Dyskinesia Impairment Scale scores in Dutch pre-school children after neonatal therapeutic hypothermia.

BACKGROUND: Neonatal therapeutic hypothermia (TH) can ameliorate or prevent the development of dyskinetic cerebral palsy (CP) after hypoxic-ischemic encephalopathy (HIE). The Dyskinesia Impairment Scale (DIS) was recently launched to quantify dyskinetic (dystonic and choreatic) motor features in patients with CP. In TH treated children, who are at risk of developing dyskinetic CP, we aimed to determine DIS-scores at pre-school age. METHOD: In 21 Dutch pre-school children (3-6 years of age) who had received TH according to the Dutch-Flemish treatment protocol, we determined DIS-scores. We associated DIS-scores with 1. age-matched control values (Kuiper et al., 2018) [1], and 2. previously reported DIS-score range in dyskinetic CP (Monbaliu E et al., 2015). RESULTS: The motor phenotype was determined as: normal (n = 18/21), mildly impaired (reduced coordination (n = 2/21)) and abnormal (dyskinetic CP; n = 1/21). In absence of CP (n = 20/21), DIS-scores were lower (more favorable) than in dyskinetic CP, without any overlapping group scores (mean difference: 71 points; p < .05). However, the obtained DIS-scores were still higher than previously reported in healthy age-matched controls (mean difference: 14 points; p < .05). There was an association between DIS-scores and retrospective neonatal MRI (basal ganglia and thalamus injury on diffusion weighted imaging (DWI)) and (a)EEG parameters (p < .05). CONCLUSION: In the vast majority (95%) of Dutch TH-HIE treated pre-school children, the phenotypic motor outcome was favorable. However, DIS-scores were moderately increased compared with healthy age-matched controls. Future studies may elucidate the significance of moderately increased DIS-scores should to further extent.

The splenium of the corpus callosum: embryology, anatomy, function and imaging with pathophysiological hypothesis.

BACKGROUND AND PURPOSE: The splenium of the corpus callosum is the most posterior part of the corpus callosum. Its embryological development, anatomy, vascularization, function, imaging of pathology, possible pathophysiological mechanisms by which pathology may develop and the clinical consequences are discussed. METHODS: A literature-based description is provided on development, anatomy and function. MR and CT images are used to demonstrate pathology. The majority of pathology, known to affect the splenium, and the clinical effects are described in three subsections: (A) limited to the splenium, with elaboration on pathophysiology of reversible splenial lesions, (B) pathology in the cerebral white matter extending into or deriving from the splenium, with special emphasis on tumors, and (C) splenial involvement in generalized conditions affecting the entire brain, with a hypothesis for pathophysiological mechanisms for the different diseases. RESULTS: The development of the splenium is preceded by the formation of the hippocampal commissure. It is bordered by the falx and the tentorium and is perfused by the anterior and posterior circulation. It contains different caliber axonal fibers and the most compact area of callosal glial cells. These findings may explain the affinity of specific forms of pathology for this region. The fibers interconnect the temporal and occipital regions of both hemispheres reciprocally and are important in language, visuospatial information transfer and behavior. Acquired pathology may lead to changes in consciousness. CONCLUSION: The development, location, fiber composition and vascularization of the splenium make it vulnerable to specific pathological processes. It appears to play an important role in consciousness.

Imaging of Clival Hypoplasia in CHARGE Syndrome and Hypothesis for Development: A Case-Control Study.

