Neurologic Causes of Weakness and Paralysis¶

Chapter 26 | Part 2: Cardinal Manifestations and Presentation of Diseases

KEY CLINICAL POINTS¶

Weakness must be distinguished from fatigue, pain-limited movement, bradykinesia, and apraxia - true weakness is reduction in power exerted by muscles
Distribution of weakness (hemiparesis, paraparesis, quadriparesis, monoparesis) combined with associated signs (tone, reflexes, atrophy) localizes the lesion
Upper motor neuron lesions produce spasticity, hyperreflexia, and Babinski sign; lower motor neuron lesions cause flaccidity, atrophy, fasciculations, and hyporeflexia
Myopathic weakness is typically proximal and symmetric; neuromuscular junction disorders produce fatigable weakness
Acute weakness requires urgent evaluation to distinguish CNS causes (imaging) from peripheral causes (EMG/nerve conduction studies)

1. DEFINITION & OVERVIEW¶

Normal motor function involves integrated muscle activity modulated by the cerebral cortex, basal ganglia, cerebellum, red nucleus, brainstem reticular formation, lateral vestibular nucleus, and spinal cord. Motor system dysfunction leads to weakness or paralysis, ataxia, or abnormal movements.

1.1 Definition of Weakness¶

Weakness is a reduction in the power that can be exerted by one or more muscles. It must be distinguished from: - Fatigue/increased fatigability - inability to sustain performance of an activity normal for age, sex, and size - Pain or articular stiffness - limitation in function due to discomfort - Proprioceptive sensory loss - impaired motor activity due to inadequate feedback about direction and power of movements - Bradykinesia - increased time required for full power to be exerted - Apraxia - disorder of planning and initiating skilled movements unrelated to motor or sensory deficit

1.2 Terminology¶

Paralysis (or suffix "-plegia") - weakness so severe that muscle cannot be contracted at all
Paresis - less severe weakness with some retained function
Hemi- prefix - one-half of the body affected
Para- prefix - both legs affected
Quadri- prefix - all four limbs affected

1.3 Motor Unit Concept¶

A motor unit consists of a single lower motor neuron and all the muscle fibers that it innervates. The α motor neurons are larger, more numerous, and innervate extrafusal muscle fibers. The smaller, less numerous γ motor neurons innervate intrafusal muscle fibers of the muscle spindle and contribute to normal tone and stretch reflexes.

2. LOCALIZATION BY DISTRIBUTION OF WEAKNESS¶

The distribution of weakness helps localize the underlying lesion. Different patterns of weakness are associated with specific anatomical sites of pathology.

Signs That Distinguish the Origin of Weakness¶

Sign	Upper Motor Neuron	Lower Motor Neuron	Myopathic	Psychogenic
Atrophy	None	Severe	Mild	None
Fasciculations	None	Common	None	None
Tone	Spastic	Decreased	Normal/decreased	Variable/paratonia
Distribution of weakness	Pyramidal/regional	Distal/segmental	Proximal	Variable/inconsistent with daily activities
Muscle stretch reflexes	Hyperactive	Hypoactive/absent	Normal/hypoactive	Normal
Babinski sign	Present	Absent	Absent	Absent

2.1 Upper Motor Neuron Pattern¶

Weakness from upper motor neuron involvement occurs particularly in: - Upper limb: extensors and abductors affected more than flexors - Lower limb: flexors affected more than extensors This reflects the preferential involvement of antigravity muscles in the opposite pattern (flexors in arms, extensors in legs are antigravity).

2.2 Lower Motor Neuron Pattern¶

Lower motor neuron weakness depends on the level of involvement: - Anterior horn cells - specific myotomes affected - Nerve root - dermatomal and myotomal distribution - Limb plexus - multiple nerve territories in one limb - Peripheral nerve - muscles supplied by that specific nerve Only muscles supplied by the affected structure are weak.

