An oligodendrocyte silencer element underlies the pathogenic impact of lamin B1 structural variants.

The role of non-coding regulatory elements and how they might contribute to tissue type specificity of disease phenotypes is poorly understood. Autosomal Dominant Leukodystrophy (ADLD) is a fatal, adult-onset, neurological disorder that is characterized by extensive CNS demyelination. Most cases of ADLD are caused by tandem genomic duplications involving the lamin B1 gene ( ) while a small subset are caused by genomic deletions upstream of the gene.

Brain MRI features and scoring of leukodystrophy in adult-onset Krabbe disease.

Objective: To perform a systematic analysis and scoring of brain MRI white matter hyperintensities (WMH) in adult-onset Krabbe disease.

Methods: We retrospectively collected basic clinical data and the first available brain MRI from patients with confirmed Krabbe disease with first clinical manifestations beyond 10 years of age. Data were obtained from our reference center for lysosomal diseases (n = 6) and from contacted authors of published articles describing patients with adult-onset Krabbe disease (n = 15).

Genomic deletions upstream of lamin B1 lead to atypical autosomal dominant leukodystrophy.

Objective: Clinical, radiologic, and molecular analysis of patients with genomic deletions upstream of the gene.

Methods: Detailed neurologic, MRI examinations, custom array comparative genomic hybridization (aCGH) analysis, and expression analysis were performed in patients at different clinical centers. All procedures were approved by institutional review boards of the respective institutions.

The value of magnetic resonance spectroscopy as a supplement to MRI of the brain in a clinical setting.

Background: There are different opinions of the clinical value of MRS of the brain. In selected materials MRS has demonstrated good results for characterisation of both neoplastic and non-neoplastic lesions. The aim of this study was to evaluate the supplemental value of MR spectroscopy (MRS) in a clinical setting.

Intracranial pressure elevations in diffuse axonal injury: association with nonhemorrhagic MR lesions in central mesencephalic structures.

Objective: Increased intracranial pressure (ICP) in patients with severe traumatic brain injury (TBI) with diffuse axonal injury (DAI) is not well defined. This study investigated the occurrence of increased ICP and whether clinical factors and lesion localization on MRI were associated with increased ICP in patients with DAI.

Methods: Fifty-two patients with severe TBI (median age 24 years, range 9-61 years), who had undergone ICP monitoring and had DAI on MRI, as determined using T2*-weighted gradient echo, susceptibility-weighted imaging, and diffusion-weighted imaging (DWI) sequences, were enrolled.

Glucose metabolism in the brain in LMNB1-related autosomal dominant leukodystrophy.

Objective: LMNB1-related autosomal dominant leukodystrophy is caused by an overexpression of the protein lamin B1, usually due to a duplication of the LMNB1 gene. Symptoms start in 5 to 6 decade. This slowly progressive disease terminates with death.

Novel SACS mutations associated with intellectual disability, epilepsy and widespread supratentorial abnormalities.

We describe eight subjects from two consanguineous families segregating with autosomal recessive childhood onset spastic ataxia, peripheral neuropathy and intellectual disability. The degree of intellectual disability varied from mild to severe and all four affected individuals in one family developed aggressive behavior and epilepsy. Using exome sequencing, we identified two novel truncating mutations (c.

Extended Anatomical Grading in Diffuse Axonal Injury Using MRI: Hemorrhagic Lesions in the Substantia Nigra and Mesencephalic Tegmentum Indicate Poor Long-Term Outcome.

Clinical outcome after traumatic diffuse axonal injury (DAI) is difficult to predict. In this study, three magnetic resonance imaging (MRI) sequences were used to quantify the anatomical distribution of lesions, to grade DAI according to the Adams grading system, and to evaluate the value of lesion localization in combination with clinical prognostic factors to improve outcome prediction. Thirty patients (mean 31.

YKL-40 is a CSF biomarker of intrathecal inflammation in secondary progressive multiple sclerosis.

YKL-40 (CHI3L1) is a glycoprotein predominantly produced by reactive astrocytes in chronic active MS lesions, which are common in secondary progressive MS. In this study, YKL-40 was investigated in different stages of MS and in relation to MRI findings. YKL-40 levels in CSF samples from two independent patient cohorts of MS patients were determined with ELISA.

LMNB1-related autosomal-dominant leukodystrophy: Clinical and radiological course.

Objective: Duplication of the LMNB1 gene encoding lamin B1 causes adult-onset autosomal-dominant leukodystrophy (ADLD) starting with autonomic symptoms, which are followed by pyramidal signs and ataxia. Magnetic resonance imaging (MRI) of the brain reveals characteristic findings. This is the first longitudinal study on this disease.

A novel AP4M1 mutation in autosomal recessive cerebral palsy syndrome and clinical expansion of AP-4 deficiency.

Background: Cerebral palsy (CP) is a heterogeneous neurodevelopmental disorder associated with intellectual disability in one-third of cases. Recent findings support Mendelian inheritance in subgroups of patients with the disease. The purpose of this study was to identify a novel genetic cause of paraplegic CP with intellectual disability in a consanguineous Pakistani family.

The cerebrospinal fluid cytokine signature of multiple sclerosis: a homogenous response that does not conform to the Th1/Th2/Th17 convention.

In this cross-sectional study, we wanted to identify key cytokines characteristic of different stages of multiple sclerosis (MS). To this end, cerebrospinal fluid from patients with MS was investigated with a multiplexed fluorescent bead-based immunoassay. In total 43 cytokines were assessed and related to clinical and imaging data.

