Publications by authors named "Raili Raininko"

36 Publications

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

Neurology 2019 08 23;93(7):e647-e652. Epub 2019 Jul 23.

From the Department of Neurology, Reference Center for Lysosomal Diseases, UF Neuro-Genetics and Metabolism (L.C., R.D., Y.N.), and Department of Neuroradiology (B.L.-Y., N.P., D.L.), Pitié-Salpêtrière Hospital, Paris; Service de Biochimie et Biologie Moléculaire Grand Est (R.F., M.P.), Unité Médicale Pathologies Métaboliques, Erythrocytaires et Dépistage Périnatal, Centre de Biologie et de Pathologie Est, Hospices Civils de Lyon, Bron; UMR 5305 CNRS/UCBL (R.F.), Lyon, France; Department of Medicine, Surgery and Neurosciences (A.F., S.S.), Unit of Neurology and Neurometabolic Diseases, Medical School, University of Siena; Neuroradiology Unit (A.C.), Azienda Ospedaliera Universitaria Senese, Siena, Italy; Department of Neurology (M.C.M., J.D.), Coimbra Hospital and University Centre, Portugal; Department of Neurology (S.H.K.), College of Medicine, Hanyang University, Seoul, Korea; Division of Neurology (H.A.), Hyogo Prefectural Amagasaki General Medical Center, Hyogo, Japan; Department of Neurology (B.A.), La Timone Hospital; Aix-Marseille University (B.A.), CNRS, CRMBM UMR, Marseille; Department of Neurology (X.A.), Montpellier University Hospital, France; Department of Neurology (Y.D.), Xuan Wu Hospital, Capital Medical University, Beijing, China; Department of Neurology (R.H.), Royal Brisbane Hospital, Brisbane, Australia; Laboratory of Neurogenetics of Motion and Department of Neuroradiology (R.L.P.), Montréal Neurological Institute and Hospital, McGill University, Montréal; Department of Radiology (C.L.), Department of Pathology and Laboratory Medicine (C.L.), International Collaboration on Repair Discoveries (ICORD) (C.L.), Department of Physics and Astronomy (C.L.), and Division of Endocrinology, Department of Medicine (S.M.S.), University of British Columbia, Vancouver, Canada; Department of Neurology (K.N.), Division of Clinical Medicine, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan; Department of Radiology (R.R.), Uppsala University, Sweden; Department of Neurology and Hertie-Institute for Clinical Brain Research (L.S.), Eberhard-Karls-University; German Center of Neurodegenerative Diseases (DZNE) (L.S.), Tübingen, Germany; Department of Neurology (F.V.), Caen-Normandie University Hospital, Caen; Inserm U1077 (F.V.), EPHE, Caen-Normandie University, Caen, France; and Department of Neurology and Stroke (K.J.), Medical University of Lodz, Poland.

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). T2-weighted fluid-attenuated inversion recovery images of each patient were analyzed and scored using a radiologic score of WMH in a single center.

Results: The corticospinal tract was always affected by WMH (100% of patients), however, with some distinctions along the tract: the precentral gyrus (100%), corona radiata (95%), and posterior internal capsule (81%) were highly abnormal, whereas the mesencephalon (57%), pons (52%), and medulla oblongata (5%) were less affected. WMH were also frequently present in the posterior lateral periventricular white matter (95%), optic radiations (86%), postcentral gyrus (71%), medial lemniscus (62%), and corpus callosum, especially in the isthmus (71%), whereas the genu was always normal. A few patients did not have the classical MRI pattern but extensive hyperintensities (n = 3), or patchy distribution of hyperintensities mimicking an acquired etiology (n = 2), or very subtle hyperintensities of the corticospinal tract (n = 1).

Conclusions: We specified the main locations of WMH, which were observed in the earliest stages of the disease and were also present in patients with atypical MRI pattern, highlighting the importance of radiologic features to guide the diagnosis.
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http://dx.doi.org/10.1212/WNL.0000000000007943DOI Listing
August 2019

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

Neurol Genet 2019 Feb 24;5(1):e305. Epub 2019 Jan 24.

Department of Human Genetics (B.N., Q.S.P.), Graduate School of Public Health, University of Pittsburgh; Department of Medical Sciences (E.G., A.B.), University of Torino, Italy; Department of Radiology (R.R.), Uppsala University, Sweden; Department of Medical Genetics (A.L.), British Columbia Children's Hospital, Vancouver, Canada; Department of Genome Sciences (M. Spielmann), University of Washington, Seattle; Department of Pediatrics (M.K.K., R.A., M.K.), McGovern Medical School, University of Texas, Houston; Departments of Clinical Genomics and Neurology (R.G.), Mayo Clinic, Rochester, MN; Department of Pathology (M.A.), King Abdulaziz University, Jeddah, Saudi Arabia; Department of Medical Imaging (M. Sharma), Western University, London, Canada; Departments of Pathology and Clinical Neurological Sciences (R.H.), Western University and London Health Sciences Centre, Canada; Office of the Clinical Director (W.A.G., C.T.), NHGRI; and NIH Undiagnosed Diseases Program (W.A.G., C.T.), Office of the Director, NIH, Bethesda, MD.

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.

