Case 1: Sudden Bilateral Lower Extremity Weakness and Urinary Incontinence in a 13-year-old Girl.

Abstract

I spent a week with medical students and family medicine residents in northeast Africa earlier this year. There, bright, clinically astute trainees at a major university use Pediatrics in Review as a core foundation of their pediatric curriculum. Wherever you are in the world this month, may these Index of Suspicion cases help you advance your knowledge and practice of pediatrics.Philip R. Fischer, MDAssociate Editor, Index of SuspicionA 13-year-old girl presented to the emergency department with acute onset of lower extremity weakness. She first awoke with dizziness but soon developed severe back pain, bilateral lower extremity pain and numbness, slurred speech, and inability to move her lower extremities or ambulate.She reports having a 2-day history of headaches and back pain. Due to worsening of her symptoms, she went to an urgent care center the previous day. A rapid viral test showed she was influenza positive, and she took 2 doses of oseltamivir before admission. The patient had an upper respiratory tract infection approximately 2 to 3 weeks ago. In the emergency department, the patient is unable to void spontaneously despite being able to at home, and a urinary catheter is placed.On physical examination her vital signs are as follows: temperature, 98.6°F (37.0°C); heart rate, 77 beats/min; respiratory rate, 20 breaths/min; and blood pressure, 119/74 mm Hg. Her BMI was within the 75th to 85th percentile. Her lower extremities bilaterally had 1/5 strength, diminished sensation to pinprick and temperature, and 0/5 patellar reflexes. She also had a 0/5 right Achilles reflex but a 1/5 left Achilles reflex. Her upper extremity strength, sensation, and reflexes were intact. Examination of her back showed no spinal tenderness to palpation or erythema. The rest of the physical examination findings were normal. Initial laboratory findings were normal, including complete blood cell count, complete metabolic panel, C-reactive protein level, creatine phosphokinase level, lactate level, and urinanalysis. Polymerase chain reaction for common upper respiratory tract infection pathogens as well as cerebrospinal fluid (CSF) cultures were negative. CSF studies showed a white blood cell (WBC) count of 1/μL (0.001×109/L), a red blood cell count of 0×106/μL (0×1012/L), a protein level of 0.015 g/dL (0.15 g/L), and a glucose level of 53 mg/dL (2.9 mmol/L). Magnetic resonance imaging (MRI) of her brain and spinal cord with contrast was normal.Despite the normal CSF findings, there was concern for a treatable condition such as Guillain-Barré syndrome, so intravenous immunoglobulin (IVIG) was initiated for 5 days. Electromyography (EMG) with nerve conduction studies (NCSs) was performed and demonstrated normal motor and sensory unit action potentials with normal latencies, amplitudes, and conduction velocities but significantly reduced recruitment of motor unit action potentials (MUAPs) bilaterally, worse on the right leg. This indicated a possible demyelinating motor neuropathy, and a regimen of 1 g of methylprednisolone daily for 5 days was added. Subsequent examinations demonstrated mixed upper (UMN) and lower (LMN) motor neuron findings. Her bilateral diminished lower extremity strength and sensation improved dramatically, left slightly more than right. Her right patellar and left Achilles reflexes became brisk, and her left patellar and right Achilles reflexes remained absent. She also developed crossed adductor reflexes and a positive left Babinski sign. The absent or diminished reflexes in the left patella and right Achilles indicated an LMN process, and the brisk reflexes in the right patella and right ankle, crossed adductor reflexes, and positive Babinski sign indicated a UMN process. The patient’s muscle tone was consistently normal. Repeated MRI studies 3 days after admission demonstrated new spinal cord lesions spanning from T6-7 down to the conus medullaris (Fig 1) with bilateral symmetrical T2 signal changes limited to the anterior gray matter (Fig 2).Findings from further infectious, autoimmune, and metabolic evaluation were also negative or normal: serum human immunodeficiency virus, Epstein-Barr virus and CSF enterovirus, mycoplasma, and herpes simplex virus polymerase chain reaction; antinuclear antibodies, anti–double-stranded DNA, anti–SS-B, anti–myelin oligodendrocyte glycoprotein, and Lyme antibodies; CSF oligoclonal bands and immunoglobulin G index; serum vitamins B12, D, and E; biotinidase; erythrocyte sedimentation rate; copper; and zinc. Test results were positive (after IVIG treatment) for anti–SS-A, human T-lymphotropic virus types 1 and 2, and mycoplasma immunoglobulin G antibodies.Possible conditions that the patient could have experienced can be split into 2 categories (1): peripheral (acute polyneuropathy, acute radiculoneuropathy [eg, Guillain-Barré], acute anterior poliomyelitis, acute flaccid myelitis) and central (acute transverse myelitis, acute flaccid myelitis, multiple sclerosis, neuromyelitis optica, subacute combined degeneration of the spinal cord, Wilson disease, infectious myelitis, cauda equina syndrome, lumbosacral neuritis, spinal stroke).Acute flaccid myelitis (AFM) is a rare neurologic disease of unknown etiology. Despite numerous studies implicating enterovirus-68 (EV-68) and other polioviruses as the cause, none have been definitively established to date. Currently, the Centers for Disease Control and Prevention (CDC) defines a confirmed case of AFM as having 1) acute onset of focal limb weakness and 2) an MRI showing a spinal cord lesion largely restricted to gray matter spanning 1 or more spinal