Alex Mun-Ching Wong

Chinese Patients with Defective IL-12/23-Interferon-γ Circuit in Taiwan: Partial Dominant Interferon-γ Receptor 1 Mutation Presenting as Cutaneous Granuloma and IL-12 Receptor β1 Mutation as Pneumatocele

BackgroundIL-12/23-interferon-γ circuit enhances reactive oxygen species (ROS) synthesis in macrophage to attack intracellular pathogens such as mycobacteria and salmonella. Defective ROS in patients with chronic granulomatous disease (CGD) have increased susceptibility to these pathogens. However, patients with defective IL-12/23-interferon-γ circuit rather than CGD are not recognized in Taiwan, endemic for tuberculosis and salmonella.AimThe purpose of this study was to identify Taiwanese patients with defective IL-12/23-IFN-γ circuit.Patients and MethodsIn a long-term molecular study of primary immunodeficiency diseases (PIDD), the tentative CGD patients presenting with Bacille Calmette–Guerin (BCG)-induced infection, refractory atypical mycobacterial cutaneous granuloma and osteomyelitis, recurrent salmonella sepsis, and pneumatocele were studied for the IL-12/23-IFN-γ circuit. ROS was first measured to exclude CGD. Candidate genes of IL12RB1, IFNRG1, IL12p40, IFNRG2, signal transducer and activator of transcription-1, and NF-κB essential modulator and their encoding protein expressions were analyzed.ResultsOf the 175 Taiwanese PIDD patients during a 28-year period, three patients from two unrelated families were identified with the hotspot INFRG1 deletion mutation (818del4) and had CGD features, presenting as cutaneous granuloma, and multiple osteomyelitis infected by non-tuberculosis mycobacteria, Mycobacteria avium complex and Mycobacterium scrofulaceum. Another with mis-sense IL12RB1 mutation (Arg211Pro) was noted as recurrent Salmonella enteritidis D sepsis and pneumatocele.ConclusionPatients with defective IL-12/23-IFN-γ circuit may resemble or overlap CGD manifestations of refractory cutaneous atypical mycobacterial granuloma and salmonella pneumatocele.

Comparison of three-dimensional pseudo-continuous arterial spin labeling perfusion imaging with gradient-echo and spin-echo dynamic susceptibility contrast MRI

To compare the relative cerebral blood flow (CBF) obtained by pseudo‐continuous arterial spin labeling sequence incorporated with volumetric fast spin‐echo readout (3D‐PCASL) with those by gradient‐echo (GE) and spin‐echo (SE) dynamic susceptibility contrast (DSC) MRI.

Risk factors and outcomes of childhood ischemic stroke in Taiwan

In this retrospective study, we reviewed the charts and collected clinical and radiographic data on children (age range, 1 month to 18 years) with symptoms and radiographic confirmation of ischemic stroke for the period of January 1996 to July 2006. Ninety-four children were enrolled. Eighty-eight had arterial ischemic stroke and six had sinovenous thrombosis. Twenty-nine percent of the children had seizures. Twenty-six percent had diffuse neurological signs and 76% had focal neurological signs. Risk factors included vascular disease (33%), infection (27%), metabolic disorders (18%), trauma (11%), prothrombotic states (13%), cardiac disease (10%), and mitochondrial disease (6%). Ten percent (n=9) had no identifiable cause. Twenty-two percent of the children had more than one risk factor. Anterior territory (70%) was more involved than posterior territory (18%) in arterial ischemic stroke. Unilateral infarctions were more common on the left side (51%) than on the right (24.5%). Neurological deficits were present in 45% (n=34/75) of the children; the most frequent deficit was motor impairment (24%). Seven children (9%) died in the acute stage. There were 12 children (16%) who had recurrent stroke and 8 children (8/12) who had underlying vascular disease. The vascular disease included moyamoya disease (5), CNS lupus (1) and ill-defined vasculopathy (2). The etiology pattern in Taiwan was different from that in Western countries. Vascular disease was a significant risk factor for recurrence in childhood ischemic stroke.

Seizures in childhood ischemic stroke in Taiwan

In this retrospective study, we collected clinical and radiographic data on children (age range, 1 month to 18 years) with symptoms and radiographic confirmation of seizure after ischemic stroke for the period of January 1996 to July 2006. Thirty-nine out of 94 children with ischemic stroke had poststroke seizures. Thirty-three out of 39 children with poststroke seizures had new onset seizures but only data of 28 were available. Infection was the most common etiology in the early poststroke seizure group (52.4%) but not in the late poststroke seizure group (0%). Infarction involving arterial ischemic stroke of anterior circulation were the most common in both the early poststroke seizure (61.9%) and the late poststroke seizure group (57.1%). Epilepsy was the most common sequelae in both the early poststroke seizure (38.1%) and late poststroke seizure group (100%). Children who had initial focal neurological sign (100% vs. 38.1%; P=0.007) or the focal cortical dysfunction on EEG (85.7% vs. 33.3%; P=0.029) were prone to develop late poststroke seizures. Late poststroke seizures had a high risk of developing poststroke epilepsy (100% vs. 38.1%; P=0.007). We conclude that seizures commonly occur in childhood ischemic stroke. Most poststroke seizures developed at an early stage. Infection was the most common etiology that caused early poststroke seizures in childhood ischemic stroke. Initial focal neurological signs and focal cortical dysfunction on EEG are risk factors for developing epilepsy. Poststroke seizures did not affect mortality, but there was a significant difference in normal outcome and epilepsy between those with or without poststroke seizures.

