Lissencephaly With Cerebellar Hypoplasia Due To a New RELN Mutation.

Lissencephaly with cerebellar hypoplasia (LCH) is a rare variant form of lissencephaly, its distinctive neuroradiological phenotype being an important investigation clue regarding the potential involved genes, including variants in RELN gene. We report on a case of LCH whose clinical and neuroradiological features led to the identification of a homozygous pathogenic variant in RELN gene that has not been previously reported in the scientific literature.

Endocrine and Growth Abnormalities in 4H Leukodystrophy Caused by Variants in POLR3A, POLR3B, and POLR1C.

CONTEXT: 4H or POLR3-related leukodystrophy is an autosomal recessive disorder typically characterized by hypomyelination, hypodontia, and hypogonadotropic hypogonadism, caused by biallelic pathogenic variants in POLR3A, POLR3B, POLR1C, and POLR3K. The endocrine and growth abnormalities associated with this disorder have not been thoroughly investigated to date. OBJECTIVE: To systematically characterize endocrine abnormalities of patients with 4H leukodystrophy. DESIGN: An international cross-sectional study was performed on 150 patients with genetically confirmed 4H leukodystrophy between 2015 and 2016. Endocrine and growth abnormalities were evaluated, and neurological and other non-neurological features were reviewed. Potential genotype/phenotype associations were also investigated. SETTING: This was a multicenter retrospective study using information collected from 3 predominant centers. PATIENTS: A total of 150 patients with 4H leukodystrophy and pathogenic variants in POLR3A, POLR3B, or POLR1C were included. MAIN OUTCOME MEASURES: Variables used to evaluate endocrine and growth abnormalities included pubertal history, hormone levels (estradiol, testosterone, stimulated LH and FSH, stimulated GH, IGF-I, prolactin, ACTH, cortisol, TSH, and T4), and height and head circumference charts. RESULTS: The most common endocrine abnormalities were delayed puberty (57/74; 77% overall, 64% in males, 89% in females) and short stature (57/93; 61%), when evaluated according to physician assessment. Abnormal thyroid function was reported in 22% (13/59) of patients. CONCLUSIONS: Our results confirm pubertal abnormalities and short stature are the most common endocrine features seen in 4H leukodystrophy. However, we noted that endocrine abnormalities are typically underinvestigated in this patient population. A prospective study is required to formulate evidence-based recommendations for management of the endocrine manifestations of this disorder.

Proinflammatory and anti-inflammatory cytokines in the CSF of patients with Alzheimer's disease and their correlation with cognitive decline.

Cumulative data suggest that neuroinflammation plays a prominent role in Alzheimer's disease (AD) pathogenesis. The purpose of this work was to assess if patients with AD present a specific cerebrospinal fluid (CSF) cytokine profile and if it correlates to disease progression. We determined the levels of 27 cytokines in CSF of patients with AD and compared them with patients with frontotemporal dementia and nondemented controls. In addition, we correlated the cytokine levels with cognitive status and disease progression after 12 months. Patients with AD had higher levels of proinflammatory and anti-inflammatory cytokines (eotaxin, interleukin [IL]-1ra, IL-4, IL-7, IL-8, IL-9, IL-10, IL-15, granulocyte colony-stimulating factor, monocyte chemotactic protein 1, platelet-derived growth factor, tumor necrosis factor alfa) compared to nondemented controls. There was a negative correlation between the disease progression and the levels of several cytokines (IL-1ß, IL-4, IL-6, IL-9, IL-17A, basic fibroblast growth factor, granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, interferon gamma, macrophage inflammatory proteins-1ß). To the best of our knowledge, this is the first study reporting a "protective" role of the upregulation of specific intrathecal cytokine levels in AD. This finding supports that a fine "rebalancing" of the immune system represents a new target in AD therapeutic approach.

Fetal lipomyelomeningocele: A closed neural tube defect diagnosed at second-trimester ultrasound examination.

Fetal lipomyelomeningocele was suspected during the second-trimester ultrasound and confirmed by magnetic resonance imaging. The pregnancy took its course and a term neonate was delivered. At 2 years of age lipomyelomeningocele surgical removal was performed. The patient is now 4 years old and, despite neurogenic bladder, is a healthy boy with normal psychomotor development for his age. This case illustrates the favorable prognosis of this entity and the importance of prompt diagnosis and multidisciplinary counseling.

Language comprehension in nonspeaking children with severe cerebral palsy: Neuroanatomical substrate?

