Routine Neuroimaging: Understanding Brain Injury in Pediatric Extracorporeal Membrane Oxygenation.

OBJECTIVES: This project aims to describe brain injuries on routine neuroimaging in a large single-center neonatal and pediatric cohort supported by extracorporeal membrane oxygenation. The study also aims to examine the association of these injuries with neurocognitive outcomes in survivors and identify laboratory findings associated with neurologic injury. DESIGN: Retrospective observational single-center cohort study. SETTING: Tertiary care PICU. PATIENTS: Pediatric patients with noncardiac indications for extracorporeal membrane oxygenation supported by venoarterial or venovenous extracorporeal membrane oxygenation, with on-extracorporeal membrane oxygenation brain CT or postextracorporeal membrane oxygenation brain CT/MRI. INTERVENTIONS: Extracorporeal membrane oxygenation support. MEASUREMENTS AND MAIN RESULTS: Occurrence of brain injury on CT and MRI was reviewed; injuries were scored. Clinical and laboratory results associated with injury were identified. Survivor neurocognitive outcomes were obtained using the Pediatric Overall Performance Category scale and Pediatric Cerebral Performance Category scale. Of 132 imaged patients, 98 (74%) had radiological evidence of brain injury. Mean injury score was 6.5 (± 3.8). Head ultrasounds and clinician suspicion performed poorly in suspecting the presence of injury. Of 104 respondents to neurodevelopmental assessments, 61 (59%) had normal scores; 12.5%, 17%, and 11.5% had mild, moderate, or severe disability. A neuroimaging score greater than 10 was associated with an unfavorable outcome on the Pediatric Cerebral Performance Category (odds ratio, 3.4; p < 0.01) and Pediatric Overall Performance Category (odds ratio, 1.7; p < 0.05). Ischemic injury correlated with worse neurodevelopmental outcome. Preextracorporeal membrane oxygenation lactate, Vasoactive-Inotropic Scores, transaminitis, elevated bilirubin and creatinine levels, and thrombocytopenia were associated with injury occurrence. CONCLUSIONS: Brain injury is frequent in extracorporeal membrane oxygenation patients, although the majority of survivors have favorable neurocognitive outcomes. More research is needed in order to understand the etiology of such injuries. Head ultrasound and clinician suspicion are not sensitive in detecting extracorporeal membrane oxygenation-related brain injuries. Protocolizing postextracorporeal membrane oxygenation imaging with brain MRI allows the identification of injuries and provision of timely neurocognitive intervention.

EEG is A Predictor of Neuroimaging Abnormalities in Pediatric Extracorporeal Membrane Oxygenation.

The goal of this project was to evaluate if severity of electroencephalogram (EEG) during or shortly after being placed on extracorporeal membrane oxygenation (ECMO) would correlate with neuroimaging abnormalities, and if that could be used as an early indicator of neurologic injury. This was a retrospective chart review spanning November 2009 to May 2018. Patients who had an EEG recording during ECMO or within 48 hours after being decannulated (early group) or within 3 months of being on ECMO (late group) were included if they also had ECMO-related neuroimaging. In the early EEG group, severity of the EEG findings of mild, moderate, and severe EEG correlated to mild, moderate, and severe neuroimaging scores. Patients on venoarterial (VA) ECMO were noted to have higher EEG and neuroimaging severity; this was statistically significant. There was no association in the late EEG group to neuroimaging abnormalities. Our study highlights that EEG severity can be an early predictor for neuroimaging abnormalities that can be identified by computed tomography (CT) and or magnetic resonance imaging (MRI). This can provide guidance for both the medical team and families, allowing for a better understanding of overall prognosis.

Cerebral Hemodynamic Profile in Ischemic and Hemorrhagic Brain Injury Acquired During Pediatric Extracorporeal Membrane Oxygenation.