Results: Five patients from 3 independent families presented at ages ranging from 32 to 52 years with neurologic symptoms that included progressive hypophonia, upper and lower limb weakness and spasticity, and cerebellar dysfunction and MRIs characterized by widespread white matter alterations. Patients had unique nonrecurrent deletions upstream of the , varying in size from 250 kb to 670 kb. Deletion junctions were embedded in repetitive elements. Expression analysis revealed increased expression in patient cells.

Conclusions: Our findings confirmed the association between upstream deletions and leukodystrophy previously reported in a single family, expanding the phenotypic and molecular description of this condition. Although clinical and radiologic features overlapped with those of autosomal dominant leukodystrophy because of duplications, patients with deletions upstream of had an earlier age at symptom onset, lacked early dysautonomia, and appeared to have lesser involvement of the cerebellum and sparing of the spinal cord diameter on MRI. aCGH analysis defined a smaller minimal critical region required for disease causation and revealed that deletions occur at repetitive DNA genomic elements. Search for structural variants (duplications and upstream deletions) should be an integral part of the investigation of patients with autosomal dominant adult-onset leukodystrophy.
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http://dx.doi.org/10.1212/NXG.0000000000000305DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6384018PMC
February 2019

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

PLoS One 2018 15;13(11):e0207336. Epub 2018 Nov 15.

Department of Radiology, Uppsala University, Uppsala, Sweden.

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.

Material And Methods: MRI and MRS were re-evaluated in 208 cases with a clinically indicated MRS (cases with uncertain or insufficient information on MRI) and a confirmed diagnosis. Both single voxel spectroscopy (SVS) and chemical shift imaging (CSI) were performed in 105 cases, only SVS or CSI in 54 and 49 cases, respectively. Diagnoses were grouped into categories: non-neoplastic disease, low-grade tumour, and high-grade tumour. The clinical value of MRS was considered very beneficial if it provided the correct category or location when MRI did not, beneficial if it ruled out suspected diseases or was more specific than MRI, inconsequential if it provided the same level of information, or misleading if it provided less or incorrect information.

Results: There were 70 non-neoplastic lesions, 43 low-grade tumours, and 95 high-grade tumours. For MRI, the category was correct in 130 cases (62%), indeterminate in 39 cases (19%), and incorrect in 39 cases (19%). Supplemented with MRS, 134 cases (64%) were correct, 23 cases (11%) indeterminate, and 51 (25%) incorrect. Additional information from MRS was beneficial or very beneficial in 31 cases (15%) and misleading in 36 cases (17%).

Conclusion: In most cases MRS did not add to the diagnostic value of MRI. In selected cases, MRS may be a valuable supplement to MRI.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0207336PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6237369PMC
April 2019

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

J Neurosurg 2018 09;131(2):604-611

1Department of Neuroscience/Neurosurgery, Uppsala University; and.

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. The proportion of good monitoring time (GMT) with ICP > 20 mm Hg during the first 120 hours postinjury was calculated and associations with clinical and MRI-related factors were evaluated using linear regression.

Results: All patients had episodes of ICP > 20 mm Hg. The mean proportion of GMT with ICP > 20 mm Hg was 5%, and 27% of the patients (14/52) spent more than 5% of GMT with ICP > 20 mm Hg. The Glasgow Coma Scale motor score at admission (p = 0.04) and lesions on DWI sequences in the substantia nigra and mesencephalic tegmentum (SN-T, p = 0.001) were associated with the proportion of GMT with ICP > 20 mm Hg. In multivariable linear regression, lesions on DWI sequences in SN-T (8% of GMT with ICP > 20 mm Hg, 95% CI 3%-13%, p = 0.004) and young age (-0.2% of GMT with ICP > 20 mm Hg, 95% CI -0.07% to -0.3%, p = 0.002) were associated with increased ICP.

Conclusions: Increased ICP occurs in approximately one-third of patients with severe TBI who have DAI. Age and lesions on DWI sequences in the central mesencephalon (i.e., SN-T) are associated with elevated ICP. These findings suggest that MR lesion localization may aid prediction of increased ICP in patients with DAI.
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http://dx.doi.org/10.3171/2018.4.JNS18185DOI Listing
September 2018

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

Acta Neurol Scand 2019 Feb 25;139(2):135-142. Epub 2018 Sep 25.

Radiology, Uppsala University, Uppsala, Sweden.

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. We studied brain glucose metabolism in this disease using F-fluorodeoxyglucose positron emission tomography (PET).

Methods: We examined 8 patients, aged 48-64 years, in varying stages of clinical symptomatology. Two patients were investigated with quantitative PET on clinical indications after which six more patients were recruited. Absolute glucose metabolism was analyzed with the PVElab software in 6 patients and 18 healthy controls. A semiquantitative analysis using the CortexID software was performed in seven investigations, relating local metabolism levels to global glucose metabolism.

Results: The clinical quantitative PET revealed low global glucose metabolism, with the most marked reduction in the cerebellum. In the PVElab analysis, patients presented low mean glucose metabolism in the cerebellum, brainstem and global grey matter. In the semiquantitative analysis, 2 patients showed a decreased metabolism in the cerebellum and 4 patients a relatively higher metabolism in parts of the temporal lobes. Since none of the patients showed an increased metabolism in the quantitative analysis, we interpret these increases as "pseudo-increases" related to a globally reduced metabolism.

