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1.
J Neurol Neurosurg Psychiatry ; 95(5): 471-476, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38041670

RESUMO

BACKGROUND: Non-convulsive status epilepticus (NCSE) is a time-dependent neurological disorder often misdiagnosed in the emergency setting. Electroencephalography (EEG) is often not available on a 24/7 basis, and Salzburg criteria may at times miss the diagnosis. Here, we tested the accuracy of hyperperfusion on CT perfusion imaging (CTP) in the identification of NCSE against Salzburg criteria, to define its potential role in a pragmatic diagnostic workflow. METHODS: We enrolled consecutive patients with suspected acute seizure or seizure disorder undergoing brain imaging with CTP and EEG from January 2021 to March 2023. EEG recordings, Salzburg criteria and CTP hyperperfusion were rated and adjudicated by two independent experts blinded to patient status. A reference standard including all clinical, lab, imaging, EEG and therapeutic data was used to adjudicate NCSE diagnosis. Sensitivity, specificity, diagnostic accuracy, positive and negative predictive values (NPV) were calculated for CTP hyperperfusion and Salzburg criteria versus NCSE adjudicated according to reference standard. RESULTS: Seventy-seven patients were enrolled. Among 21 NCSE cases, 17 were adjudicated according to Salzburg criteria (81%) and 4 received NCSE diagnosis according to reference standard. Agreement between EEG and CTP emerged in 16/21 NCSE cases, reaching sublobar level in 37.5% of cases. Receiver operator curve analysis suggested good accuracy for CTP hyperperfusion for the diagnosis of NCSE (AUROC 0.79, 95% CI 0.69 to 0.89). CTP hyperperfusion had a high NPV for NCSE (NPV 0.97, 95% CI 0.86 to 1). CONCLUSION: CTP hyperperfusion may be implemented in the emergency fast-track to rule out NCSE, given very high NPV. Further validation studies are needed to evaluate CTP application in real-world setting for NCSE codes.


Assuntos
Estado Epiléptico , Humanos , Encéfalo , Eletroencefalografia/métodos , Perfusão , Estado Epiléptico/diagnóstico por imagem , Estudos Prospectivos
2.
Stroke ; 53(12): 3671-3678, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36039754

RESUMO

BACKGROUND: Symptomatic intracerebral hemorrhage (sICH) and major bleeding can be fatal complications of intravenous thrombolysis (IVT) for acute ischemic stroke. We investigated the impact of early fibrinogen depletion after IVT on major bleeding events. METHODS: This multicenter observational prospective cohort study enrolled 1678 consecutive patients receiving IVT for acute ischemic stroke at 6 Italian centers, undergoing fibrinogen concentration assessment at baseline, 2 hours and 6 hours after IVT. Fibrinogen depletion was defined as a reduction below 200 mg/dL after 2 hours from IVT, or as a reduction below 50% of baseline fibrinogen levels after 2 hours from IVT. Main outcomes were (1) sICH (National Institute of Neurological Disorders and Stroke criteria) and (2) major bleeding defined as fatal bleeding, decrease in the hemoglobin level>2 g/dL/>1 unit transfusion, or bleeding at critical site. Additional outcomes were (1) any ICH, (2) any bleeding, (3) fatal ICH, and (4) sICH according to ECASSII definition. Good functional recovery was defined as modified Rankin Scale score 0 to 2 at 3 months. RESULTS: Overall, 1678 patients were included (mean age 72 years, 46% female). sICH (n=116) and major bleeding (n=297) were associated with lower rate of good functional recovery (P<0.001). Despite similar fibrinogen levels at admission, fibrinogen depletion after 2 hours from IVT was more common in people with sICH, major bleeding and all additional bleeding outcomes. In the backward stepwise multivariable logistic regression model, fibrinogen depletion remained a significant predictor of sICH (OR, 1.55 [95% CI, 1.04-2.32]) and major bleeding (OR, 1.36 [95% CI, 1.03-1.8]). Thirty-one percent of sICH could be attributable to fibrinogen depletion. The association between fibrinogen depletion and worse clinical outcome at 3 months after stroke (P=0.012) was attributable to the higher risk of major bleeding/sICH. CONCLUSIONS: Fibrinogen depletion significantly increases the risk of sICH and major bleeding after IVT for acute ischemic stroke. Fibrinogen depletion represents an independent risk factor for bleeding, and routine assessment could be considered to stratify the risk of ICH. Trials on early fibrinogen repletion are needed to investigate mitigation of bleeding risk.