BACKGROUND AND PURPOSE: We present the largest case series to date on basiocciput abnormalities in CHARGE syndrome (Coloboma of the eye, Heart defects, Atresia of the choanae, Retardation of growth and/or development, Genital and/or urinary abnormalities, and Ear abnormalities and/or deafness). We aimed to show that basiocciput abnormalities are common and may aid in diagnosis. We furthermore explored whether clivus size correlates with the type of chromodomain-helicase-DNA binding protein 7 gene (CHD7) mutation, which causes CHARGE syndrome, and with clinical criteria according to Blake et al and Verloes. MATERIALS AND METHODS: We retrospectively analyzed the clivus of 23 patients with CHARGE syndrome with CHD7 mutations on MR imaging or CT. We recorded the size of the clivus, the Welcher angle, basilar invagination, and Chiari I malformations. We compared the clival size and Welcher angle of patients with CHARGE syndrome with those of 72 age-matched controls. Additionally, we tested for correlations between clivus size and mutation type or clinical criteria. RESULTS: Eighty-seven percent of the patients with CHARGE syndrome had an abnormal clivus; 61% had a clivus >2.5 SD smaller than that of age-matched controls. An abnormally large Welcher angle was observed in 35%. Basiocciput hypoplasia was found in 70%, and basilar invagination, in 29%. None of the patients had a Chiari I malformation. At the group level, patients with CHARGE syndrome had a smaller clivus and larger Welcher angle than controls. No significant correlation between clivus size and mutation type or clinical criteria was found. CONCLUSIONS: Most patients with CHARGE syndrome have an abnormal clivus. This suggests that clivus abnormalities may be used as an additional diagnostic tool. Our results provide evidence that CHD7, which is expressed in the presomitic mesoderm during somitogenesis, plays an important role in the formation of the clivus.

Amplitude-Integrated EEG and Cerebral Near-Infrared Spectroscopy in Cooled, Asphyxiated Infants.

OBJECTIVE: To assess the predictive value of amplitude-integrated electroencephalography EEG (aEEG) and near-infrared spectroscopy (NIRS) during therapeutic hypothermia. PATIENTS AND METHODS: We studied 39 cooled, asphyxiated infants. We assessed aEEG and calculated mean regional cerebral oxygen saturation (rcSO2) during and after treatment. At 30 months, we performed a neurological examination and administered the Bayley Scales of Infant and Toddler Development, 3rd edition. We calculated the odds ratios (ORs) of abnormal aEEG and rcSO2 for severely abnormal outcome. RESULTS: At 6 and 12 hours, severely abnormal aEEGs predicted severely abnormal outcomes (OR, 7.7 [95% confidence interval, CI, 1.39-42.6] and 24.4 [95% CI 4.2-143] respectively), as did epileptic activity (OR 28.9, 4.6-183). During the first 48 hours, rcSO2 was not associated with outcome, but at 72 hours after birth and after rewarming it was, with ORs for severely abnormal outcomes of 12.8 (1.31-124) and 21.6 (1.05-189), respectively. In multivariate analyses, aEEG and rcSO2 remained independently predictive in the model at 48 hours and significantly from 72 hours after birth onward. CONCLUSION: aEEG was a strong predictor of adverse outcome. After 48 hours of cooling, a higher rcSO2 was associated with a severely abnormal outcome, adding to the predictive value of aEEG in cooled, asphyxiated infants.

Imaging in cutis laxa syndrome caused by a dominant negative ALDH18A1 mutation, with hypotheses for intracranial vascular tortuosity and wide perivascular spaces.

The autosomal dominant progeroid form of cutis laxa is a recently identified multiple congenital anomaly disorder characterized by thin, wrinkled skin, a progeroid appearance, intra-uterine growth retardation, postnatal growth restriction, psychomotor developmental delay, microcephaly, cataract, hypotonia and contractures. De novo heterozygous mutations in ALDH18A1 have been described in this condition. We present neuroimaging abnormalities in three patients. One patient had intracranial arterial and venous tortuosity, widened ventricular and extra-axial cerebrospinal fluid (CSF) spaces, wide perivascular spaces and increased T2 signal intensity in the cerebral white matter over time. The second patient had vascular tortuosity. The third patient had prominent ventricular and extra-axial cerebrospinal fluid (CSF) spaces on CT. We propose an embryological mechanism for the development of intracranial vascular tortuosity and discuss the anatomical basis of wide perivascular spaces in relation to this syndrome. Although we do not know the clinical implications of these cerebral vascular anomalies, we suggest inclusion of neuroimaging in the baseline evaluation of these patients.