Conclusions: Global reduction of grey matter glucose metabolism in this white matter disease most likely depends on a combination of cortical afferent dysfunction and, in later stages, neuronal loss. The lowest metabolism in the cerebellum is consistent with histopathological findings and prominent cerebellar symptoms.
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http://dx.doi.org/10.1111/ane.13024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6585974PMC
February 2019

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

J Neurol Sci 2016 Dec 21;371:105-111. Epub 2016 Oct 21.

Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, 751 08 Uppsala, Sweden. Electronic address:

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.2656C>T (p.Gln886*)) and (c.4756_4760delAATCA (p.Asn1586Tyrfs*3)) in the SACS gene responsible for autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS). MRI revealed typical cerebellar and pontine changes associated with ARSACS as well as multiple supratentorial changes in both families as likely contributing factors to the cognitive symptoms. Intellectual disability and behavioral abnormalities have been reported in some cases of ARSACS but are not a part of the characteristic triad of symptoms that includes cerebellar ataxia, spasticity and peripheral neuropathy. Our combined findings bring further knowledge to the phenotypic spectrum, neurodegenerative changes and genetic variability associated with the SACS gene of clinical and diagnostic importance.
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http://dx.doi.org/10.1016/j.jns.2016.10.032DOI Listing
December 2016

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

J Neurotrauma 2017 01 25;34(2):341-352. Epub 2016 Jul 25.

1 Department of Neuroscience, Neurosurgery, Uppsala University , Uppsala, Sweden .

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 31.2 years ±14.3 standard deviation) with severe DAI (Glasgow Motor Score [GMS] <6) examined with MRI within 1 week post-injury were included. Diffusion-weighted (DW), T2*-weighted gradient echo and susceptibility-weighted (SWI) sequences were used. Extended Glasgow outcome score was assessed after 6 months. Number of DW lesions in the thalamus, basal ganglia, and internal capsule and number of SWI lesions in the mesencephalon correlated significantly with outcome in univariate analysis. Age, GMS at admission, GMS at discharge, and low proportion of good monitoring time with cerebral perfusion pressure <60 mm Hg correlated significantly with outcome in univariate analysis. Multivariate analysis revealed an independent relation with poor outcome for age (p = 0.005) and lesions in the mesencephalic region corresponding to substantia nigra and tegmentum on SWI (p = 0.008). We conclude that higher age and lesions in substantia nigra and mesencephalic tegmentum indicate poor long-term outcome in DAI. We propose an extended MRI classification system based on four stages (stage I-hemispheric lesions, stage II-corpus callosum lesions, stage III-brainstem lesions, and stage IV-substantia nigra or mesencephalic tegmentum lesions); all are subdivided by age (≥/<30 years).
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http://dx.doi.org/10.1089/neu.2016.4426DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5220564PMC
January 2017

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

J Neuroimmunol 2016 Mar 22;292:52-7. Epub 2016 Jan 22.

Department of Clinical Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden. Electronic address:

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. CSF YKL-40 was increased in patients with active relapsing-remitting MS and correlated with the number of gadolinium enhancing lesions. Patients with secondary progressive MS had similar high levels of YKL-40, whereas not active relapsing-remitting MS patients had YKL-40 levels comparable to healthy controls.
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http://dx.doi.org/10.1016/j.jneuroim.2016.01.013DOI Listing
March 2016

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

Ann Neurol 2015 Sep 27;78(3):412-25. Epub 2015 Jul 27.

Department of Radiology, Uppsala University, Uppsala, Sweden.

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. Our objective is to describe the natural clinical and radiological course of LMNB1-related ADLD.

Methods: Twenty-three subjects in two families with LMNB1 duplications were studied over two decades with clinical assessment and MRI of the brain and spinal cord. They were 29 to 70 years old at their first MRI. Repeated MRIs were performed in 14 subjects over a time period of up to 17 years.

Results: Pathological MRI findings were found in the brain and spinal cord in all examinations (i.e., even preceding clinical symptoms). MRI changes and clinical symptoms progressed in a definite order. Autonomic dysfunction appeared in the fifth to sixth decade, preceding or together with gait and coordination difficulties. Motor signs developed ascending from spastic paraplegia to tetraplegia and pseudobulbar palsy in the seventh decade. There were clinical, radiological, and neurophysiological signs of myelopathy. Survival lasted more than two decades after clinical onset.

Interpretation: LMNB1-related ADLD is a slowly progressive neurological disease. MRI abnormalities of the brain and spinal cord can precede clinical symptoms by more than a decade and are extensive in all symptomatic patients. Spinal cord involvement is a likely contributing factor to early autonomic symptoms and spastic paraplegia.
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http://dx.doi.org/10.1002/ana.24452DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5054845PMC
September 2015

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

BMC Med Genet 2014 Dec 14;15:133. Epub 2014 Dec 14.

Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala 751 08, Sweden.

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.

Methods: We performed whole-exome sequencing (WES) in two brothers with CP and intellectual disability. Analysis of AP4M1 mRNA was performed using quantitative real-time PCR on total RNA from cultured fibroblasts. The brothers were investigated clinically and by MRI.