Assuntos
Transtornos da Coagulação Sanguínea , Isquemia Encefálica , Hemostáticos , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Feminino , Idoso , Masculino , Ativador de Plasminogênio Tecidual/efeitos adversos , Terapia Trombolítica/efeitos adversos , Fibrinolíticos/efeitos adversos , Fibrinogênio , Estudos Prospectivos , Hemorragia Cerebral/complicações , Transtornos da Coagulação Sanguínea/complicações , Hemostáticos/uso terapêutico , Resultado do Tratamento , Isquemia Encefálica/complicações , Isquemia Encefálica/tratamento farmacológico
3.
Epilepsia ; 63(10): 2534-2542, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35793391

RESUMO

OBJECTIVE: Nonconvulsive status epilepticus (NCSE) is misdiagnosed in >50% of cases in the emergency department. Computed tomographic perfusion (CTP) has been implemented in the hyperacute setting to detect seizure-induced hyperperfusion. However, the diagnostic value of CTP is limited by the lack of thresholds for hyperperfusion and high interrater variability. This pilot case-control study aims at identifying the diagnostic value of reverse Tmax (rTmax) in differentiating NCSE from acute ischemic stroke in the hyperacute setting. METHODS: We enrolled patients with NCSE (Salzburg criteria-based diagnosis) and stroke cases 1:1 matched for clinical features and time of presentation. CTP standard maps (mean transit time [MTT]-cerebral blood volume-cerebral blood flow [CBF]) and rTmax maps were elaborated and rated by two experts in CTP blinded to the final diagnosis. Hyperperfusion was adjudicated for standard CTP maps as an increase in CBF and a decrease in MTT, and for rTmax as the presence of a black area on 3-, 2-, and 1-s threshold maps. Cronbach alpha was used for interrater agreement; receiver operating curve analysis was run to measure accuracy with area under the curve. RESULTS: Overall, 34 patients were included (17 NCSE, 17 stroke; time from onset to imaging = 2 h for both groups). People with NCSE were older and more frequently had a history of epilepsy. NCSE patients had hyperperfusion on rTmax maps in 11 of 17 cases versus zero of 17 in stroke. Intra- and interrater reliability was higher for rTmax than for standard CTP maps (κ = 1 vs. κ = .6). rTmax was 82% (95%CI = 67-97%) accurate in predicting NCSE versus stroke in the hyperacute setting. Agreement between neuroimaging and electroencephalography (EEG) was limited at a hemispheric level for standard CTP maps, whereas rTMax had agreement with EEG largely reaching the sublobar level. SIGNIFICANCE: rTmax mapping might represent a reliable tool to spot NCSE-induced hyperperfusion with a threshold-based reproducible approach. Further studies are needed for validation and implementation in the differential diagnosis of focal neurological deficit in the hyperacute setting.


Assuntos
AVC Isquêmico , Estado Epiléptico , Acidente Vascular Cerebral , Humanos , Estudos de Casos e Controles , Eletroencefalografia , Reprodutibilidade dos Testes , Estudos Retrospectivos , Estado Epiléptico/diagnóstico por imagem , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/diagnóstico por imagem
4.
Neurol Sci ; 43(9): 5633-5636, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35708792

RESUMO

Autoimmune encephalitis (AE) associated to antibodies against GABA A R is a rare form of encephalitis. On the other hand, thymoma has been linked to antibodies against both muscular and neuronal epitopes, even if concurrent positivity for more than one antibody is exceptional, and their contribution to the clinical course and treatment decision is unclear. We report a case of a 73-year-old male with AE associated with thymoma secreting both anti-GABAaR and anti-titin antibodies. Clinical presentation included status epilepticus, behavioural changes and cognitive decline. While the status was stopped with lacosamide, AE treatment included first- and second-line immunomodulation, in addition to thymoma's removal. Nonetheless, the patient experienced a worsening in cognitive and behavioural status.


