A High-Pressure Case of Constipation and Seizures

An 8-year-old previously healthy boy presents to a community emergency department (ED) for constipation and altered mentation. Over the past several weeks, he has developed mild intermittent abdominal pain that occurs several times daily. The patient is unable to describe the pain, but his parents deny any inciting or alleviating factors. He has had associated decreased appetite, abdominal distension, and strained stooling, with his stool itself becoming progressively loose. Parents report large-volume diarrhea beginning the day prior to presentation, at which time they noticed a “bulge” in his perianal area. There has been no gross blood in his stool or at his rectal orifice. For the past day he has been acting differently, with episodic slurred speech and disorientation that spontaneously resolve. Parents deny recent emesis, headache, weight loss, fever, or apparent discrete illness. He has no history of constipation or laxative use. Further history reveals several weeks of paroxysmal bilateral lower extremity pain noted to occur every few days. without clear precipitating factors, diurnal variation, nighttime awakening, or functional impairment. He has been evaluated multiple times by his pediatrician for his leg pain. Physical examination, vital signs, complete blood count, and plain film results of his legs were normal, and parents were counseled that his symptoms likely represented growing pains. Although not previously affecting his gait, the pain has increased in frequency and is now accompanied by 3 weeks of subjective weakness with occasional hunched posture while walking. He has attention deficit hyperactivity disorder (ADHD) managed with methylphenidate at a stable dose. A few days prior to this presentation to the ED, he was started on clonidine to assist with chronically poor sleep. He has normal neurodevelopment and has appropriately progressed through school. His behavior, school attendance, and academic performance have not changed over the past several months. He has not received any recent immunizations and is up to date on age-appropriate vaccines.While in the ED, he has 2 generalized tonic-clonic seizures, the first while straining to defecate. He received parenteral benzodiazepines for both seizures and did not return to baseline between events. Initial vital signs shortly after his first seizure reveal blood pressure of 155/112 mm Hg with heart rate 120 beats per minute (bpm), temperature 36.9 °C (98.5 °F), and respiratory rate 21 breaths per minute with 96% oxygen saturation on room air. His blood pressure remains serially elevated in the ED (maximum 177/116 mm Hg). Physical examination after the second seizure reveals mild rectal prolapse without focal abdominal or neurologic findings. He is noted to be sleepy but appropriately oriented. Selected results from initial laboratory evaluation are summarized in Table 1. Radiographs are ordered to evaluate his abdominal distension. Abdominal x-ray shows a moderate proximal colonic stool burden with complete opacification of the recto-sigmoid colon and a nonobstructive bowel gas pattern (Figure 1). On chest x-ray, there are incidentally noted rounded opacities in both lungs, interpreted as possible pulmonary interstitial thickening (Figure 2).The inpatient pediatrics team at the nearest children’s hospital is contacted for admission. Concerns regarding the patient’s hypertension, seizures, and rapid-onset stooling difficulties are jointly acknowledged by the referring and accepting teams. However, after collaborative discussion, expedited transfer to the pediatrics unit is deemed prudent to prioritize patient safety, stabilization, and continuation of necessary evaluation. It is not known whether neuroimaging, abdominal ultrasound, or advanced abdominal imaging were considered or available at the referring facility.Upon arrival to the inpatient unit, he remains tired but appropriately oriented and interactive. Admission manual blood pressure is 166/112 mm Hg with heart rate 90 bpm; other vitals are within normal limits. He weighs 23 kg (15th percentile for age and sex) and is 1.26 m tall (23rd percentile) with a corresponding body mass index of 14.6 (16th percentile). He appears well-nourished with a thin body habitus and normal craniofacial features. Pupils are symmetrically dilated and readily reactive to light. Extraocular movements and cranial nerves II to XII are intact. Head is atraumatic, oropharynx is clear, and neck is supple with full range of motion and no lymphadenopathy. Cardiac auscultation shows normal rate and regular rhythm without murmurs. Lungs are clear and well-aerated bilaterally without adventitious sounds. Abdomen is soft, nondistended, and nontender without appreciable mass or hepatosplenomegaly. His bladder is distended with the superior dome palpable several centimeters inferior to the umbilicus; parents note that he has not voided in 10 hours. Rectum