2.3 Myopathic Pattern¶

Myopathic weakness is generally most marked in proximal muscles, affecting shoulder and pelvic girdle muscles symmetrically. Distal myopathies exist but are rare.

2.4 Neuromuscular Junction Pattern¶

Weakness from impaired neuromuscular transmission has no specific pattern of involvement but characteristically fluctuates with activity and time of day. Fatigable weakness is the hallmark.

3. MUSCLE TONE ABNORMALITIES¶

Tone is the resistance of a muscle to passive stretch. Abnormalities in tone provide important localizing information.

3.1 Spasticity¶

Spasticity is increased tone associated with upper motor neuron disease. Characteristics: - Velocity dependent - faster stretch produces more resistance - Clasp-knife phenomenon - sudden release after reaching maximum resistance - Predominantly affects antigravity muscles (upper limb flexors, lower limb extensors)

3.2 Rigidity¶

Rigidity is hypertonia associated with extrapyramidal disorders such as Parkinson's disease. Characteristics: - Present throughout the range of motion ("lead pipe" or "plastic" stiffness) - Affects flexors and extensors equally - May have cogwheel quality enhanced by voluntary movement of contralateral limb (reinforcement)

3.3 Paratonia (Gegenhalten)¶

Paratonia is increased tone that: - Varies irregularly, seemingly related to degree of relaxation - Present throughout range of motion - Affects flexors and extensors equally - Usually results from frontal lobe disease

3.4 Flaccidity¶

Weakness with decreased tone (flaccidity) or normal tone occurs with disorders of motor units (lower motor neuron, neuromuscular junction, or muscle disease).

4. PATHOGENESIS BY LESION SITE¶

Understanding the pathophysiology of weakness at each anatomical level helps guide diagnosis and treatment.

4.1 Upper Motor Neuron Weakness¶

Lesions of upper motor neurons or their descending axons to the spinal cord produce weakness through decreased activation of lower motor neurons. Clinical features: - Distal muscle groups affected more severely than proximal - Axial movements spared unless lesion is severe and bilateral - Spasticity typical but may not be present acutely - Rapid repetitive movements slowed and coarse, but normal rhythmicity maintained Corticobulbar involvement: - Weakness in lower face and tongue - Extraocular, upper facial, pharyngeal, and jaw muscles typically spared Bilateral corticobulbar lesions produce pseudobulbar palsy: - Dysarthria, dysphagia, dysphonia - Emotional lability - Bilateral facial weakness - Brisk jaw jerk EMG findings: Motor units have diminished maximal discharge frequency.

4.2 Lower Motor Neuron Weakness¶

Results from disorders of lower motor neurons in brainstem motor nuclei and anterior horn of spinal cord, or dysfunction of their axons. Mechanism: Weakness due to decrease in number of muscle fibers that can be activated through loss of α motor neurons or disruption of connections to muscle. Loss of γ motor neurons: - Does not cause weakness - Decreases tension on muscle spindles - Decreases muscle tone - Attenuates stretch reflexes Absent stretch reflex suggests involvement of spindle afferent fibers. Fasciculations: When motor unit becomes diseased (especially in anterior horn cell diseases), it may discharge spontaneously, producing visible or palpable twitches within muscle. Fibrillation potentials: When α motor neurons or their axons degenerate, denervated muscle fibers discharge spontaneously. Cannot be seen clinically but recorded on EMG. EMG findings: Delayed or reduced recruitment of motor units, with fewer than normal activated at particular discharge frequency.

