This article outlines a systematic approach to weakness. The examination of the motor system is covered elsewhere (See Motor System Examination)
When evaluating weakness the following distinction is made:
- Upper motor neuron lesions (lesion in cerebral cortex, brainstem, or descending motor pathway of spinal cord). Also called pyramidal tract disease, long tract signs, or central weakness. Causes increased tone, increased reflexes, pyramidal pattern of weakness (weak extensors in the arm, weak flexors in the leg)
- Lower motor neuron lesions (lesion in peripheral nerve and anterior horn cells of the spinal cord). Also called denervation disease or peripheral weakness. Causes wasting, fasciculation, decreased tone, and absent reflexes
- Muscle disease: Causes wasting, decreased tone, impaired or absent reflexes
- Neuromuscular junction disorders: Causes fatigable weakness, normal or decreased tone, normal reflexes
- Functional weakness: Causes normal tone, normal reflexes without wasting with erratic power.
The first two are the most common. Each of them is associated with distinct physical signs, neuroanatomy, and causes. Table 1 outlines some characteristic findings, however the findings are only help if present, not if absent. Also full lower or upper motor neuron syndromes are often incomplete. For example up to a quarter of patients with upper motor neuron weakness lack hyperreflexia. Also in many lower motor neuron weakness conditions there is no clinical reflex (e.g. median or ulnar neuropathy). Table 2 outlines the differential diagnosis.
|Location of Lesion||Muscle Tone||Atrophy or Fasiculations||Sensory Findings||Muscle Stretch Reflexes||Other Findings|
|Upper motor neuron||Spasticity||No||Sometimes||Increased||Babinski or Hoffman Sign|
|Lower motor neuron||Hypotonia||Yes||Usually‡||Decreased/absent||Depends on lesion, e.g. Tinel's|
|Neuromuscular junction||Normal or hypotonia||No||No||Normal/decreased||Ptosis, diplopia|
|Muscle||Normal||No (except if late)||No||Normal/decreased||Myotonia|
|Functional||Normal||No||Non-anatomical||Normal||Multiple, e.g. Hoover's sign|
|‡ in the distribution of the spinal segment, plexus, or peripheral nerve.|
|Diagnostic category||Site of lesion|
|Upper motor neuron||Anterior horn cell||Peripheral nerve||NM junction||Muscle|
|Genetic||Leukodystrophies||Spinal muscular atrophy||Peroneal muscular atrophy||Myasthenia gravis||Muscular dystrophies|
|Inflammatory||Vasculitis||Amyotrophic lateral sclerosis||Guillain- Barre||Myasthenia gravis||Polymyositis|
|Neoplastic||Brain tumor||Paraneoplastic syndrome||Myeloma/ amyloid||Eaton-Lambert syndrome||Malignancy- associated myositis|
|Metabolic/ endocrine||Vitamin B12 deficiency||Diabetes||---||Hypothyroid
To assist with the differential diagnosis, muscle weakness can also be categorised into proximal predominance, distal predominance, proximal and distal involvement, proximal involvement in the upper extremities and distal involvement in the lower extremities, oculobulbar predominance, and isolated neck flexor or extensors.
Upper Motor Neuron Weakness
Upper motor neuron lesion: weak and flaccid (generally distal) muscles that eventually become spastic, hypertonic, and hyperreflexive. There is an association with pathologic reflexes (such as Babinski's and Hoffmann) and induced clonus of the ankle or wrist. Spasticity is prominent in the antigravity muscles (flexors of the upper extremities and extensors of the lower extremities). Spasticity is associated with clasp-knife finding due to a variable degree of resistance to passive motion.
Upper motor neurons cross over to the contralateral side at the decussation of the pyramids (between the brainstem and spinal cord). Therefore upper motor neuron type weakness can result from:
- Ipsilateral spinal cord lesion: In spinal cord lesions there may be both upper and lower motor neuron type weakness. Lower motor neuron type weakness occurs at the level of the lesion, and upper motor neuron type weakness occurs below the level of the lesion.
- Contralateral brainstem lesion
- Contralateral cerebral hemisphere lesion:
Common aetiologies are cerebrovascular disease, multiple sclerosis, and brain tumours.