[Acute flaccid myelitis after a respiratory tract infection; first Dutch case related to enterovirus type D68 infection]. / Acute slappe verlamming na een luchtweginfectie.

BACKGROUND: Acute flaccid myelitis (AFM) is a relatively rare disorder affecting the anterior horn of the spinal cord and brain stem. It is characterised by rapid progressive weakness of the limbs and respiratory muscles, often combined with cranial nerve dysfunction. This used to be seen in infections with the polio virus, but in recent years, AFM has been mainly associated with enterovirus D68 infection. CASE DESCRIPTION: A boy of nearly 4 years-old developed rapidly progressive weakness and respiratory failure after an upper airway infection. Initially, Guillain-Barré syndrome was suspected, but after further investigations enterovirus D68 was detected in the nasopharyngeal aspirate and the diagnosis of AFM was made. CONCLUSION: Progressive weakness after a respiratory tract infection should raise the suspicion of enterovirus-associated AFM. This syndrome can be distinguished from Guillain-Barré syndrome by its more rapid progression, asymmetrical weakness and greater involvement of the upper limbs. The diagnosis can be confirmed by typical findings on MRI and electromyography of the spinal cord and brain stem, combined with the detection of enterovirus D68 in nasopharyngeal specimens.

Sulphonylurea therapy improves cognition in a patient with the V59M KCNJ11 mutation.

BACKGROUND: KCNJ11 mutations are a common cause of diabetes diagnosed in the first 6 months of life, and approximately 25% of patients have neurological features. Sulphonylureas have been shown to improve glycaemic control and also motor function, but the impact on cognitive function has not been extensively addressed previously. METHODS: The patient had a low birth weight and was found to have diabetes at the age of 2 days. The patient was treated with insulin from diagnosis. The child also had marked developmental delay so that his average functional age was 2.5 years when he was 12 years old. A V59M mutation in KCNJ11 was found on sequencing, resulting in a diagnosis of intermediate developmental delay, epilepsy, neonatal diabetes (DEND) syndrome. Identification of a Kir6.2 mutation allowed insulin injections to be replaced by glibenclamide tablets. RESULTS: This resulted not only in improved glycaemic control (HbA(1c) fell from 8.1 to 6.5%), but also an impressive improvement in many aspects of cognitive function, with the functional age increasing to 4 years within 6 months of treatment change. CONCLUSIONS: This is the first clear report of cognitive function improving in a patient with the neurological features associated with a K(ATP) channel mutation following transfer to sulphonylureas. The finding of cognitive improvement suggests that glibenclamide is likely to be acting directly on the brain and not just on nerve and muscle, improving muscle strength.

Diffusion tensor imaging and chemical shift imaging assessment of heterogeneity in low grade glioma under temozolomide chemotherapy.

Diffusion tensor imaging and multiple voxel magnetic resonance spectroscopy were performed in the MRI follow-up of a patient with a glioma treated with temozolomide chemotherapy. Tumor shrinkage was paralleled by reductions in choline level and by increases in apparent diffusion coefficient indicating decreased cellularity. Within the tumor, choline level and apparent diffusion coefficient showed a significant inverse correlation (P < 0.01). Fractional anisotropy distribution in the tumor correlated positively with N-acetyl aspartate level (P < 0.001), indicating that these parameters reflect (remaining) axonal structure. Tumor lactate level, also found to decrease under therapy, did not correlate with any other parameter.

MR spectroscopy and diffusion tensor imaging of the brain in congenital muscular dystrophy with merosin deficiency: metabolite level decreases, fractional anisotropy decreases, and apparent diffusion coefficient increases in the white matter.