4.3 Neuromuscular Junction Weakness¶

Disorders of the neuromuscular junction produce weakness of variable degree and distribution. Key features: - Number of muscle fibers activated varies over time depending on state of rest - Strength influenced by preceding activity of affected muscle - In myasthenia gravis, sustained or repeated contractions decline in strength despite continuing effort - Fatigable weakness is suggestive of neuromuscular junction disorders - Functional loss of muscle fibers due to failure of activation Reflex responses may be affected by preceding voluntary activity: - May lead to enhancement of initially depressed reflexes in Lambert-Eaton myasthenic syndrome - May lead to depression of reflexes from myopathic weakness (occasionally) Distinguishing neuropathic from myopathic weakness: - Distal weakness likely neuropathic - Symmetric proximal weakness likely myopathic - Fasciculations and early atrophy indicate neuropathic origin

4.4 Myopathic Weakness¶

Produced by decrease in number or contractile force of muscle fibers activated within motor units. Mechanisms: - Muscular dystrophies, inflammatory myopathies, myopathies with muscle fiber necrosis: reduced number of muscle fibers within motor units - Some myopathies: loss of contractile force or selective involvement of type II (fast) fibers EMG findings: - Decreased size of each motor unit action potential - Motor units must be recruited more rapidly than normal to produce desired power - Some myopathies may not affect motor unit action potential size - detected by discrepancy between electrical activity and force

4.5 Psychogenic Weakness¶

Weakness may occur without recognizable organic basis. Characteristics: - Variable and inconsistent - Pattern of distribution cannot be explained on neuroanatomic basis - On formal testing, antagonists may contract when patient is supposedly activating agonist muscle - Severity of weakness out of keeping with patient's daily activities

5. UPPER MOTOR NEURON PATHWAYS¶

The corticospinal and bulbospinal systems constitute the descending motor pathways that control voluntary movement and posture.

5.1 Corticospinal (Pyramidal) System¶

Origin: - Cell bodies in layer V of primary motor cortex (precentral gyrus, Brodmann area 4) - Premotor and supplemental motor cortex (area 6) - Somatotopically organized Descending pathway: - Subcortical white matter → posterior limb of internal capsule - Cerebral peduncle of midbrain → basis pontis → medullary pyramids - At cervicomedullary junction: most axons decussate into contralateral lateral corticospinal tract - 10-30% remain ipsilateral in anterior spinal cord Connections: - Synapse on premotor interneurons - Some make direct monosynaptic connections with lower motor neurons (especially cervical enlargement and distal limb muscles) - Most densely innervate lower motor neurons of hand muscles - Involved in execution of learned, fine movements Corticobulbar neurons are similar but innervate brainstem motor nuclei.

5.2 Bulbospinal (Extrapyramidal) System¶

Ventromedial bulbospinal pathways: - Tectospinal pathway - originates in tectum of midbrain - Vestibulospinal pathway - originates in vestibular nuclei - Reticulospinal pathway - originates in reticular formation - Function: influence axial and proximal muscles; maintenance of posture and integrated movements of limbs and trunk Ventrolateral bulbospinal pathways: - Rubrospinal pathway - originates predominantly in red nucleus - Function: facilitate distal limb muscles These pathways influence strength and tone but are not part of the pyramidal system.

6. CLINICAL PATTERNS OF WEAKNESS¶

Specific patterns of weakness distribution guide the differential diagnosis and investigation strategy.

Causes of Episodic Generalized Weakness¶

Category	Specific Causes
Electrolyte disturbances	Hypokalemia, hyperkalemia, hypercalcemia, hypernatremia, hyponatremia, hypophosphatemia, hypermagnesemia
Muscle disorders - Channelopathies	Periodic paralyses
Muscle disorders - Metabolic defects	Impaired carbohydrate utilization, impaired fatty acid utilization, abnormal mitochondrial function
Neuromuscular junction disorders	Myasthenia gravis, Lambert-Eaton myasthenic syndrome
CNS disorders	Transient ischemic attacks of brainstem, transient global cerebral ischemia, multiple sclerosis
Lack of voluntary effort	Anxiety, pain or discomfort, somatization disorder

