Paralysis

Paralysis is the loss of voluntary motor function in one or more skeletal muscles, ranging from complete to partial and from temporary to permanent, and it is caused by interruption of the motor pathway anywhere from the motor cortex through the corticospinal tract, anterior horn cell, peripheral nerve and neuromuscular junction to the muscle.

Stroke is the commonest cause worldwide, with 12.2 million incident strokes and 143 million disability-adjusted life years in 2019, while traumatic spinal cord injury occurs in about 40 to 80 people per million each year.

Terminology and classification

• Paralysis is the loss of motor function in one or more skeletal muscles, and it may be complete or partial, temporary or permanent.
• It is distinct from paresis, which denotes weakness rather than complete loss, and from sensory loss, although the two frequently coexist after nerve injury.
• Topographic terms define the pattern, with monoplegia affecting one limb, hemiplegia one side of the body, paraplegia both legs and tetraplegia or quadriplegia all four limbs.
• Flaccid paralysis denotes lower motor neuron damage with reduced tone and absent reflexes, whereas spastic paralysis follows upper motor neuron lesions.
• ICD-10 assigns paralytic syndromes to G80 to G83 with G83.9 for unspecified paralysis, MeSH indexes the concept as D010243 and Wikidata uses Q107231.
• The word derives from the Greek παράλυσις, meaning disabling of the nerves, and palsy is the traditional term for paralysis accompanied by involuntary tremor.
• Pseudoparalysis describes voluntary restriction of movement caused by pain or incoordination, and it must be distinguished from true neurological paralysis.

History

• Ancient Egyptian and Greek texts described paraplegia after spinal injury, and Hippocratic writings distinguished paraplegia from hemiplegia.
• Charles Bell and François Magendie established the distinction between the anterior motor and posterior sensory spinal roots in 1811 and 1822 respectively.
• Jean-Martin Charcot described the clinical and pathological features of amyotrophic lateral sclerosis in 1874, linking upper and lower motor neuron degeneration to progressive paralysis.
• Landry described ascending paralysis in 1859, and Guillain, Barré and Strohl identified the cerebrospinal fluid protein-cell dissociation in 1916.
• The poliomyelitis epidemics of the 1940s and 1950s, and the introduction of the Salk vaccine in 1955 and the Sabin vaccine in 1961, transformed the epidemiology of paralytic disease.
• Franklin Delano Roosevelt's paralysis from poliomyelitis in 1921 made the condition a public health priority and contributed to the founding of the March of Dimes in 1938.
• The development of mechanical ventilation, notably the iron lung in 1928, reduced mortality from bulbar and respiratory paralysis.

Epidemiology

• In the United States, about 1 in 50 people report some form of permanent or temporary paralysis according to patient advocacy estimates.
• Stroke is the leading cause of hemiplegia worldwide, and the Global Burden of Disease study estimated 12.2 million incident strokes and 143 million disability-adjusted life years in 2019.
• Traumatic spinal cord injury has a global incidence of about 40 to 80 cases per million people per year, and road traffic crashes are the leading cause in young adults.
• Guillain-Barré syndrome has an incidence of about 1 to 2 per 100,000 person-years and leaves residual weakness in roughly 20 percent of patients.
• Poliomyelitis remains endemic in Afghanistan and Pakistan, and vaccine-derived outbreaks have appeared in Africa and Asia since 2019.
• Cerebral palsy affects about 2 per 1,000 live births in high-income countries, and paralysis or paresis is the dominant motor feature.
• Global data come from the Global Burden of Disease study, WHO poliomyelitis surveillance, national spinal cord injury registries and national stroke audits.

• Stroke incidence in low- and middle-income countries has more than doubled since 1990, and the absolute number of people living with stroke-related paralysis continues to rise as populations age.

Pathophysiology

• Paralysis results from interruption of the motor pathway anywhere from the motor cortex through the corticospinal tract, the anterior horn cell, the peripheral nerve and the neuromuscular junction to the muscle.
• Upper motor neuron lesions cause spasticity, hyperreflexia, clonus and extensor plantar responses, and they spare acute muscle atrophy.
• Lower motor neuron lesions cause flaccid weakness, atrophy, fasciculations and reduced or absent reflexes.
• Neuromuscular junction disorders such as myasthenia gravis and botulism produce fatigable or descending weakness without sensory loss.
• Demyelinating disease, ischaemic stroke, haemorrhage, tumour, abscess and trauma are the main central causes, and peripheral nerve transection produces Wallerian degeneration distal to the lesion.
• Spinal shock after acute cord injury causes transient flaccid paralysis with areflexia before spasticity develops over weeks.
• Metabolic and toxic causes include severe hypokalaemia, hypermagnesaemia, organophosphate poisoning, curare and tetrodotoxin, all of which interfere with membrane excitability or neuromuscular transmission.