The upper motor neuron pathway extends from the cerebral cortex down through the spinal cord. It travels in tight quarters with central neurons that innervate other structures. Therefore there are localising lesions in this pathway to pinpoint its location:
|Anatomic Location||Associated Finding|
|Aphasia (right hemiparesis)|
|Inattention to left body, apraxia (left hemiparesis)|
|Cortical sensory loss|
|Hyperactive jaw jerk|
|Brainstem||Crossed motor findings|
|—Contralateral third nerve palsy (midbrain)|
|—Contralateral sixth nerve palsy (pons)|
|Spinal cord||Sensory level|
|Pain and temperature sensory loss on contralateral arm and leg|
|No sensory or motor findings in face|
|Additional lower motor neuron findings (atrophy, fasciculations)|
Lower Motor Neuron Weakness
Lower motor neuron lesion: weakness and paralysis of (generally distal) affected muscles. Flaccidity, hypotonia, diminished or absent stretch reflexes, and eventually atrophy. Fasciculations occur which are visible twitches of small groups of muscle fibres. There are no pathologic reflexes.
In monoparesis of lower motor neuron type, first determine if the affected muscles are supplied by a single spinal segment (radiculopathy), peripheral nerve (peripheral neuropathy), or a combination (plexopathy). The lesion is always ipsilateral to the side of the weakness. Some discussion on how differentiation can be done is provided in the pages on cervical radicular pain and lumbar radicular pain. The myotomal pattern of innervation is different to the dermatomal pattern of innervation. By referencing the complete myotomes chart, one can differentiate between a proximal lesion (spinal nerve or root) versus a lesion in a peripheral nerve (radial, ulnar, median, peroneal nerve, etc). For example, patients with C6 radiculopathy may have scapular winging in addition to distal weakness. A peripheral nerve lesion is not going to cause proximal motor weakness.
Try and determine the distribution of weakness. Generalised weakness can occur in myasthenia gravis, long-standing periodic paralysis, prolonged bed rest-induced disuse atrophy, muscle wasting from malignancy, and longstanding motor neuron disease.
If weakness is not generalized, it can be classified as symmetric or asymmetric. Asymmetric weakness is likely to indicate central or peripheral nervous system disease. Moreover, lesions of the motor cortex, spinal cord, spinal nerve root, and peripheral nerve have distinct distribution patterns. Symmetric patterns of weakness can be further classified as distal, proximal, or specific distributions.
Distal weakness is characterized by decreased grip strength, weakness of wrist flexion or extension, decreased plantar flexion strength, and foot drop. Patients with distal symmetric weakness face difficulty walking on their heels or toes. Distal symmetric weakness is typical of early motor neuron disease or peripheral neuropathy.
Proximal weakness involves the axial muscle groups, deltoids, and hip flexors. Patients with proximal weakness may face difficulty flexing or extending the neck against resistance, and rising from a seated position. Proximal muscle weakness is commonly seen in various myopathies, certain muscular dystrophies, and myasthenia gravis.
Specific distributions of weakness are characteristic of certain neuropathies or muscular dystrophies. Examples of localized disorders include facioscapulohumeral dystrophy, scapuloperoneal dystrophy, and scapulohumeral dystrophy.
Combined Upper and Lower Motor Neuron Weakness
Seen in myelopathy and amyotrophic lateral sclerosis
Differentiating Upper from Lower Motor Neuron Weakness
Both cause a weakness that is typically confined to the distal muscles and both can be either symmetric or asymmetric.
Hemiparesis is a feature of upper motor neuron disease. Other than hemiparesis, location of weakness doesn't distinguish upper from lower motor neuron disease.
What does distinguish them is associated findings especially muscle tone, reflexes, fasciculations and atrophy. Lower motor neuron disease weakens or paralyses muscles, while upper motor neuron disease impairs their movements (see Table 1).
The "upper motor neuron" pattern of weakness of weaker extensors than flexors in the upper limb and vice versa in the lower limb may be an illusion. In normal individuals this is the case. More diagnostic weight should be put on other signs of an UMN lesion than the pattern of weakness.
