Acute Inflammatory Demyelinating Polyradiculoneuropathy Clinical Presentation

• Acute inflammatory demyelinating polyneuropathy typically manifests as an ascending paralysis.
• Even in these cases, the clinical presentation and course vary. Additionally, many variants exist that differ markedly from classic AIDP in disease onset or course.
• Progressive weakness

  • The hallmark of classic AIDP is progressive weakness that usually begins in the feet before involving all 4 limbs. At presentation, 60% of patients have weakness in all 4 limbs.
  • Weakness plateaus at 2 weeks after onset in 50% of patients and by 4 weeks in over 90%. It is usually symmetric, although mild asymmetry is not uncommon early in the disease course.
  • In the arms, weakness may be worse proximally than distally. At presentation, half of patients have some facial weakness, although only 5% have varying degrees of ophthalmoplegia.
  • Oropharyngeal or respiratory weakness is a presenting symptom in 40% of patients. Improvement in strength usually begins 1-4 weeks after the plateau. About one third of patients require mechanical ventilation because of respiratory failure.
• Sensory symptoms

  • Mild to moderately severe paresthesias in the distal limbs are common and often precede the onset of weakness by 1 or more days.
  • Proximal sensory changes are uncommon but may occur in more severe cases of AIDP.
• Autonomic dysfunction

  • About two thirds of patients have one or more autonomic abnormalities. Sustained sinus tachycardia is the most common dysfunction. Postural hypotension leading to presyncope or syncope can occur.
  • Sweating dysfunction is common but rarely noted by patients. Urinary retention and constipation are more likely to occur later in the course of AIDP. Autonomic dysfunction is more common in intubated patients.
• Pain

  • Mild lower back and/or hip pain is very common and occasionally precedes the onset of weakness.
  • The pain is severe in about 15% of patients.
• AIDP may vary early in the course. More than 95% of patients eventually have the classic symptoms; other patients may have one of the characterized variants.

  • The Miller-Fisher variant, appearing with ophthalmoplegia, areflexia, and ataxia, is the most common variant and is seen in as many as 5% of patients with AIDP. Although usually seen in adults, this variant is also common in children. Most patients with the Miller-Fisher variant have antibodies against ganglioside GQ1b.
  • Regional variants of Guillain-Barré syndrome, such as pharyngeal-cervical-brachial weakness or only leg weakness, are rare and resemble AIDP in time course.
  • Pure pandysautonomia with little, if any, weakness parallels classic AIDP in time course and antecedent infections. The difference is that this variant is manifested primarily by autonomic failure. Many of these patients also have areflexia.
  • The AMAN variant is seen in China and in developing countries. It presents with weakness only.
  • Acute motor-sensory axonal neuropathy resembles classic Guillain-Barré syndrome in presentation but is related pathologically to AMAN.

A detailed physical examination can help support the diagnosis of acute inflammatory demyelinating polyneuropathy and/or exclude disorders in the differential diagnosis.

• Weakness

  • Although patients often report only weakness in the legs, careful examination usually demonstrates arm weakness (proximally and distally).
  • Some patients with Miller-Fisher or other regional variants may have weakness of cranial muscles only.
• Deep tendon reflexes

  • Hyporeflexia or areflexia is seen in 70% of patients at presentation and eventually in all patients.
  • A progressive decrease in reflexes is a useful finding that may precede electromyographic (EMG) changes.
• Autonomic dysfunction

  • Fluctuations in heart rate, specifically a sustained sinus tachycardia, are seen often.
  • Some intubated patients also may have bradycardia, especially after vagal stimulation with Valsalva and/or tracheal suctioning maneuvers.
  • Orthostatic hypotension can occur and is likely due to dysfunction of the baroreceptor reflex.
  • At times, the labile blood pressure is observed with severe hypertension that may be due to dysfunction of the afferent limb of the baroreceptor reflex.
  • Urinary retention is common, especially in intubated patients. The rare patient may even develop an ileus.
• Findings that are inconsistent with a diagnosis of AIDP