is mildly prolapsed. Extremities are normal without injury, deformity, swelling, or ecchymosis. No rashes or dermatologic lesions are visible. There are no gross focal motor deficits. He can ambulate with assistance. Gait is slow but coordinated. Further neurologic examination, including fundoscopy and testing for strength, sensation, and reflexes, cannot be adequately performed due to rapidly escalating bilateral thigh pain. Several minutes later, he has a 2-minute generalized tonic seizure that readily aborts with intravenous (IV) lorazepam. Antihypertensive therapy is indicated given the severity of hypertension and neurologic sequelae; he receives emergent intervention with IV hydralazine. He is taken for an emergent noncontrast head computed tomography (CT), which is normal without evidence of intracranial space-occupying mass, hemorrhage, hydrocephalus, or edema. Upon return from the radiology suite, he is transferred to the pediatric intensive care unit (PICU) for closer neurologic and hemodynamic surveillance, where he is started on an antihypertensive infusion.Our patient’s array of clinical features necessitated an organized, problem-based approach to his differential diagnosis. The 2 most immediate problems to address, and thus the focus of our approach, were his new-onset generalized seizures and severe hypertension. His subtle mental status changes altered stool patterns, paroxysmal leg pain, and incidentally discovered pulmonary radiographic abnormalities were also considered as contributory. Although his more indolent symptoms could have been unrelated to his acute deterioration, attempts to find a unifying diagnosis for his entire presentation guided our diagnostic approach.The initial evaluation of his seizures favored secondary causes of seizures as opposed to a primary seizure disorder, given his associated clinical findings. Our most immediate etiologic concern was increased intracranial pressure (ICP), which can induce both seizures and hypertension.1 However, his unremarkable head CT offered no evidence to support a cause for increased ICP, such as a mass or hemorrhage. Additionally, there were no historical or examination concerns for preceding head trauma to suggest a traumatic brain injury.Other potential causes of new-onset seizures in children were deemed less likely, as they did not explain his hypertension, subacute leg pain, or altered stooling. For example, he lacked fever to support an intracranial infection such as meningitis, encephalitis, or cerebral abscess; his neutrophilic leukocytosis was instead attributed to the profound stress response and peripheral neutrophil demargination that often accompanies afebrile status epilepticus.2 Serum chemistries refuted causative metabolic derangements such as hypoglycemia, hyponatremia, and hypocalcemia. Although considered, neuronal migration disorders (eg, lissencephaly, schizencephaly) characteristically present much earlier in life with focal seizures and impaired neurodevelopment, features not present in our patient.3His unremarkable head CT results and lack of strong evidence for other etiologies for seizure increased our suspicion that his hypertension was not just comorbid with his seizures but instead the direct pathophysiologic cause. Indeed, severe hypertension is a well-known cause of posterior reversible encephalopathy syndrome (PRES), which can manifest as seizures and would also explain his altered mentation.4 Given the high concern for PRES in this patient, early consideration for brain magnetic resonance imaging (MRI) would be recommended to aid in diagnostic delineation once the patient is sufficiently stable to undergo the study.We then shifted our attention to the etiology of his symptomatic hypertension. His degree of hypertension, normal body habitus, and lack of historically elevated blood pressure all favored against a diagnosis of primary hypertension. As such, causes of secondary hypertension were explored with an emphasis on pathologies that might encompass his nonneurologic symptoms and ambiguous chest x-ray findings.The causes of pediatric secondary hypertension are numerous and include cardiovascular (eg, aortic coarctation, renal artery stenosis), renal (eg, chronic kidney disease, glomerulonephritis [GN], reflux nephropathy), endocrinologic (eg, hyperthyroidism, Cushing syndrome), intracranial (eg, increased ICP), neoplastic (eg, Wilms tumor, neuroblastoma), and medication-related (eg, psychostimulants, anticholinergic agents, serotonergic agents) etiologies.5 His head CT did not support increased ICP or space-occupying lesion as contributing causes. Renal disease was immediately considered higher on the differential diagnosis due to his abnormally high serum creatinine for age and height. Renal pathology can be broadly organized into 3 categories by the site of the primary insult: prerenal, intrinsic, and postrenal. Although prerenal disease infrequently induces hypertension, notable