Myxoid glioneuronal tumor: Histopathologic, neuroradiologic, and molecular features in a single center series.

BACKGROUND: Myxoid glioneuronal tumor (MGT) is a benign glioneuronal neoplasm recently introduced in the World Health Organization (WHO) classification of the central nervous system (CNS) tumors. MGTs are typically located in the septum pellucidum, foramen of Monro or periventricular white matter of the lateral ventricle. They were previously diagnosed as dysembryoplastic neuroepithelial tumors (DNT), showing histological features almost indistinguishable from classical cortical DNT. Despite that, MGTs have been associated with a specific dinucleotide substitution at codon 385 in the platelet-derived growth factor receptor alpha (PDGFRA) gene, replacing a lysine residue with either leucine or isoleucine (p. LysK385Leu/Iso). This genetic variation has never been described in any other CNS tumor. MATERIALS AND METHODS: Thirty-one consecutive tumors, previously diagnosed as DNTs at the Meyer Children's Hospital IRCCS between January 2010 and June 2021 were collected for a comprehensive study of their clinical, imaging, pathological features, and molecular profile. RESULTS: In six out of the thirty-one tumors we had previously diagnosed as DNTs, we identified the recurrent dinucleotide mutation in the PDGFRA. All six tumors were typically located within the periventricular white matter of the lateral ventricle and in the septum pellucidum. We then renamed these lesions as MGT, according to the latest WHO CNS classification. In all patients we observed an indolent clinical course, without recurrence. CONCLUSION: MGT represent a rare but distinct group of neoplasm with a typical molecular profiling, a characteristic localization, and a relative indolent clinical course.

Central olfactory processing in patients with disorders of consciousness.

BACKGROUND AND PURPOSE: Previous studies have demonstrated that individuals suffering from disorder of consciousness (DOC) maintain some minor neural processing of percepts mediated by senses that early in their pathway intersect the thalamus, a key dysfunctional area in DOC patients. Here the degree of sensory preservation within the olfactory system, a system that lacks an obligatory thalamic relay, and its relationship to the consciousness level in DOC patients of various etiologies was assessed. METHODS: Clinical Coma Recovery Scale - Revised (CRS-R) as well as cerebral responses to odors by means of functional magnetic resonance were obtained in a group of vegetative state/unresponsive wakefulness syndrome (n = 26) patients, minimally conscious state (n = 7) patients and healthy controls (n = 25). RESULTS: A majority of vegetative state/unresponsive wakefulness syndrome patients (58%) and 100% of minimally conscious state patients demonstrated a significant preservation of olfactory neural processing, manifested by activation within the piriform cortex, an area considered as a primary olfactory region. Degree of preservation of olfactory processing differed linearly in line with the patients' etiologies where groups demonstrating greater conscious awareness demonstrated more significant processing. Viewed over all DOC patients, there was a significant negative association between odor-related activity in the orbitofrontal cortex and CRS-R scores. CONCLUSIONS: It is demonstrated that DOC patients exhibit a significant preservation of olfactory neural processing with a clear relationship to etiopathologies and clinical measures even years after of chronification of DOC.

Significance of multiple neurophysiological measures in patients with chronic disorders of consciousness.

OBJECTIVE: The aim of this study was to verify the value of multiple neurophysiological tests in classifying disorders of consciousness (DOCs) in patients in a chronic vegetative or minimal consciousness state categorised on the basis of the Coma Recovery Scale (CRS). METHODS: The study included 142 patients, all of whom underwent long (18h) EEG-polygraphic recordings including one night. The EEG was scored using the Synek scale and sleep patterns using an arbitrary scale. Absolute total power and relative EEG power were evaluated in different frequency bands. Multimodal evoked potentials (EPs), including auditory event-related potentials, were also evaluated and scored. RESULTS: The most information came from the combined multimodal EPs and sleep EEG scores. A two-step cluster analysis based on the collected information allowed a satisfactory evaluation of DOC severity. Spectral EEG properties seemed to be significantly related to DOC classes and CRS scores, but did not seem to make any significant additional contribution to DOC classification. CONCLUSIONS: Multiple electrophysiological evaluations based on EEG, sleep polygraphic recordings and multimodal EPs are helpful in assessing DOC severity and residual functioning in patients with chronic DOCs. SIGNIFICANCE: Simple electrophysiological measures that can be easily applied at patients' bedsides can significantly contribute to the recognition of DOC severity in chronic patients surviving a severe brain injury.

Preoperative language lateralization in temporal lobe epilepsy (TLE) predicts peri-ictal, pre- and post-operative language performance: An fMRI study.

