A 14-year-old boy presents to the emergency department (ED) with a 10-day history of progressive weakness. The patient reports experiencing rhinorrhea, cough, and malaise approximately 3 weeks before admission. He developed lower-extremity weakness and difficulty walking 8 days after the onset of the upper respiratory tract infection symptoms. He was evaluated at a local hospital, where he was diagnosed with dehydration, treated with intravenous fluids, and discharged to home. Despite these measures, his lower-extremity weakness did not improve. Over the following 7 days, he began experiencing diffuse muscle pain and progressive weakness that extended to his upper extremities. During the 3 days before this presentation, he developed a hoarse voice and shortness of breath. He also notes that he is now having difficulty urinating and has decreased oral intake. He currently denies having any fever, cough, vomiting, or diarrhea. The patient’s past medical history is significant only for attention deficit hyperactivity disorder (ADHD), for which he takes methylphenidate. He has had no previous hospitalizations, has no known drug allergies, and has had all recommended childhood immunizations. His family history is noncontributory.
The physical examination reveals an afebrile, ill-appearing teenager, with a heart rate of 118 bpm, a respiratory rate of 28 breaths/min, a blood pressure of 168/122 mm Hg, and an oxygen saturation of 93% while breathing room air. Auscultation of the lungs reveals diffuse, poor aeration. His heart sounds are normal, without any appreciable murmur. His strength is symmetric but diminished to 2/5 in his lower extremities and 4/5 in his upper extremities (5/5 being normal strength). The patient’s sensation is intact to light touch, but there is a loss of vibratory sense. He has no deep tendon reflexes in his lower extremities, diminished deep tendon reflexes (1+) in his upper extremities, and absent plantar reflexes. Cranial nerves II-XII are intact; however, he has a weak cough and gag reflex, with impaired handling of secretions. The remainder of his examination is unremarkable.
The patient is intubated for progressive respiratory distress and loss of airway-protective reflexes. He is fluid-resuscitated with a liter of intravenous normal saline. An electrocardiogram (ECG) is obtained, which demonstrates sinus tachycardia. The initial laboratory analysis, including a complete blood cell (CBC) count and a basic metabolic panel, is within normal limits. A lumbar puncture is performed, with an opening pressure of 15 cm H20. The cell count and Gram stain of the cerebrospinal fluid (CSF) demonstrates 2 white blood cells per high power field, 4 red blood cells per high power field, and no organisms. Additional analysis of the CSF shows a protein concentration of 96 mg/dL (960 mg/L) and glucose concentration of 72 mg/dL (3.99 mmol/L). The patient is sent for magnetic resonance imaging (MRI) of his brain and spine (see Figure 1) and is transported to the pediatric intensive care unit (ICU) for further management
|What is the patient’s condition as verified by the MRI?Hint: Look closely at the cauda equina on the MRI images.|
|a) Spinal epidural abscess|
|b) Guillain-Barré syndrome|
|c) Transverse myelitis|
|d) Multiple sclerosis DISCUSSION
The lumbrosacral MRIs (see Figures 1 and 2) demonstrate nerve root enhancement of the cauda equina on axial post-contrast T1-weighted sequences. The localization of progressive weakness includes spinal cord lesions (such as transverse myelitis or anterior spinal artery syndrome), peripheral neuropathies (such as those caused by heavy metals), neuromuscular junction diseases (such as that caused by organophosphate pesticides), myasthenia gravis, botulism, and myopathies (such as dermatomyositis). The presence of progressive ascending weakness, areflexia, autonomic dysfunction, elevated CSF protein without pleocytosis, and enhancement of the cauda equina nerve roots on lumbrosacral MRIs make the diagnosis of Guillain-Barré syndrome most probable in this patient.
Guillain-Barré syndrome is an acute, idiopathic, monophasic, acquired inflammatory demyelinating polyradiculoneuropathy (AIDP) that affects both children and adults. It is a heterogeneous syndrome, with several variant forms. AIDP is the prototype of Guillain-Barré syndrome, and it is the most common form in North America, Europe, and most of the developed world (where it accounts for about 85-90% of cases). Guillain-Barré syndrome can occur at any age, but there appears to be a bimodal distribution, with peaks in young adulthood (15-35 y) and in the elderly (50-75 y). The cause of Guillain-Barré syndrome is unknown, but the disorder is thought to result from a postinfectious immune-mediated process called molecular mimicry that predominantly damages the myelin sheath of peripheral nerves. Approximately two thirds of patients report a history of an antecedent respiratory tract or gastrointestinal infection 2-4 weeks before the onset of neurologic symptoms. A variety of infectious agents have been associated with Guillain-Barré syndrome, although Campylobacter is the most frequent. Other organisms that commonly precede Guillain-Barré syndrome include cytomegalovirus, Epstein-Barr virus, Haemophilus influenzae, Mycoplasma pneumoniae, the enterovirus family, hepatitis A and B, herpes simplex virus, and Chlamydophila (formerly Chlamydia) pneumoniae.
The typical presentation of Guillain-Barré syndrome is fine paresthesias in the toes and fingertips, followed by symmetric lower-extremity weakness that may ascend, over hours to days, to involve the arms and the muscles of respiration. Pain, predominately back, lower-limb and abdominal pain, is often a prominent feature of the syndrome. The physical examination reveals symmetric weakness, with diminished or absent reflexes and variable loss of sensation in a stocking-glove distribution. Signs of autonomic dysfunction are present in 50% of patients, and they include cardiac dysrhythmias, orthostatic hypotension, transient or persistent hypertension, ileus, constipation, and bladder dysfunction. Deviation from the classic presentation of ascending progression of weakness is not uncommon. In what is known as the Miller-Fisher variant, cranial nerves are affected in 30-40% of patients at any time in the course of the syndrome. This form of the disease is also characterized by areflexia, ataxia and ophthalmoplegia. The facial nerves are most commonly involved, resulting in bilateral facial weakness.
