Neurologic Causes of Weakness and Paralysis

Harrison 21 edition, Chapter 24 page 165

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▪ Normal motor function ▪ sudden release after reaching a maximum (the

o involves integrated muscle activity modulated by the “clasp-knife” phenomenon),
activity of the cerebral cortex, basal ganglia, cerebellum, ▪ predominantly affects the antigravity muscles
red nucleus, brainstem reticular formation, lateral ▪ upper-limb flexors and lower-limb extensors
vestibular nucleus, and spinal cord. o Rigidity → hypertonia that is present throughout the
o Motor system dysfunction leads to: range of motion (a “lead pipe” or “plastic” stiffness)
▪ weakness or paralysis ▪ affects flexors and extensors equally;
▪ ataxia ▪ sometimes has a cogwheel quality that is
▪ abnormal movements enhanced by voluntary movement of the
▪ Weakness → reduction in the power that can be exerted by contralateral limb (reinforcement).
one or more muscles. Must be distinguished from: ▪ extrapyramidal disorders (Parkinson’s disease)
o increased fatigability (i.e., the inability to sustain the o Paratonia (or gegenhalten) → increased tone that
performance of an activity that should be normal for a varies irregularly in a manner seemingly related to the
person of the same age, sex, and size), degree of relaxation,
o limitation in function due to pain or articular stiffness, ▪ is present throughout the range of motion,
o impaired motor activity because severe proprioceptive ▪ affects flexors and extensors equally.
sensory loss prevents adequate feedback information ▪ disease of the frontal lobes.
about the direction and power of movements. ▪ Weakness with decreased tone (flaccidity) or normal tone
o Bradykinesia → increased time is required for full occurs with disorders of motor units.
power to be exerted. ▪ A motor unit consists of a single lower motor neuron and all
o apraxia → disorder of planning and initiating a skilled the muscle fibers that it innervates.
or learned movement unrelated to a significant motor ▪ Muscle bulk generally is not affected by upper motor
or sensory deficit. neuron lesions, although mild disuse atrophy eventually
▪ Paralysis or the suffix “-plegia” indicates weakness so may occur. By contrast, atrophy is often conspicuous when
severe that a muscle cannot be contracted at all. a lower motor neuron lesion is responsible for weakness
o paresis → less severe weakness. and may occur with advanced muscle disease.
▪ “hemi-” refers to one-half of the body, ▪ Muscle stretch (tendon) reflexes are usually increased
▪ “para-” to both legs, and with UMN lesions but may be decreased or absent for a
▪ “quadri-” to all four limbs. variable period immediately after onset of an acute lesion.
▪ The distribution of weakness helps to localize the underlying ▪ Hyperreflexia is usually—but not invariably—accompanied
lesion. by loss of cutaneous reflexes (such as superficial abdominals;
o upper motor neurons → extensors and abductors of and by an extensor plantar (Babinski) response.
the upper limb and the flexors of the lower limb. ▪ The muscle stretch reflexes are depressed with LMN
o Lower motor neuron → weakness depends on lesions directly involving specific reflex arcs. They generally
whether involvement is at the level of the anterior horn are preserved in patients with myopathic weakness except
cells, nerve root, limb plexus, or peripheral nerve—only in advanced stages, when they sometimes are attenuated.
muscles supplied by the affected structure are weak. ▪ In disorders of the neuromuscular junction, reflex responses
o Myopathic weakness is generally most marked in may be affected by preceding voluntary activity of affected
proximal muscles. muscles; such activity may lead to enhancement of initially
o Weakness from impaired neuromuscular transmission depressed reflexes in Lambert-Eaton myasthenic
has no specific pattern of involvement. syndrome and, conversely, to depression of initially
▪ Weakness often is accompanied by other neurologic normal reflexes in myasthenia gravis.
abnormalities that help indicate the site of the responsible ▪ The distinction of neuropathic (lower motor neuron) from
lesion. myopathic weakness is sometimes difficult clinically,
although distal weakness is likely to be neuropathic, and
symmetric proximal weakness myopathic.
▪ Fasciculations → visible or palpable twitches within a
muscle due to the spontaneous discharge of a motor unit
and early atrophy indicate that weakness is neuropathic.

PATHOGENESIS
Upper Motor Neuron Weakness
▪ Lesions of the UMN or their descending axons to the spinal
cord (Fig. 24-1) produce weakness through decreased
activation of lower motor neurons.
▪ Tone is the resistance of a muscle to passive stretch.
▪ Increased tone may be of several types.
o Spasticity → increase in tone associated with disease of
UMN.
▪ velocity dependent
▪ Lower Motor Neuron Weakness
▪ This pattern results from disorders of lower motor neurons
in the brainstem motor nuclei and the
▪ anterior horn of the spinal cord or from dysfunction of the
axons of these neurons as they pass to skeletal muscle.