Clinical features

• Patients present with inability to move an affected limb or region, and the distribution immediately suggests the level of the lesion.
• Acute hemiplegia with facial involvement and dysphasia points to a cortical or capsular lesion, while flaccid areflexic weakness suggests a peripheral cause.
• Bulbar paralysis causes dysarthria, dysphagia, drooling and aspiration, and it is a major determinant of mortality.
• Respiratory muscle paralysis produces hypoventilation with falling vital capacity, paradoxical abdominal movement and early morning headache from hypercapnia.
• Complications include pressure ulcers, deep vein thrombosis, urinary retention, aspiration pneumonia, contractures, spasticity and depression.
• Immobility-related osteoporosis and heterotopic ossification occur after spinal cord injury, and autonomic dysreflexia is a medical emergency in lesions above T6.
• Children with cerebral palsy may show delayed motor milestones, persistent primitive reflexes and gait abnormalities rather than sudden loss of function.

Diagnosis

• Diagnosis begins with a detailed neurological examination mapping the distribution, tone, reflexes, plantar responses and sensory level.
• Urgent neuroimaging with computed tomography or magnetic resonance imaging distinguishes ischaemic stroke, haemorrhage, tumour and myelitis in acute presentations.
• Magnetic resonance imaging of the spine is the investigation of choice for suspected cord compression, and it should be performed within hours when deficits are progressive.
• Cerebrospinal fluid examination is indicated when Guillain-Barré syndrome, myelitis, infection or malignant infiltration is suspected.
• Nerve conduction studies and needle electromyography distinguish axonal from demyelinating lesions and localise the level of peripheral involvement.
• Serum potassium, magnesium, calcium, thyroid function, creatine kinase and toxicology screening identify reversible metabolic and toxic causes.
• Differential diagnosis includes psychogenic paralysis, catatonia, pain-related pseudoparalysis, locked-in syndrome and severe deconditioning, each of which requires a different approach.

Management

• Acute stroke paralysis is managed in a stroke unit with thrombolysis within 4.5 hours and thrombectomy within 24 hours for selected large vessel occlusions.
• Guillain-Barré syndrome is treated with intravenous immunoglobulin or plasma exchange, and corticosteroids are not effective.
• Spinal cord injury requires immobilisation, early decompression when indicated and prevention of secondary injury with mean arterial pressure targets.
• Rehabilitation begins early and combines physiotherapy, occupational therapy, functional electrical stimulation and gait training.
• Spasticity is managed with baclofen, tizanidine, botulinum toxin type A and intrathecal baclofen pumps, while contractures require stretching and splinting.
• Respiratory failure requires non-invasive or invasive ventilation, and tracheostomy is considered when weaning is prolonged beyond two weeks.
• Prognosis depends on the cause, with most stroke patients recovering some function within six months, whereas complete cord transection leaves permanent deficits below the lesion.

• Multidisciplinary rehabilitation improves functional independence after spinal cord injury, robotic gait training and functional electrical stimulation are used adjunctively, and severe spasticity is managed with oral baclofen, botulinum toxin injections or an intrathecal baclofen pump.

Research and controversies

• Cell-based therapies, including oligodendrocyte progenitor transplantation and mesenchymal stem cells, are in early-phase trials for spinal cord injury with no confirmed benefit.
• Brain-computer interfaces and neuroprostheses have restored grasp and communication in small trials, and several systems received regulatory clearance in the 2020s.
• Chondroitinase ABC and other enzyme-based approaches that degrade glial scar tissue are in preclinical and early clinical development.
• Epidural spinal cord stimulation has produced voluntary movement in chronic paraplegia, but durability and safety data remain limited.
• Whether intensive rehabilitation improves outcomes more than usual care remains contested, and trials are limited by difficulties in blinding and in standardising dose.
• The definition of recovery and the choice of outcome measures vary between trials, which hampers comparison across studies.
• Access to rehabilitation varies widely between countries, and workforce shortages limit the delivery of evidence-based therapy in low-income settings.