Results: We identified a novel homozygous AP4M1 mutation c.194_195delAT, p.Y65Ffs*50 in the affected brothers. Quantitative RT-PCR analysis showed markedly reduced AP4M1 mRNA levels suggesting partial non-sense mediated mRNA decay. Several clinical and MRI features were consistent with AP-4 complex deficiency. However, in contrast to previously reported cases with AP4M1 mutations our patients show an aggressive behavior and a relatively late onset of disease.

Conclusion: This study shows an AP4M1 mutation associated with aggressive behavior in addition to mild dysmorphic features, intellectual disability, spastic paraparesis and reduced head circumference. Our findings expand the clinical spectrum associated with AP-4 complex deficiency and the study illustrates the importance of MRI and WES in the diagnosis of patients with CP and intellectual disability.
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http://dx.doi.org/10.1186/s12881-014-0133-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4292821PMC
December 2014

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

J Neuroimmunol 2014 Dec 18;277(1-2):153-9. Epub 2014 Oct 18.

Department of Immunology, Genetics and Pathology, Science for Life Laboratories, Uppsala University, Uppsala, Sweden.

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. Increased levels of CCL22, CXCL10 and sCD40L characterized relapsing-remitting MS patients with the presence of gadolinium-enhancing lesions; decreased CCL2 and increased CXCL1 and CCL5 were typical of relapsing-remitting MS patients irrespectively of the presence of gadolinium-enhancing lesions. These homogenous patterns of cytokine activation do not conform to conventional Th1/Th2/Th17 responses.
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http://dx.doi.org/10.1016/j.jneuroim.2014.10.005DOI Listing
December 2014

Recurrence of Susac Syndrome following 23 Years of Remission.

Case Rep Neurol 2014 May 21;6(2):171-5. Epub 2014 May 21.

Neurology, Department of Neuroscience, Oncology and Radiation Science, Uppsala University, Uppsala, Sweden.

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. She subsequently developed BRAO in the right eye 2.5 months after having given birth. MRI findings included round lesions in the corpus callosum which are pathognomonic for Susac syndrome. Previous patient records documented encephalopathy, sudden deafness of the right ear and visual field defects in the left eye at the age of 12, followed by permanent hearing and visual defects. We expand on the variability in the course of Susac syndrome as recurrence may occur after as long as 23 years. Cases of monophasic self-limiting Susac syndrome may in fact turn polycyclic with an interval of more than 2 decades between the bouts of the disease. In these cases, suspecting the development of exacerbation early is important in order to start the treatment promptly.
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http://dx.doi.org/10.1159/000362868DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4067733PMC
May 2014

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

J Rehabil Med 2013 Sep;45(8):721-8

Department of Neuroscience, Rehabilitation Medicine, Sandviken Hospital, SE-811 89 Sandviken, Sweden.

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.

Methods: The patients were examined on day 2 or 3 and 3-7 months after the injury. The magnetic resonance protocol comprised conventional T1- and T2-weighted sequences including fluid attenuated inversion recovery (FLAIR), two susceptibility-weighted sequences to reveal haemorrhages, and diffusion-weighted sequences. Computer-aided volume comparison was performed. Clinical outcome was assessed by the Rivermead Post-Concussion Symptoms Questionnaire (RPQ), Hospital Anxiety and Depression Scale (HADS) and Glasgow Outcome Scale Extended (GOSE).

Results: At follow-up, 7 patients (37%) reported ≥  3 symptoms in RPQ, 5 reported some anxiety and 1 reported mild depression. Fifteen patients reported upper level of good recovery and 4 patients lower level of good recovery (GOSE 8 and 7, respectively). Magnetic resonance pathology was found in 1 patient at the first examination, but 4 patients (21%) showed volume loss at the second examination, at which 3 of them reported < 3 symptoms and 1 ≥ 3 symptoms, all exhibiting GOSE scores of 8.

Conclusion: Loss of brain volume, demonstrated by computer-aided magnetic resonance imaging volumetry, may be a feasible marker of brain pathology after mild traumatic brain injury.
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http://dx.doi.org/10.2340/16501977-1169DOI Listing
September 2013

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

Cleft Palate Craniofac J 2013 Sep 6;50(5):513-9. Epub 2013 Feb 6.

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. Both normal and cleft MRIs had postnatal confirmation. The upper lip, primary palate, secondary palate, and nasal septum were scored into four levels, from evidently normal to evidently abnormal. In case of a suspected pathology, the readers attempted a diagnosis. Setting : Collaboration between a university hospital and a large private practice MRI center. Results : Interobserver agreement (weighted kappa) was 0.79 for the upper lip, 0.70 for the primary palate, 0.86 for the secondary palate, and 0.90 for the nasal septum. The scoring levels of the readers did not change significantly across gestational age. Normality was correctly scored in 96% to 100% of the normal lips and primary palates and in 93% to 97% of the normal secondary palates depending on the reader. A deviated septum was only scored in two fetuses with unilateral cleft palates. The readers identified all pathological cases. Conclusion : Brain-targeted fetal MRI in experienced hands seems to be highly accurate for the evaluation of the lip and palate in fetuses above 20 GW, regardless of gestational age. The assessment of the secondary palate may be slightly more limited than the lip or primary palate.
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http://dx.doi.org/10.1597/12-079DOI Listing
September 2013

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

Neuroradiology 2011 Dec 18;53(12):1001-8. Epub 2011 Aug 18.