Assuntos
Encefalite , Timoma , Neoplasias do Timo , Idoso , Autoanticorpos , Doença de Hashimoto , Humanos , Masculino , Receptores de GABA-A , Timoma/complicações , Neoplasias do Timo/complicações
5.
Neurol Sci ; 38(2): 255-262, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27807698

RESUMO

Incidence of neuroepithelial Primary Brain Tumors (nPBT) varies, ranging from 7.3 to 11.6 cases/100,000/year across Europe. We present incidence and survival of nPBT in the Emilia-Romagna region (ER), Italy. This study is the largest in Southern Europe. Specialists in neurosurgery, neurology, neuroradiology, oncology, radiotherapy, genetics, and pathology of ER notified all suspected nPBT adult cases residing in ER (4,337,966 inhabitants) observed during 2009. Furthermore, through ICD-9 discharge codes, we identified and reviewed all possible cases. Neuroepithelial PBT diagnosis was based on histological or radiological findings. We included 400 incident nPBT cases, of which 102 (25%) were retrospectively identified. These latter were significantly older. The standardized incidence was 10.5/100,000/year (95% CI 9.4-11.5), higher for men. It was 9.2/100,000/year (95% CI 8.3-10.2) for astrocytic tumors, 0.6/100,000/year (95% CI 0.4-0.9) for oligodendroglial tumors, and 7.1 (95% CI 6.3-8.0) for glioblastoma (GBM). Among GBM patients, median survival was 249 days if prospectively identified vs. 132 days when identified through ICD-9 codes (p < 0.0001). The incidence of nPBT in the ER region is among the highest in the literature. Older patients were more likely to escape an active surveillance system. This should be considered when comparing incidence rates across studies, giving the increasing number of elderly people in the general population.


Assuntos
Neoplasias Encefálicas/epidemiologia , Neoplasias Neuroepiteliomatosas/epidemiologia , Sistema de Registros/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/mortalidade , Feminino , Glioblastoma/epidemiologia , Humanos , Incidência , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Neoplasias Neuroepiteliomatosas/mortalidade
6.
J Biol Chem ; 289(48): 33073-82, 2014 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-25288803

RESUMO

A missense mutation in ATP2A1 gene, encoding sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA1) protein, causes Chianina cattle congenital pseudomyotonia, an exercise-induced impairment of muscle relaxation. Skeletal muscles of affected cattle are characterized by a selective reduction of SERCA1 in sarcoplasmic reticulum membranes. In this study, we provide evidence that the ubiquitin proteasome system is involved in the reduced density of mutated SERCA1. The treatment with MG132, an inhibitor of ubiquitin proteasome system, rescues the expression level and membrane localization of the SERCA1 mutant in a heterologous cellular model. Cells co-transfected with the Ca(2+)-sensitive probe aequorin show that the rescued SERCA1 mutant exhibits the same ability of wild type to maintain Ca(2+) homeostasis within cells. These data have been confirmed by those obtained ex vivo on adult skeletal muscle fibers from a biopsy from a pseudomyotonia-affected subject. Our data show that the mutation generates a protein most likely corrupted in proper folding but not in catalytic activity. Rescue of mutated SERCA1 to sarcoplasmic reticulum membrane can re-establish resting cytosolic Ca(2+) concentration and prevent the appearance of pathological signs of cattle pseudomyotonia.


Assuntos
Doenças dos Bovinos/enzimologia , Síndrome de Isaacs/enzimologia , Síndrome de Isaacs/veterinária , Proteínas Musculares/metabolismo , Complexo de Endopeptidases do Proteassoma/metabolismo , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/metabolismo , Retículo Sarcoplasmático/enzimologia , Ubiquitina/metabolismo , Animais , Cálcio/metabolismo , Bovinos , Doenças dos Bovinos/genética , Doenças dos Bovinos/patologia , Cricetinae , Células HEK293 , Humanos , Síndrome de Isaacs/genética , Síndrome de Isaacs/patologia , Leupeptinas/farmacologia , Proteínas Musculares/genética , Mutação , Complexo de Endopeptidases do Proteassoma/genética , Inibidores de Proteassoma/farmacologia , Dobramento de Proteína/efeitos dos fármacos , Retículo Sarcoplasmático/genética , Retículo Sarcoplasmático/patologia , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/genética , Ubiquitina/genética
8.
PLoS Genet ; 6(8)2010 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-20865119