OBJECTIVES: To describe the cerebral hemodynamic profiles associated with ischemic and hemorrhagic brain injury during neonatal and pediatric extracorporeal membrane oxygenation. DESIGN: A retrospective cohort study. SETTING: Tertiary PICU. PATIENTS: Forty-seven neonatal and pediatric patients (0-15 yr of age) placed on extracorporeal membrane oxygenation from January 2014 to December 2018. MEASUREMENTS AND MAIN RESULTS: Continuous monitoring of mean arterial pressure and cerebral tissue oxygen saturation was conducted through entire extracorporeal membrane oxygenation run. Wavelet analysis was performed to assess changes in cerebral autoregulation and to derive pressure-dependent autoregulation curves based on the mean arterial pressure and cerebral tissue oxygen saturation data. Patients were classified into three brain injury groups: no-injury, ischemic injury, and hemorrhagic injury based on neuroimaging results. No-injury patients (n = 23) had minimal variability in the autoregulation curve over a broad range of blood pressure. Ischemic injury (n = 16) was more common than hemorrhagic injury (n = 8), and the former was associated with increased mortality and morbidity. Ischemic group showed significant abnormalities in cerebral autoregulation in the lower blood pressure range, suggesting pressure-dependent cerebral perfusion. Hemorrhagic group had highest average blood pressure as well as the lowest cerebral tissue oxygenation saturation, suggesting elevated cerebral vascular resistance. Mean heparin dose during extracorporeal membrane oxygenation was lower in both ischemic and hemorrhagic groups compared with the no-injury group. CONCLUSIONS: This study outlines distinct differences in underlying cerebral hemodynamics associated with ischemic and hemorrhagic brain injury acquired during extracorporeal membrane oxygenation. Real-time monitoring of cerebral hemodynamics in patients acquiring brain injury during extracorporeal membrane oxygenation can help optimize their management.

Correcting B0 Field Distortions in MRI Caused by Stainless Steel Orthodontic Appliances at 1.5 T Using Permanent Magnets - A Head Phantom Study.

Susceptibility artifacts caused by stainless steel orthodontic appliances (braces) pose significant challenges in clinical brain MRI examinations. We introduced field correction device (FCD) utilizing permanent magnets to cancel the induced B0 inhomogeneity and mitigate geometric distortions in MRI. We evaluated a prototype FCD using a 3D-printed head phantom in this proof of concept study. The phantom was compartmented into anterior frontal lobe, temporal lobe, fronto-parieto-occipital lobe, basal ganglia and thalami, brain stem, and cerebellum and had built-in orthogonal gridlines to facilitate the quantification of geometric distortions and volume obliterations. Stainless steel braces were mounted on dental models of three different sizes with total induced magnetic moment 0.15 to 0.17 A·m2. With braces B0 standard deviation (SD) ranged from 2.8 to 3.7 ppm in the temporal and anterior frontal lobes vs. 0.2 to 0.3 ppm without braces. The volume of brain regions in diffusion weighted imaging was obliterated by 32-38% with braces vs. 0% without braces in the cerebellum. With the FCD the SD of B0 ranged from 0.3 to 1.2 ppm, and obliterated volume ranged from 0 to 6% in the corresponding brain areas. These results showed that FCD can effectively decrease susceptibility artifacts from orthodontic appliances.

Brain magnetic resonance imaging of infants with bacterial meningitis.

OBJECTIVES: To describe the results of brain magnetic resonance imaging (MRI) of infants with bacterial meningitis and how the findings affected clinical management. STUDY DESIGN: This retrospective study included all infants <12 months of age who were hospitalized at Children's Medical Center, Dallas and had culture-confirmed bacterial meningitis and a brain MRI from January 1, 2001 to December 1, 2011. Infants were identified by review of all positive bacterial cultures of cerebrospinal fluid (CSF) from the Children's Medical Center Microbiology Laboratory. Demographic, clinical, laboratory, and neuroimaging data were reviewed. Infants with ventriculoperitoneal shunt or whose CSF culture yielded skin commensals were excluded. A neuroradiologist blinded to clinical information reviewed all MRI studies. RESULTS: Of the 440 infants who had a positive CSF culture result, 111 (25%) had a pathogen isolated from CSF and were enrolled in the study. Of these, 68% (75/111) had a brain MRI performed during the hospitalization; abnormalities included leptomeningeal enhancement (57%), cerebral infarct (43%), subdural empyema (52%), cerebritis (26%), hydrocephalus (20%), and abscess (11%). By multiple logistic regression analysis, infants with late seizures and an abnormal neurologic examination were more likely to have an abnormal MRI (P < .05). MRI results led to neurosurgical intervention in 23% of infants; a positive bacterial culture of CSF obtained >48 hours after initiation of antibiotic therapy was associated with neurosurgical intervention (P = .01). Fourteen (19%) infants with bacterial meningitis had a normal brain MRI. CONCLUSIONS: Brain MRIs were performed frequently and often were abnormal in infants with bacterial meningitis, leading to changes in clinical management.

