AMY T. WALDMAN
HISTORY OF PRESENT ILLNESS
A 4-year-old Caucasian boy presented to the emergency department after a 1-week history of leg pain. Initially, the pain was described as bilateral, primarily surrounding his knees. However, the pain gradually became more diffuse and consistently woke the patient from sleep. In addition, the parents also noted that their son was more clumsy. He had difficulty walking and was dropping objects from both of his hands. Review of systems was significant for constipation, urinary incontinence, and fatigue. Three weeks ago, the patient had an upper respiratory infection, which had resolved.
There was no significant medical history. He had reached all of his developmental milestones on time, and had been walking since 9 months of age.
T 36.3°C; RR 24/min; HR 120 bpm; BP 120/70 mmHg; Height under 5th percentile; Weight 10th percentile
Initial examination revealed an alert and interactive young boy. His cranial nerve examination was normal for cranial nerves II-XII. Notably, extraocular movements were normal and facial weakness was absent. His neurologic examination was remarkable for decreased strength in his lower extremities and hand grip bilaterally. Deep tendon reflexes were not elicited in the upper or lower extremities. His gait was limited by pain and weakness. The remainder of the examination was unremarkable.
Laboratory analysis included a normal complete blood count and sedimentation rate. Computed tomography of the head demonstrated mild mucosal thickening of the maxillary sinus. Cerebral spinal fluid demonstrated one WBC/mm3 and 25 RBCs/mm3. Protein was 106 mg/dL and glucose was 69 mg/dL. He was admitted to the hospital for further evaluation.
COURSE OF ILLNESS
What is the most likely diagnosis?
DISCUSSION CASE 16-1
The combination of symptoms including weakness, pain, and areflexia suggests a peripheral neuropathy. There are many causes of peripheral neuropathies. Guillain-Barré syndrome (GBS) is the most common cause of acute generalized weakness. However, at the onset of disease, it is difficult to distinguish GBS from its chronic and relapsing variant, chronic inflammatory demyelinating polyneuropathy. Many drugs have been implicated in inducing neuropathies including isoniazid, vincristine, heavy metals (mercury and lead), and organophosphates. While common in GBS, bilateral facial weakness is not often seen in other neuropathies. In patients with bilateral facial weakness and ataxia but normal or hyperactive reflexes, pathology in the brainstem and cerebellum should also be considered. Asymmetric weakness and sensory symptoms along with urinary retention suggests involvement of the spinal cord as is seen in transverse myelitis. Acute paraparesis or quadriparesis also occurs in the setting of a compressive myelopathy. Myopathies may present with similar symptoms but without sensory involvement and reflexes are preserved. An elevated creatine kinase may also be present in myopathies.
In this case, the physical finding of absent deep tendon reflexes was very important in establishing the proper diagnosis. The elevated cerebrospinal fluid protein with a normal number of white blood cells (cytoalbuminologic dissociation) was also consistent with the diagnosis of GBS. Electromyography (EMG) showed prolonged distal motor latencies in all motor nerves and a slowed conduction velocity that was consistent with a demyelinating process. The diagnosis is Guillain-Barré syndrome. At this point, the patient did not show any signs of respiratory compromise. He was treated with intravenous immunoglobulin (IVIg) and his symptoms gradually improved.
INCIDENCE AND EPIDEMIOLOGY
GBS, the most common cause of acute generalized weakness, occurs in 0.4-1.7/100 000 children. It is an acquired inflammatory disease of the peripheral nervous system. While the exact pathogenesis is unknown, GBS may be mediated by an immune response against myelin antigens of the peripheral nerves, which leads to demyelination and axonal degeneration of motor and sensory nerves. Many cases are postinfectious in which there is a history of gastrointestinal or respiratory illness within 4 weeks of symptom onset. Infections associated with the development of GBS include Campylobacter jejuni, varicella, cytomegalovirus, hepatitis, measles, mumps, and Mycoplasma pneumoniae.