RESUMO

Arachnomelia is a monogenic recessive defect of skeletal development in cattle. The causative mutation was previously mapped to a ∼7 Mb interval on chromosome 5. Here we show that array-based sequence capture and massively parallel sequencing technology, combined with the typical family structure in livestock populations, facilitates the identification of the causative mutation. We re-sequenced the entire critical interval in a healthy partially inbred cow carrying one copy of the critical chromosome segment in its ancestral state and one copy of the same segment with the arachnomelia mutation, and we detected a single heterozygous position. The genetic makeup of several partially inbred cattle provides extremely strong support for the causality of this mutation. The mutation represents a single base insertion leading to a premature stop codon in the coding sequence of the SUOX gene and is perfectly associated with the arachnomelia phenotype. Our findings suggest an important role for sulfite oxidase in bone development.


Assuntos
Desenvolvimento Ósseo , Doenças dos Bovinos/enzimologia , Bovinos/genética , Códon sem Sentido , Doenças Genéticas Inatas/veterinária , Sulfito Oxidase/genética , Animais , Sequência de Bases , Bovinos/crescimento & desenvolvimento , Bovinos/metabolismo , Doenças dos Bovinos/genética , Feminino , Doenças Genéticas Inatas/enzimologia , Doenças Genéticas Inatas/genética , Masculino , Dados de Sequência Molecular , Linhagem , Análise de Sequência de DNA , Sulfito Oxidase/metabolismo
9.
BMC Vet Res ; 8: 186, 2012 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-23046865

RESUMO

BACKGROUND: Bovine congenital pseudomyotonia (PMT) is an impairment of muscle relaxation induced by exercise preventing animals from performing rapid movements. Forms of recessively inherited PMT have been described in different cattle breeds caused by two independent mutations in ATP2A1 encoding a skeletal-muscle Ca2+-ATPase (SERCA1). We observed symptoms of congenital PMT in four related Romagnola beef cattle from Italy and evaluated SERCA1 activity and scanned ATP2A1 for possible causative mutations. RESULTS: We obtained four PMT affected Romagnola cattle and noted striking clinical similarities to the previously described PMT cases in other cattle breeds. The affected animals had a reduced SERCA1 activity in the sarcoplasmic reticulum. A single affected animal was homozygous for a novel complex variant in ATP2A1 exon 8 (c.[632 G>T; 857 G>T]). Three out of four cases were compound heterozygous for the newly identified exon 8 variant and the exon 6 variant c.491 G>A(p. Arg146Gly), which has previously been shown to cause PMT in Chianina cattle. Pedigree analysis showed that the exon 8 double mutation event dates back to at least 1978. Both nucleotide substitutions are predicted to alter the SERCA1 amino acid sequence (p.[(Gly211Val; Gly284Val)]), affect highly conserved residues, in particular the actuator domain of SERCA1. CONCLUSION: Clinical, biochemical and DNA analyses confirmed the initial hypothesis. We provide functional and genetic evidence that one novel and one previously described ATP2A1 mutation lead to a reduced SERCA1 activity in skeletal muscles and pseudomyotonia in affected Romagnola cattle. Selection against these mutations can now be used to eliminate the mutant alleles from the Romagnola breed.


Assuntos
Doenças dos Bovinos/genética , Síndrome de Isaacs/veterinária , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/genética , Animais , Bovinos , Doenças dos Bovinos/enzimologia , DNA/química , DNA/genética , Feminino , Genótipo , Histocitoquímica/veterinária , Síndrome de Isaacs/enzimologia , Síndrome de Isaacs/genética , Masculino , Músculo Esquelético/enzimologia , Mutação , Linhagem , Análise de Sequência de DNA
11.
Am J Pathol ; 174(2): 565-73, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19116366