Transverse myelitis plus syndrome and acute disseminated encephalomyelitis plus syndrome: a case series of 5 children.

IMPORTANCE: Classically, transverse myelitis and acute disseminated encephalomyelitis are considered central nervous system demyelinating conditions. In both conditions, the spinal cord is involved to varying degrees, and there is a variety of presentations, usually involving some degree of progressive paralysis of the upper and/or lower extremities. Treatment usually consists of high-dose intravenous steroids in addition to plasma exchange and/or intravenous immunoglobulin. In some cases, immunosuppressive medications, such as intravenous cyclophosphamide, have been used with variable success. Cases with atypical features on examination, imaging, or with neurophysiological studies may be helpful in shedding light on the etiology and/or pathophysiology because many of these patients have permanent disabilities despite appropriate treatment. OBSERVATIONS: This case series presents 5 pediatric cases observed from 2009-2012 at our medical center, Children's Medical Center Dallas. These cases were notable because they provided evidence of autoimmune events affecting the central nervous system but with additional peripheral axonal pathology. CONCLUSIONS AND RELEVANCE: We describe these cases with respect to findings that suggest a variant of these conditions that have concomitant nerve-root involvement. These patients had worse outcomes than typical patients with transverse myelitis/acute disseminated encephalomyelitis, and these observations build on previous work by other investigators that highlighted persistent flaccid paralysis and electrophysiological evidence of axonal loss portending a poorer prognosis. Furthermore, these cases suggest a potential role for approaching how we classify subtypes of transverse myelitis and acute disseminated encephalomyelitis.

Predictive value of neonatal MRI showing no or minor degrees of brain injury after hypothermia.

BACKGROUND: Magnetic resonance imaging is a surrogate biomarker for major neurodevelopmental disabilities in survivors of perinatal hypoxic-ischemic encephalopathy because injury to the basal ganglia/thalami is highly predictive of major neuromotor and cognitive problems. Major disabilities and the appearance of neonatal magnetic resonance imaging are improved with therapeutic hypothermia. We evaluated neurodevelopmental outcomes when conventional magnetic resonance imaging showed minimal or no brain injury. METHODS: Institutional review board-approved series of 62 infants (≥36 weeks; ≥1800 g; 34 boys/28 girls) cooled for hypoxic-ischemic encephalopathy between 2005 and 2011 who underwent neonatal magnetic resonance imaging and Bayley Scales of Infant and Toddler Development-III at 22 ± 7 months of age. Magnetic resonance imaging at 5-14 (mean 8) days was scored as normal (score = 0), showing focal gray or white matter injury only (score = 1), or basal ganglia/thalamic and/or watershed lesions with or without more extensive hemispheric injury (score = 2). Sensitivity, specificity, and positive and negative predictive values for magnetic resonance scores 0 and 1 and statistical interaction between magnetic resonance imaging score and age at magnetic resonance imaging were determined. RESULTS: Magnetic resonance score = 0 was seen in 35/62 patients; 26/35 (74%) were typically developing, seven (20%) had moderate and two (6%) had severe delay. Magnetic resonance score = 1 was seen in 17/62 (27%) patients; 5/17 (29%) were normal, 11/17 (65%) had moderate delay, and 1/17 (6%) had severe neurodevelopmental delay. Of the 52 patients with magnetic resonance scores of 0 and 1, 40% were abnormal. The negative predictive value of a normal magnetic resonance imaging was 74%. For score 1, sensitivity was 95% (confidence interval 63%-83%), specificity 84% (confidence interval 70%-90%), positive predictive value 84% (confidence interval 71%-93%), and negative predictive value 74% (confidence interval 62%-82%). CONCLUSIONS: Caution is warranted when prognosticating about neurodevelopmental status in early childhood after hypoxic ischemic encephalopathy with cooling, and longer follow-up studies are needed to determine the prognostic significance of a neonatal magnetic resonance imaging showing no or minor degrees of brain injury.

Short-term outcomes of newborns with perinatal acidemia who are not eligible for systemic hypothermia therapy.

