Xing-Chang Wei

Inflammatory biomarkers of pediatric focal cerebral arteriopathy

Focal cerebral arteriopathy (FCA), defined as unifocal or multifocal stenosis of the large or medium-sized blood vessels, is a leading etiology of childhood arterial ischemic stroke (AIS).[1][1] Pathophysiology is poorly understood but inflammatory mechanisms are suspected.[2][2] Recurrence is high

Acute glomerulonephritis presenting with PRES: a report of 4 cases.

OBJECTIVEnPosterior reversible encephalopathy syndrome (PRES) occurs most commonly in the setting of known hypertension or use of immunosuppressive agents.nnnDESIGN AND METHODSnWe report four previously-well children who presented acutely with altered mentation, seizures and visual disturbances and were diagnosed with PRES.nnnRESULTSnOnly one child had a history of gross hematuria prior to the seizure. All four were discovered to be hypertensive only after onset of their neurological symptoms, and were subsequently diagnosed with glomerulonephritis. All four had rapid resolution of neurological symptoms with adequate treatment of hypertension.nnnCONCLUSIONSnBlood pressure must be measured promptly in all children presenting with these symptoms. If elevated, the diagnosis of PRES should be strongly considered and a workup for renal disease pursued.

Polio-Like Illness Associated With Outbreak of Upper Respiratory Tract Infection in Children.

Poliomyelitis is a historically devastating neurological complication of poliovirus infection. Poliovirus vaccines have decreased the incidence of poliomyelitis to 209 global cases in 2014, with new cases of acute flaccid myelitis primarily associated with nonpolio enteroviruses. Recently, during outbreaks of enterovirus D68 throughout North America and Europe, cases of acute flaccid myelitis have been reported, suggesting another nonpolio enterovirus associated with acute flaccid myelitis. The authors describe 3 patients diagnosed with acute flaccid myelitis during a province-wide outbreak of enterovirus D68 with the virus detected in 2 of the patients. Given the significant morbidity associated with acute flaccid myelitis and potential for nonpolio enterovirus to cause outbreaks, prompt identification and notification of public health authorities are warranted.

Cerebellar Atrophy in Childhood Arterial Ischemic Stroke Acute Diffusion MRI Biomarkers

Background and Purpose— Crossed cerebellar atrophy is uncommon in childhood arterial ischemic stroke. Acute corticospinal tract diffusion–weighted imaging (CST-DWI) changes occur in stroke of all ages. Contralateral CST-DWI is unexplained but approximates corticopontocerebellar pathways. We hypothesized that cerebellar atrophy can be quantified on clinical neuroimaging in childhood arterial ischemic stroke and is predicted by contralesional CST-DWI. Methods— Consecutive children (>28 days–18 years) were included with the following features: (1) acute, unilateral, middle cerebral artery arterial ischemic stroke, (2) DWI <14 days from stroke onset, (3) anatomic T1 MRI >6 months, and (4) Pediatric Stroke Outcome Measure >12 months. Blinded scorers measured cerebellar volumes (left/right/hemisphere/vermis/total) using Osirix software. Cerebellar volumes ratios (nonstroke/stroke) were expressed as asymmetry indices (AI), with chronic/acute ratio <1.0 suggesting crossed atrophy. Acute brain stem and cerebellum (peduncle, hemisphere) DWI ratios were scored. Software measures were compared with visual inspection. Associations between AI, motor outcome (good/poor), and contralesional CST-DWI were sought. Rater reliabilities were assessed. Results— Twenty-three children were studied (median age, 6.3±4.4 years; 62% male). Baseline cerebellar volumes were comparable (right=56.9 cm3, left=57.1 cm3). Cerebellar atrophy was suggested across the sample with overall AI <1.0 (0.973±0.05; P=0.009). Visual atrophy detection was specific (≈100%) but insensitive (54%). Children with poor motor outcome did not have lower AI (0.983±0.027 versus 0.965±0.068; P=0.40); however, children with acute contralesional CST-DWI did (0.928±0.078 versus 986±0.040; P=0.03). Acute cerebellar DWI did not predict atrophy. Rater reliabilities were excellent (>0.92). Conclusions— Cerebellar atrophy can be demonstrated on MRI in childhood arterial ischemic stroke. Association with acute contralesional pontine DWI signal suggests early degeneration of corticopontocerebellar connections. The clinical significance of cerebellar atrophy in childhood stroke remains to be determined.