  • Weakness that remains markedly asymmetric
  • Sharp sensory level
  • Severe bladder or bowel dysfunction at onset
• Diagnostic criteria for Guillain-Barré syndrome include the presence of progressive weakness and areflexia, relative symmetry, mild sensory involvement, cranial nerve involvement, at least partial recovery, autonomic dysfunction, and absence of fever. Cerebrospinal fluid features that strongly support the diagnosis are an increase in protein beyond the first week, cell count < 10 (albuminocytological dissociation). Electrophysiologic evidence of conduction slowing, block, prolonged distal latency or F-wave latencies are also strongly supportive (80% of the case), though these abnormalities may be delayed for several weeks. Marked persistent asymmetry of weakness, the presence of a sensory level, bowel/bladder involvement at onset, and a prominent pleocytosis, often cast doubt on the diagnosis, so is the presence of another cause for the neuropathy.
• In 1986, Ropper described 3 patients who experienced acute progression of oropharyngeal, neck, and shoulder weakness. Clinically, they had facial palsy, blepharoptosis, absence of sensory disturbance, and preserved tendon jerk in the legs. Based on elevated CSF protein levels and electrophysiological findings (a denervation pattern and decreased conduction velocity in peripheral nerves), he speculated that these patients had a Guillain-Barré syndrome variant, which he called pharyngeal-cervical-brachial weakness (PCB).^[5]
• Since then, PCB is considered a rare variant of Guillain-Barré syndrome. Nagashima et al identified the clinical profiles of PCB. They feel that the clinical overlapping, frequent Campylobacter jejuni infection, and common antiganglioside antibodies present in PCB, Guillain-Barré syndrome, Fisher syndrome, and Bickerstaff brainstem encephalitis provide conclusive evidence that PCB and these conditions form a continuous spectrum.^[6]

Acute inflammatory demyelinating polyneuropathy is thought to be caused by a dysregulated immune response against myelin. This response may be triggered by several illnesses and conditions. Two thirds of patients with AIDP recall an antecedent upper respiratory or gastrointestinal infection or syndrome from 1-6 weeks prior to the onset of weakness.

• Viral

  • Infection with influenza, coxsackie, Epstein-Barr virus, or cytomegalovirus can cause upper respiratory infection. Immunoglobulin M (IgM) antibodies to each have been identified in some individuals.
  • Acute infection with either herpes simplex virus or human immunodeficiency virus (HIV) also has been associated with AIDP in some individuals.
    • Patients with HIV-associated AIDP often have a pleocytosis with up to 200 WBC/µL CSF.
    • Rare cases also have been reported after infection with rubella, measles, varicella-zoster, hepatitis B, Q fever, and Hantavirus.^[7]
    • Wagner at al presented a case of acute motor axonal neuropathy in a patient with previously unrecognized human immunodeficiency virus (HIV) infection. To their knowledge, this is the first case of acute motor axonal neuropathy in HIV outside of a seroconversion reaction.^[8]
• Bacterial

  • Strains of C jejuni that cause enteritis are associated closely with the subsequent development of AMAN.
  • Molecular mimicry between gangliosidelike epitopes of the C jejuni lipopolysaccharide and peripheral nerve gangliosides in nerve is a proposed mechanism.
  • In children, an association exists between AIDP and Mycoplasma pneumoniae infection.
• Other: Rare cases of AIDP in individuals infected with toxoplasma, malaria, or filaria have been reported.
• Vaccination

  • Many cases of AIDP were reported after vaccination for swine influenza (especially in 1976).
  • Several cases have been reported after immunization against rabies, influenza, measles, mumps, or rubella.
• Malignancies and systemic illnesses

  • Case reports document patients with AIDP associated with Hodgkin lymphoma, acute myelogenous lymphoma, Castleman disease, systemic lupus erythematosus, and hypothyroidism.
  • The rarity of these combinations raises doubts on the significance of these associations.
• Pregnancy: Most cases occur during the last trimester or during the first 2 weeks of the postpartum period.
• Bone marrow transplantation
• Surgery: Most patients also had an infection or blood transfusion.
• Other problems to be considered