RESUMO

Recently, a muscular disorder defined as "congenital pseudomyotonia" was described in Chianina cattle, one of the most important Italian cattle breeds for quality meat and leather. The clinical phenotype of this disease is characterized by an exercise-induced muscle contracture that prevents animals from performing muscular activities. On the basis of clinical symptoms, Chianina pseudomyotonia appeared related to human Brody's disease, a rare inherited disorder of skeletal muscle function that results from a sarcoplasmic reticulum Ca(2+)-ATPase (SERCA1) deficiency caused by a defect in the ATP2A1 gene that encodes SERCA1. SERCA1 is involved in transporting calcium from the cytosol to the lumen of the sarcoplasmic reticulum. Recently, we identified the genetic defect underlying Chianina cattle pseudomyotonia. A missense mutation in exon 6 of the ATP2A1 gene, leading to an R164H substitution in the SERCA1 protein, was found. In this study, we provide biochemical evidence for a selective deficiency in SERCA1 protein levels in sarcoplasmic reticulum membranes from affected muscles, although mRNA levels are unaffected. The reduction of SERCA1 levels accounts for the reduced Ca(2+)-ATPase activity without any significant change in Ca(2+)-dependency. The loss of SERCA1 is not compensated for by the expression of the SERCA2 isoform. We believe that Chianina cattle pseudomyotonia might, therefore, be the true counterpart of human Brody's disease, and that bovine species might be used as a suitable animal model.


Assuntos
Síndrome de Isaacs/metabolismo , Síndrome de Isaacs/veterinária , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/deficiência , Animais , Western Blotting , Bovinos , Feminino , Imuno-Histoquímica , Síndrome de Isaacs/congênito , Masculino , Microscopia Confocal , Microscopia de Fluorescência , Músculo Esquelético/enzimologia , Mutação de Sentido Incorreto , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Retículo Sarcoplasmático/enzimologia
12.
Genomics ; 92(6): 474-7, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18786632

RESUMO

Congenital pseudomyotonia in Chianina cattle is a muscle function disorder very similar to that of Brody disease in humans. Mutations in the human ATP2A1 gene, encoding SERCA1, cause Brody myopathy. The analysis of the collected Chianina pedigree data suggested monogenic autosomal recessive inheritance and revealed that all 17 affected individuals traced back to a single founder. A deficiency of SERCA1 function in skeletal muscle of pseudomyotonia affected Chianina cattle was observed as SERCA1 activity in affected animals was decreased by about 70%. Linkage analysis showed that the mutation was located in the ATP2A1 gene region on BTA25 and subsequent mutation analysis of the ATP2A1 exons revealed a perfectly associated missense mutation in exon 6 (c.491G>A) leading to a p.Arg164His substitution. Arg164 represents a functionally important and strongly conserved residue of SERCA1. This study provides a suitable large animal model for human Brody disease.


Assuntos
Bovinos/genética , Modelos Animais de Doenças , Síndrome de Isaacs/veterinária , Mutação de Sentido Incorreto , Miotonia Congênita/genética , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/genética , Sequência de Aminoácidos , Animais , Arginina/genética , Análise Mutacional de DNA , Feminino , Humanos , Síndrome de Isaacs/congênito , Síndrome de Isaacs/genética , Masculino , Dados de Sequência Molecular , Linhagem , Condicionamento Físico Animal
13.
J Neurol ; 255(1): 16-23, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18004642

RESUMO

INTRODUCTION: Familial mesial temporal lobe epilepsy (FMTLE) is characterized by prominent psychic and autonomic seizures, often without hippocampal sclerosis (HS) or a previous history of febrile seizures (FS), and good prognosis. The genetics of this condition is largely unknown.We present the electroclinical and genetic findings of 15 MTLE Italian families. PATIENTS AND METHODS: FMTLE was defined when two or more first-degree relatives had epilepsy suggesting a mesial temporal lobe origin. The occurrence of seizures with auditory auras was considered an exclusion criterion. Patients underwent video-EEG recordings, 1.5-Tesla MRI particularly focused on hippocampal analysis, and neuropsychological evaluation. Genetic study included genotyping and linkage analysis of candidate loci at 4q, 18q, 1q, and 12q as well as screening for LGI1/Epitempin mutations. RESULTS: Most of the families showed an autosomal dominant inheritance pattern with incomplete penetrance. Fifty-four (32 F) affected individuals were investigated. Twenty-one (38.8 %) individuals experienced early FS. Forty-eight individuals fulfilled the criteria for MTLE. Epigastric/visceral sensation (72.9 %) was the most common type of aura, followed by psychic symptoms (35.4 %), and déjà vu (31.2 %). HS occurred in 13.8% of individuals, three of whom belonged to the same family. Prognosis of epilepsy was generally good. Genetic study failed to show LGI1/Epitempin mutations or significative linkage to the investigated loci. DISCUSSION: FMTLE may be a more common than expected condition, clinically and genetically heterogeneous. Some of the reported families, grouped on the basis of a specific aura, may represent an interesting subgroup on whom to focus future linkage studies.


