What is causing this teenager's neurologic symptoms?

CASE A 16-year-old girl's parents brought her to the ED due to acute-onset right-sided weakness and word-finding difficulties. History The patient was playing online video games with her boyfriend when he noted that her speech became slurred and nonsensical. He called her parents, who found the patient altered and transported her to the ED, arriving within 40 minutes of symptom onset. Per the patient's parents, she had a remote history of a benign childhood murmur and used an etonogestrel implant for contraception. She had no known sick contacts and denied the use of any other medications or illicit substances. Physical examination The patient's vital signs were as follows: oral temperature, 97.9 °F (36.6 °C); heart rate, 131 beats/minute; BP, 118/71 mm Hg; and Spo2, 98% on room air. She was anxious appearing. Her initial physical examination was limited to a neurologic examination given the acuity of her situation. She demonstrated moderate-to-severe expressive aphasia, mild-to-moderate dysarthria, right lower facial weakness, no antigravity effort in the right upper extremity, and drift in the right lower extremity, with an initial National Institutes of Health Stroke Scale (NIHSS) score of 11. DIFFERENTIAL DIAGNOSIS Acute stroke Todd paralysis (postictal) Functional neurologic disorder Multiple sclerosis OUTCOME Upon arrival to the ED, a stroke alert was activated and the neurology team responded. The patient's fingerstick glucose was 146 mg/dL. A complete blood cell count demonstrated a leukocytosis of 14.4 x 109/L (normal range, 3.8 to 10.4 x 109/L) and was otherwise unremarkable. The patient's prothrombin time was 13.5 seconds (normal range, 9.4 to 12.5 seconds), and her international normalized ratio was normal. A point-of-care metabolic panel demonstrated hypokalemia of 2.9 mmol/L (normal range, 3.6 to 5.2 mmol/L). A pregnancy test and urine drug toxicity screen were both negative. An electrocardiogram demonstrated sinus tachycardia. A head CT scan demonstrated early ischemic changes in the left insular cortex as well as basal ganglia without evidence of hemorrhage. A CT angiogram (CTA) of the head and neck demonstrated an occlusion of the left middle cerebral artery (MCA; Figure 1). The patient's presentation and imaging were consistent with an acute embolic stroke involving the left MCA.FIGURE 1.: An axial CT angiogram of the head demonstrates an abrupt cutoff of the proximal left middle cerebral artery.After a discussion with the patient's parents regarding off-label use of IV thrombolytics, they consented to treatment, which was initiated 70 minutes after her last neurologic baseline. Following administration of IV thrombolytics, the patient underwent thrombectomy, during which a calcified embolus was removed from her left proximal MCA and sent to pathology. She was subsequently admitted to the ICU under the neurology team for postintervention monitoring. The next morning, the patient had significant improvement in her neurologic examination, with only mild right face and arm weakness and a repeat NIHSS score of 0. The patient did not have additional stereotyped episodes suggestive of seizure, nor did she have the fluctuating and distractible symptoms—symptoms that improve or lessen when a patient's attention is diverted from them—of a functional neurologic disorder. Due to concern that her etonogestrel implant may have been a risk factor for her current stroke and could increase her risk of future stroke, it was removed. Her stroke workup laboratory tests demonstrated a normal lipid panel, hemoglobin A1c, and thyroid-stimulating hormone; the patient was also not anemic. Her leukocytosis resolved without treatment. As part of her stroke workup, a transthoracic echocardiogram (TTE) showed normal ejection fraction and mild to moderate mitral valve regurgitation with a myxomatous anterior mitral leaflet, noted by the interpreting cardiologist to be a risk factor for developing infective vegetations. Following the TTE findings, a transesophageal echocardiogram (TEE) demonstrated similar mitral valve findings and a small patent foramen ovale (PFO). An MRI of the brain showed a small acute infarct in the left posterior putamen, superior left caudate, and left periventricular white matter as well as scattered tiny microhemorrhages (Figure 2). There was no evidence of other conditions such as demyelinating disease, ruling out multiple sclerosis.FIGURE 2.: An axial MRI diffusion-weighted image of the brain shows hyperintensity consistent with an acute ischemic stroke.On day 2 of hospitalization, pathology of the thrombus demonstrated numerous colonies of gram-positive cocci consistent with septic embolus, subsequently speciated as Streptococcus mitis. Three sets of blood cultures were drawn; the infectious disease team was consulted and recommended that the patient be started on broad-spectrum antibiotics with vancomycin and ceftriaxone due to concern for infective endocarditis (IE). Her erythrocyte sedimentation rate and C-reactive protein levels were elevated at 83 mm/1 hour (normal range, 0 to 29 mm/1 hour) and 17.1 mg/L (normal range, <5.0 mg/L), respectively, raising