TUBA1A Mutation Associated With Eye Abnormalities in Addition to Brain Malformation.

OBJECTIVEnWe describe the case of a boy with a TUBA1A mutation presenting with microphthalmia and congenital cataracts in addition to microcephaly and severe brain malformation.nnnMETHODSnA boy presented in early infancy with microphthalmia, congenital cataracts, and microcephaly. His neurological course included severe hypotonia and drug-resistant epilepsy. Magnetic resonance imaging of the brain revealed a complex malformation that included agenesis of the corpus callosum, severely hypoplastic cerebellar vermis, mildly hypoplastic and dysplastic cerebellar hemispheres, mildly hypoplastic brainstem, mild posterior simplified cerebral gyral pattern, dysplastic basal ganglia and thalami, hypoplastic optic nerves, and absent olfactory bulbs.nnnRESULTSnTUBA1A genetic testing was conducted and revealed a previously unreported heterozygous 808G>T missense mutation. Parental genetic testing was negative, indicating that the childs mutation was de novo.nnnCONCLUSIONnThe TUBA1A gene encodes tubulin alpha-1A, a protein with an important role in microtubule function and stability. Human mutations can result in a wide spectrum of brain malformations including lissencephaly, microlissencephaly, cerebellar hypoplasia, agenesis of the corpus callosum, pachygyria and polymicrogyria. Although TUBA1A is expressed in both developing brain and retinal tissue, there are no reported cases of TUBA1A mutations in association with major developmental ophthalmologic abnormalities.

Unilateral Foot Drop as an Initial Presentation of a Brain Tumor in a Child

Foot drop is commonly caused by compromise of the peripheral nervous system. Unilateral foot drop as the first sign of a parasagittal brain tumor has been reported in the adult literature but never previously in the pediatric population. We report a child with a right parietal rhabdomyosarcoma in which foot drop was the only abnormal neurologic finding at initial presentation. Localization to the central nervous system should be included in children presenting with foot drop.

Cerebral Edema in Maple Syrup Urine Disease Despite Newborn Screening Diagnosis and Early Initiation of Treatment

A 7-day-old girl had an elevated leucine level on newborn screen drawn at 2 days of age and was suspected of having maple syrup urine disease (MSUD). When reported, the patient was immediately admitted to hospital, and started on a modified diet involving high calories with reduced branched chain amino acid (BCAA) formula. Clinical exam was normal at initial assessment. Despite rapid initiation of treatment, the baby became lethargic and somnolent over the next day. Diet was stopped and infusions of 12.5% dextrose and 20% intravenous lipids at 2 g/kg per day were immediately started. Lethargy improved within 3 h of intravenous therapy initiation. Brain magnetic resonance imaging demonstrated diffuse cerebral edema, and symmetric restricted diffusion in bilateral cerebellar white matter, dorsal brainstem, thalami, globi pallidi, posterior limbs of internal capsules, and corona radiata. Plasma leucine was 1.98 mmol/L on admission (normal 0.05-0.17 mmol/L), decreasing to 1.34 mmol/L with diet, however clinical deterioration occurred despite improving leucine levels.Cerebral edema in MSUD is thought secondary to a combination of increased cerebral BCAA levels, and depleted levels of other essential amino acids, as well as neurotransmitters. Our case illustrates that newborns can develop encephalopathy with cerebral edema despite treatment with special formula initiated while asymptomatic. These findings suggest decompensation may begin early on, so that early introduction of high dextrose infusion and intravenous lipids, in combination with reduced BCAA formula, should be initiated for any patient with a positive newborn screen for MSUD.