In patients with temporal lobe epilepsy (TLE), assessment of language lateralization is important as anterior temporal lobectomy may lead to language impairments. Despite the widespread use of fMRI, evidence of its usefulness in predicting postsurgical language performance is scant. We investigated whether preoperative functional lateralization is related to the preoperative language performance, peri-ictal aphasia, and can predict language outcome one year post-surgery. We studied a total of 72 TLE patients (42 left, 30 right), by using three fMRI tasks: Naming, Verb Generation and Fluency. Functional lateralization indices were analyzed with neuropsychological scores and presence of peri-ictal aphasia. The key findings are:1)Both left and right TLE patients show decreased left lateralization compared to controls.2)Lateralization correlates with language performance before surgery. In left TLE, decreased left lateralization correlates with better fluency performance. In right TLE, increased left lateralization during the Naming task correlates with better naming.3)Left lateralization correlates with peri-ictal aphasia in left TLE patients.4)Lateralization correlates with language performance after surgery. In a subgroup of left TLE who underwent surgery (17 left), decreased left lateralization is predictive of better naming performance at 6 and 12 months after surgery. The present study highlights the clinical relevance of fMRI language lateralization in TLE, especially to predict language outcome one year post-surgery. We also underline the importance of using fMRI tasks eliciting frontal and anterior temporal activations, when studying left and right TLE patients.

Pendular nystagmus in hypomyelinating leukodystrophy.

We report the case of a 49-year old woman affected by hypomyelinating leukodystrophy. She presented with typical pendular nystagmus that was analyzed with video-oculography which is provided in the supplementary material of the report. The pendular nystagmus was accompanied by upper limb ataxia on the index-to-nose test. The video was partly recorded with a slow-motion technique in order to better demonstrate the ataxia and the pendular nystagmus. The brain MRI demonstrated a characteristic pattern of hypomyelination. Pendular nystagmus is a key clinical sign that contributes to the diagnosis of CNS hypomyelination when a leukodystrophic pattern is observed on brain MRI.

CT and MRI of brain tumors.

Imaging plays a crucial role in the management of patients with brain tumors. The technical improvement of computed tomography (CT) and magnetic resonance (MRI) with the development of, new imaging techniques strongly improved the detection and characterization of brain tumors. For the optimal therapeutic management of the oncologic patient not only the recognition of the lesion is needed, but also the exclusion of other diseases that can mimic brain tumors. The preoperative assessment of malignancy and of relationships of the tumor with surrounding eloquent structures are also necessary to allow the correct choice of therapy and to warn surgeons of possible risks of the surgical approach. This article is an overview of the current state of neuroimaging of the most frequent brain tumors including CT and MRI, perfusion weighted imaging (PWI), diffusion weighted imaging (DWI), diffusion tensor imaging (DTI), proton magnetic resonance spectroscopy (1H-MRS) and functional MRI based on blood oxygen level (fMRI BOLD). Indeed, in the last years, a transition took place from a purely anatomy-based radiology to one that incorporates functional, hemodynamic, metabolic, cellular, and cytoarchitectural alterations. Neuroimaging has evolved into a comprehensive diagnostic tool that allows the characterization of morphologic as well as biologic alterations to diagnose and grade brain tumors and to monitor and assess treatment response and patient prognosis.

Combined 7-T MRI and histopathologic study of normal and dysplastic samples from patients with TLE.

OBJECTIVES: The purpose of the study was to investigate the abnormalities of cortical lamination observed in temporal lobe specimens obtained during surgery for intractable temporal lobe epilepsy (TLE) with hippocampal sclerosis. Specifically, we aimed to 1) correlate high-field ex vivo MRI with histopathologic analysis and 2) evaluate the effect of tissue fixation on image contrast. METHODS: A cohort of 13 specimens was considered. T2-weighted imaging and relaxometry were performed during and after fixation using a 7-T experimental scanner. After imaging, the specimens were studied with histopathologic (Black Gold myelin fiber staining) and immunohistochemical (NeuN neuronal staining) methods in order to explore the correspondence between MRI and histopathologic features. RESULTS: The principal findings of this study are that 1) superior MRI contrast is obtained among the cortical layers using completely fixed specimens as opposed to recently excised tissue, 2) the intensity of the T2-weighted MRI signal is lowest (hypointensity) at the site of highest fiber concentration and cellular density, and highest (hyperintensity) when the density of fibers and cells is lowest, and 3) the MRI signal is altered in presence of abnormal cortical lamination (focal cortical dysplasia type IA). CONCLUSIONS: High resolution ex vivo MRI enables the study of intracortical organization in normal and pathologic areas. Comparisons between MRI, NeuN, and Black Gold indicate that the differences apparent in T2-weighted images are mainly related to fiber concentration, although neuronal density might also play a role.

Bio-image warehouse system: concept and implementation of a diagnosis-based data warehouse for advanced imaging modalities in neuroradiology.

