Paraparesis and quadriparesis

Paraparesis is weakness of both legs; quadriparesis is weakness of all four limbs. Most are due to disease of the spinal cord, cauda equina or peripheral nerves.

Anatomy and localisation.

• Cervical cord lesion: quadriparesis with upper motor neuron signs in all limbs and a sensory level on the trunk.
• Thoracic cord lesion: spastic paraparesis with a truncal sensory level.
• Conus and cauda equina: flaccid paraparesis, saddle anaesthesia, urinary retention or incontinence, loss of anal tone, and reduced reflexes.
• Peripheral neuropathy and neuromuscular junction: symmetrical flaccid weakness with reduced reflexes and no sensory level.
• Parasagittal brain lesion: spastic leg weakness with bladder symptoms.

Mechanisms. Compression (tumour, disc, abscess, haematoma, vertebral collapse), vascular (infarction in the anterior spinal artery territory, dural arteriovenous fistula), inflammation (myelitis), infection, toxic and nutritional injury, degenerative disease, metabolic muscle weakness, and demyelinating neuropathy.

Temporal patterns. Hyperacute (minutes to hours: cord infarct, haematoma, trauma, periodic paralysis), acute (hours to days: compression, myelitis, Guillain Barré syndrome), subacute (weeks: tumour, abscess, tuberculosis, nutritional), chronic (months to years: degenerative, hereditary, tropical spastic paraparesis).

Key distinctions. Upper motor neuron signs and a sensory level suggest the cord. Flaccid, areflexic weakness without a sensory level suggests neuropathy, motor neuron disease or muscle disease. Spinal shock can cause flaccidity and areflexia in the first days to weeks of an acute cord lesion.

History. Speed of onset, back or neck pain (and its character: mechanical or night, radiating), sensory loss and level, paraesthesia, bladder and bowel dysfunction (retention, incontinence), erectile dysfunction, trauma, fever, weight loss, cancer history, immunosuppression, injecting drug use.

Also ask about recent infection (gastroenteritis, respiratory), vaccination, tick bites, diet (cassava, grass pea), alcohol, nitrous oxide use, recent surgery or spinal procedure (epidural, lumbar puncture), anticoagulation, pregnancy, and family history.

Examination.

• Respiratory: respiratory rate, ability to count to 20 on one breath, single breath count, forced vital capacity, neck flexion strength, use of accessory muscles.
• Neurological: power in each limb and trunk, tone, reflexes, plantar responses, clonus, sensory level by pinprick, vibration, proprioception, abdominal reflexes, anal tone and perianal sensation, cranial nerves (facial weakness, bulbar function), and gait if safe.
• Spine: tenderness over the vertebrae, deformity (gibbus), paraspinal mass, skin changes.
• General: blood pressure and heart rate (autonomic dysfunction), bladder scan, temperature, pulse, nutritional state, signs of malignancy (breast, prostate, lung), lymph nodes, skin signs, and signs of infection or injecting drug use.

Red flags

• Sudden onset with back pain, or onset after trauma
• Sensory level, bladder or bowel dysfunction, or saddle anaesthesia
• Respiratory difficulty, single breath count under 20, bulbar weakness, or autonomic instability
• Fever with back pain, injecting drug use, or recent spinal procedure
• Cancer or unexplained weight loss
• Rapidly ascending weakness over hours to days
• Anticoagulation with new back pain
• Pregnancy or postpartum

Special groups. Older adults: degenerative myelopathy and metastatic compression. Children: transverse myelitis, acute flaccid myelitis, tumours. Region specific: spinal tuberculosis (Pott disease), HTLV-1 associated myelopathy, schistosomal myelopathy, HIV vacuolar myelopathy, konzo (cassava), lathyrism (grass pea), neurosyphilis, poliomyelitis.

Spinal cord compression and structural

• Metastatic epidural disease (lung, breast, prostate, myeloma, lymphoma), primary spinal tumour (meningioma, neurofibroma, ependymoma)
• Disc herniation, cervical spondylotic myelopathy, ossification of the posterior longitudinal ligament, atlantoaxial subluxation
• Spinal epidural abscess, vertebral osteomyelitis and discitis, spinal tuberculosis, epidural haematoma
• Vertebral fracture, trauma
• Syringomyelia, arachnoid cyst, Chiari malformation

Cord vascular

• Spinal cord infarction (anterior spinal artery syndrome), aortic dissection or surgery related
• Dural arteriovenous fistula, spinal arteriovenous malformation

Cord inflammatory and infective

• Transverse myelitis, multiple sclerosis, neuromyelitis optica spectrum disorder, MOG antibody disease
• Acute flaccid myelitis, poliomyelitis
• HTLV-1 associated myelopathy, HIV vacuolar myelopathy, neurosyphilis, schistosomiasis, tuberculosis, herpes zoster myelitis, sarcoidosis, systemic lupus erythematosus