▪ Weakness is due to a decrease in the number of muscle

fibers that can be activated through a loss of α motor
neurons or disruption of their connections to muscle.
▪ In general, distal muscle groups are affected more ▪ Loss of γ motor neurons does not cause weakness but
severely than proximal ones, and axial movements are decreases tension on the muscle spindles, which decreases
spared unless the lesion is severe and bilateral. muscle tone and attenuates the stretch reflexes.
▪ Spasticity is typical but may not be present acutely. ▪ An absent stretch reflex suggests involvement of spindle
▪ Rapid repetitive movements are slowed and coarse, but afferent fibers.
normal rhythmicity is maintained. ▪ When a motor unit becomes diseased, especially in anterior
▪ With corticobulbar involvement, weakness occurs in the horn cell diseases, it may discharge spontaneously,
lower face and tongue; extraocular, upper facial, pharyngeal, producing fasciculations.
and jaw muscles are typically spared. ▪ When α motor neurons or their axons degenerate, the
▪ Bilateral corticobulbar lesions produce a pseudobulbar denervated muscle fibers also may discharge spontaneously.
palsy: dysarthria, dysphagia, dysphonia, and emotional ▪ These single muscle fiber discharges, or fibrillation
lability accompany bilateral facial weakness and a brisk jaw potentials, cannot be seen but can be recorded with EMG.
jerk.
▪ Weakness leads to delayed or reduced recruitment of motor
▪ Electromyogram (EMG) shows that with weakness of the
units, with fewer than normal activated at a particular
upper motor neuron type, motor units have a diminished
maximal discharge frequency. discharge frequency.

LemonChan
 internal capsule, cerebral peduncle in the midbrain, or
Neuromuscular Junction Weakness upper pons.
▪ produce weakness of variable degree and distribution. o brainstem lesions →“crossed paralyses,” consisting of
▪ The number of muscle fibers that are activated varies over ipsilateral cranial nerve signs and contralateral
time, depending on the state of rest of the neuromuscular hemiparesis.
junctions. o The absence of cranial nerve signs or facial weakness →
▪ Strength is influenced by preceding activity of the affected hemiparesis is due to a lesion in the high cervical
muscle. spinal cord, especially if associated with Brown-
▪ Example: Sequard syndrome, consisting of loss of joint position
o In myasthenia gravis and vibration sense on the side of the weakness, and
▪ sustained or repeated contractions of affected loss of pain and temperature sense on the opposite side.
muscle decline in strength despite continuing ▪ Acute or episodic hemiparesis → usually results from focal
effort → fatigable weakness is suggestive of structural lesions, particularly vascular etiologies, rapidly
disorders of the neuromuscular junction, which expanding lesions, or an inflammatory process.
cause functional loss of muscle fibers due to o Subacute hemiparesis that evolves over days or weeks
failure of their activation. may relate to:
▪ subdural hematoma,
Myopathic Weakness ▪ infectious or inflammatory disorders
▪ produced by a decrease in the number or contractile force • cerebral abscess,
of muscle fibers activated within motor units. • fungal granuloma or meningitis,
▪ With muscular dystrophies, inflammatory myopathies, or • parasitic infection,
myopathies with muscle fiber necrosis, the number of
• multiple sclerosis,
muscle fibers is reduced within many motor units.
• sarcoidosis
▪ On EMG, the size of each motor unit action potential is
▪ primary or metastatic neoplasms.
decreased, and motor units must be recruited more rapidly
▪ AIDS may present with subacute hemiparesis due
than normal to produce the desired power.
to toxoplasmosis or primary central nervous
▪ Some myopathies produce weakness through loss of
system (CNS) lymphoma.
contractile force of muscle fibers or through relatively
o Chronic hemiparesis that evolves over months usually
selective involvement of type II (fast) fibers.
is due to:
▪ These myopathies may not affect the size of individual
▪ neoplasm or vascular malformation
motor unit action potentials and are detected by a
▪ chronic subdural hematoma,
discrepancy between the electrical activity and force of a
▪ degenerative disease.
muscle.
o Investigation of hemiparesis (Fig. 24-3) of acute origin
usually starts with a CT scan of the brain and laboratory
Psychogenic Weakness
studies.
▪ Weakness may occur without a recognizable organic basis.
▪ It tends to be variable, inconsistent, and with a pattern of
distribution that cannot be explained on a neuroanatomic
basis.
▪ On formal testing, antagonists may contract when the
patient is supposedly activating the agonist muscle.
▪ The severity of weakness is out of keeping with the patient
’s daily activities.