Although the associated autonomic dysfunction may produce life-threatening complications, mortality from Guillain-Barré syndrome is largely secondary to respiratory failure associated with respiratory muscle weakness. Approximately 20% of children with Guillain-Barré syndrome require mechanical ventilation for respiratory failure. The need for intubation should be anticipated early so that it can be done nonemergently in a controlled environment. Progression to respiratory failure has been predicted in patients with rapid disease progression, bulbar dysfunction, bilateral facial weakness, or dysautonomia. Emergent intubation should be performed in any patient with loss of the gag reflex, declining respiratory function, or pharyngeal dysfunction. Care should be taken during intubation, as autonomic dysfunction may complicate the use of vasoactive and sedative drugs.
After the first week of symptoms, analysis of the CSF typically reveals normal opening pressures, fewer than 10 white blood cells per high power field (typically mononuclear), and an elevated protein concentration (greater than 45 mg/dL). This finding, also known as albuminocytologic dissociation, may be delayed. As a result, a repeat lumbar puncture may be required as the protein values may not rise for 1-2 weeks, and maximum protein values may not be seen for 4-5 weeks. In addition, gadolinium-enhanced lumbosacral MRI may demonstrate enhancement of the cauda equina nerve roots. This imaging modality has been described to be 83% sensitive for acute Guillain-Barré syndrome, and abnormalities are present in 95% of typical cases. Electrophysiologic studies are the most specific and sensitive tests for confirming the diagnosis. Most patients demonstrate slowing of nerve conduction 2-3 weeks after the onset of symptoms. There are a variety of abnormalities seen in Guillain-Barré syndrome that indicate evolving multifocal axonal demyelination in peripheral nerves, spinal roots and/or cranial nerves. Abnormalities seen on electromyography include partial motor conduction block, slowed nerve conduction velocities, abnormal temporal dispersion, and prolonged distal latencies. The earliest finding, which may be present within days of symptom onset, is prolongation or absence of the F responses, which indicates demyelination involving the proximal nerve roots.
Any patient presenting with a clinical picture consistent with Guillain-Barré syndrome requires immediate hospitalization. The indications for admission to the ICU include, but are not limited to, respiratory insufficiency or failure, loss of airway-protective reflexes, and severe autonomic instability.
The main modalities of therapy for Guillain-Barré syndrome include plasma exchange and intravenously administered immunoglobulin (IVIG). Corticosteroids have not been shown to be beneficial. The American Academy of Neurology issued a practice parameter regarding immunotherapy for Guillain-Barré syndrome that concluded IVIG and plasma exchange are options for children with severe disease and should be reserved for those with the following findings:
Several trials have demonstrated that IVIG is at least as effective as plasma exchange in the treatment of Guillain-Barré syndrome and is associated with a lower rate of complications. IVIG administered at 0.4 g/kg/day for 5 days has been shown to hasten recovery and lower the relapse rate. Doses of 1 g/kg/day over 2 days have also been demonstrated to hasten recovery time, but early relapses are more prevalent. The combination of plasma exchange and IVIG does not improve outcomes or shorten the duration of illness.
Complications associated with Guillain-Barré syndrome include arrhythmia, sepsis, pneumonia, ileus, deep venous thrombosis and pulmonary embolism. The risk of sepsis and infection may be decreased by aggressive physiotherapy and mechanical ventilation with positive end expiratory pressure (PEEP). Administration of anticoagulant therapy and intermittent pneumatic compression devices may lower the risk of deep venous thrombosis and pulmonary embolism. Cardiac telemetry is useful to monitor for arrhythmias, which are a common cause of morbidity and mortality in Guillain-Barré syndrome. In addition, physical and occupational therapy should be initiated early and may be beneficial in helping patients to regain their baseline functional status.
More than 90% of patients reach the nadir of their function within 4 weeks of the onset of symptoms, with return of normal function occurring slowly over the course of weeks to months. The majority of patients with Guillain-Barré syndrome achieve a full and functional recovery within 6-12 months. The clinical course of Guillain-Barré syndrome in children is shorter than it is in adults, and recovery is more complete.
Upon transferring this patient to the ICU, a dialysis catheter was placed and plasmapheresis was initiated. His hypertension was controlled with a nicardipine drip. Prophylaxis for deep venous thrombosis was started. On hospital day 3, the patient had improved strength in his lower extremities and pressure support trials on the ventilator were initiated. On hospital day 6, he was extubated successfully to room air after receiving a total of 5 sessions of plasmapheresis. He was transferred to a pediatric ward 1 week after admission with intensive physical and occupational therapies. At the time of the transfer, the patient’s bulbar symptoms were resolved, and his strength was 3/5 in his lower extremities and 4/5 in his upper extremities
What is the patient’s condition as verified by the MRI?
Hint: Look closely at the cauda equina on the MRI images.
Which of the following findings is NOT likely to be seen on analysis of the cerebrospinal fluid (CSF) of a patient with Guillain-Barré syndrome who has had symptoms for 3 weeks?
Which of the following symptoms is NOT associated with a progression to respiratory failure in children with the above presentation?