Advanced neuroimaging techniques, such as functional magnetic resonance imaging (fMRI), chemical shift spectroscopy imaging (CSI), diffusion tensor imaging (DTI), and perfusion-weighted imaging (PWI) create novel challenges in terms of data storage and management: huge amounts of raw data are generated, the results of analysis may depend on the software and settings that have been used, and most often intermediate files are inherently not compliant with the current DICOM (digital imaging and communication in medicine) standard, as they contain multidimensional complex and tensor arrays and various other types of data structures. A software architecture, referred to as Bio-Image Warehouse System (BIWS), which can be used alongside a radiology information system/picture archiving and communication system (RIS/PACS) system to store neuroimaging data for research purposes, is presented. The system architecture is conceived with the purpose of enabling to query by diagnosis according to a predefined two-layered classification taxonomy. The operational impact of the system and the time needed to get acquainted with the web-based interface and with the taxonomy are found to be limited. The development of modules enabling automated creation of statistical templates is proposed.

L-2-hydroxyglutaric aciduria and brain malignant tumors: a predisposing condition?

L-2-hydroxyglutaric aciduria is a rare metabolic encephalopathy displaying a subcortical leukoencephalopathy on MRI. Diagnosis rests on detection of an abnormal accumulation of L-2-hydroxyglutaric acid in body fluids. The authors report on four patients who developed a malignant brain tumor during the course of the disease. This association points to a possible role of L-2-hydroxyglutaric aciduria in predisposing to brain tumorigenesis.

Spinal radiological findings in nine patients with spontaneous intracranial hypotension.

Cranial magnetic resonance imaging (MRI) findings in spontaneous intracranial hypotension (SIH) are well known, while spinal studies have received less attention. Radiological spinal findings in nine patients with SIH are presented, looking for possible characteristic features. Five of the nine patients had histories of previous minor trauma, one of previous surgery; in three patients possible relevant preceding events were completely absent. All nine patients had cervical, seven thoracic, and four lumbar spine MRI studies; post-contrast studies were obtained in seven cases, MRI myelograms in five. Radioisotope myelocisternography was performed in four patients and myelo-CT in four. Epidural fluid collections were found in seven patients. In six cases the dural sac had collapsed, with a festooned appearance; intense epidural enhancement on post-contrast studies demonstrated marked dilatation of the epidural venous plexus. In three cases an irregular root sleeve suggested a possible point of cerebrospinal fluid (CSF) leakage. Myelo-CT demonstrated the CSF fistula in two cases, radioisotope myelocisternography in three. The pattern of spinal abnormalities is different from that seen in cranial MRI for anatomical reasons: in the spinal canal the dura is not adherent to the bone; therefore, collapse of the dural sac and dilatation of epidural venous plexus occur, rather than subdural hematomas. In most cases the search for the dural tear is difficult. Radioisotope cisternography is probably the most sensitive examination for documenting the leakage of CSF out of the subarachnoid space; myelo-CT may precisely demonstrate the point of the CSF fistula, whereas MRI may only suggest it.

Effect of bilateral subthalamic electrical stimulation in Parkinson's disease.

BACKGROUND: Bilateral high frequency subthalamic stimulation has been reported to be effective in the treatment of Parkinson's disease and levodopa-induced dyskinesias. To analyze the results of this surgical procedure we critically reviewed 17 parkinsonian patients with advanced disease complicated by motor fluctuations and dyskinesias. METHODS: Between January 1998 and June 1999 these 17 consecutive patients (age 48-68 years; illness duration 8-27 years) underwent bilateral stereotactically guided implantation of electrodes into the subthalamic nucleus in the Department of Neurosurgery of the Istituto Nazionale Neurologico "C. Besta." Parameters used for continuous high-frequency stimulation were: frequency 160 Hz, pulse width 90 microsec, mean amplitude 2.05 +/- 0.45 V. Parts II and III of the UPDRS were used to assess motor performance before and after operation by the neurologic team. The follow-up ranged between 6 and 18 months. RESULTS: At latest examination, mean UPDRS II and III scores had improved by 30% (on stimulation, off therapy) with mean 50% reduction in daily off time. Peak dyskinesias and early morning dystonias also improved in relation to therapy reduction. Side effects were persistent postoperative supranuclear oculomotor palsy and postural instability in one case, worsened off-medication hypophonia in three, and temporary nocturnal confusion episodes in three. Postoperative MRI revealed a clinically silent intracerebral haematoma in one case. One electrode required repositioning. CONCLUSIONS: Continuous high frequency STN stimulation is an effective treatment for advanced PD. A functionally useful and safe electrode placement can be performed without microrecording.

A novel mtDNA mutation in the ND5 subunit of complex I in two MELAS patients.

