Case report: Subacute transverse myelitis with gait preservation secondary to Lyme disease and a review of the literature.

Subacute presentation with gait preservation is rare in the initial presentation of transverse myelitis (TM) in children. Lyme TM is poorly described in the literature. Here, we present the case of a 10-year-old boy who presented with neck pain with irradiation in the upper limbs for 13 days, accompanied by a right latero-torticollis. Magnetic resonance imaging (MRI) of the spine showed a hypersignal in the centromedullary T2 weighted image (WI) between C1 and C7, which was suggestive of cervical TM. A lumbar puncture revealed pleocytosis and proteinorachia. The test results of Borrelia IgG in the blood and intrathecal IgG synthesis were positive, confirming the diagnosis of TM secondary to Lyme disease. The patient was treated with high doses of steroids and antibiotics, following which he recovered completely. After a review of the clinical features of the eight previously published pediatric cases, we can conclude that Lyme TM usually has a subacute clinical presentation and is frequently limited to the cervical spine with pure sensory symptoms and gait preservation. Moreover, acute and chronic sphincter dysfunction is rare, and recovery is usually complete.

Ruptured Renal Angiomyolipoma.

Teaching Point: This case highlights the importance of extending the medical analysis to other areas with lumbar computed tomography, especially to the kidneys and the retroperitoneum.

Synthetic MRI for stroke: a qualitative and quantitative pilot study.

Synthetic MR provides qualitative and quantitative multi-parametric data about tissue properties in a single acquisition. Its use in stroke imaging is not yet established. We compared synthetic and conventional image quality and studied synthetic relaxometry of acute and chronic ischemic lesions to investigate its interest for stroke imaging. We prospectively acquired synthetic and conventional brain MR of 43 consecutive adult patients with suspected stroke. We studied a total of 136 lesions, of which 46 DWI-positive with restricted ADC (DWI + /rADC), 90 white matter T2/FLAIR hyperintensities (WMH) showing no diffusion restriction, and 430 normal brain regions (NBR). We assessed image quality for lesion definition according to a 3-level score by two readers of different experiences. We compared relaxometry of lesions and regions of interest. Synthetic images were superior to their paired conventional images for lesion definition except for sFLAIR (sT1 or sPSIR vs. cT1 and sT2 vs. cT2 for DWI + /rADC and WMH definition; p values < .001) with substantial to almost perfect inter-rater reliability (κ ranging from 0.711 to 0.932, p values < .001). We found significant differences in relaxometry between lesions and NBR and between acute and chronic lesions (T1, T2, and PD of DWI + /rADC or WMH vs. mirror NBR; p values < .001; T1 and PD of DWI + /rADC vs. WMH; p values of 0.034 and 0.008). Synthetic MR may contribute to stroke imaging by fast generating accessible weighted images for visual inspection derived from rapidly acquired relaxometry data. Moreover, this synthetic relaxometry could differentiate acute and chronic ischemic lesions.

Middle interhemispheric variant of holoprosencephaly: First prenatal report of a ZIC2 missense mutation.

We present a case of a middle interhemispheric variant of antenatal discovery associated with a de novo missense variant (NM_007129.5: c.1109G>A p.(Cys370Tyr)) in the ZIC2 gene. Our case represents the first prenatal description of a ZIC2 missense mutation found in association with syntelencephaly.

A New DARS2 Mutation Discovered in an Adult Patient.

We report a case of an adult patient suffering from leukoencephalopathy with brainstem and spinal cord involvement and elevated white matter lactate (LBSL) caused by a DARS2 polymorphism. DARS2 mutation was identified by combining MRI and genetic analysis. Our patient was affected by compound heterozygosity for a pathogenic mutation and a common variant, but with reduced aspartyl-tRNA synthetase activity. Brain and spinal cord magnetic resonance imaging revealed extensive white matter abnormalities; spectroscopy revealed no lactate elevation. A new compound heterozygous DARS2 variant combined with a polymorphism in the other allele in an adult patient with LBSL was identified, resulting in reduced DARS2 activity. This combination is rare and has consequences on how we should consider benign variant polymorphisms in the future.

Magnetic Resonance Imaging Features of the Nigrostriatal System: Biomarkers of Parkinson's Disease Stages?