Segmental Diffusion Properties of the Corticospinal Tract and Motor Outcome in Hemiparetic Children With Perinatal Stroke

Perinatal stroke injures developing motor systems, resulting in hemiparetic cerebral palsy. Diffusion tensor imaging can explore structural connectivity. We used diffusion tensor imaging to assess corticospinal tract diffusion in hemiparetic children with perinatal stroke. Twenty-eight children (6-18 years) with unilateral stroke underwent diffusion tensor imaging. Four corticospinal tract assessments included full tract, partial tract, minitract and region of interest. Diffusion characteristics (fractional anisotropy, mean, axial, and radial diffusivity) were calculated. Ratios (lesioned/nonlesioned) were compared across segments and to validated long-term motor outcomes (Pediatric Stroke Outcome Measure, Assisting Hand Assessment, Melbourne Assessment). Fractional anisotropy and radial diffusivity ratios decreased as tract size decreased, while mean diffusivity showed consistent symmetry. Poor motor outcomes were associated with lower fractional anisotropy in all segments and radial diffusivity correlated with both Assisting Hand Assessment and Melbourne Assessment. Diffusion imaging of segmented corticospinal tracts is feasible in hemiparetic children with perinatal stroke. Correlations with disability support clinical relevance and utility in model development for personalized rehabilitation.

Olfactory Development, Part 1: Function, From Fetal Perception to Adult Wine-Tasting:

Discrimination of odorous molecules in amniotic fluid occur after 30 weeks’ gestation; fetuses exhibit differential responses to maternal diet. Olfactory reflexes enable reliable neonatal testing. Olfactory bulbs can be demonstrated reliably by MRI after 30 weeks’ gestation, and their hypoplasia or aplasia also documented by late prenatal and postnatal MRI. Olfactory axons project from nasal epithelium to telencephalon before olfactory bulbs form. Fetal olfactory maturation remains incomplete at term for neuronal differentiation, synaptogenesis, myelination, and persistence of the transitory fetal ventricular recess. Immaturity does not signify nonfunction. Olfaction is the only sensory system without thalamic projection because of its own intrinsic thalamic equivalent. Diverse malformations of the olfactory bulb can be diagnosed by clinical examination, imaging, and neuropathology. Some epileptic auras might be primarily generated in the olfactory bulb. Cranial nerve 1 should be tested in all neonates and especially in patients with brain malformations, endocrinopathies, chromosomopathies, and genetic/metabolic diseases.

Systematic review of MRI findings in children with developmental delay or cognitive impairment

AIMnTo summarize the reported rates of magnetic resonance imaging (MRI) abnormalities in children with isolated global developmental delay (GDD) or intellectual disability (ID).nnnMETHODnA literature search was conducted using electronic databases for studies reporting the rate of MRI abnormalities in children with clinically diagnosed ID or GDD and no other neurological signs, symptoms, or previously determined aetiology. All investigations with participants from birth to 18years were considered. Study quality was evaluated using the Joanna Briggs Institute Meta-Analysis of Statistics Assessment and Review Instrument (MAStARI) critical appraisal checklist items.nnnRESULTSnEighteen cross sectional, and 11 case-controlled studies adhered to inclusion criteria. Reported rates of abnormalities ranged from 0% to 98%. When all subjects with developmental delay from all papers were considered (n=2299) the total percentage found to have abnormalities was 38%. Abnormalities led to an etiological diagnosis for delay in 7.9% of cases.nnnINTERPRETATIONnDefinitions of abnormalities varied widely between studies, and drastically different rates of abnormalities are reported. Currently available evidence is not of sufficient quality to make firm recommendations on the use of neuroimaging in ID or GDD but MRI should be considered for children that do not have a diagnosis after thorough clinical evaluation.