6.1 Hemiparesis¶

Results from upper motor neuron lesion above midcervical spinal cord; most lesions are above foramen magnum. Localizing features: - Language disorders - cortical lesion - Homonymous visual field defects - cortical or subcortical hemispheric lesion - "Pure motor" hemiparesis (face, arm, leg) - small discrete lesion in posterior limb of internal capsule, cerebral peduncle (midbrain), or upper pons - Brainstem lesions may produce "crossed paralyses" - ipsilateral cranial nerve signs with contralateral hemiparesis - Absence of cranial nerve signs or facial weakness - suggests high cervical cord lesion, especially with Brown-Séquard syndrome Brown-Séquard syndrome: - Loss of joint position and vibration sense ipsilateral to weakness - Loss of pain and temperature sense contralateral to weakness Etiologies by temporal course: Acute/episodic: - Vascular etiologies - Rapidly expanding lesions - Inflammatory process Subacute (days to weeks): - Subdural hematoma - Infectious/inflammatory disorders (cerebral abscess, fungal granuloma/meningitis, parasitic infection, multiple sclerosis, sarcoidosis) - Primary or metastatic neoplasms - AIDS-related (toxoplasmosis, primary CNS lymphoma) Chronic (months): - Neoplasm - Vascular malformation - Chronic subdural hematoma - Degenerative disease

6.2 Paraparesis¶

ACUTE PARAPARESIS: Most commonly caused by intraspinal lesion. Spinal cord origin may not be recognized initially if legs are flaccid and areflexic. Features suggesting spinal cord origin: - Sensory loss in legs with upper level on trunk - Dissociated sensory loss (loss of pain/temperature but preserved touch, position, vibration) - suggests central cord syndrome - Hyperreflexia in legs with normal arm reflexes Spinal cord imaging may reveal: - Compressive lesions - Infarction (proprioception usually spared) - Arteriovenous fistulas or other vascular anomalies - Transverse myelitis Cerebral hemisphere causes: - Anterior cerebral artery ischemia (shoulder shrug also affected) - Superior sagittal sinus or cortical venous thrombosis - Acute hydrocephalus Cauda equina syndrome: - Causes: trauma to low back, midline disk herniation, intraspinal tumor - Features: sphincters commonly affected; hip flexion often spared; sensation preserved over anterolateral thighs Rare causes: - Rapidly evolving anterior horn cell disease (poliovirus, West Nile virus) - Peripheral neuropathy (Guillain-Barré syndrome) - Myopathy SUBACUTE/CHRONIC PARAPARESIS: Spastic paraparesis suggests upper motor neuron disease. With lower-limb sensory loss and sphincter involvement: - Consider chronic spinal cord disorder With hemispheric signs: - Parasagittal meningioma - Chronic hydrocephalus Absence of spasticity in long-standing paraparesis: - Suggests lower motor neuron or myopathic etiology

6.3 Quadriparesis or Generalized Weakness¶

May be due to disorders of CNS or motor unit. - Quadriparesis - term used when upper motor neuron cause suspected - Generalized weakness - term used when motor unit disease likely Distinguishing features: CNS disorders: - Changes in consciousness or cognition - Spasticity - Hyperreflexia - Sensory disturbances Neuromuscular causes: - Normal mental function - Hypotonia - Hypoactive muscle stretch reflexes ACUTE QUADRIPARESIS (onset over minutes): Upper motor neuron causes: - Anoxia - Hypotension - Brainstem or cervical cord ischemia - Trauma - Systemic metabolic abnormalities Muscle causes: - Electrolyte disturbances - Inborn errors of muscle energy metabolism - Toxins - Periodic paralyses Onset over hours to weeks: - Above causes plus Guillain-Barré syndrome SUBACUTE/CHRONIC QUADRIPARESIS: Upper motor neuron causes: - Chronic myelopathies - Multiple sclerosis - Brain or spinal tumors - Chronic subdural hematomas - Metabolic, toxic, and infectious disorders Lower motor neuron causes: - Chronic neuropathy (weakness often most profound distally) Myopathic causes: - Typically proximal weakness

