Doris Lin

Sensory and motor deficits in children with cerebral palsy born preterm correlate with diffusion tensor imaging abnormalities in thalamocortical pathways

Aim  Cerebral palsy (CP) is frequently linked to white matter injury in children born preterm. Diffusion tensor imaging (DTI) is a powerful technique providing precise identification of white matter microstructure. We investigated the relationship between DTI‐observed thalamocortical (posterior thalamic radiation) injury, motor (corticospinal tract) injury, and sensorimotor function.

Routine clinical brain MRI sequences for use at 3.0 Tesla.

To establish image parameters for some routine clinical brain MRI pulse sequences at 3.0 T with the goal of maintaining, as much as possible, the well‐characterized 1.5‐T image contrast characteristics for daily clinical diagnosis, while benefiting from the increased signal to noise at higher field.

Diffusion Tensor Imaging in Children with Periventricular Leukomalacia: Variability of Injuries to White Matter Tracts

BACKGROUND AND PURPOSE: Conventional MR imaging shows evidence of brain injury and/or maldevelopment in 70%–90% of children with cerebral palsy (CP), though its capability to identify specific white matter tract injury is limited. The great variability of white matter lesions in CP already demonstrated by postmortem studies is thought to be one of the reasons why response to treatment is so variable. Our hypothesis is that diffusion tensor imaging (DTI) is a suitable technique to provide in vivo characterization of specific white matter tract lesions in children with CP associated with periventricular leukomalacia (PVL). MATERIALS AND METHODS: In this study, 24 children with CP associated with PVL and 35 healthy controls were evaluated with DTI. Criteria for identification of 26 white matter tracts on the basis of 2D DTI color-coded maps were established, and a qualitative scoring system, based on visual inspection of the tracts in comparison with age-matched controls, was used to grade the severity of abnormalities. An ordinal grading system (0 = normal, 1 = abnormal, 2 = severely abnormal or absent) was used to score each white matter tract. RESULTS: There was marked variability in white matter injury pattern in patients with PVL, with the most frequent injury to the retrolenticular part of the internal capsule, posterior thalamic radiation, superior corona radiata, and commissural fibers. CONCLUSION: DTI is a suitable technique for in vivo assessment of specific white matter lesions in patients with PVL and, thus, a potentially valuable diagnostic tool. The tract-specific evaluation revealed a family of tracts that are highly susceptible in PVL, important information that can potentially be used to tailor treatment options in the future.

Cavernous malformations: natural history, diagnosis and treatment

Cavernous malformations (CMs) consist of dilated vascular channels that have a characteristic appearance on MRI. CMs are usually found intracranially, although such lesions can also affect the spinal cord. Individuals with CMs can present with epilepsy and focal neurological deficits or acute intracranial hemorrhage. In many cases, however, patients with such lesions are asymptomatic at diagnosis. Furthermore, several natural history studies have documented that a substantial proportion of asymptomatic CMs follow a benign course. Surgical resection is recommended for CMs that require intervention. Radiosurgery has been advocated for many lesions that have not been easily accessible by conventional surgery. The outcomes of radiosurgery and surgery for deep lesions, however, vary widely between studies, rendering treatment recommendations for such CMs difficult to make. In addition to reviewing the literature, this article will discuss the current understanding of lesion pathophysiology and explore the controversial issues in the management of CMs, such as when to use radiosurgery or surgery in deep-seated lesions, the treatment of epilepsy, and the safety of anticoagulation.

Neurologic features of horizontal gaze palsy and progressive scoliosis with mutations in ROBO3

Objective: To review the neurologic, neuroradiologic, and electrophysiologic features of autosomal recessive horizontal gaze palsy and progressive scoliosis (HGPPS), a syndrome caused by mutation of the ROBO3 gene on chromosome 11 and associated with defective decussation of certain brainstem neuronal systems. Methods: The authors examined 11 individuals with HGPPS from five genotyped families with HGPPS. Eight individuals had brain MRI, and six had electrophysiologic studies. Results: Horizontal gaze palsy was fully penetrant, present at birth, and total or almost total in all affected individuals. Convergence, ocular alignment, congenital nystagmus, and vertical smooth pursuit defects were variable between individuals. All patients developed progressive scoliosis during early childhood. All appropriately studied patients had hypoplasia of the pons and cerebellar peduncles with both anterior and posterior midline clefts of the pons and medulla and electrophysiologic evidence of ipsilateral corticospinal and dorsal column-medial lemniscus tract innervation. Heterozygotes were unaffected. Conclusions: The major clinical characteristics of horizontal gaze palsy and progressive scoliosis were congenital horizontal gaze palsy and progressive scoliosis with some variability in both ocular motility and degree of scoliosis. The syndrome also includes a distinctive brainstem malformation and defective crossing of some brainstem neuronal pathways.