Tuberous Sclerosis Complex With Multiple Intracranial Aneurysms in an Infant

Tuberous sclerosis complex is a protean, genetically determined disease that may involve any organ or tissue and lead to a great number of signs and clinical features. Occlusive vascular disease and aneurysms of the cerebral and visceral arteries were described in these patients. We report on an 8-month-old boy who manifested tuberous sclerosis complex with multiple intracranial aneurysms involving the internal carotid artery and middle cerebral artery. The unusual features of our case favor the concepts of the presence of an arterial dysplasia in tuberous sclerosis complex, and of developmental defects as the cause of intracranial aneurysms.

Occult infarct with acute hemorrhagic stroke in juvenile diabetic ketoacidosis

Diabetes ketoacidosis (DKA) is one of the common complications of type I insulin-dependent diabetes mellitus. Neurological deterioration during an episode of DKA is usually assumed to be caused by cerebral edema and cerebral vascular accidents. However, hemorrhagic stroke is a very rare complication of juvenile DKA. We describe a girl who had newly diagnosed insulin-dependent diabetes mellitus with juvenile DKA developed intracerebral hemorrhage.

Kimura's disease: clinical and imaging parameters for the prediction of disease recurrence.

Kimuras disease is a rare chronic inflammatory disorder with a high rate of recurrence. The clinical and imaging features of Kimuras disease have been documented in the literature, but the relationship between these features and disease recurrence is still unclear. We conclude that disease duration of greater than 5 years, bilateral involvement, a lesion diameter of greater than 3 cm, a blood eosinophil count greater than 20%, and ill-defined lesions are predictive factors for the recurrence of Kimuras disease.

Prenatal MR imaging of a meconium pseudocyst extending to the right subphrenic space with right lung compression

Meconium pseudocyst results from a loculated inflammation occurring in response to spillage of meconium into the peritoneal cavity after a bowel perforation. Certain cystic lesions, such as abscesses and dermoid and epidermoid cysts, are known to show reduced water diffusion on DWI. MRI has recently become a valuable adjunct to ultrasonography for fetal gastrointestinal anomalies. Complementary to ultrasonography, prenatal MRI can help further characterize the lesion and can clearly demonstrate the anatomical relationship between the lesion and adjacent organs. We report a case of meconium pseudocyst that was prenatally imaged with ultrasonography and MRI, postnatally complicated by pneumoperitoneum, and proved by postnatal surgery and histopathology. We emphasize the MRI of the pseudocyst, particularly T1-weighted and diffusion-weighted imaging.

Moyamoya Syndrome in a Child with Noonan Syndrome

Previous studies have rarely described the association between Noonan syndrome and moyamoya syndrome. Although most affected children with moyamoya exhibit ischemic symptoms, headache is also a frequent symptom. We report the case of a 9-year-old girl with Noonan syndrome and moyamoya syndrome that manifested as recurrent headaches without history of transient ischemic attack. Brain magnetic resonance imaging and magnetic resonance angiography revealed bilateral moyamoya syndrome and mild ventriculomegaly with focal encephalomalacia at right peritrigonal region. Disruption of vascular development during the prenatal stage has been proposed as the cause of cerebrovascular disease in Noonan syndrome. However, genetic factors may also contribute.

Cerebral Diffusion Tensor MR Tractography in Tuberous Sclerosis Complex: Correlation with Neurologic Severity and Tract-Based Spatial Statistical Analysis

BACKGROUND AND PURPOSE: The neurologic significance of residual cerebral white matter tracts, identified on diffusion tensor tractography, has not been well studied in tuberous sclerosis complex. We aimed to correlate the quantity of reconstructed white matter tracts with the degree of neurologic impairment of subjects with the use of DTI and determined differences in white matter integrity between patients with tuberous sclerosis complex and controls with the use of voxelwise analysis. MATERIALS AND METHODS: In this case-control study, 16 patients with tuberous sclerosis complex and 12 control subjects underwent DTI. Major white matter tracts, comprising bilateral PF and CF, were reconstructed and assessed for quantity, represented by NOP and NOF. A neurologic severity score, based on the presence of developmental disability, seizure, autism, and other neuropsychiatric disorders, was calculated for each subject. We then correlated this score with white matter quantity. Voxelwise tract-based spatial statistics was used to determine differences in FA, axial, and radial diffusivity values between the tuberous sclerosis complex group and the control subjects. RESULTS: NOP and NOF of CF, bilateral PF, and MWT in the tuberous sclerosis complex group were all significantly lower than those in the control subjects (P < .05). The neurologic severity score was moderately negatively correlated with NOF and NOP regarding CF (r = −.70; r = −.75), bilateral PF (r = −.66; r = −.68), and MWT (r = −.71; r = −.74). Tract-based spatial statistics revealed that patients with tuberous sclerosis complex showed a widespread reduction (P < .05) in FA and axial diffusivity in most cerebral white matter regions. CONCLUSIONS: Patients with tuberous sclerosis complex with reduced residual white matter were neurologically more severely affected. Tract-based spatial statistics revealed decreased FA and axial diffusivity of the cerebral white matter in the tuberous sclerosis complex group, suggesting reduced axonal integrity.