6.4 Monoparesis¶

Usually due to lower motor neuron disease, with or without sensory involvement. Upper motor neuron weakness occasionally presents as monoparesis of distal and nonantigravity muscles. Myopathic weakness rarely limited to one limb. ACUTE MONOPARESIS: Upper motor neuron type (predominantly distal, no sensory impairment or pain): - Focal cortical ischemia likely Lower motor neuron type (sensory loss and pain usually present): - Single nerve root involvement - Peripheral nerve involvement - Occasionally plexus involvement SUBACUTE/CHRONIC MONOPARESIS: Weakness and atrophy over weeks to months - usually lower motor neuron origin. With sensory symptoms: - Peripheral cause likely (nerve, root, or plexus) Without sensory symptoms: - Consider anterior horn cell disease Upper motor neuron type: - Discrete cortical (precentral gyrus) lesion - Cord lesion

6.5 Distal Weakness¶

Involvement of two or more limbs distally suggests lower motor neuron or peripheral nerve disease. Acute distal lower-limb weakness: - Acute toxic polyneuropathy (occasionally) - Cauda equina syndrome Subacute/chronic distal symmetric weakness with numbness: - Peripheral neuropathy (develops over weeks, months, or years) Asymmetric distal weakness without numbness: - Anterior horn cell disease (may begin distally) Rarely: - Myopathies presenting with distal weakness

6.6 Proximal Weakness¶

Symmetric weakness of pelvic or shoulder girdle muscles suggests: - Myopathy (most common) - Neuromuscular junction disorders (e.g., myasthenia gravis) - often associated with ptosis, diplopia, or bulbar weakness; fluctuates in severity during day - Anterior horn cell disease - usually asymmetric, but may be symmetric especially in genetic forms Numbness does not occur with any of these diseases.

6.7 Weakness in Restricted Distribution¶

Weakness may be limited to specific muscle groups: - Extraocular muscles - Hemifacial muscles - Bulbar muscles - Respiratory muscles If unilateral, restricted weakness is more likely to represent a focal lesion.

7. INVESTIGATIONS & DIAGNOSIS¶

The diagnostic approach is guided by the pattern of weakness, tempo of onset, and associated clinical features.

7.1 Diagnostic Algorithm Overview¶

Step 1: Determine distribution of weakness (hemiparesis, paraparesis, quadriparesis, monoparesis, distal, proximal, restricted) Step 2: Identify upper motor neuron vs lower motor neuron vs myopathic vs psychogenic pattern based on: - Atrophy - Fasciculations - Tone - Distribution - Muscle stretch reflexes - Babinski sign Step 3: Select appropriate investigations based on pattern and suspected localization

7.2 Investigations for Hemiparesis¶

Acute onset: - CT scan of brain (initial test) - Laboratory studies - If CT normal: MRI of brain and/or cervical spine (including foramen magnum) Subacute/chronic: - MRI of brain - MRI of cervical spine if clinically indicated

7.3 Investigations for Paraparesis¶

Initial test: - Spinal MRI If upper motor neuron signs with hemispheric symptoms (drowsiness, confusion, seizures): - Brain MRI also indicated If neuromuscular disorder suspected: - Electrophysiologic studies

7.4 Investigations for Quadriparesis¶

Acute onset in obtunded patients: - CT or MRI scan of brain Acute onset with upper motor neuron signs in alert patient: - MRI of cervical cord Lower motor neuron, myopathic, or uncertain origin: - Blood studies: muscle enzymes, electrolytes - EMG and nerve conduction studies Subacute/chronic onset with upper motor neuron signs: - Imaging directed at clinically suspected site of pathology Subacute/chronic with lower motor neuron, myopathic, or uncertain origin: - Muscle enzyme levels and electrolytes - EMG and nerve conduction studies

7.5 Investigations for Monoparesis¶

Acute upper motor neuron type: - Similar evaluation as acute hemiparesis (brain imaging) Acute lower motor neuron type: - EMG and nerve conduction studies Subacute/chronic lower motor neuron type: - Electrodiagnostic study Subacute/chronic upper motor neuron type: - Appropriate imaging (brain or cord)