INTRODUCTION: Magnetic resonance imaging (MRI) can be used to identify biomarkers in Parkinson's disease (PD); R2* values reflect iron content related to high levels of oxidative stress, whereas volume and/or shape changes reflect neuronal death. We sought to assess iron overload in the nigrostriatal system and characterize its relationship with focal and overall atrophy of the striatum in the pivotal stages of PD. METHODS: Twenty controls and 70 PD patients at different disease stages (untreated de novo patients, treated early-stage patients and advanced-stage patients with L-dopa-related motor complications) were included in the study. We determined the R2* values in the substantia nigra, putamen and caudate nucleus, together with striatal volume and shape analysis. We also measured R2* in an acute MPTP mouse model and in a longitudinal follow-up two years later in the early-stage PD patients. RESULTS: The R2* values in the substantia nigra, putamen and caudate nucleus were significantly higher in de novo PD patients than in controls. Early-stage patients displayed significantly higher R2* values in the substantia nigra (with changes in striatal shape), relative to de novo patients. Measurements after a two-year follow-up in early-stage patients and characterization of the acute MPTP mouse model confirmed that R2* changed rapidly with disease progression. Advanced-stage patients displayed significant atrophy of striatum, relative to earlier disease stages. CONCLUSION: Each pivotal stage in PD appears to be characterized by putative nigrostriatal MRI biomarkers: iron overload at the de novo stage, striatal shape changes at early-stage disease and generalized striatal atrophy at advanced disease.

A new approach to corpus callosum anomalies in idiopathic scoliosis using diffusion tensor magnetic resonance imaging.

PURPOSE: Idiopathic scoliosis (IS) is a frequent 3D structural deformity of the spine with a multi-factorial aetiology which remains largely unclear. In the last decade, human magnetic resonance imaging (MRI) morphometry studies (e.g. cortical thickness, 2D shape of the corpus callosum) have aimed to investigate the potential contribution of the central nervous system in the etiopathogenesis of IS. Recent developments in diffusion tensor imaging (DTI) allow us to extend the previous work to the study of white matter microstructure. Here, we hypothesized that part of the corpus callosum could show a difference in white matter microstructure in IS patients as compared to healthy controls. METHODS: We acquired DTI in 10 girls with IS and in 49 gender-matched controls to quantify the fractional anisotropy (FA) along the corpus callosum. RESULTS: Despite a very similar pattern of FA along the corpus callosum (maxima in the splenium and the genu and minimum in the isthmus), we found a significantly lower FA in the body in patients with IS as compared to control subjects. This region is known to connect the motor and premotor cortices of the two hemispheres. CONCLUSION: This first diffusion magnetic resonance imaging brain study in IS patients, suggests that differences in white matter development, such as synchronization of axonal myelination and pruning could be involved in the etiopathogenesis of IS.

Targeting chelatable iron as a therapeutic modality in Parkinson's disease.

AIMS: The pathophysiological role of iron in Parkinson's disease (PD) was assessed by a chelation strategy aimed at reducing oxidative damage associated with regional iron deposition without affecting circulating metals. Translational cell and animal models provided concept proofs and a delayed-start (DS) treatment paradigm, the basis for preliminary clinical assessments. RESULTS: For translational studies, we assessed the effect of oxidative insults in mice systemically prechelated with deferiprone (DFP) by following motor functions, striatal dopamine (HPLC and MRI-PET), and brain iron deposition (relaxation-R2*-MRI) aided by spectroscopic measurements of neuronal labile iron (with fluorescence-sensitive iron sensors) and oxidative damage by markers of protein, lipid, and DNA modification. DFP significantly reduced labile iron and biological damage in oxidation-stressed cells and animals, improving motor functions while raising striatal dopamine. For a pilot, double-blind, placebo-controlled randomized clinical trial, early-stage Parkinson's patients on stabilized dopamine regimens enrolled in a 12-month single-center study with DFP (30 mg/kg/day). Based on a 6-month DS paradigm, early-start patients (n=19) compared to DS patients (n=18) (37/40 completed) responded significantly earlier and sustainably to treatment in both substantia nigra iron deposits (R2* MRI) and Unified Parkinson's Disease Rating Scale motor indicators of disease progression (p<0.03 and p<0.04, respectively). Apart from three rapidly resolved neutropenia cases, safety was maintained throughout the trial. INNOVATION: A moderate iron chelation regimen that avoids changes in systemic iron levels may constitute a novel therapeutic modality for PD. CONCLUSIONS: The therapeutic features of a chelation modality established in translational models and in pilot clinical trials warrant comprehensive evaluation of symptomatic and/or disease-modifying potential of chelation in PD.