Neuroradiology Section C. Campos Costa, Rua Armando Rocha, S/N 3505-406, Fragosela, Viseu, Portugal.

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.

Results: The components of the inner and middle ear were fully delineated in 100% of the post-mortem examinations, but the external auditory canals were only seen in only 25%. In the in vivo group, the imaging detail was much lower. Cochlear turns could be identified in 75% of the fetuses, the vestibule and the lateral semicircular canals in 72% andossicles in 70%. Before 25 GW, the ability to identify these individual parts was 50%, 30%, and 33%, respectively, and above it was 89%, 93%, and 90% . In most cases, the external auditory canals could only be seen after 29 GW.

Conclusion: In fetal MRI studies in vivo, it is possible to depict the components of the ear in the majority of the fetuses, in such a manner as to exclude major malformations. However, MRI might not provide enough detail to rule out pathology of the ear before 25 GW, this being a critical age for pregnancy management in many countries.
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http://dx.doi.org/10.1007/s00234-011-0938-zDOI Listing
December 2011

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

Neurogenetics 2011 Feb 12;12(1):65-72. Epub 2011 Jan 12.

Department of Genetics and Pathology, The Rudbeck Laboratory and Science for Life Laboratory, Uppsala University and University Hospital, SE-751 85, Uppsala, Sweden.

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. There is a characteristic pattern of white matter changes in the brain and spinal cord on magnetic resonance imaging (MRI), mild atrophy of the brain, and a more marked atrophy of the spinal cord. ADLD is associated with duplications of the lamin B1 (LMNB1) gene but the mechanism by which the rearrangement conveys the phenotype is not fully defined. We analyzed four unrelated families segregating ADLD with autonomic symptoms for duplications of the LMNB1 gene. A single nucleotide polymorphism (SNP) array analysis revealed novel duplications spanning the entire LMNB1 gene in probands from each of the four families. We then analyzed the expression of lamin B1 in peripheral leukocytes by Western blot analysis in five patients from two available families. The protein levels of lamin B1 were found significantly increased. These results indicate that the ADLD phenotype associated with LMNB1 duplications is mediated by increased levels of the lamin B1 protein. Furthermore, we show that a molecular diagnosis for ADLD with autonomic symptoms can be obtained by a direct analysis of lamin B1 in peripheral leukocytes.
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http://dx.doi.org/10.1007/s10048-010-0269-yDOI Listing
February 2011

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

Neuroradiology 2011 Jan 29;53(1):43-8. Epub 2010 Sep 29.

Neuroradiology Section C. Campos Costa, Porto, Portugal.

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.

Results: The median, maximum, and minimum values for each parameter were displayed for each individual GW.

Conclusion: The recorded data might contribute to a better assessment of fetal health by providing normal boundaries for the brain growth.
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http://dx.doi.org/10.1007/s00234-010-0772-8DOI Listing
January 2011

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

Neuroradiology 2010 Jun 30;52(6):489-94. Epub 2010 Mar 30.

Department of Radiology, University Hospital, Uppsala University, Uppsala, Sweden.

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. However, incomplete hippocampal inversion (IHI) is found in 19% of the common population. The aim of this study was to study fetal hippocampal development by examining neonates born preterm.

Methods: We analyzed cranial ultrasound examinations, performed as a part of the routine assessment of all preterm infants, over a 3-year period and excluded the infants with brain pathology. The final material consisted of 158 children born <35 GW. A rounded form (the ratio between the horizontal and vertical diameters of the hippocampal body
Results: The age at examination was 23-24 GW in 24 neonates, 25-28 GW in 70 neonates, and 29-36 GW in 64 neonates. IHI was found in 50%, 24%, and 14%, respectively. The difference between the neonates <25 GW and >or=25 GW was statistically highly significant (p < 0.001). The frequency of bilateral IHI was highest in the youngest age group. In the other groups, the left-sided IHI was the most common.

Conclusion: In about 50% of the neonates, hippocampal inversion is not completed up to GW 24; but from 25 GW onwards, the frequency and laterality of IHI is similar to that in the adult population.
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http://dx.doi.org/10.1007/s00234-010-0673-xDOI Listing
June 2010

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

Acta Radiol 2010 Apr;51(3):309-15

Departments of Radiology, Uppsala University, Uppsala, Sweden.

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).

Material And Methods: Supraventricular white matter of 57 healthy subjects (25 women, 32 men), aged 13 to 72 years, was examined with a single-voxel MRS at 1.5T using a TR of 6000 ms and a TE of 22 ms. Tissue water was used as a reference in quantification.

Results: Myoinositol increased slightly and total N-acetyl aspartate (NAA) decreased slightly with increasing age. Glutamine/glutamate complex (Glx) showed U-shaped age dependence, with highest concentrations in the youngest and oldest subjects. No significant age dependence was found in total choline and total creatine. No gender differences were found. Macromolecule/ lipid (ML) fractions were reliably measurable only in 36/57 or even fewer subjects and showed very large deviations.

