A Case of Pediatric Pain. Edward C. Jauch, MD MS FACEP. Dawn Kleindorfer, MD

Transcription

1 A Case of Pediatric Pain FACEP Dawn Kleindorfer, MD M.E. is a 12yo Caucasian female who presents to the emergency department accompanied by her parents with a chief complaint of pain over her entire body. Patient notes that the pain in her body began one week ago, and was initially only in her toes, and fingers, and gradually progressed to now involve all four extremities, her trunk, but spares her head/neck/face. History is difficult to obtain, as the patient is extremely tearful and requesting pain medication throughout the history. Pain is described as intense, and has a burning quality. Her parents note that she has stayed home from school for the past 4 days due to the pain. She states she has trouble walking, but when asked regarding weakness, she denies it. No bowel or bladder changes. What is your differential diagnosis and how would you proceed?

2 A Case of Pediatric Pain Page 2 of 14 PMH: No serious medical problems. Her mother notes a recent gastrointestinal illness lasting 2-3 days 6 weeks ago. Meds: none, NKDA Social history: parents state that they recently moved, and she has been having some difficulty adjusting to her new school. They didn t bring her to a doctor earlier because they thought she just needed a break from school. Family history: negative ROS: Pt denies nausea/vomiting. When asked, she states that she sometimes can t get her breath, especially when the pain is bad. No chest pain, no rashes, no fever/chills, no urinary symptoms. Physical exam: VS: BP 98/60, HR 110, temp 98.9 In general, very tearful young female, some regressive behaviors noted (clinging to mom, refusing to cooperate) Pulmonary: lungs clear to auscultation bilaterally Cardiovascular: S1, S2, no rubs/murmurs/gallops Abdomen: soft, non-distended, non-tender Extremities: no clubbing, cyanosis, or edema Neuro: Cranial nerves: Extraocular movements intact, pupils equal round and reactive to light. Facial sensation and strength intact. Sensory exam notable for extreme pain to even cotton wisp sensation in lower extremities which the patient unable to tolerate, and the pain involved the trunk as well as extremities. Motor exam limited by patient effort, but appeared to have full strength in all extremities. Tone examination was normal or slightly decreased. Deep tendon reflexes could not be obtained. Patient refused to walk. Laboratory examinations: CBC, renal panel normal, mildly increased transaminases noted, with normal cholestatic parameters Chest x-ray normal The patient was sent home from the emergency department, with the diagnosis viral syndrome and with follow-up planned by her pediatrician within a week. However, 2 days later, the patient returned with complaints of profound weakness, and shortness of breath. Her repeat examination is as follows: VS: BP 130/78 HR 125 temp General exam unchanged from previous exam, except that the patient appears extremely short of breath. Neuro exam: Cranial nerves: pupils equal, round and reactive, extraocular movements intact. Facial strength is decreased bilaterally, and patient has difficulty closing her eyes. Sensory exam: pt has less sensitivity to light touch than previous exam, but still has burning pain to light touch in all 4 extremities and her trunk. Motor exam: bilateral lower extremities were flaccid, with no movement noted. Upper extremities were extremely weak, and the patient was unable to raise arms off of the bed. Tone was markedly decreased in all 4 extremities, and deep tendon reflexes could not be obtained.