BACKGROUND AND AIMS: To identify relations between brain abnormalities and spoken language comprehension, MRI characteristics of 80 nonspeaking children with severe CP were examined. METHODS: MRI scans were analysed for patterns of brain abnormalities and scored for specific MRI measures: white matter (WM) areas; size of lateral ventricles, WM abnormality/reduction, cysts, subarachnoid space, corpus callosum thinning and grey matter (GM) areas; cortical GM abnormalities, thalamus, putamen, globus pallidus and nucleus caudatus and cerebellar abnormalities. Language comprehension was assessed with a new validated instrument (C-BiLLT). RESULTS: MRI scans of 35 children were classified as a basal ganglia necrosis (BGN) pattern, with damage to central GM areas; in 60% of these children damage to WM areas was also found. MRI scans of 13 children were classified as periventricular leukomalacia (PVL) with little concomitant damage to central GM areas, 13 as malformations and 19 as miscellaneous. Language comprehension was best in children with BGN, followed by malformations and miscellaneous, and was poorest in PVL. Linear regression modelling per pattern group (malformations excluded), with MRI measures as independent variables, revealed that corpus callosum thinning in BGN and parieto-occipital WM reduction in PVL were the most important explanatory factors for poor language comprehension. No MRI measures explained outcomes in language comprehension in the miscellaneous group. CONCLUSIONS: Comprehension of spoken language differs between MRI patterns of severe CP. In children with BGN and PVL differences in language comprehension performance is attributed to damage in the WM areas. Language comprehension was most affected in children with WM lesions in the subcortical and then periventricular areas, most characteristic for children with PVL.

The unique features of traumatic brain injury in children. review of the characteristics of the pediatric skull and brain, mechanisms of trauma, patterns of injury, complications, and their imaging findings--part 2.

Traumatic brain injury (TBI) is a major cause of morbidity and mortality in children. The unique biomechanical, hemodynamical, and functional characteristics of the developing brain and the age-dependent variance in trauma mechanisms result in a wide range of age specific traumas and patterns of brain injuries. Detailed knowledge of the main primary and secondary pediatric injuries, which enhance sensitivity and specificity of diagnosis, will guide therapy and may give important information about the prognosis. In recent years, anatomical but also functional imaging methods have revolutionized neuroimaging of pediatric TBI. The purpose of this article is (1) to comprehensively review frequent primary and secondary brain injuries and (2) to give a short overview of two special types of pediatric TBI: birth related and nonaccidental injuries.

Clinical, neuropathological, and genetic characteristics of the novel IVS9+1delG GRN mutation in a patient with frontotemporal dementia.

Frontotemporal lobar degeneration (FTLD) refers to a clinically, pathologically, and genetically heterogeneous group of dementias that arises from the degeneration of the frontal and temporal lobes. Mutations in the progranulin gene (GRN) are a major cause of FTLD with TDP-43 inclusions. Herein, we describe the clinical, neuropathological, and genetic findings in a case of autosomal dominant behavioral variant of frontotemporal dementia (bvFTD) with asymmetrical parkinsonism and prominent visuospatial deficits that carries a novel GRN mutation. This case highlights important clinical characteristics that seem to be common in FTLD GRN-associated patients, such as asymmetrical parkinsonism and parietal symptoms, and that are correlated to the pathological involvement of striatum (rather than substantia nigra in our case) and parietal lobe. We also emphasize that plasma progranulin level can be useful to infer about the pathogenicity of new GRN mutations.

The unique features of traumatic brain injury in children. Review of the characteristics of the pediatric skull and brain, mechanisms of trauma, patterns of injury, complications and their imaging findings--part 1.

Traumatic head/brain injury (TBI) is a leading cause of death and life-long disability in children. The biomechanical properties of the child's brain and skull, the size of the child, the age-specific activity pattern, and higher degree of brain plasticity result in a unique distribution, degree, and quality of TBI compared to adult TBI. A detailed knowledge about the various types of primary and secondary pediatric head injuries is essential to better identify and understand pediatric TBI. The goals of this review article are (1) to discuss the unique epidemiology, mechanisms, and characteristics of TBI in children, and (2) to review the anatomical and functional imaging techniques that can be used to study common and rare pediatric traumatic brain injuries and their complications.

Normal rates of neuroradiological findings in children with high functioning autism.

