Limb Weakness (Part II), spinal cord to muscles

A lecture given by Prof. Dr. Osama Shukir Muhammed Amin FRCP to semester 4 students of the International Medical University, Malaysia (now IMU University), about Limb Weakness (Part 1).

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?

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?

10. Motor End-Plates (Neuromuscular Junction or Myoneural Junction)?

11. Skeletal Muscles of the Limbs?

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?

14. Spinal ventral horn cells damage?

15. 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 hyporeflexia 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 overflow 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?

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:

22. Motor End-Plates?

23. Lambert-Eaton Syndrome?

24. Myopathy?

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. 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?

29. 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).

30. 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.

31. Neurophysiological Tests?

32. NCS?

33. 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).

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

35. 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.

36. 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.