Conclusion: The concentrations of several metabolites in cerebral supraventricular white matter are age dependent on (1)H MRS, even in young and middle-aged people, and age dependency can be nonlinear. Each (1)H MRS study of the brain should therefore take age into account, whereas sex does not appear to be so important. The use of macromolecule and lipid evaluations is compromised by less successful quantification and large variations in healthy people.
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http://dx.doi.org/10.3109/02841850903476564DOI Listing
April 2010

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

Eur Spine J 2009 Dec 22;18(12):1963-70. Epub 2009 Aug 22.

Finnish Institute of Occupational Health, Helsinki, Finland.

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. The purpose of the current study was to examine the association of IL1 cluster polymorphisms with Modic changes amongst middle-aged men in Southern Finland. The final study sample consisted of 108 men from three different occupations, who underwent magnetic resonance imaging (MRI) with a 0.1 T-scanner. Six single nucleotide polymorphisms (SNP) in the IL1 gene cluster (IL1A c.1-889C>T; IL1B c.3954C>T; IL1RN c.1812G>A; IL1RN c.1887G>C; IL1RN c.11100T>C; IL1RN c.1506G>A) were genotyped with the SNP-TRAP method or by allele-specific primer extension on modified microarray. In all, 45 subjects had Modic changes at one or more disc levels. The presence of the minor allele of IL1A (c.1-889C>T) was associated with these changes (any Modic change p = 0.031, type II changes p = 0.036). The carriers of the T-allele had a 2.5-fold risk of Modic change and the association was independent of the other IL1 gene cluster loci studied. In addition, a minor haplotype, with a frequency of 7.5% in the study population, including the minor alleles of IL1A c.1-889C>T, IL1RN c.1812G>A, and IL1RN c.1506G>A, was significantly associated with Modic changes. This observation is in accordance with the previous finding from a different geographical area, and thus confirms the importance of the IL1A gene in the pathophysiology of Modic changes.
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http://dx.doi.org/10.1007/s00586-009-1139-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2899448PMC
December 2009

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

Pediatr Res 2009 Sep;66(3):306-11

Department of Gynecology and Pediatrics, Helsinki University Central Hospital, 00290 Helsinki, Finland.

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. Compared with controls, subjects with intellectual disabilities in SE level 3 showed greater regional gray matter volumes bilaterally in the ventral and dorsal anterior cingulate cortex and smaller regional gray matter volumes in the left thalamus and cerebellar hemisphere. Further, they had greater WM volume in the left frontoparietal region and smaller WM volumes in the posterior limbs of the internal capsules. Subjects in SE level 1 and 2 groups showed the same tendency, but the results were nonsignificant. In conclusion, compared with controls, subjects with intellectual disabilities showed in voxel-based morphometry analysis several regional brain alterations.
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http://dx.doi.org/10.1203/PDR.0b013e3181b1bd6aDOI Listing
September 2009

Incomplete hippocampal inversion-is there a relation to epilepsy?

Eur Radiol 2009 Oct 14;19(10):2544-50. Epub 2009 May 14.

Department of Radiology, Uppsala University Hospital, 75185, Uppsala, Sweden.

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. Of these, 99 were excluded because of a disease or condition affecting the temporal lobes or incomplete data. Controls were 150 subjects without epilepsy or obvious intracranial developmental anomalies. The coronal MR images were analysed without knowledge of the clinical data. Among epilepsy patients, 30% had IHI (40 left-sided, 4 right-sided, 16 bilateral). Of controls, 18% had IHI (20 left-sided, 8 bilateral). The difference was statistically significant (P < 0.05). Of temporal lobe epilepsy (TLE) patients, 25% had IHI, which was not a significantly higher frequency than in controls (P = 0.34). There was no correlation between EEG and IHI laterality. A total of 44% of Rolandic epilepsy patients and 57% of cryptogenic generalised epilepsy patients had IHI. The IHI frequency was very high in some epileptic syndromes, but not significantly higher in TLE compared to controls. No causality between TLE and IHI could be found. IHI can be a sign of disturbed cerebral development affecting other parts of the brain, maybe leading to epilepsy.
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http://dx.doi.org/10.1007/s00330-009-1438-yDOI Listing
October 2009

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

Am J Med Genet B Neuropsychiatr Genet 2009 Oct;150B(7):984-92

Department of Genetics and Pathology, The Rudbeck Laboratory, Uppsala University and University Hospital, Uppsala, Sweden.

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. Kjellin syndrome is characterized by central retinal degeneration in addition to ARHSP-TCC and the disease is associated with mutations in the SPG15 gene. We identified five patients in four unrelated kindreds with spastic paraplegia and mental impairment. Magnetic resonance imaging revealed TCC, atrophy elsewhere in the brain and increased T2 signal intensity in the periventricular white matter. Probands from the four kindreds were screened for mutations in the SPG11 gene. All patients were found homozygous or compound heterozygous for truncating SPG11 mutations of which four are reported for the first time. Ophthalmological investigations revealed that the four index cases have central retinal degeneration consistent with Kjellin syndrome. PET examinations with N-[11C-methyl]-L-deuterodeprenyl (DED) and fluor-18 2-fluorodeoxyglucose (FDG) were performed in two patients with Kjellin syndrome. We observed a reduced glucose uptake in the thalami, anterior cingulum, and sensorimotor cortex indicating neuronal loss, and an increased DED binding in the thalami and pons which suggests astrogliosis. From our results we extend the SPG11 associated phenotype to comprise also Kjellin syndrome, previously found to be associated with mutations in the SPG15 gene. We anticipate that degeneration of the central retina is a common and previously unrecognized feature in SPG11 related disease.
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http://dx.doi.org/10.1002/ajmg.b.30928DOI Listing
October 2009

A patient with two mitochondrial DNA mutations causing PEO and LHON.