Cord metabolic, toxic and nutritional

• Subacute combined degeneration (vitamin B12 deficiency, nitrous oxide misuse), copper deficiency
• Konzo, lathyrism, radiation myelopathy

Cauda equina and root

• Cauda equina syndrome (central disc prolapse, tumour, abscess), lumbar canal stenosis
• Polyradiculopathy: cytomegalovirus, lymphomatous or carcinomatous meningitis, Lyme disease

Peripheral nerve and neuromuscular

• Guillain Barré syndrome (acute inflammatory demyelinating polyradiculoneuropathy, acute motor axonal neuropathy), chronic inflammatory demyelinating polyneuropathy
• Critical illness polyneuropathy and myopathy, toxic neuropathy (arsenic, thallium, organophosphates, vincristine), diphtheritic neuropathy
• Myasthenic crisis, botulism, tick paralysis
• Hypokalaemic and thyrotoxic periodic paralysis, hyperkalaemic periodic paralysis, hypophosphataemia, hypomagnesaemia
• Acute myopathy: rhabdomyolysis, inflammatory myopathy, steroid myopathy
• Motor neuron disease, Charcot Marie Tooth disease

Central non-spinal

• Parasagittal meningioma, anterior cerebral artery infarct, bilateral hemispheric lesions, hydrocephalus
• Functional paraparesis

Reasoning. Establish the level, decide between spinal cord, cauda equina, peripheral and muscle origin, then scan the corresponding site without delay. Check respiratory function in every acute case.

Immediate bedside tests. Single breath count, forced vital capacity (sitting and lying), oxygen saturation, ECG, capillary glucose, bladder scan or catheter volume, potassium by blood gas.

Imaging. Emergency MRI of the whole spine with contrast for suspected cord compression, myelitis, infarct, abscess or cauda equina syndrome (MRI of the spine covering the clinical level and adjacent regions, because skip lesions occur). MRI brain for demyelination and neuromyelitis optica. CT spine for trauma and when MRI cannot be done. CT myelography if MRI contraindicated.

Blood tests. Full blood count, ESR and C reactive protein, urea, electrolytes, creatinine, potassium (urgent), calcium, magnesium, phosphate, glucose, liver function, creatine kinase, thyroid function, vitamin B12 and methylmalonic acid, copper, HIV test, syphilis serology, HTLV-1 serology, blood cultures, prostate specific antigen in men, serum protein electrophoresis. Add aquaporin-4 and MOG antibodies, antinuclear antibody, anti-Ro and anti-La antibodies, angiotensin converting enzyme in selected patients.

Lumbar puncture after imaging excludes a compressive lesion: cell count, protein (raised in Guillain Barré syndrome with normal cell count: albuminocytological dissociation, which may be absent in the first week), glucose, oligoclonal bands, cytology, infective studies.

Neurophysiology. Nerve conduction studies and electromyography for Guillain Barré syndrome (abnormal after the first week; early studies can be normal), neuropathy, myopathy and neuromuscular junction disorders.

Targeted tests. Tissue biopsy or CT guided sampling for suspected malignancy or infection of the spine; CT chest, abdomen and pelvis for primary tumour; tuberculosis tests (sputum, tuberculin or interferon gamma release assay, chest radiograph, biopsy); schistosomiasis serology and stool or rectal biopsy; nitrous oxide history.

Limitations. Early MRI can be normal in cord infarction (diffusion weighted imaging helps). Guillain Barré syndrome has a normal CSF protein in a fifth of patients in the first week. Spinal shock can mimic a lower motor neuron lesion.

Immediate care. Airway, breathing, circulation. Spinal immobilisation after trauma. Respiratory support: intubate for forced vital capacity under 15 to 20 mL/kg, a fall of more than 30 percent from baseline, maximal inspiratory pressure under 30 cmH2O, bulbar failure, or exhaustion. Cardiac monitoring for autonomic instability. Urinary catheter for retention. Pressure area care and venous thromboembolism prophylaxis with enoxaparin 40 mg subcutaneously daily (20 mg when creatinine clearance is under 30 mL/min) unless bleeding risk.

Metastatic spinal cord compression. Dexamethasone 16 mg orally or IV daily (or 10 mg IV then 4 mg every 6 hours) with gastric protection, started immediately for suspected cord compression with neurological signs; avoid when lymphoma is suspected until biopsy has been discussed. Flat bed rest until spinal stability is known. Emergency oncology, neurosurgical or radiotherapy referral within 24 hours (surgery for unstable spine, or radiotherapy). Monitor glucose.

Spinal epidural abscess and vertebral osteomyelitis. Emergency MRI and neurosurgical review, blood cultures before antibiotics when this causes no delay.

Empirical therapy: vancomycin 25 to 30 mg/kg IV loading dose (maximum 3 g), then 15 to 20 mg/kg every 8 to 12 hours adjusted to creatinine clearance and levels, plus ceftriaxone 2 g IV every 12 hours. Use ceftazidime 2 g every 8 hours instead when Pseudomonas is likely, as in injecting drug use. Total duration is adjusted to culture results and is usually 6 to 8 weeks.

