| 1. |
- Abu Hamdeh, Sami, et al.
(author)
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Extended anatomical grading in diffuse axonal injury using MRI : Hemorrhagic lesions in the substantia nigra and mesencephalic tegmentum indicate poor long-term outcome
- 2017
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In: Journal of Neurotrauma. - : Mary Ann Liebert Inc. - 0897-7151 .- 1557-9042. ; 5:34, s. 341-352
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Journal article (peer-reviewed)abstract
- 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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| 2. |
- Abu Hamdeh, Sami, et al.
(author)
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Intracranial pressure elevations in diffuse axonal injury : association with nonhemorrhagic MR lesions in central mesencephalic structures
- 2019
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In: Journal of Neurosurgery. - 0022-3085 .- 1933-0693. ; 131:2, s. 604-611
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Journal article (peer-reviewed)abstract
- 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.Abbreviations: ADC = apparent diffusion coefficient; CPP = cerebral perfusion pressure; DAI = diffuse axonal injury; DWI = diffusion-weighted imaging; EVD = external ventricular drain; GCS = Glasgow Coma Scale; GMT = good monitoring time; GOSE = Glasgow Outcome Scale–Extended; ICC = intraclass correlation coefficient; ICP = intracranial pressure; MAP = mean arterial blood pressure; NICU = neurointensive care unit; SN-T = substantia nigra and mesencephalic tegmentum; SWI = susceptibility-weighted imaging; TBI = traumatic brain injury; T2*GRE = T2*-weighted gradient echo.
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| 3. |
- Abu Hamdeh, Sami, et al.
(author)
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MRI analysis of diffuse axonal injury - Hemorrhagic lesions in the mesencephalon idicate poor long-term outcome
- 2016
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In: MRI analysis of diffuse axonal injury - Hemorrhagic lesions in the mesencephalon idicate poor long-term outcome. - : Springer.
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Conference paper (peer-reviewed)abstract
- Purpose: Clinical outcome after traumatic diffuse axonal injury (DAI) is difficult to predict. Three MRI techniques were compared in demonstrating acute brain lesions. Relationship of the anatomical distribution of the lesions in combination with clinical prognostic factors to outcome after 6 months was evaluated. Methods and Materials: Thirty patients, aged 16-60 years (mean 31.2 years) with severe DAI (Glasgow Motor Score = GMS < 6) were examined with MRI at 1.5T within one week after the injury. A diffusion-weighted (DW) sequence (SE-EPI, b value 1000 s/mm2), a T2*-weighted gradient echo (T2*GRE) sequence and a susceptibility-weighted (SWI) sequence were evaluated by two independent reviewers with short and long neuroradiological experiences. Clinical outcome was assessed with Extended Glasgow Outcome Score (GOSE) after ≥ 6 months.Results: Interreviewer agreement for DAI classification was very good (ҡ 0.82 – 0.91) with all three sequences. SWI visualized more lesions than the T2*GRE or DW sequence. In univariate analysis, number of DW lesions in the deep gray matter area including the internal capsules, number of SWI lesions in the mesencephalon, age, and GMS at admission and discharge correlated significantly with poor outcome. Multivariate analysis only revealed an independent relation with poor outcome for age (p = 0.011) and lesions in the mesencephalic region including crura cerebri, substantia nigra and tegmentum on SWI (p = 0.032).Conclusion: SWI is the most sensitive technique to visualize lesions in DAI. Age over 30 years and hemorrhagic mesencephalic lesions anterior to the tectum are indicators of poor long-term outcome in DAI.
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| 4. |
- Ali, Zafar, et al.
(author)
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Homozygous GRID2 missense mutation predicts a shift in the D-serine binding domain of GluD2 in a case with generalized brain atrophy and unusual clinical features
- 2017
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In: BMC Medical Genetics. - : Springer Science and Business Media LLC. - 1471-2350. ; 18:1
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Journal article (peer-reviewed)abstract
- BACKGROUND: Spinocerebellar ataxias comprise a large and heterogeneous group of disorders that may present with isolated ataxia, or ataxia in combination with other neurologic or non-neurologic symptoms. Monoallelic or biallelic GRID2 mutations were recently reported in rare cases with cerebellar syndrome and variable degree of ataxia, ocular symptoms, hypotonia and developmental delay.CASE PRESENTATION: We report on a consanguineous family with autosomal recessive childhood onset of slowly progressive cerebellar ataxia and delayed psychomotor development in three siblings. MRI of an adult and affected family member revealed slightly widened cerebral and cerebellar sulci, suggesting generalized brain atrophy, and mild cerebellar atrophy. Using whole exome sequencing we identified a novel homozygous missense variant [c.2128C > T, p.(Arg710Trp)] in GRID2 that segregates with the disease. The missense variant is located in a conserved region encoding the extracellular serine-binding domain of the GluD2 protein and predicts a change in conformation of the protein.CONCLUSION: The widespread supratentorial brain abnormalities, absence of oculomotor symptoms, increased peripheral muscle tone and the novel missense mutation add to the clinical and genetic variability in GRID2 associated cerebellar syndrome. The neuroradiological findings in our family indicate a generalized neurodegenerative process to be taken into account in other families segregating complex clinical features and GRID2 mutations.