Cerebellum: links between development, developmental disorders and motor learning.

The study of the links and interactions between development and motor learning has noticeable implications for the understanding and management of neurodevelopmental disorders. This is particularly relevant for the cerebellum which is critical for sensorimotor learning. The olivocerebellar pathway is a key pathway contributing to learning of motor skills. Its developmental maturation and remodeling are being unraveled. Advances in genetics have led to major improvements in our appraisal of the genes involved in cerebellar development, especially studies in mutant mice. Cerebellar neurogenesis is compartmentalized in relationship with neurotransmitter fate. The Engrailed-2 gene is a major actor of the specification of cerebellar cell types and late embryogenic morphogenesis. Math1, expressed by the rhombic lip, is required for the genesis of glutamatergic neurons. Mutants deficient for the transcription factor Ptf1a display a lack of Purkinje cells and gabaergic interneurons. Rora gene contributes to the developmental signaling between granule cells and Purkinje neurons. The expression profile of sonic hedgehog in postnatal stages determines the final size/shape of the cerebellum. Genes affecting the development impact upon the physiological properties of the cerebellar circuits. For instance, receptors are developmentally regulated and their action interferes directly with developmental processes. Another field of research which is expanding relates to very preterm neonates. They are at risk for cerebellar lesions, which may themselves impair the developmental events. Very preterm neonates often show sensori-motor deficits, highlighting another major link between impaired developments and learning deficiencies. Pathways playing a critical role in cerebellar development are likely to become therapeutical targets for several neurodevelopmental disorders.

MRI atlas of the human hypothalamus.

Gaining new insights into the anatomy of the human hypothalamus is crucial for the development of new treatment strategies involving functional stereotactic neurosurgery. Here, using anatomical comparisons between histology and magnetic resonance images of the human hypothalamus in the coronal plane, we show that discrete gray and white hypothalamic structures are consistently identifiable by MRI. Macroscopic and microscopic images were used to precisely annotate the MRI sequences realized in the coronal plane in twenty healthy volunteers. MRI was performed on a 1.5 T scanner, using a protocol including T1-weighted 3D fast field echo, T1-weighted inversion-recovery, turbo spin echo and T2-weighted 2D fast field echo imaging. For each gray matter structure as well as for white matter bundles, the different MRI sequences were analyzed in comparison to each other. The anterior commissure and the fornix were often identifiable, while the mammillothalamic tract was more difficult to spot. Qualitative analyses showed that MRI could also highlight finer structures such as the paraventricular nucleus, the ventromedial nucleus of the hypothalamus and the infundibular (arcuate) nucleus, brain nuclei that play key roles in the regulation of food intake and energy homeostasis. The posterior hypothalamic area, a target for deep brain stimulation in the treatment of cluster headaches, was readily identified, as was the lateral hypothalamic area, which similar to the aforementioned hypothalamic nuclei, could be a putative target for deep brain stimulation in the treatment of obesity. Finally, each of the identified structures was mapped to Montreal Neurological Institute (MNI) space.

Neuroimaging features and pathology of mixed glioblastoma--AVM complex: a case report.

This report is of a rare case of glioblastoma coexisting with an arteriovenous malformation in a 65-year-old man. Multimodal magnetic resonance imaging (MRI) performed at 3T revealed a necrotic and cystic lesion in the left hemisphere; morphological and metabolic findings were consistent with an infiltrating high-grade glioma, but the presence of dark vessel-like signals on T2* and susceptibility-weighted imaging (SWI) suggested the coexistence of a vascular malformation. The arteriovenous malformation was confirmed by MR angiography and cerebral angiography. The patient was operated on, and histological examination revealed atypical cells characteristic of glioblastoma multiforme and, in the same area, arteriovenous malformation. The possible role of angiogenic factors in this case is also addressed.