segments. A probable case of AFM has 1) acute onset of focal limb weakness and 2) CSF with pleocytosis (adjusted WBC count >5/μL [>0.005×109/L]). (2)This disease mostly affects children and adolescents who present with poliolike symptoms. (3) It can be preceded by a prodromal febrile illness with respiratory and gastrointestinal symptoms a few days in advance. (3)(4) The most common respiratory symptoms include rhinorrhea, cough, and sore throat, and the most common gastrointestinal symptoms are vomiting or diarrhea. (5)(6) During the acute phase of the disease, patients mostly complain of fever, headache, neck pain, or pain around the affected limb. (3)(4) Neurologic findings include upper or lower limb weakness, sensory deficits, bladder or bowel dysfunction, hyporeflexia in the flaccid limbs, and varied cranial nerve dysfunction. (3)(4)(5)(6) Limb involvement includes 1 to all 4 extremities, more commonly the upper extremities, in an asymmetrical manner, with weakness ranging from paralysis to mild weakness. (3)(5)(6) The progression of neurologic symptoms can occur quickly, from a few hours to a few days. (6)(7)Diagnostic studies such as MRI, lumbar puncture, and NCS/EMG can provide further evidence of the disease. MRI of the brain and spine reveals abnormal T2 signals localized to the anterior horn cells of the spinal cord correlating to the neurologic symptoms. These lesions can occur throughout the spine as well as in the dorsal pons and medulla. (8) Early MRIs of the spinal cord may be normal, and repeated imaging is required. (6)(7)(8) Early imaging may also show lesions throughout the gray matter that may be accompanied by edema. (8) Because the disease targets the anterior horn cells of the spinal cord, patients typically have LMN findings, but surrounding inflammation in the spinal cord leads to concomitant UMN findings. Analysis of the CSF often showed pleocytosis with a lymphocytic predominance. Although pleocytosis was not found in our patient, various case reports and reviews found the median WBC count to be approximately 43 to 44/μL (0.04×109/L), but the CDC notes a higher median count of 163/μL (0.16×109/L). (5)(6)(9)(10) Studies also found elevated CSF protein levels (>45 mg/dL [>450 g/L]; reference range, 15–45 mg/dL [150–450 g/L]) but normal glucose levels (reference range, 40–80 mg/dL [2.2–4.4 mmol/L]) in most patients. (5)(6)(9)(10) NCS/EMG performed in multiple case reports and series noted reduced compound MUAP amplitudes, recruitment of MUAPs, and denervation of affected muscles. (6)(11)(12) One study found that despite the decrease in MUAPs, sensory unit action potentials were unchanged. (11) Fibrillation potentials started appearing 1 week after the onset of symptoms. (6) These abnormal NCS/EMG findings persisted for months (>20 weeks). (6)The presence of UMN and LMN symptoms, the characteristic MRI appearance, and the NCS/EMG findings led us to the diagnosis in this patient.Management of AFM is mainly supportive, but the patient’s respiratory status must be monitored carefully. Cervical lesions can lead to respiratory distress, and various case series have reported patients having respiratory insufficiency requiring intubation. (4)(5)(6)(9)No formal guidelines have been established to acutely treat AFM, but multiple case reports and series have used various combinations of IVIG, high-dose intravenous corticosteroids, and/or plasma exchange to treat patients to various levels of improvement. (5)(6)(9)(10) There is no clear evidence or studies performed that prove that those therapies are either harmful or helpful for AFM treatment. (4) Furthermore, because of the unknown pathophysiology of the disease, the role of those therapies remains unclear. Corticosteroids are indicated for cord edema; however, it may worsen an active infectious process. (3)(4) IVIG is considered safe to use in most patients. Neutralizing antibodies against EV-68 have been found in commercially prepared IVIG. (4)(13) Plasma exchange can theoretically remove protective antibodies, which could worsen the disease process. (4) Fluoxetine has also been examined as a therapy for its antiviral effects against EV-68. (14) For long-term treatment, patients require physical and occupational therapy. Currently, the CDC is collecting CSF, blood, stool, and respiratory specimens from patients with possible AFM to search for potential causes.The prognosis of this disease is variable. One study with median follow-up of 6 months found that all the children in the study had improved neurologic outcomes. All but 1 of the children still had residual motor deficits such as weakness, difficulty ambulating, and persistent need for a ventilator. (7) Another study with follow-up of 1.5 to 3.0 months after discharge found that all the children had improved neurologic signs. Five of 9 patients had mild to no residual deficits, and the others still had deficits, including residual limb weakness. (10) In the case series examining the nationwide outbreak of AFM in 2014 (median follow-up, 4.2 months), 5% of patients reported complete recovery of strength and 18% were fully functional. Fourteen percent of patients were reported to be completely dependent on their caregivers. (9)During her hospital stay, follow-up examinations demonstrated significant improvement in her lower extremity strength and sensation, return of specific reflexes, and resolution of urinary incontinence. The patient showed improvement during the IVIG infusion, but less so during the glucocorticoid treatment. The patient was transferred to an inpatient pediatric rehabilitation center for intensive physical and occupational therapy. At her latest outpatient evaluation, the patient was ambulatory with assistance.