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| 5. |
- Bexelius, Maria, et al.
(author)
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27 forskare : Så kan EU:s murar rivas
- 2015
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In: Dagens samhälle. - : Sveriges kommuner och landsting. - 1652-6511. ; :20150923
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Journal article (pop. science, debate, etc.)
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| 6. |
- Hou, Chen, et al.
(author)
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Resolving phylogenetic relationships and species delimitations in closely related gymnosperms using high-throughput NGS, Sanger sequencing and morphology
- 2016
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In: Plant Systematics and Evolution. - : Springer Science and Business Media LLC. - 0378-2697 .- 1615-6110 .- 2199-6881. ; 302:9, s. 1345-1365
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Journal article (peer-reviewed)abstract
- Plastid genomes have been widely applied to elucidate plant evolution at higher taxonomic levels, but have rarely been considered useful for addressing close relationships. Here, we resolve the phylogeny and taxonomy of the Chinese lianoid Gnetum clade (Gnetales), using high throughput and Sanger sequencing techniques and studies of plant morphology. Despite previous efforts, relationships among taxa and the taxonomy within the clade have remained unclear. We generated 11 plastid genomes representing one arborescent and four lianoid species. Phylogenetic analyses were conducted using (a) the entire plastid genomes and (b) the protein-coding genes only. Sequence divergence among the lianoid species was substantial, with 9345 variable sites. Four variable regions were identified, targeted and sequenced for an additional 54 specimens and analyzed together with one nuclear ribosomal marker. Results from the phylogenetic analyses corroborate G. parvifolium as sister to the remaining lianoid species and support the presence of at least five additional species in the Chinese lianoid clade: G. catasphaericum, G. formosum, G. luofuense, G. montanum and G. pendulum. Following morphological investigations, G. giganteum and G. gracilipes are included in and synonymized with G. pendulum. Gnetum hainanense is included in and synonymized with G. luofuense. Two names, G. indicum and G. cleistostachyum, remain questionable. A taxonomic revision and a key to Chinese lianoid Gnetum are presented. Internal nodes in the Chinese lianoid Gnetum clade are from the Miocene and onwards and coincide with the expansion of tropical to subtropical forests in South China, which may have facilitated speciation in the clade.
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| 7. |
- Hou, Chen, et al.
(author)
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The chloroplast genome of Ephedra foeminea (Ephedraceae, Gnetales), an entomophilous gymnosperm endemic to the Mediterranean area
- 2015
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In: Mitochondrial DNA. - : Informa UK Limited. - 1940-1736 .- 1940-1744. ; 28:3, s. 330-331
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Journal article (peer-reviewed)abstract
- This study presents the chloroplast genome of Ephedra foeminea, an entomophilous gymnosperm, sister to the remaining (wind-pollinated) species of Ephedra (Ephedraceae, Gnetales). Based on the reference-guided assembly, the length of the chloroplast genome was estimated to be 109 584 bp, comprising a large single copy region of 60 027 bp, a small single copy 8079 bp, and inverted repeat regions of 20 739 bp. In total, 118 genes were detected, including 73 protein-coding genes, eight ribosomal RNA genes, and 37 transfer RNA genes. The gene density is 1.076 (genes/kb) and the GC content is 36.7%. The genomic sequence of the entomophilous, Mediterranean species E. foeminea, differs from that of the anemophilous, Asian species E. equisetina by 1018 point mutations and 1334 indels. The detected variation is useful for future development of new plastid markers for phylogenetic purposes. Our phylogenetic analysis based on 55 protein-coding chloroplast genes resolve Ephedra as monophyletic and sister to a Gnetum-Welwitschia clade. The Gnetales are sister to Cupressophytes.
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| 8. |
- Kainulainen, Kent, 1978-, et al.