OBJECTIVE: To determine short-term outcomes of infants who had perinatal acidemia and were evaluated for hypothermia therapy but did not qualify based on a standardized neurologic examination. STUDY DESIGN: Retrospective, single-site cohort study of inborn infants of ≥ 36 weeks gestation who had perinatal acidemia from October 2005-September 2008 and had a standardized neurologic examination performed by a certified neonatologist to assess eligibility for hypothermia therapy. An abnormal short-term nursery outcome was defined as death, seizures, brain magnetic resonance imaging consistent with hypoxic-ischemic encephalopathy, abnormal neurologic examination at discharge, gastrostomy tube feeding, or inability to nipple all feeds beyond the first week of age. RESULTS: One hundred forty-four (0.3%) of 46 887 newborns with perinatal acidemia had a neurologic examination performed that was either normal (n = 29) or consistent with mild encephalopathy (1 or 2 abnormal categories; n = 60). Of the latter infants classified as having mild encephalopathy, 12 (20%) experienced an abnormal short-term outcome (feeding difficulties, n = 8; abnormal neurologic examination at discharge, n = 7; abnormal brain magnetic resonance imaging, n = 6; seizures, n = 5; gastrostomy, n = 1; or death, n = 1). CONCLUSIONS: Twenty percent of newborns with perinatal acidemia and a neurologic examination that revealed only mild encephalopathy had abnormal short-term outcomes that could be attributed to the encephalopathy. Adjunctive tools or biomarkers for optimal assessment of infants with fetal acidemia for hypothermia therapy are needed.

Minimum SNR and acquisition for bias-free estimation of fractional anisotropy in diffusion tensor imaging - a comparison of two analytical techniques and field strengths.

Although it is known that low signal-to-noise ratio (SNR) can affect tensor metrics, few studies reporting disease or treatment effects on fractional anisotropy (FA) report SNR; the implicit assumption is that SNR is adequate. However, the level at which low SNR causes bias in FA may vary with tissue FA, field strength and analytical methodology. We determined the SNR thresholds at 1.5 T vs. 3 T in regions of white matter (WM) with different FA and compared FA derived using manual region-of-interest (ROI) analysis to tract-based spatial statistics (TBSS), an operator-independent whole-brain analysis tool. Using ROI analysis, SNR thresholds on our hardware-software magnetic resonance platforms were 25 at 1.5 T and 20 at 3 T in the callosal genu (CG), 40 at 1.5 and 3 T in the anterior corona radiata (ACR), and 50 at 1.5 T and 70 at 3 T in the putamen (PUT). Using TBSS, SNR thresholds were 20 at 1.5 T and 3 T in the CG, and 35 at 1.5 T and 40 at 3 T in the ACR. Below these thresholds, the mean FA increased logarithmically, and the standard deviations widened. Achieving bias-free SNR in the PUT required at least nine acquisitions at 1.5 T and six acquisitions at 3 T. In the CG and ACR, bias-free SNR was achieved with at least three acquisitions at 1.5 T and one acquisition at 3 T. Using diffusion tensor imaging (DTI) to study regions of low FA, e.g., basal ganglia, cerebral cortex, and WM in the abnormal brain, SNR should be documented. SNR thresholds below which FA is biased varied with the analytical technique, inherent tissue FA and field strength. Studies using DTI to study WM injury should document that bias-free SNR has been achieved in the region of the brain being studied as part of quality control.

Perinatal acidosis and hypoxic-ischemic encephalopathy in preterm infants of 33 to 35 weeks' gestation.

OBJECTIVES: To determine the frequency of hypoxic-ischemic encephalopathy (HIE) in preterm infants of 33 to 35 weeks' gestational age on the basis of physiological screening for perinatal acidosis and neurological assessment of encephalopathy and to correlate neurodevelopmental outcomes with brain magnetic resonance imaging findings. STUDY DESIGN: This retrospective cohort study included all inborn infants of 33 to 35 weeks' gestation admitted to the neonatal intensive care unit at Parkland Memorial Hospital with perinatal acidosis from October 2005 to September 2008. Their medical records were reviewed, and pertinent data were recorded. RESULTS: Of 1305 newborns, 2.5% (n=33) had perinatal acidosis, and 27% (n=9) of these had HIE (2, mild; 4, moderate; 3, severe). Persistence of metabolic acidosis on the first arterial blood gas obtained in the first hour of age was significantly associated with HIE (P<.005). Magnetic resonance imaging results were abnormal in 3 of 4 infants with moderate HIE and in both survivors with severe HIE. Death or disability occurred in no infants with mild or moderate HIE, but in all infants with severe HIE. CONCLUSION: Screening criteria for HIE that use biochemical and neurological assessments as performed in term newborns can be applied to preterm infants of 33 to 35 weeks' gestation.