Brain magnetic resonance spectroscopy (MRS) and diffusion tensor imaging (DTI) in one patient with merosin-deficient congenital muscular dystrophy (MDCMD) revealed significant metabolite (choline, creatine, N-acetyl aspartate) level reductions, fractional anisotropy (FA) reduction and increased apparent diffusion coefficient (ADC) in the white matter (p<0.01, all). In the gray matter, the MRS properties did not differ significantly from those in controls. The ADC and FA, however, differed significantly as in the white matter, although the differences were less pronounced. This is the first quantitative MR study of the brain in a patient with MDCMD, which revealed that the concentrations of all MRS measured metabolites were decreased only in the white matter. This observation, combined with the DTI observed ADC increases and FA decrease, indicated a presence of vasogenic edema in the white matter.

Diffusion tensor imaging and magnetic resonance spectroscopy of the brain in a patient with Sturge-Weber syndrome.

Quantitative brain MR spectroscopy (MRS) and diffusion tensor imaging (DTI) were used to characterize one patient with Sturge-Weber syndrome. Choline increases and N-acetylaspartate decreases were observed in pathologic frontal gray matter tissue compared to contralateral unaffected brain tissue without any change in the diffusion tensor imaging parameters (fractional anisotropy, apparent diffusion coefficient). The N-acetylaspartate decreases and/or choline increases observed here and in eight previously described Sturge-Weber patients probably reflect neuronal loss or dysfunction and demyelination as a result of recurrent seizures.

Cerebral 1H MR spectroscopy revealing white matter NAA decreases in glutaric aciduria type I.

MR spectroscopy in two patients with glutaric aciduria type I revealed reductions in the white matter N-acetylaspartate signal, in the more severe case accompanied by a loss of glutamate and the appearance of lactate signals.

Time-of-flight magnetic resonance angiography in the follow-up of intracranial aneurysms treated with Guglielmi detachable coils.

The purpose of this study was to evaluate time-of-flight magnetic resonance angiography (MRA) in the follow-up of intracranial aneurysms treated with Guglielmi detachable coils (GDCs). From January 1998 to January 2002 27 MRA and intra-arterial digital subtraction angiography (IADSA) examinations were analyzed for residual aneurysms and arterial patency following GDC placement. A total number of 33 intracranial aneurysms was analyzed, including 18 located in the posterior circulation. The MRA analysis was based on source images in combination with maximum intensity projections. The IADSA was used as the reference standard. Two aneurysms were excluded from evaluation, because of susceptibility artefacts from other aneurysms, which were clipped. Sensitivity and positive predictive values of MRA in revealing residual aneurysms were, respectively, 89% and 80%. Specificity in ruling out remnant necks and residual flow around coils was, respectively, 91% and 97%, with a negative predictive value of, respectively, 95% and 100%. Specificity and negative predictive value of MRA for arterial occlusion were, respectively, 87% and 100% for the parent arteries and, respectively, 85% and 100% for the adjacent arteries. MRA is a reliable diagnostic tool in the follow-up of GDC treatment, and it may replace IADSA in excluding residual flow around coils and aneurysmal necks and in ruling out arterial occlusion.

1H chemical shift imaging of the brain in guanidino methyltransferase deficiency, a creatine deficiency syndrome; guanidinoacetate accumulation in the gray matter.

MR spectroscopy results in a mild case of guanidinoacetate methyltransferase (GAMT) deficiency are presented. The approach differs from previous MRS studies in the acquisition of a chemical shift imaging spectral map showing gray and white matter with the corresponding spectra in one overview. MR spectroscopy revealed guanidinoacetate (GAA) in the absence of creatine. New is that GAA signals are more prominent in gray matter than in white. In the prevailing view, that enzyme deficiency is localized in liver and pancreas and that all GAA is transported into the brain from the blood and the cerebrospinal fluid, this would be compatible with a more limited uptake and/or better clearance of GAA from the white matter compared to the grey matter.

Cerebral activation related to skills practice in a double serial reaction time task: striatal involvement in random-order sequence learning.

