Limb Weakness II Osama S. M. Amin

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

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

3. 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.

4. 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.

5. 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.

6. 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.

7. 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 1 st 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).

8. 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.

9. 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.

10. 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 .

11. 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.

12. 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.

13. 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.

14. 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.

15. Root Lesion (radiculopathy)? Single or multiple (polyradiculopathy). Right and/or left, symmetrical or asymmetrical lesions. Accompanying sensory signs and symptoms? Level? Examples: L eft 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 .

16. 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.

17. Plexopathy ? Beyond undergraduates!

18. 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.

19. Etiologies? Long list (refer to textbooks)!

20. 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).

21. 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.

22. 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. The weakness is usually of a “ descending pattern ”, starting from the extraocular muscles, downwards.

23. 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.

24. 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.

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

26. 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.

27. 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).

28. 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.

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

30. 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?

31. 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).

32. 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.

33. 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.

34. 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.

35. 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).

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

37. 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 myopathies.

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