We identified a novel heteroplasmic mutation in the mitochodrial DNA gene encoding the ND5 subunit of complex I. This mutation (13514A-->G) hits the same codon affected by a previously reported mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes (MELAS)-associated mutation (13513G-->A), but the amino acid replacement is different (D393G vs D393N). The 13514A-->G mutation was found in two unrelated MELAS-like patients. However, in contrast to typical MELAS, lactic acidosis was absent or mild and the muscle biopsy was morphologically normal. Strongly positive correlation between the percentage of heteroplasmy and defective activity of complex I was found in cybrids. We found an additional 13513G-->A-positive case, affected by a progressive mitochondrial encephalomyopathy. Our results clearly demonstrate that the amino acid position D393 is crucial for the function of complex I. Search for D393 mutations should be part of the routine screening for mitochondrial disorders.

A case of 3-methylglutaconic aciduria misdiagnosed as cerebral palsy.

3-Methylglutaconic aciduria is a rare hereditary metabolic disorder characterized by increased urinary excretion of 3-methylglutaconic and 3-methylglutaric acids. Four clinical forms are recognized. This study presents the case of a 5-year-old male with type IV 3-methylglutaconic aciduria, initially diagnosed as "static encephalopathy." The slow evolution and other clinical characteristics, together with cerebral magnetic resonance imaging (MRI) findings, eventually directed the diagnosis to organic aciduria that was confirmed by urine test. This study proposes that the clinical criteria for childhood cerebral palsy should be rigorously respected; neuroimaging studies, particularly MRI, should be conducted to confirm the diagnosis, especially in atypical cases.

MRI in neuronal ceroid lipofuscinosis.

Magnetic resonance imaging in neuronal ceroid lipofuscinosis (NCL) demonstrates cerebral and cerebellar atrophy, T2-hyperintensity of the lobar white matter and thinning of the cerebral cortex. The association of these findings, although non specific, can be observed in all the different forms of NCL, narrows the differential diagnosis of the infantile progressive encephalopathies and may suggest the diagnosis.

Costello syndrome: a cancer predisposing syndrome?

Costello Syndrome is a specific MCA/MR syndrome mainly characterized by dysmorphic facial features, peculiar biphasic growth pattern, motor and mental retardation, ectodermal anomalies involving skin and nails, and age dependent development of nasal and perianal papillomata. Heart malformations and/or hypertrophic cardiomyopathy are frequently observed. We report a 4-year-old girl with Costello syndrome who developed an intrathoracic ganglioneuroblastoma. In previous reports two patients with ectodermal tumours have been described, a ganglioneuroblastoma of the adrenal gland and an epithelioma. This third report suggests that neural crest neoplasia may be a significant risk factor for children with Costello syndrome.

Clinical, biochemical and neuroradiological findings in L-2-hydroxyglutaric aciduria.

L-2-Hydroxyglutaric aciduria is a rare inborn error of metabolism, marked by a large and persistent increase of L-2-hydroxyglutaric acid in urine, blood and cerebrospinal fluid (CSF). We present clinical, biochemical and neuroradiological findings of seven Italian patients aged 4-19 years presenting at different stages of the disease. The disorder was characterized by a progressive neurological syndrome with cerebellar and pyramidal signs, mental deterioration, epilepsy and subcortical leukoencephalopathy on magnetic resonance imaging (MRI). We observed a good correlation between the severity of the disease and the extent of lesions on MRI. We report the result of the first positive prenatal diagnosis.

Infantile neuroaxonal dystrophy: neuroradiological studies in 11 patients.

We report the imaging findings in 11 patients with infantile neuroaxonal dystrophy. Ten patients underwent 15 MRI examinations; one patient had only CT. Of the ten patients who underwent MRI, eight had cerebellar atrophy and mildly increased signal from the cerebellar cortex on T2-weighted images. With T2 weighting there was slightly increased signal from the dentate nuclei in two patients and from the posterior periventricular white matter in three. We saw four patients with a thin optic chiasm. The only two brothers in the series had markedly low signal from the globus pallidus and substantia nigra on 1.5 T T2-weighted images, as seen in Hallervorden-Spatz disease (HSD). Abnormalities of the globus pallidus may be related to a protracted course of the disease. However, an overlap with HSD should be considered.

L-2-Hydroxyglutaric aciduria: MRI in seven cases.

The MRI findings in 7 patients with L-2-Hydroxyglutaric aciduria (L-2-OHG aciduria) are described and compared with previous neuroradiological reports and the only three published pathological cases. Signal abnormalities involved peripheral subcortical white matter, basal ganglia and dentate nuclei. Cerebellar atrophy was present. Although similar appearances may be seen in other metabolic disorders, the distribution of signal abnormalities in L-2-OHG aciduria is highly characteristic and may suggest the correct diagnosis.