Eur J Med Genet 2009 Jan-Feb;52(1):47-8. Epub 2008 Nov 5.

Department of Neuroscience, University Hospital, Uppsala, Sweden.

We report a 22-year-old man with PEO and optic atrophy. PEO developed before the onset of optic atrophy. The patient showed mitochondrial myopathy with cytochrome c oxidase deficient fibers. In skeletal muscle the patient was homoplasmic for the mtDNA G11778A Leber hereditary optic neuropathy (LHON) mutation and heteroplasmic for the mtDNA 5 kb "common" deletion mutation. In blood only the homoplasmic LHON mutation was identified. The occurrence of two pathogenic mtDNA mutations is exceedingly rare. The clinical findings in this patient indicate that the combination of the two mtDNA mutations resulted in the expected combined phenotype since the mtDNA deletion mutation accounted for the PEO and the mtDNA G11778A point mutation for the optic atrophy.
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http://dx.doi.org/10.1016/j.ejmg.2008.10.004DOI Listing
April 2009

Incomplete inversion of the hippocampus--a common developmental anomaly.

Eur Radiol 2008 Jan 9;18(1):138-42. Epub 2007 Sep 9.

Department of Radiology, Uppsala University Hospital, SE 75185 Uppsala, Sweden.

Incomplete inversion of the hippocampus, an imperfect fetal development, has been described in patients with epilepsy or severe midline malformations. We studied this condition in a nonepileptic population without obvious developmental anomalies. We analyzed the coronal MR images of 50 women and 50 men who did not have epilepsy. Twenty of them were healthy volunteers and 80 were patients without obvious intracranial developmental anomalies, intracranial masses, hydrocephalus or any condition affecting the temporal lobes. If the entire hippocampus (the head could not be evaluated) were affected, the incomplete inversion was classified as total, otherwise as partial. Incomplete inversion of the hippocampus was found in 19/100 subjects (9 women, 10 men). It was unilateral, always on the left side, in 13 subjects (4 women, 9 men): 9 were of the total type, 4 were partial. It was bilateral in six subjects (five women, one man): four subjects had total types bilaterally, two had a combination of total and partial types. The collateral sulcus was vertically oriented in all subjects with a deviating hippocampal shape. We conclude that incomplete inversion of the hippocampus is not an unusual morphologic variety in a nonepileptic population without other obvious intracranial developmental anomalies.
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http://dx.doi.org/10.1007/s00330-007-0735-6DOI Listing
January 2008

Association between the aggrecan gene variable number of tandem repeats polymorphism and intervertebral disc degeneration.

Spine (Phila Pa 1976) 2007 Jul;32(16):1700-5

Finnish Institute of Occupational Health, Helsinki, Finland.

Study Design: Cross-sectional study.

Objective: To examine the association between an aggrecan variable number of tandem repeats (VNTR) polymorphism and intervertebral disc degeneration in middle-aged Finnish men.

Summary Of Background Data: An association between the aggrecan VNTR polymorphism and multilevel disc degeneration has been previously reported in young Japanese women.

Methods: Lumbar discs of 132 men representing 3 occupations (carpenters, machine drivers, and office workers) were evaluated on magnetic resonance imaging, using decreased signal intensity of the nucleus pulposus, disc bulges, and decreased disc height as signs of degeneration. The aggrecan gene VNTR region was analyzed by Southern hybridization.

Results: The allele A26 with 26 repeats was statistically significantly overrepresented among the persons with dark nucleus pulposus. Carrying 2 copies of the A26 allele increased the risk of dark nucleus pulposus (odds ratio = 2.77; 95% confidence interval, 1.24-6.16). Carrying the alleles with either less or more than 26 repeats decreased the risk of dark nucleus pulposus. The carpenters and machine drivers with the A26 allele had a statistically significantly higher risk of disc bulge and decreased disc height than the office workers without the allele.

Conclusion: The findings provide additional support for the role of the aggrecan gene VNTR polymorphism in intervertebral disc degeneration.
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http://dx.doi.org/10.1097/BRS.0b013e3180b9ed51DOI Listing
July 2007

Coexistence of microhemorrhages and acute spontaneous brain hemorrhage: correlation with signs of microangiopathy and clinical data.

Radiology 2006 Jan;238(1):240-7

Department of Radiology, Uppsala Hospital, Uppsala, Sweden.

Purpose: To evaluate prospectively with magnetic resonance (MR) imaging the coexistence of microhemorrhages (MHs) in white patients with acute spontaneous intraparenchymal hemorrhage (IPH) and acute ischemic stroke and to study the association with imaging findings of microangiopathy and various clinical data.