We used functional Magnetic Resonance Imaging (fMRI) to examine the distribution of cerebral activation related to prolonged skill practice. In a bimanual variant of the Serial Reaction Time Task (SRT), simultaneous finger movements of the two hands were made in response to randomly ordered pairs of visual stimuli (Double SRT, DoSRT). Extended practice by a week of daily performance resulted in gradual decrease of reaction times, associated with an increased involvement of the ventral putamen and globus pallidus, reaching statistical significance only on the left side (Statistical Parametric Mapping, SPM99). This increase was complementary to a decrease of cortical activations. The striatal activation after training on random order stimuli indicates that the striatum is not exclusively involved in sequence learning. This extended function implies a role in the acquisition of basic visuomotor skills that includes the specific selection of the appropriate muscles in response to independent stimuli.

Evidence of enhancement of spatial attention during inhibition of a visuo-motor response.

A visuo-motor task was used as the setting for a study into inhibition in six healthy volunteers using fMRI. The task involved responding to colored stimuli, which appeared at random positions in the left and right visual field, with the corresponding hand. The volunteers were asked to respond to green colored stimuli ("go" response) and to inhibit responses to red stimuli ("no-go" response). The task was presented in a block design with blocks of three types; only "go" trials, a pseudo-random mixture of "go" and "no-go" tasks ("go/no-go" block), and "visual control." ANCOVA analysis of the fMRI data was performed within the framework of SPM99. Increased activation in the go vs visual control comparison was found in the bilateral motor and medial premotor cortices associated with the action of the button press response, as well as parietal regions attending to the task of identifying the visual field. The go/no-go vs visual control comparison showed a similar pattern, plus additional prefrontal areas that have previously been shown to be associated with inhibition. The direct comparison of the go and go/no-go blocks highlighted large differences not only in the prefrontal cortices, associated with inhibition, but also particularly in the right parietal cortex. We interpret the increased parietal activation, during inhibition, as representing a heightened spatial attention required for the correct execution of the inhibition task.

Curved reconstructions versus three-dimensional surface rendering in the demonstration of cortical lesions in patients with extratemporal epilepsy.

RATIONALE AND OBJECTIVES: To compare the visibility and localization of extratemporal cortical lesions in extratemporal epilepsy by using curved reconstruction (CR) and three-dimensional surface rendering (3D SR) of 3D-acquired MR images and to study the degree of confidence with which localizations are made, particularly at the gyral level. METHODS: Twenty patients with extratemporal epilepsy, based on seizure symptomatology and/or scalp electroencephalographic registrations, with an extratemporal structural lesion on conventional MR imaging, were selected for this study by a neuroradiologist with extensive experience in the assessment of epilepsy patients. Transverse T2 spin-echo, coronal fluid-attenuated inversion recovery, and transverse 3D-acquired/two-dimensionally reconstructed T1 MR images were used for the selection. A second neuroradiologist (observer 1) and a radiology resident (observer 2) assessed CR and 3D SR in random order. Both observers were masked to all patient data. The subjective visibility of lesions and gyral location were scored. The interobserver agreements for lesion visibility and localization and for degree of confidence were compared for CR and 3D SR. RESULTS: For both observers, the lesion was visible in 55% of 3D SRs and 95% of CRs. The proportion with "very clearly visible" lesions on 3D SR was 19% (4/20) according to observer 1 and 30% (6/20) according to observer 2. For CR, this proportion was substantially higher: 55% for both observers. This difference was significant for observer 1 but not for observer 2. The interobserver agreement was high for both methods. Agreement on gyral localization was 28% for CR and 40% for 3D SR. The percentage of similar confidence scores for the same gyral localization and for gyral localization with a maximum difference of one gyrus between the observers did not differ significantly for CR or 3D SR. The observers were more often confident in agreed cases in CR and moderately confident in 3D SR. CONCLUSIONS: These results suggest that CRs of the brain surface are superior to 3D SR for the visualization of extratemporal cortical lesions in patients with drug-resistant extratemporal epilepsy. If lesions are seen, no significant difference was found between the two techniques for localization; however, the degree of confidence appears higher for CR at the gyral level.