Assuntos
Epilepsia do Lobo Temporal/genética , Epilepsia do Lobo Temporal/fisiopatologia , Predisposição Genética para Doença/genética , Mutação/genética , Lobo Temporal/fisiopatologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Transtornos Cromossômicos/genética , Transtornos Cromossômicos/patologia , Transtornos Cromossômicos/fisiopatologia , Mapeamento Cromossômico , Análise Mutacional de DNA , Eletroencefalografia , Epilepsia do Lobo Temporal/patologia , Feminino , Genes Dominantes/genética , Testes Genéticos , Genótipo , Humanos , Padrões de Herança/genética , Itália , Masculino , Pessoa de Meia-Idade , Transtornos Neurocognitivos/genética , Transtornos Neurocognitivos/fisiopatologia , Linhagem , Transtornos de Sensação/genética , Transtornos de Sensação/fisiopatologia , Lobo Temporal/patologia
14.
Epilepsy Res ; 80(1): 9-17, 2008 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-18508238

RESUMO

PURPOSE: To describe a familial epileptic condition combining a peculiar electro-clinical pattern with developmental language dysfunction in a large Italian kindred. METHODS: We studied the clinical and neurophysiological features of a 4-generation family with 10 affected members (3 deceased). We also analysed in 7 affected and 7 healthy members microsatellite markers for 51 candidate loci for epilepsy, including 42 loci containing ion channel genes expressed in the brain, as well as the SPCH1 and SRPX2 loci. RESULTS: Five of the seven living affected members (aged 20-58 years) had the full phenotype (seizures, EEG epileptiform abnormalities and dysphasia). The language dysfunction was the first symptom, becoming evident since the period of language development and mainly consisting of phonemic and syntactic paraphasias, difficulty of expression and reduced verbal fluency. The seizures had their onset between 2 and 23 years and were reported as epileptic falls (4) associated or not with myoclonic features, absences (3), tonic-clonic (1) and complex partial seizures (1). The seizures were easily controlled by antiepileptic treatment in all patients except one. In the five patients with a good response of seizures to treatment, the EEG tracings showed the coexistence of focal and generalized epileptiform abnormalities; in the refractory patient the interictal EEG demonstrated bilateral asynchronous fronto-temporal paroxysms with left predominance and ictal SEEG recording suggested a multifocal origin of the discharges. MRI of the brain was normal in all patients. Linkage analysis provided negative LOD scores for all the investigated loci. CONCLUSION: We have described a novel familial pattern of epilepsy and developmental dysphasia which is not genetically linked to epilepsy or speech disorder loci, as documented by a candidate-gene linkage approach.


Assuntos
Afasia/etiologia , Afasia/genética , Epilepsia/complicações , Epilepsia/genética , Genes Dominantes , Linhagem , Adulto , Idade de Início , Eletroencefalografia/métodos , Saúde da Família , Feminino , Fatores de Transcrição Forkhead/genética , Ligação Genética/fisiologia , Humanos , Itália , Masculino , Proteínas de Membrana , Pessoa de Meia-Idade , Proteínas de Neoplasias , Proteínas do Tecido Nervoso/genética , Fenótipo
15.
Vet J ; 177(1): 144-6, 2008 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-17502161

RESUMO

Brachyspina syndrome, a rare lethal skeletal malformation, is described in two Italian Holstein calves. Both calves were stillborn and had shortened trunks with long legs. Radiography demonstrated several abnormalities of the cervical and thoracolumbar vertebral column. Visceral malformations involving the heart, kidney, genital tract and gastrointestinal system were also found. Both calves were traced back to the same sire and an inherited basis was strongly suspected.