3 A Case of Pediatric Pain Page 3 of 14 Pediatric Guillain Barré Syndrome Background, Epidemiology, Pathophysiology, and Risk factors Three physicians, Guillain, Barre, and Strohl first described Guillain-Barre Syndrome (GBS) in the early 1900 s. They described elevated CSF proteins in a group of patients with areflexia. Their description, now considered the classic form of GBS, also called acute inflammatory demyelinating polyradiculoneuropathy (AIDP), is characterized by a progressive motor weakness associated with areflexia. Additionally, in the classic form autonomic and sensory abnormalities are frequently seen. Multiple variations on the classic form exist, sharing a common set of clinical and laboratory characteristics. Other forms include pure sensory, pure dysautonomic, and pharyngeal-brachial-cervical variants. 11 Guillain Barre Syndrome is one form of a spectrum of acute immune neuropathies, in this case a demyelinating form. Most cases of GBS or AIDP share the same pathophysiology, a multifocal autoimmune (humoral and cell mediated) injury to the myelin sheath of peripheral nerves and spinal nerve roots. The central nervous system is largely spared in classic GBS. Some forms of acute immune neuropathies develop secondary axonal injury and these variants carry a worse prognosis. The autoimmune trigger in most cases appears to be an antecedent infection. GBS has an incidence of 1 to 2 new cases per 100,000 per year. It affects males slightly more than females (1.5:1) and has a biphasic age distribution, with a peak in young adults, and a second in the elderly. New data suggest a genetic risk factor for higher risk of severe disease, which is interestingly on the same allele protective against lupus nephritis. 1 As noted above most cases of GBS follow a preceding gastrointestinal or respiratory infection in the previous 1-3 weeks. 5,11 Typical infections associated with GBS include Campylobacter jejuni, Chlamydia, Cytomegalovirus, Epstein-Barr virus, hepatitis B, HIV, and Mycoplasma pneumoniae. Other potential triggers include vaccinations (influenza, hepatitis, MMR, oral polio, rabies, tetanus toxoid), malignancies, systemic lupus erythematosis, drugs, surgery, and pregnancy. Clinical Features Clinical features of GBS evolve over the course of the illness. Typically patients first describe weakness in both legs that progress cephalad over time, associated with areflexia or hyporeflexia. They may also complain of low back pain and pain in the proximal legs, and they may also note paresthesias in the lower extremities. As the disease progresses, the clinical features evolve. Motor weakness progresses and is accompanied by respiratory muscle weakness, and in over half of all patients cranial nerve weakness (VII typically symmetric, and XII). Extra-ocular weakness is less common and overlaps with Miller-Fisher Syndrome when diplopia, ophthalmoplegia, pupillary dysfunction, and ataxia accompany areflexia with minimal motor weakness. Sensory dysfunction is not as well known (or remembered) in GBS yet is present in 70-90% at some point in the course of the illness. 10 Paresthesias occur early and are typically peripheral. Pain is also prominent, occurring in three quarters of all patients with GBS, and occurs more

4 A Case of Pediatric Pain Page 4 of 14 commonly in children, as in our case. 3 Pain is typically located in the back, hips, and legs and presents more like myalgias rather than radicular pain. Lastly, autonomic dysfunction is common and is second to respiratory failure in the cause of death in patients with GBS. In one review, 31% of deaths in acute GBS were related to cardiac arrhythmias. Autonomic abnormalities include cardiac (supraventricular tachycardia / bradycardia, arrhythmias), blood pressure (both transient hypotension and hypertension), anhidrosis or excessive sweating, and GI/GU (urinary retention, paralytic ileus, and constipation). Special care must be taken in the treatment of blood pressure abnormalities since patient s blood pressure is labile at baseline and patients show increased sensitivity to medications. Differential Diagnosis of Guillain Barré Syndrome I. Acute Neuropathies 1. Critical illness neuropathy 2. Diphtheria 3. Hepatic porphyries 4. Inflammatory meningoradiculopathies 5. Lyme disease, CMV 6. Toxins (arsenic, thallium, organophosphates, glue sniffing/huffing, lead, neurotoxic fish, heavy metals) 7. Tick paralysis 8. Vasculitis II. Disorders of neuromuscular junction 1. Botulism 2. Myasthenia gravis III. Myopathies 1. Critical illness myopathy 2. Hypocalcemia, hypokalemia, hypophosphatemia 3. Polymyositis 4. Rhabdomyolysis IV. CNS disorders 1. Acute spinal cord syndrome (tumor or extrinsic compression) 2. Basilar artery thrombosis 3. Poliomyelitis, rabies 4. Transverse myelitis Note: Careful examination of a child with GBS symptoms is critical to identify a tick or potential acute spinal cord syndromes. Emergency Department Evaluation While the diagnosis of GBS is largely clinical certain laboratory and neuroimaging findings may support the clinician s diagnosis. Most tests are performed to exclude other potential causes in the differential diagnosis, yet early testing is essential to identify potential complications associated with GBS.

