DESCRIPTION

• Flaccid paralysis begins in the lower limbs and progresses upward to involve arms as well as respiratory and facial muscles.
• Peripheral neuropathy, tetrodotoxin, and tick paralysis are also addressed in separate chapters.

PATHOPHYSIOLOGY

• Guillain-Barré syndrome (GBS) is the demyelinating disease of peripheral and cranial nerves, which causes ascending paralysis.
• Tick-borne paralysis involves a neurotoxin that causes ascending paralysis by inhibiting acetylcholine and thereby motor neuron transmission.
• The fruit of Karwinskia humboldtiana (buckthorn, coyotillo, tullidora) causes ascending paralysis by demyelination of motor nerves.
• Tetrodotoxin is a neurotoxin that blocks sodium channels and neuromuscular transmission.
• Severe arsenic toxicity results in diffuse axon destruction, which, in severe cases, may result in ascending paralysis.
• Acute intermittent porphyria (AIP) is a multisystem disease that involves motor neuropathy, occasionally including ascending flaccid paralysis.

EPIDEMIOLOGY

• GBS is the most common type of acute ascending paralysis.
  • Most cases are associated with antecedent infections (e.g., Campylobacter jejuni, HIV, cytomegalovirus, mycoplasma, and Epstein-Barr virus, among others).
  • Other precipitants include neoplasms, surgical procedures, autoimmune disorders, and vaccinations.
• Tick-borne paralysis (see SECTION IV, Tick Paralysis chapter) in North America primarily occurs during the spring and summer in the Rocky Mountains and the Northwestern United States or Canada. Most cases occur in girls.
• Ingestion of the fruit of K. humboldtiana (buckthorn, coyotillo, tullidora) may cause ascending paralysis. Most cases are reported in the southwestern United States.
• AIP is a genetically transmitted disorder.
  • Acute attacks usually require an additional trigger because over one third of patients with this enzyme deficiency never develop disease.
  • Therapeutic doses of barbiturates, anticonvulsants, estrogens, contraceptives, and alcohol may trigger acute attacks. Fasting or infection also may trigger AIP.

Section Outline:

• DESCRIPTION
• PATHOPHYSIOLOGY
• EPIDEMIOLOGY

DIFFERENTIAL DIAGNOSIS

See SECTION II, Peripheral Neuropathy chapter for related discussion.

Toxicologic Causes

• Further information on each poison is available in SECTION IV, CHEMICAL AND BIOLOGICAL AGENTS.
• Tick-borne paralysis. Symmetric, ascending flaccid paralysis progresses over hours to days. Decreased deep tendon reflexes (DTRs). Sensory symptoms and mental status changes are usually absent.
• Tetrodotoxin poisoning. Rapid-onset headache, cranial nerve palsies, paresthesia of face, hands, and feet, nausea, vomiting, dysphagia, weakness, fasciculation, and ascending paralysis may occur within an hour of ingesting puffer fish.
• Organophosphate toxicity. Acute or chronic exposure may result in lower extremity weakness, ataxia, and paresthesia, which may ascend to the upper extremities.
• Arsenic. Pain and paresthesia are prominent features of arsenic-associated peripheral neuropathy. Nausea, vomiting, diarrhea, and anorexia are common. Rash and alopecia also may occur. Sensory loss, decreased DTRs, weakness, and ascending paralysis are later findings of severe poisoning.
• Chronic solvent abuse results in ataxia, cranial nerve palsies, and cognitive impairment. Reflexes are usually preserved. Ascending flaccid paralysis occurs rarely in patients with massive exposure.
• Botulism. Botulism typically causes a descending paralysis, beginning with the cranial nerves.
• Severe lead poisoning
  • Wrist or foot drop and encephalopathy may develop.
  • Anemia and gastrointestinal symptoms usually develop before neurologic effects.
  • Ascending paralysis does not occur.