DISTRIBUTION OF WEAKNESS
Hemiparesis
▪ Hemiparesis results from an UMN lesion above the
midcervical spinal cord; most such lesions are above the
foramen magnum.
▪ The presence of other neurologic deficits helps localize the
lesion.
o language disorders → cortical lesion.
o Homonymous visual field defects → either a cortical or
a subcortical hemispheric lesion.
o A “pure motor” hemiparesis of the face, arm, and leg
→ small, discrete lesion in the posterior limb of the
LemonChan
 o If the CT is normal, or in subacute or chronic cases of ▪ Generalized weakness may be due to disorders of the CNS
hemiparesis, MRI of the brain and/or cervical spine or the motor unit.
(including the foramen magnum) is performed, ▪ quadriparesis is commonly used when an upper motor
depending on the clinical accompaniments. neuron cause is suspected, and generalized weakness is used
when a disease of the motor units is likely.
Paraparesis ▪ Weakness from CNS disorders usually is associated with
▪ Acute paraparesis → caused most commonly by an changes in consciousness or cognition and accompanied by
intraspinal lesion, but its spinal origin may not be spasticity, hyperreflexia, and sensory disturbances.
recognized initially if the legs are flaccid and areflexic. ▪ Most neuromuscular causes of generalized weakness are
Usually, however, there is: associated with normal mental function, hypotonia, and
o sensory loss in the legs with an upper level on the trunk. hypoactive muscle stretch reflexes.
o a dissociated sensory loss (loss of pain and temperature ▪ The major causes of intermittent weakness are listed in
but not touch, position, and vibration sense) suggestive Table 24-2.
of a central cord syndrome.
o or hyperreflexia in the legs with normal reflexes in the
arms
o Imaging the spinal cord, may reveal compressive
lesions, infarction (proprioception usually is spared),
arteriovenous fistulas or other vascular anomalies, or
transverse myelitis)
▪ Diseases of the cerebral hemispheres that produce acute
paraparesis include:
o anterior cerebral artery ischemia (shoulder shrug also
is affected),
o superior sagittal sinus or cortical venous thrombosis,
o acute hydrocephalus.
o Paraparesis may also result from a cauda equina
syndrome.
▪ For ex., after trauma to the low back, a midline
disk herniation, or an intraspinal tumor.
▪ The sphincters are commonly affected, whereas hip flexion
often is spared, as is sensation over the anterolateral thighs.
▪ Rarely, paraparesis is caused by: ▪ A patient with generalized fatigability without objective
o a rapidly evolving anterior horn cell disease (such as weakness may have chronic fatigue syndrome.
poliovirus or West Nile virus infection),
o peripheral neuropathy (such as Guillain-Barre ACUTE QUADRIPARESIS
syndrome; or ▪ Quadriparesis with onset over minutes may result from
o myopathy disorders of:
▪ Subacute or chronic spastic paraparesis → caused by o upper motor neurons
upper motor neuron disease. When associated with lower- ▪ anoxia, hypotension, brainstem or cervical cord
limb sensory loss and sphincter involvement, a chronic ischemia, trauma, and systemic metabolic
spinal cord disorder should be considered. abnormalities) or
▪ If hemispheric signs are present, a parasagittal meningioma o muscle (electrolyte disturbances, certain inborn errors
or chronic hydrocephalus is likely. of muscle energy metabolism, toxins, and periodic
▪ The absence of spasticity in a long-standing paraparesis paralyses).
suggests a lower motor neuron or myopathic etiology. ▪ Onset over hours to weeks may, in addition to these
▪ Investigations typically begin with spinal MRI, but when disorders, be due to lower motor neuron disorders such as
upper motor neuron signs are associated with drowsiness, Guillain-Barre syndrome.
confusion, seizures, or other hemispheric signs, brain MRI ▪ In obtunded patients, evaluation begins with a CT or MRI
should also be performed, sometimes as the initial scan of the brain.
investigation. ▪ If upper motor neuron signs are present but the patient is
▪ Electrophysiologic studies are diagnostically helpful when alert, the initial test is usually an MRI of the cervical
clinical findings suggest an underlying neuromuscular ▪ cord.
disorder. ▪ If weakness is lower motor neuron, myopathic, or uncertain
in origin, the clinical approach begins with blood studies to
Quadriparesis or Generalized Weakness determine the level of muscle enzymes and electrolytes and
with EMG and nerve conduction studies.
LemonChan
 ▪ Acute distal lower-limb weakness results occasionally from
SUBACUTE OR CHRONIC QUADRIPARESIS an acute toxic polyneuropathy or cauda equina syndrome.
▪ Quadriparesis due to UMN disease may develop over weeks ▪ Distal symmetric weakness usually develops over weeks,
to years from: months, or years and, when associated with numbness, is
o chronic myelopathies, multiple sclerosis, brain or spinal due to peripheral neuropathy
tumors, chronic subdural hematomas, and various ▪ Anterior horn cell disease may begin distally but is typically
metabolic, toxic, and infectious disorders. asymmetric and without accompanying numbness
▪ It may also result from LMN disease, a chronic neuropathy ▪ Rarely, myopathies present with distal weakness.
(in which weakness is often most profound distally), or ▪ Electrodiagnostic studies help localize the disorder.
myopathic weakness (typically proximal).
▪ When quadriparesis develops acutely in obtunded patients, Proximal Weakness
evaluation begins with a CT scan of the brain. ▪ Myopathy often produces symmetric weakness. of the pelvic
▪ If upper motor neuron signs have developed acutely but the or shoulder girdle muscles.
patient is alert, the initial test is usually an MRI of the ▪ Diseases of the neuromuscular junction, such as myasthenia
cervical cord. gravis may present with symmetric proximal weakness
▪ When onset has been gradual, disorders of the cerebral often associated with ptosis, diplopia, or bulbar weakness
hemispheres, brainstem, and cervical spinal cord can and fluctuate in severity during the day.
usually be distinguished clinically, and imaging is directed ▪ In anterior horn cell disease, proximal weakness is usually
first at the clinically suspected site of pathology. asymmetric, but it may be symmetric especially in genetic
▪ If weakness is lower motor neuron, myopathic, or uncertain forms.
in origin, laboratory studies can determine the levels of ▪ Numbness does not occur with any of these diseases. The
muscle enzymes and electrolytes, and EMG and nerve evaluation usually begins with determination of the serum
conduction studies help to localize the pathologic process. creatine kinase level and electrophysiologic studies.