(author)
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Island hopping, long-distance dispersal and species radiation: historical biogeography of the Coffeeae alliance (Rubiaceae)
- 2017
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In: Journal of Biogeography. - : Wiley. - 0305-0270 .- 1365-2699. ; 44, s. 1966-1979
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Journal article (peer-reviewed)abstract
- Aim. The Western Indian Ocean region (WIOR) is home to a very diverse and largely unique flora that has mainly originated via long-distance dispersals. The aim of this study is to gain insight into the origins of the WIOR biodiversity and to understand the dynamics of colonization events between the islands. We investigate spatial and temporal hypotheses of the routes of dispersal, and compare the dispersal patterns of plants of the Coffeeae alliance (Rubiaceae) and their dispersers. Rubiaceae is the second most species-rich plant family in Madagascar, and includes many endemic genera. The neighbouring archipelagos of the Comoros, Mascarenes and Seychelles also harbour several endemic Rubiaceae.Location. The islands of the Western Indian Ocean.Methods. Phylogenetic relationships and divergence times were reconstructed from plastid DNA data of an ingroup sample of 340 species, using Bayesian inference. Ancestral areas and range evolution history were inferred by a maximum likelihood method that takes topological uncertainty into account.Results. At least 15 arrivals to Madagascar were inferred, the majority of which have taken place within the last 10 Myr. Most dispersal events were supported as being from mainland Africa, but Catunaregam may have dispersed from Asia. Although most Coffeeae alliance lineages are zoochorous, the general pattern of dispersals from Africa is incongruent with the biogeographic origins of the extant Malagasy volant frugivores. Several out-of-Madagascar dispersals were inferred to the neighbouring islands, as well as back-colonizations of Africa.Main conclusions. The African flora has been of foremost importance as source of dispersal to the islands of the Western Indian Ocean. Following the colonization of Madagascar, rapid radiations appear to have taken place in some clades, and Madagascar has also been an important source area for subsequent dispersal to the Comoros, Mascarenes and Seychelles.
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| 9. |
- Kainulainen, Kent, et al.
(author)
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Island hopping, long-distance dispersal and species radiation in the Western Indian Ocean : historical biogeography of the Coffeeae alliance (Rubiaceae)
- 2017
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In: Journal of Biogeography. - : Wiley. - 0305-0270 .- 1365-2699. ; 44:9, s. 1966-1979
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Journal article (peer-reviewed)abstract
- Aim The Western Indian Ocean region (WIOR) is home to a very diverse and largely unique flora that has mainly originated via long-distance dispersals. The aim of this study is to gain insight into the origins of the WIOR biodiversity and to understand the dynamics of colonization events between the islands. We investigate spatial and temporal hypotheses of the routes of dispersal, and compare the dispersal patterns of plants of the Coffeeae alliance (Rubiaceae) and their dispersers. Rubiaceae is the second most species-rich plant family in Madagascar, and includes many endemic genera. The neighbouring archipelagos of the Comoros, Mascarenes and Seychelles also harbour several endemic Rubiaceae.Location The islands of the Western Indian Ocean.Methods Phylogenetic relationships and divergence times were reconstructed from plastid DNA data of an ingroup sample of 340 species, using Bayesian inference. Ancestral areas and range evolution history were inferred by a maximum likelihood method that takes topological uncertainty into account.Results At least 15 arrivals to Madagascar were inferred, the majority of which have taken place within the last 10 Myr. Most dispersal events were supported as being from mainland Africa, but Catunaregam may have dispersed from Asia. Although most Coffeeae alliance lineages are zoochorous, the general pattern of dispersals from Africa is incongruent with the biogeographic origins of the extant Malagasy volant frugivores. Several out-of-Madagascar dispersals were inferred to the neighbouring islands, as well as back-colonizations of Africa.Main conclusions The African flora has been of foremost importance as source of dispersal to the islands of the Western Indian Ocean. Following the colonization of Madagascar, rapid radiations appear to have taken place in some clades, and Madagascar has also been an important source area for subsequent dispersal to the Comoros, Mascarenes and Seychelles.
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| 10. |
- Klar, Joakim, 1974-, et al.
(author)
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A missense variant in ITPR1 provides evidence for autosomal recessive SCA29 with asymptomatic cerebellar hypoplasia in carriers.
- 2017
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In: European Journal of Human Genetics. - : Springer Science and Business Media LLC. - 1018-4813 .- 1476-5438. ; 25:7, s. 848-853
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Journal article (peer-reviewed)abstract
- Spinocerebellar ataxias (SCA) comprise a heterogeneous group of inherited neurological disorders characterized by a range of symptoms from both cerebellar and extra cerebellar structures. We investigated the cause of autosomal recessive, congenital SCA in six affected family members from a large consanguineous family. Using whole-exome sequencing, we identified a homozygous ITPR1 missense variant [c.5360T>C; p.(L1787P)] segregating in all affected individuals. Heterozygous carriers were asymptomatic despite cerebellar hypoplasia. Variants in the ITPTR1 gene have previously been associated exclusively with autosomal dominant SCA15 and SCA29 with slow or no progression. The L1787 residue is highly conserved and the leucine to proline substitution has a predicted destabilizing effect on the protein structure. Additionally, the L1787P variant is located in a domain separated from previously described and dominant-acting missense variants consistent with a distinct effect on IP3R1 tetramer structure and function. Taken together, we show for the first time that a biallelic ITPR1 missense variant may cause an autosomal recessive and infantile onset SCA29, albeit with subclinical cerebellar hypoplasia in carriers. Our findings add to the genetic complexity of SCA29 and broaden the correlations between ITPR1 variants and their clinical expression.
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