Language localization in cases of left temporal lobe arachnoid cyst: evidence against interhemispheric reorganization.

We investigated whether left-hemisphere arachnoid cysts lead to reorganization of the language function using PET. A group analysis demonstrated that patients showed no more right-hemisphere activation than a matched control group. Several patients had clear language localizations in the left hemisphere during language comprehension; none of the patients showed right-hemisphere activation. We conclude that left-hemisphere tissue must suffer considerable compromise before reorganization of language into the right hemisphere becomes necessary. Language activations within the left hemisphere are clearly displaced. This is consistent with mere physical displacement in some patients rather than reorganization within the left hemisphere; in others intrahemispheric reorganization cannot be excluded.

Proton magnetic resonance spectroscopy of temporal lobe white matter in patients with histologically proven hippocampal sclerosis.

The purpose of this study was to assess temporal lobe white matter changes accompanying hippocampal sclerosis on magnetic resonance (MR) imaging using single-voxel 1H MR spectroscopy and to strengthen the hypothesis that these white matter changes are caused by myelin alterations. In 11 patients with histologically proven hippocampal sclerosis, preoperative coronal fluid-attenuated inversion recovery images were visually assessed by two experienced neuroradiologists for hippocampal signal increase and size decrease, atrophy of collateral white matter, and temporal lobe gray/white matter demarcation loss. Single-voxel 1H MR spectroscopy of the white matter of each anterior temporal lobe was also performed, excluding the amygdala and hippocampus. The N-acetyl-aspartate (NAA)/choline and NAA/creatine ratios were calculated. In 12 healthy volunteers both temporal lobes were spectroscopically examined. In all patients the excised hippocampi were histologically assessed for the presence of sclerosis, and the excised neocortical temporal lobes were examined for gray and white matter abnormalities. MRI abnormalities were found on the right in six patients, on the left in four, and one scan was normal. Hippocampal signal increase was seen in nine patients, hippocampal size decrease in ten, atrophy of collateral white matter in nine, and gray/white matter demarcation loss in six. A significant decrease in the NAA/choline ratio was found in temporal lobe white matter ipsilateral to the pathologic hippocampus (symptomatic side), compared with the contralateral, asymptomatic side (P < 0.01), and also compared with controls (P < 0.001). The ipsilateral NAA/creatine ratio was also significantly decreased (P < 0.05) compared with the contralateral side and the control subjects (P < 0.001). Histological examination showed hippocampal sclerosis to a different degree in all patients. Neither gliosis nor cortical dysplasia was found in the ipsilateral, symptomatic temporal lobe. Significant decrease in the mean of NAA/choline ratios is found in temporal lobe white matter of patients with histologically confirmed hippocampal sclerosis. As this indicates neuronal loss or dysfunction, the number of axons may be reduced, with associated decrease in myelin density.

Subcortical laminar heterotopia in two sisters and their mother: MRI, clinical findings and pathogenesis.

MR imaging, clinical data and underlying pathogenesis of subcortical laminar heterotopia (SCLH), also known as band heterotopia, in two sisters and their mother are presented. On MR imaging a different degree of SCLH was found in all three affected family-members. The inversion recovery sequence was considered most useful in the demonstration of the heterotopic band of gray matter and the assessment of cortical thickness. The younger sister presented with epileptic seizures at the age of five months and a delayed achievement of developmental milestones. The older sister of seven years had epileptic seizures since the age of one year, and developmental delay. Their mother has only had one seizure-like episode at the age of 39. Her psychomotor development had been normal. Investigation of DNA samples of the three female family-members revealed a mutation in the X-linked doublecortin gene. Within families with band heterotopia, this gene has also been related to male family members with lissencephaly.