Spinal tuberculosis. Give four drugs daily for 2 months: isoniazid 5 mg/kg (maximum 300 mg), rifampicin 10 mg/kg (maximum 600 mg), pyrazinamide 25 mg/kg (maximum 2 g) and ethambutol 15 mg/kg.

Then continue isoniazid and rifampicin for at least 7 to 10 months (total 9 to 12 months for bone and spinal disease). Give pyridoxine 10 to 25 mg daily and monitor liver function and visual acuity. Add dexamethasone for neurological deficit, and surgery for instability or deficit.

Cauda equina syndrome. Emergency MRI and surgical decompression, ideally within 24 hours of onset of retention or bladder dysfunction.

Guillain Barré syndrome

• Intravenous immunoglobulin 0.4 g/kg daily for 5 days, started within 2 weeks of onset, or plasma exchange 200 to 250 mL/kg in 5 sessions over 1 to 2 weeks (no benefit from combining both). Check IgA deficiency and renal function before immunoglobulin; monitor for thrombosis, aseptic meningitis and renal injury. Corticosteroids are not effective and are avoided.
• Monitoring: forced vital capacity twice daily, bulbar function, cardiac rhythm, blood pressure (autonomic storms), sodium (syndrome of inappropriate antidiuretic hormone), bladder, and thromboprophylaxis. Intensive care for deterioration.
• Pain: gabapentin 300 mg three times daily or carbamazepine, titrated; avoid opioids when possible because of ileus and respiratory depression.

Myasthenic crisis. Intensive care, intravenous immunoglobulin 0.4 g/kg daily for 5 days or plasma exchange, and withdrawal of aggravating drugs (fluoroquinolones, aminoglycosides, macrolides, magnesium, beta blockers). Specialist care.

Transverse myelitis and neuromyelitis optica. Methylprednisolone 1 g IV daily for 3 to 5 days; escalate to plasma exchange or intravenous immunoglobulin for poor response, and specialist immunotherapy for neuromyelitis optica spectrum disorder.

Subacute combined degeneration. Hydroxocobalamin 1 mg IM on alternate days until no further improvement (up to 3 weeks), then 1 mg every 2 months; never give folic acid alone first; stop nitrous oxide exposure, with copper replacement when copper is low.

Spinal cord infarction. Supportive care, avoid hypotension (mean arterial pressure over 85 mmHg), antiplatelet therapy by specialist decision, and investigation of aortic and embolic sources.

Hypokalaemic periodic paralysis. Potassium chloride 20 to 40 mmol orally, repeated every 30 to 60 minutes with ECG monitoring while weakness persists.

If giving IV, use no more than 10 mmol/hour peripherally (20 mmol/hour centrally) in 0.9 percent sodium chloride without glucose (glucose can worsen weakness). Avoid overcorrection because of rebound hyperkalaemia. Thyrotoxic periodic paralysis needs propranolol 40 mg orally every 6 hours with potassium and treatment of thyrotoxicosis; avoid dextrose containing fluids.

Neurosyphilis. Benzylpenicillin 3 to 4 million units IV every 4 hours (18 to 24 million units daily) for 10 to 14 days; Jarisch Herxheimer reaction possible. HIV myelopathy: antiretroviral therapy.

Schistosomal myelopathy. Praziquantel 40 mg/kg orally as a single dose (or 60 mg/kg divided in 2 or 3 doses) with prednisolone 1 mg/kg daily, under specialist care.

Organophosphate or botulism poisoning. Respiratory support; for organophosphates atropine 1 to 2 mg IV doubled every 5 minutes until secretions dry; botulism antitoxin when available.

Rehabilitation and supportive care. Physiotherapy, occupational therapy, bladder and bowel programme, pressure sore prevention, pain management, mood support, and driving and employment advice.

Spasticity management: baclofen 5 mg orally three times daily, increased by 5 mg every 3 days to a maximum of 100 mg daily. Reduce in renal impairment and withdraw gradually.

Monitoring. Respiratory function (forced vital capacity twice daily in acute neuromuscular disease), neurological level and power every 4 hours initially, potassium and electrolytes, cardiac rhythm, bladder volumes, skin, temperature, bowel function, and venous thromboembolism signs.

Referral and escalation. Immediate neurosurgery or spinal surgery for compression, abscess, haematoma and cauda equina syndrome. Oncology for malignant compression. Intensive care for respiratory compromise or autonomic instability. Neurology for myelitis, Guillain Barré syndrome, myasthenia and unexplained cases. Infectious disease for tuberculosis, HIV and syphilis.

Admission criteria. All acute or rapidly progressive paraparesis or quadriparesis. Chronic stable myelopathy can be assessed in outpatients with urgent MRI.

Discharge and safety netting. Return urgently for worsening weakness, urinary retention, new numbness, breathing difficulty or fever. Advise on pressure care, bladder care and driving.