The Fcγ receptor IIIA-158F allele is a major risk factor for the development of lupus nephritis among Caucasians but not non-Caucasians

OBJECTIVE To determine whether inheritance of Fcgamma receptor (FcgammaR) alleles conferring lower affinity for IgG binding increases the risk of developing lupus nephritis. METHODS We compared the frequency of low-affinity alleles of two FcgammaR polymorphisms (FcgammaRIIA and FcgammaRIIIA) among 235 patients with systemic lupus erythematosus (SLE) and proven nephritis (nephritis patients) and among 352 SLE patients with no evidence of renal disease (non-nephritis control subjects). The ethnic distribution of patients in the study was 49% Caucasian, 20% Hispanic, 17% Asian/Pacific Islander, 12% African American, and 2% from other ethnic groups. All patients were genotyped for the FcgammaRIIA-131R/H and FcgammaRIIIA-158V/F polymorphisms. We used contingency table analysis to compare allele and genotype distributions for nephritis patients and nonnephritis control subjects, including ethnic-specific strata. Multivariate logistic regression analyses included sex and disease duration as covariates. RESULTS Univariate and multivariate analyses demonstrated a striking association between the low-affinity FcgammaRIIIA-158F allele and FF genotype and the risk of nephritis among Caucasians, but not among non-Caucasians (multivariate odds ratio [OR] 2.6 for Caucasians with FF genotype), (P = 0.0017). This association was even stronger among Caucasians with severe nephritis (OR 4.4, P < 0.0001). In contrast, inheritance of the low-affinity FcgammaRIIA-131R allele (and RR genotype) was not associated with an increased risk of lupus nephritis among any of the ethnic groups examined. CONCLUSION The FcgammaRIIIA-158F allele is a major risk factor for the development of lupus nephritis among Caucasians, but not among non-Caucasians. These results suggest that ethnic variation is critical in defining the specific genetic factors underlying the pathogenesis of SLE, and they have important prognostic and therapeutic implications as well.

Lymphatic drainage patterns of head and neck cutaneous melanoma observed on lymphoscintigraphy and sentinel lymph node biopsy

The purpose of this study was to evaluate lymphatic drainage patterns of head and neck cutaneous melanoma observed on preoperative lymphoscintigraphy and sentinel lymph node biopsy (SLNB) and determine discordancy from clinically predicted lymphatic drainage patterns.

Prevalence of Chiari I malformation and cerebellar ectopia in patients with pseudotumor cerebri

BACKGROUND Chiari I malformation (CM) may be present pre-surgically in pseudotumor cerebri (PTC) patients. Whether inferior tonsillar displacement (ITD) is coincidental or linked to increased intracranial pressure is unclear. This study aimed to identify the prevalence of both CM and cerebellar ectopia (CE) (ITD below the foramen magnum > or = 5 mm and 2-4 mm, respectively) in PTC patients. METHODS Retrospective review combined with prospective assessment of 68 PTC patients with available brain magnetic resonance imaging (MRI) scans and reports. Data collected included patient demographics, height, weight, co-morbid conditions, and medications. MRIs were analyzed for cerebellar tonsillar position, and results were compared with original reports. RESULTS Of 68 PTC patients, 60 (88%) had normal position of the cerebellar tonsils and 8 (12%) had ITD by report. Of the latter group, 4 were identified as CM and 4 as CE. On review of MRIs, however, 16 patients (24%) had ITD, 7 having CM and 9 having CE. All patients with ITD were female, most were overweight or obese, and most had presumed idiopathic intracranial hypertension (IIH). CONCLUSION ITD exists pre-surgically in a significant percentage of PTC patients. ITD is most common in obese or overweight women with presumed IIH. In fact, this subset of patients may actually represent a secondary form of PTC and may benefit from correction of ITD to restore normal intracranial pressure.

Serial imaging of human embryonic stem-cell engraftment and teratoma formation in live mouse models

Two new types of lentiviral vectors expressing a reporter transgene encoding either firefly luciferase (fLuc) for bioluminescence imaging or the HSV1 thymidine kinase (HSV1-TK) for radiopharmaceutical-based imaging were constructed to monitor human embryonic stem cell (hESC) engraftment and proliferation in live mice after transplantation. The constitutive expression of either transgene did not alter the properties of hESCs in the culture. We next monitored the formation of teratomas in SCID mice to test (1) whether the gene-modified hESCs maintain their developmental pluripotency, and (2) whether sustained reporter gene expression allows noninvasive, whole-body imaging of hESC derivatives in a live mouse model. We observed teratoma formation from both types of gene-modified cells as well as wild-type hESCs 2-4 months after inoculation. Using an optical imaging system, bioluminescence from the fLuc-transduced hESCs was easily detected in mice bearing teratomas long before palpable tumors could be detected. To develop a noninvasive imaging method more readily translatable to the clinic, we also utilized HSV1-TK and its specific substrate, 1-(2′-deoxy-2′-fluoro-β-D-arabinofuranosyl)-5-[125I]iodouracil ([125I]FIAU), as a reporter/probe pair. After systemic administration, [125I]FIAU is phosphorylated only by the transgene-encoded HSV1-TK enzyme and retained within transduced (and transplanted) cells, allowing sensitive and quantitative imaging by single-photon emission computed tomography. Noninvasive imaging methods such as these may enable us to monitor the presence and distribution of transplanted human stem cells repetitively within live recipients over a long term through the expression of a reporter gene.

Dynamic MR perfusion and proton MR spectroscopic imaging in Sturge-Weber syndrome: correlation with neurological symptoms.

To investigate physiological alterations in Sturge‐Weber syndrome (SWS) using MR perfusion imaging (PWI) and proton spectroscopic imaging (MRSI), and their association with neurological status.