  • Poliomyelitis: Classic poliomyelitis is very rare. However, coxsackievirus and echovirus can cause a similar, milder paralysis, especially in children.
  • Buckthorn shrub poisoning: This plant is found in the southwestern United States and Central America and bears a fruit that causes paralysis by an unknown mechanism. The CSF is usually normal.
  • Critical illness polyneuropathy: Weakness is more common in the setting of sepsis and/or multiorgan failure.
  • Diphtheria: Weakness may follow the pharyngeal infection by 2-3 weeks, beginning with palatal paralysis and, often, paralysis of accommodation. Limb weakness is not common.
  • Hypophosphatemia: An acute areflexic paralysis may follow hypophosphatemia in the setting of total parenteral nutrition, alcohol abuse, or rapid refeeding after starvation. The weakness rapidly responds to phosphate replacement.
  • Malingering and conversion reaction: Bizarre or nonphysiologic abnormalities may be seen on neurologic examination.
  • The antidepressant drug zimeldine, a serotonin reuptake blocker, was reported to be associated with Guillain-Barré syndrome and the drug has been withdrawn.
• Variants

  • A number of entities are related to acute demyelinating neuropathy. Although they are acute, likely inflammatory, and immune mediated, they are not necessarily demyelinating. The acute panautonomic neuropathy is characterized by widespread and severe sympathetic and parasympathetic failure. Acute motor axonal neuropathy (AMAN) results in motor axonal degeneration, with little or no demyelination or inflammation. Many follow C jejuni infection. Axonal Guillain-Barré syndrome is at the other end of the spectrum, where the illness predominantly involves the axis cylinder of the somatic nervous system, and is fairly common. Hyperacute axonal polyradiculoneuropathy has a hyperacute course with onset to respiratory failure within 48 hours. These patients have a high mortality rate. Recovery when it occurs, is delayed, very prolonged, and characteristically quite incomplete.
  • Critical illness polyneuropathy has an uncertain relationship to the acute inflammatory neuropathies. Sensory Guillain-Barré syndrome, where sensory symptoms occur in isolation, are rare.
  • The Fisher syndrome is an uncommon variant of AIDP (about 5% of the cases) characterized by the triad of ophthalmoplegia, ataxia, and areflexia. Occasionally papillary abnormalities occur, and many cases are associated with some evidence of more widespread motor involvement. Miller-Fisher variant may be associated with a particular serotype of C jejuni.
  • Other unusual variants include the pharyngeal-cervical brachial variant, with deficits limited to these regions alone, and the paraparetic variant, where the weakness is confined to the lower extremities only, as the name implies. Acute sensory neuronopathy is usually associated with autonomic failure. It is likely inflammatory-immune-mediated. The brunt of the attack is borne on the dorsal root ganglia cells.
  • The demonstration in some studies of demyelination in excess of control sera when injected into peripheral nerve, and the demonstration of IgM antibodies that bind to carbohydrate residues of peripheral nerve in 90% of Guillain-Barré syndrome patients at the onset of the disease, support of an antibody as the mechanism of Guillain-Barré syndrome.
  • Over the past decade, great progress has been made in Guillain-Barré syndrome research, and the highlights include (1) the emerging correlations between antiganglioside antibodies and specific clinical phenotypes, notably between anti-GM1/anti-GD1a antibodies and the acute motor axonal variant and anti-GQ1b/anti-GT1a antibodies and the Miller Fisher syndrome; (2) the identification of molecular mimicry between Guillain-Barré syndrome–associated C jejuni oligosaccharides and GM1, GD1a, and GT1a gangliosides as a mechanism for antiganglioside antibody induction; and (3) the development of rodent models of Guillain-Barré syndrome with sensory ataxic or motor phenotypes induced by immunization with GD1b or GM1 gangliosides, respectively.^[9]
• Comparison of clinical features of Guillain-Barré syndrome with CIDP

  • Patients with CIDP have a more slowly progressive weakness and a protracted course either monophasic or relapsing, and relapses are much more common with CIDP. While a history of viral infection is often obtained with Guillain-Barré syndrome, this is rather uncommon in CIDP. Occurrence of respiratory failure is very uncommon with CIDP. Both conditions are associated with areflexia, typical CSF findings of increased protein, abnormal nerve conduction studies (patchy conduction slowing with Guillain-Barré syndrome and diffuse slowing with CIDP). While prednisone therapy on its own has no proven role in Guillain-Barré syndrome, CIDP patients are sensitive to prednisone therapy.
  • Guillain-Barré syndrome and CIDP have been associated with HIV-1 infection. They are most common in infected patients who are otherwise asymptomatic. In certain cases, Guillain-Barré syndrome may occur with seroconversion. The clinical features of Guillain-Barré syndrome and CIDP in HIV-1 infected patients are similar to patients without HIV-1 infection.