concern for an infectious or inflammatory process. Human immunodeficiency virus testing was negative. One of three blood cultures grew Streptococcus viridans. Further discussion revealed that the patient had undergone a minor dental procedure approximately 1 month prior to her ED presentation. Shortly after the dental procedure, she developed mild fatigue, had one episode of joint swelling, and experienced several nights of sweats and chills. The patient did not have other risk factors for IE, such as IV drug use, mechanical valve replacement, or implanted cardiac devices.1 Given that the patient's thrombus grew Streptococcus mitis, it was determined that the source of her stroke was septic emboli from an infected mitral valve. The patient therefore met Duke-International Society for Cardiovascular Infectious Diseases definite criteria for IE.1 Cardiology and cardiothoracic surgery were consulted regarding these results and recommended outpatient follow-up without the need for further inpatient management or intervention on either the patient's valve or the PFO. A peripherally inserted central catheter (PICC) line was placed and the patient was discharged home to complete a 6-week course of IV antibiotics, with a repeat TEE and cardiology follow-up after completion. At the time of her outpatient neurology evaluation, she had no neurologic deficits. Her repeat TEE revealed mild to moderate mitral valve regurgitation and a tiny PFO. No intervention was recommended, but annual echocardiograms to monitor mitral valve regurgitation were ordered. DISCUSSION The differential diagnosis for this young patient was broad. Her presentation was ultimately consistent with an ischemic stroke, as demonstrated by CTA findings, thrombus retrieval, and MRI changes. Standard of care for eligible adult patients with acute ischemic stroke (AIS) is IV thrombolytics and/or thrombectomy. Although IV thrombolytics and thrombectomy are not FDA-approved for children under 18, these therapies are used in pediatric patients with AIS throughout North America.2,3 Studies have shown that, when administered to appropriate pediatric patients, the rates of adverse events are comparable to those observed in young adults.4,5 A confirmed or suspected diagnosis of IE, however, is considered a contraindication to IV thrombolytics due to risk of hemorrhagic conversion of ischemic strokes.6 Children with ischemic stroke often present with focal neurologic deficits but may also present with a fluctuating course, symptomatic seizures, or headache, which differ from adult presentation and may cause the diagnosis to be missed in the crucial time window for treatment.7 In addition to postintervention monitoring and rehabilitation, a primary reason for hospitalization is to determine the underlying cause of the stroke. Optimal secondary stroke prevention relies on identifying the cause.8 Young patients (younger than 50 to 55 years old) who have an ischemic stroke may have different risk factors such as congenital heart disease, genetic conditions, paradoxical embolism via PFO, and inherited or acquired vasculopathies.9 Approximately 20% to 40% of young adults with IE may have neurologic complications.10 IE is rare in children; underlying congenital heart disease, such as ventricular septal defect and bicuspid aortic valves, is the biggest risk factor in this population.9Staphylococcus aureus and Streptococcus viridans are the most common causative organisms.9 The mortality rate may be as high as 25% in patients with native valve endocarditis.9 Pediatric patients with IE may present with more nonspecific symptoms, and manifestations such as Osler nodes and Janeway lesions are rare. Of note, in one study, a majority of pediatric patients with IE presented with fever and/or anemia.9,10 As in adults, blood cultures are the most important microbiological test for pediatric patients with IE, along with cardiac imaging (such as TEE) to evaluate for vegetations, heart structure, and cardiac function. Early and appropriate antimicrobial treatment as dictated by likely causative organisms and local antibiogram is first-line therapy, with surgical interventions, such as debridement with or without valve replacement, reserved for severe cases.8 CONCLUSION Ischemic strokes can occur throughout an individual's life, although incidence increases with age. Although the patient in this case presented with an occlusion of the left MCA, characteristic of ischemic stroke, pediatric patients may have different clinical presentations from adults. Although thrombectomy and thrombolysis are not FDA-approved for patients under age 18 years, they have resulted in good outcomes for some pediatric patients, like the one in this case. In young patients who have a stroke, clinicians may need to consider less obvious causes, including IE. Children with IE may not appear acutely ill, such as the patient in this case, but they can also present with fever and/or anemia. Clinicians should maintain an appropriate level of suspicion in children presenting with stroke to order proper infective workup and initiate suitable empiric treatment in appropriate patients. As in this case, multidisciplinary care may be warranted.