

31. Distal Weakness:
• Decreased grip strength, weakness of wrist flexion or
extension, decreased plantar flexion strength, and
foot drop.
• Some myopathies may result in distal weakness (e.g.,
myotonic dystrophy); however, early motor neuron
disease or peripheral neuropathy can also be a cause.

32. Specific distribution of weakness (not proximal and
not distal)
• Characteristically seen in certain muscular
dystrophies, such as facioscapulohumeral muscular
dystrophy.

33. Diagnostic Approach in Lower Motor Neuron
Lesions?
• History taking.
• Medical and neurological examinations.
The above will generate a provisional diagnosis or a list
of differential diagnoses in order to choose your
investigations.
• Investigations.
We should answer these 3 questions:
Where is the lesion, what is the lesion, and why?

34. Investigations?
Long list, depending on the patient’s presentation:
CBC, ESR, blood film, blood sugar, blood urea and
electrolytes, serum total bilirubin, serum transaminases,
thyroid stimulating hormone, etc. to blood and urinary
toxicology, genetic mutations, enzymatic assessment, auto-
antibodies panel, etc.
Muscle enzymes: creatine kinase (CK), aldolase, AST, and
LDH. CK can be normal, marginally elevated (e.g.,
hypothyroidism, motor neuron disease), moderately/high
elevated (e.g., myositis), or very high (characteristic of
Duchenne muscular dystrophy).

35. Investigations?
• Imaging: this is helpful in uncovering lesions of the
spinal cord (ventral horn) or cauda equina.
• Spinal MRI may show a tumor within the substance of
the cord (damaging the ventral horns), a tumor in the
lower lumber spinal canal (cauda equina), severe
lumber spinal stenosis (cauda equina), etc.
However, this can be entirely normal, e.g., in motor
neuron disease.

36. Neurophysiological Tests?
• Nerve conduction studies (NCS) and electromyography
(EMG).
• Can uncover lesions from the ventral horn cells down to the
motor end-plates and muscles.
• Operator-dependent: needs a high expertise and background
knowledge in neurological diseases!
• NCS is especially useful in radiculopathies and neuropathies.
• EMG is helpful in diseases of the motor end-plates and
myopathies (including myositis) as well as motor neuron
diseases.

37. NCS?
• Can assess radiculopathies (F-waves), plexopathies, or
neuropathies.
• Whether the lesion is acute, subacute, or chronic.
• Axonopathy, demyelination, or a combination of both.
• Affecting sensory nerves, motor nerves, or both (sensori-
motor).
• Can map which nerves are involved in mononeuritis
multiplex.
• May give us a prognostic value.

38. EMG?
• Helpful in uncovering diseases of the anterior horn cells, e.g., in
motor neuron disease we may see high-amplitude, long-duration, and
polyphasic motor unit potentials (of chronic denervation and re-
innervation).
• Can assess diseases of the motor endplates (decremental response in
myasthenia gravis, incremental response in Lambert-Eaton), including
sub-clinically affected muscles.
• Can assess myopathies (low-amplitude, short duration, and
polyphasic motor unit potentials), myositis (with prolonged
insertional activity, resting fibrillation potentials), and myotonic
discharges (dive-bomber sound).

39. Nerve biopsy?
• Usually, sural nerve biopsy.
• Out of your scope!

40. Muscle biopsy?
• Usually taken from clinically weak muscle(s).
• Should not be taken from severely weak or atrophied muscle
(usually fibro-fatty changes will be seen).
• Usually, many diseases can be diagnosed with the use of
routine light microscopy, e.g., dermatomyositis (peri-
fascicular atrophy), polymyositis, inclusion-body myositis,
certain drug-induced myopathies, muscular dystrophies, or
vasculitis, and even motor neuron disease (checkerboard
pattern of fiber-type grouping).
• Special stains can demonstrate enzyme deficiencies and
abnormal accumulations of glycogen or lipid in the metabolic

41. Detail of a lion-hunting scene of the Assyrian king Ashurbanipal II.
Bas-relief. From the North Palace at Nineveh, Mesopotamia, Iraq.
7th century BCE. Housed in the British Museum, London.