Incidental neuroimaging findings in nonacute headache.

We studied the frequency and consequences of incidental neuroimaging findings in 400 otherwise healthy, nonacute pediatric headache patients through a retrospective, cross-sectional analysis. We excluded patients with currently recommended clinical criteria to consider diagnostic neuroimaging. We categorized neuroimaging results as normal, remarkable without clinical action, remarkable with clinical follow-up action, and abnormal. One hundred eighty-five of 400 patients (46%) had neuroimaging. Of these, 78.4% of neuroimaging studies were normal, and none was considered abnormal. Also, 21.5% had remarkable findings in the neuroradiology report. The frequency and types of all incidental findings were generally comparable to previous studies. One third of these patients received further consultation or neuroimaging because of incidental findings. In the evaluation of nonacute pediatric headache, overuse of neuroimaging leads to frequent discovery of incidental findings and increased testing. Individualized health care calls for physician-consumer discussions about current indications for neuroimaging, the general frequency of incidental findings, and potential difficulties in their interpretation.

Age-related variations in white matter anisotropy in school-age children.

BACKGROUND: Determination of diffusion tensor metrics in typically developing school-age children shows that maturational increases in fractional anisotropy (FA) vary across the brain and that age effects on FA are to increases in axial diffusivity in some regions, to decreases in radial diffusivity in some, and to both increases in axial and decreases in radial diffusivity in others. OBJECTIVE: When studying developing white matter (WM) using diffusion tensor imaging (DTI), knowledge of age-related normative tensor metrics is important, as normal variations can mask or mimic disease effects. MATERIALS AND METHODS: Right-handed English-speaking children (n = 32) 6-18 years old (mean 11.0) were studied over 31 months, 7 longitudinally. Anisotropy data were analyzed using tract-based spatial statistics; 43 regions showing significant (P < 0.05) age effects on fractional anisotropy (FA) were analyzed for age effects (r), coefficient of variability (CV), and FA, axial and radial diffusivity. This study was IRB-approved. RESULTS: The callosal genu and splenium showed the highest FA values, smallest age effects, and lowest between-subject variability. Mean FA was lower and age effects were greatest in the dorsal callosal body. The highest age effects on FA were in the cingulum, centrum semiovale, right corticospinal tract, and right temporal WM. The dorsal callosal body, calcarine WM, superior frontal and temporal gyri, and right corticospinal tract showed the highest CV. Radial diffusivity decreased while axial diffusivity increased in the cingulum, decreased in the optic tracts, and showed minimal or no age effects in most other regions. CONCLUSION: Age effects on FA and variability in FA are location-dependant in developing WM.

Neuroimaging-use trends in nonacute pediatric headache before and after clinical practice parameters.

OBJECTIVES: The objective of this study was to determine trends in diagnostic neuroimaging-use rates in nonacute pediatric headache before and after publication of clinical practice guidelines. METHODS: Retrospective, cross-sectional analysis was conducted of neuroimaging rates for 725 children and adolescents who were aged 3 to 18 years with nonacute headache and normal neurologic examination and were evaluated in a single pediatric neurology clinic during study years 1992, 1996, 2000, and 2004. Following recommendations of current practice parameters, patients with conditions that justify consideration for neuroimaging (eg, progressive headache, abnormal neurologic examination) were excluded from this analysis. We recorded the origin of any neuroimaging request at the time of the clinic visit and any abnormal neuroimaging findings that led to major clinical consequences. RESULTS: Overall, the mean rate of neuroimaging for patients with nonacute headache was 45%. Use rates remained steady during the 13-year study period (range: 41%-47%). The majority of neuroimaging studies were ordered originally by primary care providers. The proportion of neuroimaging studies that were ordered by primary care providers increased significantly from 1992 to 2004. CONCLUSIONS: In the evaluation of patients who had nonacute pediatric headache and were referred to a child neurology clinic, neuroimaging-use rates remained stable during the past decade. An increasing proportion of neuroimaging studies are ordered by primary care providers. The influence of evidence-based medicine on medical decision-making may be partly responsible for curbing increases in neuroimaging overuse. The perceived value of neuroimaging by physicians and consumers deserves ongoing study.