7.6 Investigations for Distal Weakness¶

Electrodiagnostic studies help localize the disorder

7.7 Investigations for Proximal Weakness¶

Initial evaluation: - Serum creatine kinase level - Electrophysiologic studies

7.8 Electromyography (EMG) Findings¶

Upper motor neuron weakness: - Motor units have diminished maximal discharge frequency Lower motor neuron weakness: - Fasciculations (if anterior horn cell disease) - Fibrillation potentials (denervation) - Delayed or reduced recruitment of motor units - Fewer than normal motor units activated at particular discharge frequency Myopathic weakness: - Decreased size of motor unit action potentials - Motor units recruited more rapidly than normal to produce desired power - Some myopathies: discrepancy between electrical activity and force

8. SPECIAL CONSIDERATIONS¶

Certain presentations require specific diagnostic approaches and consideration of unique etiologies.

8.1 Acute Weakness in Obtunded Patients¶

Evaluation begins with CT or MRI scan of the brain to assess for: - Structural lesions - Hemorrhage - Infarction - Mass effect If upper motor neuron signs present, cervical cord imaging may be needed.

8.2 Acute Weakness with Normal Mental Status¶

If upper motor neuron signs: - Initial test usually MRI of cervical cord (if no hemispheric signs) - Brain imaging if hemispheric signs present If lower motor neuron or myopathic pattern: - Blood studies (muscle enzymes, electrolytes) - EMG and nerve conduction studies

8.3 Chronic Fatigue vs Weakness¶

A patient with generalized fatigability without objective weakness may have myalgic encephalomyelitis/chronic fatigue syndrome rather than a primary neurologic disorder. Careful examination to distinguish true weakness from fatigue is essential.

AIDS may present with subacute hemiparesis due to: - Toxoplasmosis - Primary CNS lymphoma These diagnoses should be considered in patients with HIV presenting with focal weakness.

9. KEY POINTS & CLINICAL PEARLS¶

Essential clinical pearls for the evaluation and management of weakness.

9.1 Examination Pearls¶

Always assess for Babinski sign - present in upper motor neuron lesions, absent in lower motor neuron, myopathic, and psychogenic weakness
Fasciculations and early atrophy indicate neuropathic origin
Fatigable weakness is highly suggestive of neuromuscular junction disorders
Velocity-dependent tone with clasp-knife phenomenon = spasticity (UMN)
Lead-pipe rigidity with cogwheeling = extrapyramidal disease
Paratonia (gegenhalten) = frontal lobe disease

9.2 Distribution Pearls¶

Distal weakness = likely neuropathic
Symmetric proximal weakness = likely myopathic
Pyramidal pattern (UMN) = extensors/abductors in arms, flexors in legs
Pure motor hemiparesis without cortical signs = internal capsule, cerebral peduncle, or upper pons lesion
Crossed paralysis (ipsilateral CN + contralateral hemiparesis) = brainstem lesion

9.3 Temporal Course Pearls¶

Acute weakness with fluctuating level of consciousness = likely CNS cause
Acute flaccid paraparesis may be spinal cord (reflexes return later) - look for sensory level
Subacute symmetric ascending weakness = consider Guillain-Barré syndrome
Episodic weakness = consider channelopathies, metabolic myopathies, or neuromuscular junction disorders

9.4 Red Flags¶

Acute quadriparesis requires urgent evaluation
Respiratory muscle weakness may accompany generalized weakness and can be life-threatening
Bladder/bowel dysfunction with paraparesis suggests spinal cord emergency
Rapidly progressive weakness over hours to days requires urgent workup

9.5 Reflexes and Muscle Bulk¶

Hyperreflexia with UMN lesions, but may be decreased/absent immediately after acute lesion
Cutaneous reflexes (superficial abdominals) lost with UMN lesions
Muscle bulk generally not affected by UMN lesions (mild disuse atrophy eventually)
Conspicuous atrophy with LMN lesions and advanced muscle disease
Preserved reflexes in myopathy except in advanced stages