Magnetic resonance imaging (MRI) has been used to analyze highly specific volumetric and morphological features of the brains of individuals with autism spectrum disorder (ASD). To date, there are few comprehensive studies examining the prevalence of neuroradiologic findings seen on routine MRI scans in children with ASD. This study examined the prevalence of neuroradiologic findings in children with high functioning ASD, and compared these rates to those in children with Attention-Deficit/Hyperactivity Disorder (ADHD) and children who are typically developing (TD). Results showed that approximately 90% of children had normal MRI scans. There was no significant effect of diagnosis on the total number of neuroradiological findings or the number of specific brain findings. Implications and future research directions are discussed.

Magnetic resonance imaging features of meningiomas in children and young adults: a retrospective analysis.

OBJECTIVES: Meningiomas are rare in children and, unlike in adults, they have male predominance, unusual locations, cystic components and poorer clinical outcomes. The aims of our study were to: a) evaluate the MRI features of pediatric meningiomas; b) correlate ADC values of meningiomas with clinical and histopathological types; and c) correlate peritumoral edema with size and histopathological type of tumor. PATIENTS AND METHODS: Radiological data from 24 patients (mean age: 14.3 years) with an imaging or histopathological diagnosis of meningioma, and presurgical MRI between 1995 and 2009 from two medical institutions, were reviewed. Meningiomas were clinically classified as spontaneously arising meningiomas (SAM), NF2-associated meningiomas (NF2-M) and radiation-induced meningiomas (RIM) and, histopathologically, according to the WHO classification system. The main MRI signal characteristics and enhancement were evaluated. ADC values were compared with histopathological type and clinical group. Tumor size and peritumoral edema were also assessed. RESULTS: Thirty-four meningiomas (eight SAM, 13 NF2-M, 13 RIM) in 24 patients (12 male, 12 female) were evaluated. Unusual locations were frequently seen in SAM, including cases of intraventricular and intraparenchymal meningiomas. SAM were also always larger than either RIM or NF2-M. Cystic components were only found in SAM, and were not associated with high-grade tumors (WHO II and III). Mean ADC values were significantly different between SAM and NF2-M, but were not associated with histopathological type. Peritumoral edema correlated with tumor size, but did not differ significantly according to clinical group. CONCLUSION: Pediatric SAM have unusual locations, larger size and cystic components, and are diagnosed at a younger age than NF2-M and RIM. NF2-M can have unusual locations such as, in particular, the craniocervical junction. Tumor ADC values did not help to predict tumor grade or clinical type. Peritumoral edema correlated with tumor size, but not with clinical group or histopathological grade.

Birth-related injury to the head and cervical spine in neonates.

Birth-related injury is defined as any traumatic or ischemic event sustained during the process of delivery. Perinatally acquired disease processes secondary to birth-related injury can be traumatic or ischemic in nature. In this article, the authors focus on traumatic/mechanical injuries. Other diseases of the perinatal time period, including germinal matrix hemorrhages and hypoxic-ischemic encephalopathy, are beyond the objective of this review.

Acute hemorrhagic leukoencephalitis with severe brainstem and spinal cord involvement: MRI features with neuropathological confirmation.

Acute hemorrhagic leukoencephalitis (AHLE) is a rare and fulminant demyelinating disease considered to be the most severe form of acute disseminated encephalomyelitis (ADEM). A 70-year-old man was admitted to our emergency department (ED) after 1 week of unspecific abdominal symptoms and moderate fever in the first 3 days. Within the ED he developed a rapid onset coma and flaccid tetraparesis. Cerebrospinal fluid (CSF) analysis showed mild polymorphonuclear pleocytosis and magnetic resonance imaging (MRI) revealed supratentorial focal white matter lesions and diffuse involvement of the medulla and spinal cord. A presumptive diagnosis of ADEM was made and the patient was treated with corticosteroids followed by intravenous immunoglobulin. His neurological state did not improve and the MRI on day 8 after admission showed an increased number of lesions, mainly in the brainstem, with hemorrhagic foci. The patient died the following day and pathological features confirmed the diagnosis of AHLE. This is a unique presentation of a rare disease with detailed MRI characteristics and pathological confirmation. Although this condition is usually fatal, early recognition and aggressive therapeutic management can facilitate survival.

Non-invasive imaging of intracranial pediatric vascular lesions.

OBJECTIVES: The goal of this review is to discuss the different non-invasive imaging techniques as well as the age-specific pediatric vascular pathologies and their imaging features. MATERIAL AND METHODS: Ultrasound, computed tomography, and magnetic resonance imaging features of pediatric ischemic stroke, intracranial hemorrhage, aneurysms, cavernomas, developmental venous anomalies, and arteriovenous malformations are presented. In addition, multiple non-invasive angiographic techniques (CT and MR angiography) and functional MRI sequences (diffusion, perfusion, and susceptibility-weighted imaging) are discussed. CONCLUSION: Neurovascular imaging plays a central role in the early, sensitive, and specific diagnosis of pediatric intracranial vascular disorders. A detailed knowledge of the quality and exact angioarchitecture of pediatric vascular pathologies as well as their impact on the cerebral hemo-dynamics is essential to guide and monitor treatment options and to predict functional outcome.