Monoparesis Weakness in a Restricted Distribution

▪ Monoparesis usually is due to LMN disease, with or without ▪ Weakness may not fit any of these patterns, being limited,
associated sensory involvement. for example, to the extraocular, hemifacial, bulbar, or
▪ UMN weakness occasionally presents as a monoparesis of respiratory muscles. If it is unilateral, restricted weakness
distal and nonantigravity muscles. usually is due to lower motor neuron or peripheral nerve
▪ Myopathic weakness rarely is limited to one limb. disease, such as in a facial palsy. Weakness of part of a limb
is commonly due to a peripheral nerve lesion such as an
ACUTE MONOPARESIS entrapment neuropathy.
▪ If weakness is predominantly distal and of upper motor ▪ Relatively symmetric weakness of extraocular or bulbar
neuron type and is not associated with sensory impairment muscles frequently is due to a myopathy or neuromuscular
or pain, focal cortical ischemia is likely. junction disorder.
▪ Diagnostic possibilities are like those for acute hemiparesis. ▪ Bilateral facial palsy with areflexia suggests Guillain-Barre
▪ Sensory loss and pain usually accompany acute lower motor syndrome.
neuron weakness; the weakness commonly localizes to a ▪ Worsening of relatively symmetric weakness with fatigue is
single nerve root or peripheral nerve, but occasionally characteristic of neuromuscular junction disorders.
reflects plexus involvement. ▪ Asymmetric bulbar weakness usually is due to motor
▪ If lower motor neuron weakness is likely, evaluation begins neuron disease.
with EMG and nerve conduction studies. ▪ Weakness limited to respiratory muscles is uncommon and
usually is due to motor neuron disease, myasthenia gravis,
SUBACUTE OR CHRONIC MONOPARESIS or polymyositis/dermatomyositis.
▪ Weakness and atrophy that develop over weeks or months
are usually of lower motor neuron origin.
▪ When associated with sensory symptoms, a peripheral
cause (nerve, root, or plexus) is likely; otherwise, anterior
horn cell disease should be considered. In either case, an
electrodiagnostic study is indicated.
▪ If weakness is of the upper motor neuron type, a discrete
cortical (precentral gyrus) or cord lesion may be
responsible, and appropriate imaging is performed.

Distal Weakness
▪ Involvement of two or more limbs distally suggests lower
motor neuron or peripheral nerve disease.
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