5 A Case of Pediatric Pain Page 5 of 14 Laboratory Evaluation Basic laboratory tests (serum electrolytes, complete blood count, hepatic profile) should be performed in all suspected cases of GBS. Hyponatremia can be seen in the syndrome of inappropriate antidiuretic hormone concomitant with GBS. Mild nonspecific elevations in hepatic transaminases are also seen. As always, women even close to childbearing age should have a pregnancy test performed. Cerebral spinal fluid (CSF) studies help confirm the diagnosis of GBS. CSF studies demonstrate increase protein (often > mg/dl) in the absence of pleocytosis. While often normal in the first days of the disease, the CSF protein rises over the course of the first week. A clinical diagnosis of GBS with high CSF protein and a CSF mononuclear count of > 50 cells/ml suggest HIV as the precipitating infection. Additional laboratory investigations that will not aid the Emergency physician but are useful in the diagnosis of the disease and exclusion of its mimics include antiganglioside antibodies against GM1, GQ1b, or Ga1Nac-GD1a (often elevated in GBS and its variants), C jejuni stool cultures, antibodies for C jejuni, CMV, EBV, HIV, HSV, and M pneumoniae. 7 Electromyographic (EMG) studies While not performed in the Emergency Department, EMG studies demonstrate reduced compound action potential and reduced motor conduction, consistent with demyelination. Imaging When the CFS and EMG data are equivocal MRI can be useful in confirming the clinical diagnosis. MRI with gadolinium contrast of the spine with attention to the spinal nerve roots and the cauda equina shows enhancement (nonspecific) in the areas of inflammation. Gorson and colleagues note that anterior nerve root enhancement is strongly suggestive of GBS, and the degree of enhancement correlates with the degree of pain, disability grade, and time for recovery. 4 Emergency Department Treatment: The mainstay of GBS treatment is largely supportive. It involves attention to the ABC s and attempting to limit the body s immune system. ABC s Although stressing the ABC s can sound trite, the most likely causes of death involve abnormalities in Breathing and Circulation. Roughly a third of patients with GBS will require mechanical ventilation. Respiratory failure is the primary cause of death in GBS. Relying on the patients appearance or the results from arterial blood gases may delay timely intervention. Early in the evaluation of GBS, patients would undergo a respiratory analysis. Indication for intubation include negative inspiratory force (NIF) < 25 cmh20, vital capacity (VC) < 15 cc/kg, or hypoxia PaO2 < 80 mm Hg (although patients should be intubated typically before they become hypoxic).

6 A Case of Pediatric Pain Page 6 of 14 Cardiac and circulatory abnormalities are responsible for numerous deaths in children with GBS. Arrhythmia such as bradycardia, hypertension and hypotension may occur. Bradycardia may require atropine or temporary external pacing. Hypotension typically responds to fluid resuscitation. Hypertension, while less common, should be managed with short acting agents, such as beta-blockers, to prevent over-correction. An interesting bedside test for vagal over activity is when the patient becomes bradycardic with gentle external ocular pressure. Specific Interventions Immunomodulation treatment is the mainstay for GBS. While steroids were once used, only plasma exchange and intravenous immunoglobulin have any data to support their use. The Cochrane Library, in a review of these two therapies, conclude that plasma exchange is the only treatment superior to supportive care alone while insufficient data exist to demonstrate the effectiveness of IgG therapy. The number of plasma exchanges is largely based on the severity of the disease. Initiation of plasma exchange is best started early in the course of the disease although benefit may be present out to a month. The efficacy of plasma exchange in children is unclear due to limited data. Due to the prolonged weakened condition of patients with GBS, attention to complications is important during the convalescence. Aspiration pneumonia, urinary retention and tract infections, ileus, and deep venous thrombosis are common complications associated with GBS. Treatment Immunomodulation is the primary pharmacotherapy for GBS. While standard immunomodulation through steroids has not been shown to be beneficial, plasmapheresis and possibly intravenous immunoglobulin therapy have some impact on reducing the morbidity and mortality of GBS. Plasma exchange is the treatment of choice. 8 The duration and number of exchanges dependent on severity with some authors recommending 2-6 exchanges for mild to moderate cases, and to consider continuous flow exchange in severe cases. Benefit is maximal when initiated within the first 7 days from onset. In children the benefit of plasma exchange is unknown. Intravenous immunoglobulin therapy is frequently used but its benefits are less clear. 6 The typical dose is 0.4 grams/kg/day. The duration of therapy is still unclear and relapse after discontinuation of IV IG therapy has been documented. IV IG therapy may be superior to plasma exchange in those patients with documents serum antibodies to GM1, GM1b, or Ga1Nac- GD1a gangliosides. Consultations As noted above, respiratory therapy should be involved early in the evaluation and treatment of any patient with GBS. Neurology should also be involved and will likely assume care of the patient while hospitalized.

7 A Case of Pediatric Pain Page 7 of 14 Prognosis Prognosis in GBS is generally good. The average duration of symptoms is 12 weeks. Residual disability is more common in patients over 50 years of age, those with severe and rapid weakness early in the course of the illness, lack of early immunomodulation therapy, and those patients with disability persistent beyond 12 months from onset. Roughly 75% of patients will have a full recovery, 5% will experience a relapse and 5% will die due to the disease. 2