Utility of MR imaging in cat-scratch neuroretinitis.

About 80% of cat-scratch disease (CSD) infections occur in children, and CSD neuroretinitis (optic neuropathy with retinal exudates in a "macular star" pattern) mostly occurs in children and young adults. A recent study suggested that CSD optic neuropathy has specific features on MR imaging. However, MR imaging findings in CSD neuroretinitis are not well described in the pediatric literature. We present a patient with CSD neuroretinitis in whom these specific MR imaging features preceded the macular star, a funduscopic finding strongly suggestive of neuroretinitis. This case demonstrates how knowledge of these features is important in the appropriate diagnostic work-up of optic neuropathy. MR imaging also incidentally revealed neuritis of another cranial nerve in the auditory canal-a rare manifestation of CSD.

Lumps and bumps on the head in children: use of CT and MR imaging in solving the clinical diagnostic dilemma.

Lumps and bumps of the scalp are a common presenting complaint in children and often pose a diagnostic dilemma. These lesions can be difficult to image, with evaluation confounded by their small size. However, accuracy in diagnosis is critical because the diagnostic and therapeutic implications can vary significantly. The clinical examination can be helpful in developing the differential diagnosis and the imaging strategy. Often, however, a single imaging study is insufficient, and the radiologist finds it necessary to image with more than one modality to correctly diagnose a lesion and provide adequate information for the surgeon. Radiography and ultrasonography are often the initial screening diagnostic tests, followed by magnetic resonance (MR) imaging or computed tomography (CT) for more detail. Multidetector thin-section CT and thin-section MR imaging with surface coils are beneficial in the work-up of these small lesions of the head and neck. The use of newer MR imaging sequences such as heavily T2-weighted single-shot turbo spin-echo imaging and diffusion-weighted imaging can improve the characterization of difficult lesions. Familiarity with the variety of new imaging tools and techniques that are available can help characterize pediatric head and neck lesions and guide clinical management.

Treatment of Epstein-Barr virus lymphoproliferative disease after hematopoietic stem-cell transplantation with hydroxyurea and cytotoxic T-cell lymphocytes.

Epstein-Barr virus (EBV) lymphoproliferative disease (LPD) is a potentially fatal complication that may follow allogeneic hematopoietic stem-cell transplantation (HSCT). In this article, the authors report a 2-year-old girl with Hurler's syndrome who developed multiple central nervous system (CNS) EBV LPD lesions 1 year after unrelated donor HSCT. Before this CNS occurrence, the patient had a complete response to rituximab treatment for EBV LPD of the spleen and lymph nodes; however, treatment of the CNS disease with rituximab proved ineffective. Because of reported favorable response of primary CNS EBV LPD in two human immunodeficiency virus-positive patients, the authors treated this patient with low-dose oral hydroxyurea. The patient improved clinically, with a decrease in size of multiple EBV LPD brain lesions. Subsequently, the patient received EBV-specific cytotoxic T-cell lymphocytes and remains well. The benefit and limited toxicity of hydroxyurea therapy merit its further consideration as treatment for EBV LPD.

Congenital sucrase-isomaltase deficiency presenting with failure to thrive, hypercalcemia, and nephrocalcinosis.

BACKGROUND: Disaccharide Intolerance Type I (Mendelian Interance in Man database: *222900) is a rare inborn error of metabolism resulting from mutation in sucrase-isomaltase (Enzyme Catalyzed 3.2.1.48). Usually, infants with SI deficiency come to attention because of chronic diarrhea and nutritional evidence of malabsorption. CASE PRESENTATION: We describe an atypical presentation of this disorder in a 10-month-old infant. In addition to chronic diarrhea, the child displayed severe and chronic hypercalcemia, the evaluation of which was negative. An apparently coincidental right orbital hemangioma was detected. Following identification of the SI deficiency, an appropriately sucrose-restricted, but normal calcium diet regimen was instituted which led to cessation of diarrhea, substantial weight gain, and resolution of hypercalcemia. CONCLUSIONS: This case illustrates that, similar to congenital lactase deficiency (Mendelian Interance in Man database: *223000, Alactasia, Hereditary Disaccharide Intolerance Type II), hypercalcemia may complicate neonatal Sucrase-Isomaltase deficiency. Hypercalcemia in the presence of chronic diarrhea should suggest disaccharide intolerance in young infants.