Nontoxicologic Causes

• GBS
  • Required diagnostic criteria include ascending paralysis and areflexia.
  • Minor diagnostic criteria include symmetrical weakness, mild sensory symptoms, and facial weakness.
  • Progression may be rapid or gradual.
• AIP is characterized by recurrent attacks of abdominal pain, nausea, vomiting, hypertension, tachycardia, psychiatric symptoms, and neuropathy, sometimes associated with ascending paralysis.
• Conversion reactions may result in weakness and sensory deficits inconsistent with neurologic anatomy.
• Spinal cord compression, trauma, or inflammation may present with symmetric lower-extremity weakness and decreased reflexes.

SIGNS AND SYMPTOMS

Flaccid paralysis begins in the lower limbs and progresses upward to the trunk, arms, and respiratory and facial muscles. Depending on the cause of paralysis, other systemic symptoms may develop.

Vital Signs

• Ascending paralysis from any cause may result in hypoventilation and respiratory arrest.
• GBS may cause hemodynamic instability, hyper- and hypotension, and brady- and tachydysrhythmias as a result of autonomic dysfunction.

HEENT

• Cranial nerve involvement with facial weakness is seen in 50% of patients with GBS. Papilledema, bilateral facial weakness, diplopia, ptosis, and oculomotor weakness may occur.
• Cranial nerve palsies may be found in tetrodotoxin poisoning or botulism.

Dermatologic

A tick may be found attached to the skin or scalp of patients with tick-borne paralysis.

Arsenic poisoning may show rash, alopecia, and Mee's lines.

Pulmonary

Pulmonary manifestations from any cause include respiratory muscle weakness and paralysis.

Gastrointestinal

• Dysphagia may be seen in GBS and tetrodotoxin poisoning.
• Oral dysesthesia may precede ascending paralysis in tetrodotoxin poisoning.
• Nausea, vomiting, anorexia, abdominal pain, and diarrhea may be seen in AIP and arsenic or tetrodotoxin poisoning.

Renal

Urinary retention may develop in GBS.

Fluids and Electrolytes

Hyponatremia from inappropriate secretion of antidiuretic hormone may develop in AIP.

Musculoskeletal

Ascending muscle weakness begins in the lower extremities and progresses to the trunk and upper extremities.

Neurologic

• Ascending paralysis occurs, with areflexia and mild numbness or paresthesia of the feet and hands.
• Ataxia may occur with GBS, tick-borne paralysis, AIP, K. humboldtiana fruit ingestion, and tetrodotoxin poisoning.

PROCEDURES AND LABORATORY TESTS

Essential

• Serum electrolytes, blood urea nitrogen, creatinine, calcium, and magnesium determinations assess electrolyte-mediated causes.
• Arterial blood gases, pulse oximetry, and serial vital capacity measurements assess respiratory function and the need for intubation.
• Electrocardiography and monitoring assess rhythm and conduction defects.
• Lumbar puncture is performed to determine the absence or minimal number of lymphocytes in the presence of elevated levels of CSF protein, which suggests GBS.

Recommended

• Complete blood count is taken to determine anemia and basophilic stippling associated with lead poisoning. The whole blood lead level will confirm the diagnosis.
• A 24-hour urine collection for arsenic and other heavy metals supports the diagnosis of specific metal toxicity.
• Urinary concentrations of delta-aminolevulinic acid and porphobilinogen are elevated during acute attacks of AIP.
• Red cell and plasma cholinesterase levels are depressed in organophosphate poisoning.
• Nerve conduction studies help differentiate GBS, botulism, and other neuropathies.

Imaging

Radiographs of the spine and CT and MRI scans of the spinal column and brain can help detect underlying disease.

Section Outline:

• DIFFERENTIAL DIAGNOSIS
  • Toxicologic Causes
  • Nontoxicologic Causes
• SIGNS AND SYMPTOMS
  • Vital Signs
  • HEENT
  • Dermatologic
  • Pulmonary
  • Gastrointestinal
  • Renal
  • Fluids and Electrolytes
  • Musculoskeletal
  • Neurologic
• PROCEDURES AND LABORATORY TESTS
  • Essential
  • Recommended
  • Imaging

• Treatment should be focused on assuring adequate ventilation and assessment of etiology (e.g., the tick should be sought and removed).
• Supportive care with appropriate airway management is vital. Specific treatment should be initiated while continuing supportive care.
• The dose and time of exposure must be determined for all substances involved.