exceptions are renal artery stenosis and fibromuscular dysplasia—conditions that involve abnormalities of the afferent renal vasculature. Regarding intrinsic renal disease, GN is an important consideration for new-onset pediatric hypertension. Given his clinical instability and decreased voiding on the day of presentation, a urine specimen was not initially available to perform a screening urinalysis for GN. However, his examination and radiographs did not show interstitial or pulmonary edema to support the hypervolemic state expected in severe GN. Renal vasculitis, another form of intrinsic renal disease, can occur as a manifestation of systemic vasculitides that are known to cause pulmonary involvement and neuropathic symptoms (eg, granulomatosis with polyangiitis, microscopic polyangiitis)—which offered a potential explanation for his pulmonary opacities and leg pain, respectively.6 IgA vasculitis, the most common systemic vasculitis of childhood, was deemed unlikely without intercurrent joint disease, abdominal pain, or purpuric skin lesions.7Postrenal obstruction can present with insidious hypertension. This category can be divided into structural obstruction, such as ureteropelvic junction obstruction, and functional obstruction, such as neurogenic bladder.8 If obstructive uropathy were responsible for his hypertension, its co-occurrence with strained defecation could signal a space-occupying intra-abdominal or intrapelvic mass manifesting with direct mass effect, nerve compression, or both. Such a lesion could also produce referred neurogenic pain of the lower extremities and, if neoplastic in nature, lead to radiographically apparent pulmonary metastases. For this reason, early cross-sectional imaging of the abdomen, pelvis, and chest with CT would be indicated; abdominal ultrasound is reasonable to start with if CT is not readily available. An additional oncologic cause of secondary hypertension is a paraneoplastic syndrome, with specific consideration for underlying neuroblastoma and nephroblastoma (Wilms tumor) in the young pediatric population.The constellation of new-onset hypertension, renal injury, and seizures can characterize both hemolytic uremic syndrome and thrombotic thrombocytopenic purpura. However, our patient lacked the defining hematologic derangements of hemolytic anemia and thrombocytopenia. Excessive ingestion of psychostimulants, which he was prescribed for ADHD, can cause iatrogenic hypertension but did not explain his numerous other symptoms. Anticholinergic and serotonergic toxidromes are both associated with blood pressure elevation and altered mentation, although he had no history of exposure to common offending medications, such as antiemetics, antipsychotics, and first-generation antihistamines. Hypertension as a result of endocrinologic dysfunction, such as that seen in hypercortisolism, thyrotoxicosis, and hyperaldosteronism, is a final consideration for pediatric secondary hypertension.Inadequate control of hypertension with IV hydralazine prompts initiation of an IV nicardipine infusion, producing blood pressure normalization within 30 minutes and accompanying seizure resolution. Shortly after arrival to the PICU, interval abdominal examination reveals progressive bladder distension as well as a large, hard, fixed mass in the patient’s left lower quadrant that is both palpable and intermittently visible. Attempts at urinary catheter placement for bladder decompression are unsuccessful due to the catheter meeting resistance. Abdominal ultrasound reveals a large solid pelvic mass measuring at least 11.4 × 10.5 × 8.1 cm, concerning for solid organ neoplasm; mild bilateral hydronephrosis is also present. Immediate transfer to an institution with pediatric oncology and urology services is coordinated. At the receiving institution, CT of the abdomen and pelvis redemonstrates a large pelvic lesion (maximum dimension 15.7 cm), best visualized on subsequent MRI (Figure 3). Results from radiology-guided biopsy return several days after transfer, providing the diagnosis of embryonal rhabdomyosarcoma (RMS). MRI brain, initially deferred due to his tenuous clinical status, demonstrates scattered fluid-attenuated inversion recovery signal hyperintensities of the occipital and parietal lobes of the cerebrum (Figure 4), highly consistent with the pattern of vasogenic edema seen in PRES, thus confirming the suspected etiology of his seizures and mental status changes. Despite our patient’s normal head CT, it is crucial to note that PRES can be undetectable on CT in one-quarter of patients with MRI-confirmed disease.9 Chest CT reveals innumerable pulmonary nodules representing extensive metastatic disease, corresponding with abnormal lung opacities on initial radiographs (Figure 2). Ultimately, the etiology of his hypertension is attributed to obstructive uropathy. Although not robustly described in literature, there are indeed case reports of new-onset hypertension