Materials And Methods: Before examinations, informed consents were signed by either the patient or a relative. The study was carried out with the approval of the local ethics committee. MR imaging was performed in 90 patients with acute stroke: 45 with acute spontaneous IPHs (24 men and 21 women; median age, 65 and 68 years, respectively) and 45 age-matched control subjects without intracranial hemorrhages (26 men and 19 women; median age for both, 67 years), as determined at computed tomography. MR imaging included transverse T1- and T2-weighted spin-echo, transverse fluid-attenuated inversion recovery, transverse and coronal T2*-weighted gradient-echo, and, in 50 patients, diffusion-weighted sequences. Presence of MHs and signs of microangiopathy, such as T2 hyperintensities or lacunae, were recorded in the white and deep gray matter. The relationships between MH and IPH and between MH and T2 hyperintensities were analyzed by means of regression analysis. Different clinical features, such as arterial hypertension or diabetes, were registered and correlated with the image findings by means of regression analysis.

Results: MHs were found in 64% of patients with IPH (29 of 45) and 18% of control subjects (eight of 45). A statistically significant relationship between MH and IPH was determined (P < .001). Among the 29 patients with IPH and MH, 24 (83%) had T2 hyperintensities and 13 (45%) had lacunae; among the 16 patients without MH, seven (44%) had T2 hyperintensities and three (19%) had lacunae. A relationship between MH and occurrence and extent of T2 hyperintensities was also identified (P < .001). There was no clear relationship with the clinical data studied.

Conclusion: The results support a correlation between the presence of imaging signs of cerebral microangiopathy, clinically silent MHs, and acute IPHs.
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http://dx.doi.org/10.1148/radiol.2381040551DOI Listing
January 2006

Intervertebral disc degeneration in relation to the COL9A3 and the IL-1ss gene polymorphisms.

Eur Spine J 2006 May 17;15(5):613-9. Epub 2005 Aug 17.

Department of Epidemiology and Biostatistics, Finnish Institute of Occupational Health, 00250 Helsink, Finland.

Disc degeneration is a complex condition in which environmental factors and multiple genes are expected to act together to determine the degenerative phenotype. Recently associations of COL9A2 (Trp2 allele) and COL9A3 (Trp3 allele) polymorphisms with lumbar disc disease characterized by sciatica have been reported. However, it is not known whether the Trp2 or Trp3 alleles contribute to disc degeneration (DD). In this study, the association between the collagen genes polymorphisms and lumbar DD was investigated. Furthermore, the influence of the IL-1beta(C(3954)-T) polymorphism on the association of collagen genes polymorphisms with DD was examined. Lumbar intervertebral discs of 135 middle-aged occupationally active men were evaluated with magnetic resonance imaging, using decreased signal intensity of the nucleus pulposus, disc bulges, and decreased disc height as signs of degeneration. Blood samples were analysed for the presence of COL9A3 and COL9A2 tryptophan alleles (Trp3 and Trp2 alleles). The COL11A2, COL2A1 and IL-1beta(C(3954)-T) polymorphisms were also analysed. Multivariate logistic regression analysis allowing for occupation and body mass index showed that the carriage of the Trp3 allele in the absence of the IL-1betaT(3954) allele increased the risk of dark nucleus pulposus (OR 7.0, 95% CI 1.3-38.8) and joint occurrence of degenerative changes (OR 8.0, 95% CI 1.4-44.7). There was no effect of the Trp3 allele on DD in the presence of the IL-1betaT(3954) allele. The carriers of the COL11A2 minor allele had an increased risk of disc bulges (OR 2.1, 95% CI 1.0-4.2) as compared with non-carriers. The results suggest that the effect of the COL9A3 gene polymorphism on DD might be modified by the IL-1beta gene polymorphism.
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http://dx.doi.org/10.1007/s00586-005-0988-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3489335PMC
May 2006

Familial hypercholesterolemia patients treated with statins at no increased risk for intracranial vascular lesions despite increased cholesterol burden and extracranial atherosclerosis.

Stroke 2005 Jul 2;36(7):1572-4. Epub 2005 Jun 2.

Medical Imaging Center, Helsinki University Central Hospital, Helsinki, Finland.

Background And Purpose: To correlate known vascular disease risk factors and the signs of extracranial and intracranial changes of vascular origin in young patients with heterozygous familial hypercholesterolemia (FH).

Methods: 39 DNA test-verified heterozygous FH North Karelian patients (FH-NK), aged 6 to 48, 28 of them treated with statins, and 25 healthy controls underwent brain magnetic resonance imaging (MRI) and carotid ultrasound.

Results: Common carotid intima-media thickness was significantly greater in the patients (P=0.005). MR angiography showed no pathological changes, other than 1 incidental aneurysm. The number and size of white matter hyperintensities on T2-weighted MR images, considered as markers of microvascular alterations, did not differ between patients and controls.

Conclusions: FH-NK patients treated with statins seem to be at no increased risk for brain infarcts or other brain lesions of vascular origin when younger than age 50.
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http://dx.doi.org/10.1161/01.STR.0000169920.64180.faDOI Listing
July 2005
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