DIRECTING PATIENT COURSE

The health care provider should call the poison control center when:

• The diagnosis of ascending paralysis is considered.
• A coingestant, drug interaction, or underlying disease presents unusual problems.

Admission Considerations

The health-care provider should consider referral to a health-care facility when:

• The patient has ascending paralysis, in which case, the patient should be admitted to an ICU.
• A coingestant, drug interaction, or underlying disease presents unusual problems.

DECONTAMINATION

Decontamination is necessary if acute ingestion is suspected.

Out of Hospital

Induction of emesis is not recommended; effects develop after the toxin has been absorbed.

In Hospital

• Gastric lavage should be performed in pediatric (tube size 24-32 French) or adult (tube size 36-42 French) patients for large ingestion presenting within 1 hour of ingestion or if serious effects are present.
• One dose of activated charcoal (1-2 g/kg) should be administered without a cathartic if a substantial ingestion has occurred within the previous few hours.

ANTIDOTES

• There is no specific antidote for the causes of ascending paralysis.
• In some cases, heavy metal chelation may be indicated.

ADJUNCTIVE TREATMENT

Patients with a declining vital capacity or a vital capacity of 10 to 12 ml/kg may require endotracheal intubation and mechanical ventilation.

GBS

• GBS is typically treated with immune globulin (0.4 g/kg/day intravenously for 5 days).
• Plasmapheresis may be beneficial for GBS if started within the first 2 weeks of the onset of symptoms.

AIP

• AIP is treated with glucose (a minimum of 300 g/day at rates of up to 20 g/hour).
• Intravenous heme (lyophilized hematin or hydroxyheme at 4 mg/kg every 12 hours for 3 to 6 days) inhibits porphyrin synthesis and ameliorates symptoms, if given early.

Hypotension

• Saline (0.9%) should be administered at 10 to 20 ml/kg, and the patient should be placed in the Trendelenburg position.
• Further fluid therapy should be guided by central pressure monitoring to avoid volume overload. A vasopressor should be added, if needed.

Section Outline:

• DIRECTING PATIENT COURSE
  • Admission Considerations
• DECONTAMINATION
  • Out of Hospital
  • In Hospital
• ANTIDOTES
• ADJUNCTIVE TREATMENT
• GBS
• AIP
  • Hypotension

PATIENT MONITORING

Ventilatory function must be assessed continuously. Patients should be monitored in an ICU setting until hemodynamically and neurologically stable and improving.

EXPECTED COURSE AND PROGNOSIS

• The mortality rate associated with GBS is 3% to 5%. Most patients recover in weeks to months but may have residual deficits. Relapse occurs in 5% to 9% of patients.
• Tick-borne paralysis reverses rapidly after tick removal.
• AIP attacks usually resolve within 2 to 3 days.
• Tetrodotoxin poisoning has a rapid onset. Recovery often requires prolonged mechanical ventilation.

DISCHARGE CRITERIA/INSTRUCTIONS

• From the emergency department. Patients with possible ascending paralysis should not be discharged.
• From the hospital. Patients whose vital signs are normal and neurologic status is improving can be discharged.

Section Outline:

• PATIENT MONITORING
• EXPECTED COURSE AND PROGNOSIS
• DISCHARGE CRITERIA/INSTRUCTIONS

• Early findings of ascending paralysis may be subtle, and the patient may be inappropriately discharged.
• Patients with AIP are often misdiagnosed with psychosis.

Toxic effect of other substances, chiefly nonmedicinal as to source.

See Also: SECTION II, Hypotension and Peripheral Neuropathy chapters, as well as SECTION IV, Arsenic, Tetrodotoxin, and Tick Paralysis chapters.

RECOMMENDED READING

Awong IE, Dandurand KR, Keeys CA, et al. Drug-associated Guillain-Barré syndrome: a literature review. Ann Pharmacother 1996;30:173-180.

Author: Robin Millin

Reviewer: Richard C. Dart