Recurrence of Susac Syndrome following 23 Years of Remission.

Susac syndrome is an autoimmune microangiopathy affecting the brain, retina and inner ear (cochlea and semicircular canals), leading to encephalopathy, branch retinal artery occlusions (BRAOs) and asymmetric neurosensory hearing loss, respectively. The natural history and long-term prognosis are variable as the disease has been shown to be monophasic and self-limiting, polycyclic or chronic continuous. We describe a 35-year-old woman who presented with a sudden hearing loss in the left ear in the 37th week of her second pregnancy.

Brain pathology after mild traumatic brain injury: an exploratory study by repeated magnetic resonance examination.

Objective: To explore brain pathology after mild traumatic brain injury by repeated magnetic resonance examination.

Design: A prospective follow-up study.

Subjects: Nineteen patients with mild traumatic brain injury presenting with Glasgow Coma Scale (GCS) 14-15.

Visualization of the fetal lip and palate: is brain-targeted MRI reliable?

Objective : To evaluate the ability of brain-targeted magnetic resonance imaging (MRI) to assess the anatomy of the fetal upper lip and palate. Design : Two independent readers made a blind retrospective review of 60 brain-targeted MRIs of fetuses from 20 to 38 gestational weeks (GW). Fifty-five MRIs were normal and five had orofacial anomalies, including one isolated cleft lip and four cleft lip and palate.

The ear in fetal MRI: what can we really see?

Introduction: The aim of this study was to investigate the ability to depict the components of the ear on brain-oriented fetal MRI studies.

Methods: Retrospective evaluation of the ear in MRI studies was performed post-mortem in 16 fetuses ranging from 15 to 22 gestation weeks (GW), and in 122 examinations in vivo of fetuses ranging from 20 to 38 GW. The cochlea, vestibular apparatus, middle ear, and external auditory canal were separately graded according to the components that were delineated.

Genomic duplications mediate overexpression of lamin B1 in adult-onset autosomal dominant leukodystrophy (ADLD) with autonomic symptoms.

Adult-onset autosomal dominant leukodystrophy (ADLD) with autonomic symptoms features micturition urgency, constipation, erectile dysfunction, and orthostatic hypotension, usually followed by pyramidal signs and ataxia. Peripheral nerve conduction is normal. The disease is often mistaken for multiple sclerosis in the initial phase.

Measurements of the normal fetal brain at gestation weeks 17 to 23: a MRI study.

Introduction: To obtain measurements of the normal fetal brain before 24 weeks of gestation (GW), a deadline for medical decisions on fetal viability in a large number of countries.

Methods: We retrospectively reviewed 70 normal MR examinations of fetuses aged GW 17 to 23. The fronto-occipital diameter, the cerebral bi-parietal diameter, the transverse cerebellar diameter, the vermian height, and antero-posterior diameter were measured.

Hippocampal development at gestation weeks 23 to 36. An ultrasound study on preterm neonates.

Introduction: During fetal development, the hippocampal structures fold around the hippocampal sulcus into the temporal lobe. According to the literature, this inversion should be completed at gestation week (GW) 21. Thereafter, the hippocampal shape should resemble the adult shape.

Metabolite concentrations in supraventricular white matter from teenage to early old age: A short echo time 1H magnetic resonance spectroscopy (MRS) study.

Background: Age- and sex-related changes of metabolites in healthy adult brains have been examined with different (1)H magnetic resonance spectroscopy (MRS) methods in varying populations, and with differing results. A long repetition time and short echo time technique reduces quantification errors due to T(1) and T(2) relaxation effects and makes it possible to measure metabolites with short T(2) relaxation times.

Purpose: To examine the effect of age on the metabolite concentrations measured by (1)H MRS in normal supraventricular white matter using a long repetition time (TR) and a short echo time (TE).

Modic changes and interleukin 1 gene locus polymorphisms in occupational cohort of middle-aged men.

According to recent systematic reviews, Modic changes are associated with low-back pain. However, their pathophysiology remains largely unknown. A previous study of Northern Finnish males implicated that IL1A and MMP3 polymorphisms play a role in type II Modic changes.

Subjects with intellectual disability and familial need for full-time special education show regional brain alterations: a voxel-based morphometry study.

Subjects attending full-time special education (SE) often have multifactorial background for their cognitive impairment, and brain MRI may show nonspecific changes. As voxel-based morphometry reveals regional volume differences, we applied this method to 119 subjects with cognitive impairments and familial need for full-time SE--graded into three levels from specific disorders of cognitive processes (level 1) to intellectual disability (IQ <70; level 3)--and to 43 age-matched controls attending mainstream education (level 0). Subjects in SE groups had smaller global brain white matter (WM), cerebrospinal fluid, and total brain volume than controls.

Incomplete hippocampal inversion-is there a relation to epilepsy?

Incomplete hippocampal inversion (IHI) has been described in patients with epilepsy or severe midline malformations but also in nonepileptic subjects without obvious developmental anomalies. We studied the frequency of IHI in different epilepsy syndromes to evaluate their relationship. Three hundred patients were drawn from the regional epilepsy register.

SPG11 mutations cause Kjellin syndrome, a hereditary spastic paraplegia with thin corpus callosum and central retinal degeneration.

Autosomal recessive hereditary spastic paraplegia (ARHSP) with thin corpus callosum (TCC) is genetically heterogenous and approximately 35% of patients carry mutations in either of the SPG11 or SPG15 genes. Disease onset is during the first three decades of life with spastic paraplegia and mental impairment. Peripheral neuropathy and amyotrophy may occur.