Reevaluating brain networks activated during mental imagery of finger movements using probabilistic Tensorial Independent Component Analysis (TICA).

The cerebral and cerebellar networks involved in execution and mental imagery of the same sequential finger movements performed with the non-dominant hand were assessed by 3T functional magnetic resonance imaging using multivariate model-free analysis. Eight right-handed healthy volunteers successively performed execution and mental imagery tasks (sequential thumb to fingers opposition). The same data were analyzed by using (1) the linear General Model (p < 0.05 corrected), and (2) probabilistic tensorial independent component analysis (TICA). TICA confirmed that overt movement execution and motor imagery share a common network mainly including: premotor, parietal, insular, temporal, cerebellar cortices and putamen. Motor imagery specifically and bilaterally recruited frontopolar, prefrontal, cingulate, medial insula, neocerebellar cortices and precuneus. Non-dominant hand movements induced bilateral brain and cerebellar activation. In comparison with GLM, TICA identified a more widespread and bilateral network especially during motor imagery. TICA revealed that motor imagery also recruits frontopolar precuneal and occipital cortices, rostral M1/S1 corresponding to the hand somatotopic representation, thalamus and cerebellar lobule VIII. TICA also showed concomitant activation of (1) a cerebello-thalamo-cortical network during motor execution, and (2) a control executive network during imagination. TICA therefore allows precise identification of the brain networks collaborating in the same performance. TICA constitutes a valuable tool to assess and improve detection of brain networks engaged in mental imagery in comparison with GLM.

Sex steroid hormones-related structural plasticity in the human hypothalamus.

We investigated the effects of an artificial menstrual cycle on brain structure and activity in young women using metabolic magnetic resonance imaging (MRI). We show that the activation of the hypothalamo-pituitary-gonadal axis during the pill-free interval of low-dose combined oral contraceptive use is associated with transient microstructural and metabolic changes in the female hypothalamus but not in the thalamus, a brain structure unrelated to reproductive control, as assessed by water diffusion and proton magnetic resonance spectra measurements. Our results provide neuroanatomical insights into the mechanism by which sex steroid hormones mediate their central effects and raise the intriguing possibility that specific regions of the neuroendocrine brain use ovarian cycle-dependent plasticity to control reproduction in humans. These MRI-based physiological studies may pave the way for the development of new diagnostic and treatment strategies in the central loss of reproductive competence in human syndromes, such as hypothalamic amenorrhea.

Posterior reversible encephalopathy syndrome revealing acute post-streptococcal glomerulonephritis.

A case of acute encephalopathy with posterior corticosubcortical vasogenic edema on magnetic resonance imaging is reported. Angiography showed cerebral arterial vasospasm. A diagnosis of acute post-streptococcal glomerulonephritis was made 2 days after admission. This report highlights the fact that acute post-streptococcal glomerulonephritis can be revealed by a posterior reversible encephalopathy syndrome and that cerebral vasospasm can concur with vasogenic edema in this condition.

Ordered motor-unit firing behavior in acute cerebellar stroke.

It is known that at any given force level, the lower-threshold motor units generally fire at greater rates than the higher-threshold units during isometric tasks of extremity muscles. In addition to this hierarchical arrangement, firing rates of motor units fluctuate in unison with nearly no time delay; an observation that has led to the concept of common drive, a basic motoneuronal rule. Although it is established that the cerebellum plays a critical function in motor control, its role in the genesis, triggering, selection, and monitoring of motor-unit firing pattern discharges during isometric tasks is unknown. We applied an electromyographic (EMG) decomposition technique, known as precision decomposition, to accurately identify motor-unit firing times from the EMG signal recorded from the first dorsal interosseous muscle to unravel the features of motor-unit firings in three patients presenting a unilateral cerebellar stroke and exhibiting an acute cerebellar syndrome. We observed ataxic isometric force during visually guided abduction of the index finger on the affected side. However, the hierarchical response of individual motor units was spared. Furthermore, acute cerebellar ataxia was not associated with a loss of the common drive.