Congenital giant cervical teratoma: pre- and postnatal imaging.

Pre- and postnatal imaging findings are presented in a fetus/neonate with congenital cervical teratoma (CCT). Prenatal fetal MRI proved to be essential in the exact localization and characterization of the CCT while excluding potentially life-threatening prenatal complications. The provided information improved outcome by guiding decisions concerning delivery and postnatal care.

CT and MR imaging of extrahepatic fatty masses of the abdomen and pelvis: techniques, diagnosis, differential diagnosis, and pitfalls.

The differential diagnosis of extrahepatic abdominopelvic masses is wide. Demonstration of fat within a lesion at noninvasive imaging is an important clue for narrowing the differential diagnosis. Macroscopic fat is readily identified with both computed tomography (CT) and magnetic resonance (MR) imaging. Demonstration of microscopic fat is more difficult and may require special techniques. Identification of fat with CT is based on x-ray resorption and therefore on the attenuation (typically less than -20 HU). Several MR imaging techniques have been developed for fat suppression. Two of the most widely available are spectroscopic fat saturation and chemical shift (in-phase/opposed-phase) imaging. Entities with predominantly macroscopic fat include myelolipoma, angiomyolipoma, teratoma, liposarcoma, lipoma, epiploic appendagitis, omental infarction, and mesenteric panniculitis. Lesions with predominantly microscopic fat include adrenal adenoma and some teratomas. Other fat-containing entities involve the mesentery and bowel wall; these include fibrofatty mesenteric proliferation and submucosal fat deposition.

Disproportionate fat stranding: a helpful CT sign in patients with acute abdominal pain.

Fat stranding adjacent to thickened bowel wall seen at computed tomography (CT) in patients with acute abdominal pain suggests an acute process of the gastrointestinal tract, but the differential diagnosis is wide. The authors observed "disproportionate" fat stranding (ie, stranding more severe than expected for the degree of bowel wall thickening present) and explored how this finding suggests a narrower differential diagnosis, one that is centered in the mesentery: diverticulitis, epiploic appendagitis, omental infarction, and appendicitis. The characteristic CT findings (in addition to fat stranding) of each of these entities often lead to a final diagnosis. Diverticulitis manifests with mild, smooth bowel wall thickening and no lymphadenopathy. Epiploic appendagitis manifests with central areas of high attenuation and a hyperattenuated rim, in addition to its characteristic location adjacent to the colon. In contrast, omental infarction is always centered in the omentum. The most specific finding of appendicitis is a dilated, fluid-filled appendix. Correct noninvasive diagnosis is important because treatment approaches for these conditions range from monitoring to surgery.

Cisterna chyli at routine abdominal MR imaging: a normal anatomic structure in the retrocrural space.

The cisterna chyli, a dilated lymphatic sac in the retrocrural space, represents the origin of the thoracic duct. It is seen in approximately half of lymphangiographic studies and 20% of autopsies. Highly fluid-sensitive magnetic resonance (MR) imaging sequences such as single-shot rapid acquisition with refocused echoes, which are currently used in many abdominal MR imaging protocols, frequently result in the depiction of this structure. The cisterna chyli was evident on abdominal MR images acquired in 30 (15%) of 200 consecutive patients who underwent MR imaging at the authors' institution between February and June 2002. Its appearance varied from that of a thick tube to that of a thin tube, parallel or converging tubes, tortuous tubes, a sausage-shaped fluid collection, a focal collection, or a focal plexus. Radiologists who perform MR imaging should be familiar with the various possible appearances of this normal anatomic structure so as not to mistake it for a pathologic entity.

Spinous process fractures associated with Baastrup disease.

Patients with Baastrup disease may experience pain owing to irritation of the periosteum or adventitial bursae between abutting spinous processes. We are not aware of any reports in the literature that describe stress fractures of the spinous fractures in patients with Baastrup disease. In this case report, we present two cases of spinous process fractures in lumbar vertebrae associated with Baastrup disease and describe their appearance with conventional radiography, bone scintigraphy, computed tomography (CT) and magnetic resonance (MR) imaging.