related to obstructive uropathy and resultant hydronephrosis, even with unilateral pathology.10–15RMS is a high-grade malignant soft tissue sarcoma, named for its cellular morphology that closely resembles that of striated (skeletal) muscle.16,17 Although rare, RMS is the most common soft tissue sarcoma in children and the third most common extracranial solid tumor, constituting approximately 3% of all cancer diagnoses in children under 15 years of age.16,18,19 Incidence is highest from birth to 4 years, with nearly two-thirds of pediatric cases occurring by age 10.20–22The 2 major histologic subtypes are embryonal (ERMS) and alveolar (ARMS), with ERMS representing the large majority of diagnoses and being associated with substantially more favorable outcomes.16,17,21–24 The most common sites of primary tumor involvement are the head and neck, genitourinary tract, extremities, and trunk, although any body part can be affected.16,22 There are age-related disease patterns, with ERMS and head and neck distribution more common in young children, whereas ARMS and extremity involvement represent a greater proportion of adolescent disease.21–24 Metastatic disease at the time of diagnosis is observed in 15% to 20% of patients, with the lung being the most common site of metastasis.24,25Pelvic RMS and similarly located sarcomas are a diagnostic challenge. The symptomatic course is usually indolent, on the order of months, and is infrequently characterized by the hallmark constitutional symptoms of fever, malaise, anorexia, and weight loss associated with more common childhood cancers, namely hematologic malignancies.26 For abdomino-pelvic RMS, clinical manifestations are typically a result of mass effect. Common gastrointestinal symptoms include abdominal pain and constipation secondary to colorectal compression.27,28 Repetitive straining and increased intra-abdominal pressure can lead to rectal prolapse, as seen in our patient. Whereas rectal prolapse in resource-rich countries is typically a result of acute diarrheal illness or chronic constipation, the absence of these features on history should prompt consideration of an alternative pathology. Notably, neurologic and anatomic abnormalities can account for up to 24% of all cases of pediatric rectal prolapse.29,30 Similarly, extrinsic compression on the urinary collecting system can produce urinary retention, hematuria, and secondary hypertension.10–15,27,28 Direct pressure on the spinal cord or lumbosacral nerves can lead to neuropathic lower extremity pain and weakness as well as neurogenic bowel and bladder dysfunction.26,31 Our patient’s preceding hunched posturing was likely a reflexive attempt to alleviate this nerve compression. Like most solid organ tumors, RMS can increase the peripheral leukocyte count via paraneoplastic effect, which may confuseAlthough slight variation exists between North American and European approaches to treatment, multimodal therapy is the standard of care for RMS, incorporating multiagent chemotherapy, radiation, and, when feasible, surgery.16,32,33 is by several to with including tumor and anatomic histologic metastatic disease, and There is also of a the or absence of the its This for with to and is started at include (eg, and Further may a patient’s is considered if it organ and not a to started to weeks after is a of control that has been to in pediatric RMS have nearly regular of a The rate for all patients is with of age greater associated with The as without disease or is for both and disease and have not been observed in disease, in which remains less This as a focus of urology team an urinary catheter for bladder to strong suspicion for the diagnosis of RMS, the pediatric oncology team systemic with and the final biopsy which was deferred due to tumor site and pressure he a IV antihypertensive to and clonidine His pain was managed with and the to the neurogenic He was in stable after 2 He a course of pelvic therapy and is his of with favorable primary tumor response but pulmonary metastatic His hydronephrosis on interval He can spontaneously although has intermittent urinary His hypertension has and he now an intermittent clonidine His course is consistent with the of blood pressure normalization of urinary obstruction in case reports and is the common extracranial solid tumor in the pediatric and typically presents with indolent symptoms related to mass symptoms of abdomino-pelvic include abdominal pain, new-onset constipation and urinary retention, and lower extremity pain. of these are common and usually pediatric a high degree of suspicion is for prolapse in the absence of acute diarrheal illness or chronic constipation may suggest neurologic or anatomic acute encephalopathy with secondary PRES is a known etiology for new-onset afebrile seizures in children and can be for with blood pressure at the time of initial uropathy can induce symptomatic hypertension and be for in children with abdomino-pelvic