8 A Case of Pediatric Pain Page 8 of 14 A Case of Pediatric Pain Case Outcome and Observations: A. What clues did we have from her initial presentation? Her initial presentation was originally diagnosed as psychiatric in origin. However, there were several clues in her initial history and exam that help us in making her diagnosis. Absent reflexes is probably the most objective finding on her exam, and absent or hyporeflexia is an invariable finding with GBS. She described an antecedent gastrointestinal illness, and some kind of infection preceding GBS is extremely common, up to 70%, the most commonly identified organism being Campylobacter jejuni. Her initial liver function testing revealed a mild elevation in transaminases, a finding in 10-15% of GBS patients. B. What other testing should have been done in her initial visit? The patient presented with symptoms that could be consistent with a polyneuropathy, and she complained of shortness of breath. Neuromuscular causes of shortness of breath need to be diagnosed and managed differently from other causes of dyspnea, such as pneumonia. Neuromuscular respiratory failure is a failure of the muscles of breathing, and not the lung parenchyma, and therefore, there is usually no desaturation, or abnormalities on blood gas testing until respiratory arrest is imminent. Therefore, bedside pulmonary function testing, such as forced vital capacity, and negative inspiratory force, should be obtained immediately, and the FVC in particular should be no lower than 50% of normal. In adults, usually intubation is performed if the FVC is less than 1 liter. If bedside PFT s are not immediately available, ask the patient to count as high as they can out loud on one breath. Most people should be able to count to at least If they can t make it to 10, they probably need to be intubated shortly, even if they don t look particularly uncomfortable. An EMG will eventually be very helpful in diagnosing this patient, however, usually it takes days before an EMG becomes abnormal after an acute injury, and so with her initial visit, and EMG would not be recommended. C. Now that she is profoundly weak during her second visit, what should be done for her in the emergency department? Again, her respiratory status needs to be evaluated. As it turns out, her FVC was only 600cc, and she was intubated in the ED, and remained on the ventilator for 6 days. She was admitted to a neuro-intensive care unit, where the staff are accustomed to dealing with neuromuscular respiratory insufficiency. If she had not needed intubation, she still would have needed at least a monitored bed, as autonomic dysfunction is present in up to 65% of patients, and can include fatal arrhythmias, such as tachyarrhythmias, bradycardia, heart block, and asystole. EKG changes with autonomic dysfunction include t-wave abnormalities, ST segment depression, QRS widening, QT prolongation, and various forms of heart block. Note that our patient was tachycardic, and relatively hypertensive on repeat visit, which persisted for the first several days of hospitalization. A spinal tap should eventually be performed, however, in the emergency department, the patient s respiratory status is the top priority. Spinal taps in GBS typically have elevated protein

9 A Case of Pediatric Pain Page 9 of 14 (usually extremely elevated, at least above 100), with normal to slightly elevated white blood cell counts, normal glucose and red blood cell counts. However, the spinal tap can be normal, if the illness has been present for less than 2-3 days, and is normal throughout the illness in 10% of patients. The patient underwent a spinal tap that had a normal opening pressure and normal CSF glucose level (75 mg/dl). The CSF protein was elevated at 140 mg/dl. CSF cytology and cultures were unremarkable. A full set of blood work should be obtained again, with special attention to the serum sodium, as inappropriate SIADH can occur with resultant hyponatremia. In addition, a urinalysis should be performed, because GBS can rarely be associated with deposition of immune complexes and glomerulonephritis. The patient maintained eunatremia and The patient was extubated after a week of plasmapheresis. Fortunately she did not develop any of the potential complications associated with GBS, such as aspiration pneumonia or DVTs. She did require inpatient physical therapy followed by aggressive home base therapy for several months. She has returned to school and has reached near-baseline physical function after 9 months of convalescence.

10 A Case of Pediatric Pain Page 10 of 14 A Case of Pediatric Pain Reference List 1. Asbury AK. New concepts in Guillain-Barre Syndrome. Neurol 2000;15: Chowdhury D, Arora A. Axonal Guillain-Barre syndrome: a critical review. Acta Neurol Scand. 2001;103: Connolly AM. Chronic Inflammatory Demyelinating Polyneuropathy in Childhood. Pediatr Neurol. 2001;24: Gorson KC, Ropper AH, Muriello MA, et. Al. Prospective evaluation of MRI lumbosacral nerve root enhancement in acute Guillain Barre syndrome. Neurology 1996;47: Hatung HP, Kieseier BC, Kiefer R. Progress in Guillain-Barre Syndrome. Curr Opin Neurol 2001;14: Hughes RAC, Raphael JC, Swan AV, van Doorn PA. Intravenous immunoglobulin for Guillain-Barre syndrome (Cochrane Review). In The Cochrane library, 1, Oxford: Update Software. 7. Leger JM, Salachas F. Diagnosis of motor neuropathy. Eur J of Neur. 2001;8: Raphael JC, Chevret S, Hughes RAC, Annane D. Plasma exchange for Guillain-Barre syndrome (Cochrane Review). In: The Cochrane library, 1, Oxford: Update Software. 9. Seneviratne U. Guillain-Barre syndrome. Postgrad Med J. 2000;76: Sensory Guillain-Barre syndrome. Oh SJ. LaGanke C, Claussen GC. Neurology. 2001;56: Van der Meche FGA, van Doorn PA, Meulstee J, Jennekens FG!. Diagnostic and classification criteria for the Guillain-Barre Syndrome. Eur Neurol 2001;45:

11 A Case of Pediatric Pain Page 11 of 14 A Case of Pediatric Pain Annotated Bibliography 1. Oh S, Laganke C, Claussen G. Sensory Guillain Barre Syndrome. Neurology 2001; 56: Oh and colleagues report eight cases of sensory GBS that had minimal to no motor weakness component. They describe the clinical, laboratory, and EMG findings of their cohort. All patients had favorable outcomes with no relapse. They also provide a short discussion and review of the sensory form of GBS. 2. Chowdhury D, Arora A. Axonal Guillain Barre Syndrome: A Critical Review. Acta Neurol Scand 2001; 103: In this review Chowdhury describes the clinical and histologic features of the more severe form of GBS. Different than classic GBC, axonal GBS shows Wallerian degeneration with minimal demyelination and lymphocytic response. They also note the strong association with this form of GBS and preceding Campylobacter jejuni infections. Treatment for axonal GBS remains immunomodulation with either IVIG or plasmapheresis. 3. Raphael JC, Chevret S, Hughes RAC, Annane D. Plasma exchange for Guillain-Barre syndrome (Cochrane Review). In: The Cochrane library, 1, Oxford: Update Software. Hughes RAC, Raphael JC, Swan AV, van Doorn PA. Intravenous immunoglobulin for Guillain-Barre syndrome (Cochrane Review). In The Cochrane library, 1, Oxford: Update Software. These two brief reports summarize in Cochrane fashion the current data regarding the use of plasmapheresis and IV IG therapy in the treatment of GBS. In the review, only plasmapheresis demonstrated therapeutic benefit over placebo. No adequately powered and designed studies have been performed to determine any benefit of IV IG therapy and if so the most appropriate dose. 4. Jones Hh. Childhood Guillain-Barre Syndrome: Clinical Presentations, Diagnosis, And Therapy. J Child Neurol 1996;11:5-12. Following the motto Publish or perish Jones in this review as well as in a very similar article in Current Opinions in Pediatrics 1995, discusses GBS as it relates to children. Jones reviews the differential diagnosis of pediatric acute neuropathies and in the article from Journal of Child Neurology presents three illustrative case histories of GBS, transverse myelitis, and tick paralysis. The review in J Child Neurol is a bit more extensive and provides a more detailed description of the disease and its treatment.

12 A Case of Pediatric Pain Page 12 of Neuromuscular Website, Washington University School of Medicine, St. Louis, MO Accessed May, This site from Washington University in St. Louis contains information in outline form on various neuromuscular disorders. The section on acute immune polyneuropathies reviews the classifications of neuropathies and provides quick information in a readable form. The website itself is Spartan but very informative into neuromuscular disorder evaluation, pathophysiology, and treatment. While there check out the best website on acute stroke out there, the Internet Stroke Center, 6. Pentland B and Donald SM. Pain in the Guillain Barre syndrome: a clinical review. Pain 1994; This is the best review regarding pain associated with GBS. The article reviews the various types of pain in GBS and their treatment. This article also addresses long term pain management seldom addressed elsewhere.

13 A Case of Pediatric Pain Page 13 of 14 A Case of Pediatric Pain Questions 1. Common features of GBS include all the following except: a. Prodromal illness in over half of all patients b. Frequent relapses c. Good recovery in most patients d. Progression usually over 5-10 days 2. Typical findings on CSF evaluation include: a. Elevated protein concentration b. Normal opening pressures c. Normal glucose concentration d. Lack of CSF pleocytosis 1. a, b, c 2. a, c 3. d, e 4. all above 3. Treatment of GBS includes all the following except: a. Plasma exchange b. Intravenous immunoglobulin c. Systemic corticosteroids d. Expectant respiratory support

14 A Case of Pediatric Pain Page 14 of 14 A Case of Pediatric Pain Answers 1. Answer b. The course of GBS is typically monophasic without episodes of relapse. Recurrence is uncommon, typically 2-5% 2. Answer 4. All are typical of CSF in GBS. Normal protein concentrations however can be seen early in the course of the disease. 3. Answer c. No data supports the routine use of steroids in GBS