Neuromuscular disease: Consider in patients where the weakness varies during the day, or in those with diplopia or ptosis. Neuromuscular disease can be excluded if there are abnormalities of sensation, tone, or reflexes. Fatiguability is a unique hallmark. Resting improves strength. Neuromuscular disease symptoms are also typically very proximal, hence they affect the facial muscles with ptosis, diplopia, difficulty chewing and swallowing, slurred speech, and facial weakness. There is no sensory loss.
Autoimmune Myaesthenia Gravis is the cardinal clinical disease here. The test is AChR antibodies, but some patients have rarer antibodies like anti-MuSK, and some can be antibody negative.
There are also over 30 Congenital Myasthenic Syndromes (CMS) with different clinical manifestations, some of which can cause predominant limb-girdle weakness along with other features. See video presentation here. The initial test is neurophysiology - specifically repetitive nerve stimulation and single fibre EMG. The second test is genetic testing. However in New Zealand genetic testing may be significantly faster and more accessible than neurophysiology. See algorithm here. Differentiation between different forms is critical because of different treatment strategies.
Muscle disease: consider if a patient has symmetrical weakness of the proximal muscles of the arms and legs. This can be associated with muscle pain, dysphagia, and weakness of the neck muscles.
- Unilateral weakness, ipsilateral face
- Lesion: Contralateral cortex, internal capsule
- Causes: Stroke (sudden onset), demyelination/mass (gradual onset)
- Symptoms: Neglect, visual field cut, aphasia
- Findings: UMN signs
- Key features: Association with headache suggests hemorrhage or mass
- Unilateral weakness, contralateral face
- Lesion: Brainstem
- Causes: Vertebrobasilar insufficiency, demyelination
- Symptoms: Dysphagia, dysarthria, diplopia, vertigo, nausea/vomiting
- Findings: CN involvement, cerebellar abnormalities
- Unilateral weakness, no facial involvement
- Lesion: Contralateral medial cerebral cortex, discrete internal capsule
- Causes: Stroke
- Rare Cause: Brown-Sequard if contralateral hemibody pain and temperature sensory disturbance
- Unilateral weakness single limb (monoparesis/plegia)
- Lesion: Spinal cord, peripheral nerve, NMJ
- UMN signs: Brown-Sequard if contralateral pain and temperature sensory disturbance
- LMN signs: Radiculopathy if associated sensory disturbance
- Normal reflexes, normal sensation: Consider NMJ disorder
- Bilateral weakness of lower extremities (paraparesis/plegia)
- Lesion: Spinal cord, peripheral nerve
- UMN signs: Anterior cord syndrome (compression, ischemia, demyelination) if contralateral pain and temperature sensory disturbance
- Cauda equina: Loss of perianal sensation, loss of rectal tone, or urinary retention
- GBS: If no signs of cauda equina and sensory disturbances paralleling ascending weakness (with hyporeflexia)
- Bilateral weakness of upper extremities
- Lesion: Central cord syndrome
- Causes: Syringomyelia, hyperextension injury
- Findings: Pain and temperature sensory disturbances in upper extremities (intact proprioception)
- Bilateral weakness of all four extremities (quadriparesis/plegia)
- Lesion: Cervical spinal cord
- Findings: UMN signs below level of injury, strength/sensory testing identifies level
- Bilateral weakness, proximal groups
- Lesion: Muscle
- Causes: Rhabdomyolysis, polymyositis, dermatomyositis, myopathies
- Findings: No UMN signs or sensory disturbances
- Bilateral weakness, distal groups
- Lesion: Muscle or Nerve
- Causes: Early motor neuron disease, peripheral neuropathy, myotonic dystrophy type 1
- Findings: No UMN signs or sensory disturbances.
- Facial weakness, upper and lower face
- Lesion: CNVII
- Causes: Bell’s palsy, mastoiditis, parotitis
- Other CN involvement suggests brainstem lesion, multiple cranial neuropathies, or NMJ
- Motor System Examination
- Reflex Testing
- Pain Oriented Sensory Examination
- Spinal Cord Anatomy
- Skeletal Muscle
- Ethan Meltzer. How to Think Like a Neurologist: A Case-Based Guide to Clinical Reasoning in Neurology