The diagnosis of GBS requires areflexia and the presence of progressive motor weakness of more than one limb. The weakness is usually relatively symmetric and typically ascending, although descending weakness can also occur. Mild sensory loss, including paresthesias, numbness, and diminished position and vibratory sensation, is usually present.
Pain is a surprisingly common finding in children. A review of 29 children hospitalized with GBS demonstrated the presence of pain in 79% of cases. However, in many children the presence of pain obscured the proper diagnosis. The pain hindered accurate neurologic examination and usually caused clinicians to initially suspect a rheumatologic or inflammatory disorder. Adults typically classify the pain as a deep lower limb pain, exacerbated by straight leg raises.
Fever is not a common sign. However, there may be signs of autonomic dysfunction including labile blood pressure, tachycardia or bradycardia, as well as bladder or bowel dysfunction. Respiratory failure may be fairly rapid in onset and is seen in 20% of patients.
The Miller-Fisher variant is characterized by ophthalmoplegia, ataxia, and areflexia and is due to a specific IgG directed at a ganglioside.
The important step in making the diagnosis is to obtain a detailed history and perform a thorough general and neurologic examination.
Lumbar puncture. Cerebrospinal fluid classically demonstrates cytoalbuminologic dissociation (i.e., an elevated protein with only minimal pleocytosis, typically fewer than 10 WBCs/mm3); however, an elevated protein may not be present early in the disease course (i.e., during the first week).
Electromyography (EMG). The diagnosis is usually supported by EMG studies, which demonstrate slowed or blocked motor conduction. Within 2 weeks of illness onset, the EMG is abnormal in approximately 50% of patients; more than 85% of patients with GBS ultimately have an abnormal EMG.
Magnetic resonance imaging (MRI) of the spine. Although not usually required for diagnosis, MRI should be performed if spinal compression or central nervous system inflammation (such as transverse myelitis) is suspected. In patients with GBS, MRI frequently reveals spinal nerve root enhancement.
GBS should be considered a neurologic emergency due to the potential for respiratory and autonomic failure. Patients with suspected or confirmed GBS must be monitored closely for worsening vital capacity and negative inspiratory force as intubation may be required. While spontaneous recovery may occur within 6 months, patients with respiratory compromise or autonomic dysfunction and those unable to walk are typically treated. Plasmapheresis and intravenous immunoglobulin are the current treatment modalities. While plasmapheresis and IVIg are equally effective, IVIg is often easier to initiate. Side effects of IVIg include fever, headache, vomiting, and meningismus. A recent study concluded that 23% of children may continue to have evidence of mild muscle weakness following IVIg therapy. However, in many cases this weakness had no impact on daily function. Children who were young in age and who had a rapid progression of symptoms were more likely to have long-term weakness. Combination therapy (plasmapheresis followed by IVIg) is not superior to either treatment alone and is not recommended. Corticosteroids are not effective and should not be administered in patients with GBS. Recovery from GBS occurs in a descending manner. Physical therapy should be initiated for all patients to assist with timely recovery.
1. Evans OB, Vedanarayanan V. Guillain-Barré syndrome. Pediatr Rev. 1997;18:10-16.
2. Gordon PH, Wilbourn AJ. Early electrodiagnostic findings in Guillain-Barré syndrome. Arch Neurol. 2001; 58:913-917.
3. Nguyen DK, Agenarioti-Belanger S, Vanasse M. Pain and the Guillain-Barré syndrome in children under 6 years old. J Pediatr. 1999;134:773-776.
4. Vajsar J, Fehlings D, Stephens D. Long-term outcome in children with Guillain-Barré syndrome. J Pediatr. 2003; 142:305-309.
5. Hughes RAC, Wijdicks EFM, Barohn R, et al. Practice parameter: immunotherapy for Guillain-Barré syndrome: report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2003; 61:736-740.
6. Yuki N, Hartung HP. Guillain-Barré syndrome. N Engl J Med. 2012;366:2294-2304.