Assuntos
Doenças dos Bovinos/congênito , Coluna Vertebral/anormalidades , Coluna Vertebral/patologia , Natimorto/veterinária , Animais , Bovinos , Doenças dos Bovinos/genética
17.
J Orthop Res ; 31(2): 306-14, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22893604

RESUMO

Tendon injuries, degenerative tendinopathies, and overuse tendinitis are common in races horses. Novel therapies aim to restore tendon functionality by means of cell-based therapy, growth factor delivery, and tissue engineering approaches. This study examined the use of autologous mesenchymal stromal cells derived from peripheral blood (PB-MSCs), platelet-rich plasma (PRP) and a combination of both for ameliorating experimental lesions on deep digital flexor tendons (DDFT) of Bergamasca sheep. In particular, testing the combination of blood-derived MSCs and PRP in an experimental animal model represents one of the few studies exploring a putative synergistic action of these treatments. Effectiveness of treatments was evaluated at 30 and 120 days comparing clinical, ultrasonographic, and histological features together with immunohistochemical expression of collagen types 1 and 3, and cartilage oligomeric matrix protein (COMP). Significant differences were found between treated groups and their corresponding controls (placebo) regarding tendon morphology and extracellular matrix (ECM) composition. However, our results indicate that the combined use of PRP and MSCs did not produce an additive or synergistic regenerative response and highlighted the predominant effect of MSCs on tendon healing, enhanced tissue remodeling and improved structural organization.


Assuntos
Transplante de Células-Tronco Mesenquimais , Plasma Rico em Plaquetas , Traumatismos dos Tendões/terapia , Cicatrização/efeitos dos fármacos , Animais , Colágeno Tipo I/biossíntese , Colágeno Tipo III/biossíntese , Colagenases , Sinergismo Farmacológico , Proteínas da Matriz Extracelular/biossíntese , Feminino , Glicoproteínas/biossíntese , Membro Posterior/diagnóstico por imagem , Membro Posterior/patologia , Proteínas Matrilinas , Carneiro Doméstico , Traumatismos dos Tendões/induzido quimicamente , Traumatismos dos Tendões/patologia , Ultrassonografia , Cicatrização/fisiologia
18.
PLoS One ; 7(9): e45634, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23029151

RESUMO

In the last decade breeders of Romagnola cattle observed an outbreak of a new congenital anomaly. This lethal multi-organ developmental dysplasia is mainly characterized by facial deformities, ascites and hepatic fibrosis. Affected stillborn calves were inbred to a single founder sire suggesting autosomal monogenic recessive inheritance. We localized the causative mutation to a 1.2 Mb interval on BTA 17 by genome-wide association and identical by descent mapping. A solution-based method for targeted DNA capture combined with massively parallel sequencing was used to analyze the entire critical region containing 24 genes. Homozygosity for two non-synonymous coding sequence variants affecting the RNF34 and KDM2B genes was detected by evaluating one affected calf. Here we show that the disease phenotype is associated with a KDM2B missense mutation (c.2503G>A) leading to an amino acid exchange (p.D835N) in an evolutionary strongly conserved domain. In addition, the genetic makeup of three inbred cattle strongly supports the causality of the KDM2B mutation. This report of a naturally-occurring spontaneous mutation of a JmjC domain containing histone demethylase gene provides evidence for their important role in the endo- and mesodermal organ development.


Assuntos
Doenças Genéticas Inatas/genética , Oxirredutases N-Desmetilantes/genética , Animais , Bovinos , Mutação de Sentido Incorreto , Fenótipo
19.
Vet Radiol Ultrasound ; 51(2): 162-4, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20402403

RESUMO

Herein, we describe a calf affected by cerebellar displacement and spina bifida, diagnosed by ultrasonography. A full-term, newborn female calf with paralysis of the pelvic limbs was examined. The dorsal skin at the sacral level contained a circular defect; this was subsequently diagnosed as spina bifida. Cerebellar displacement into the cervical vertebral canal was suspected because of the frequent association of these anomalies. Spinal ultrasound examination carried out at the level of the craniocervical junction allowed identification of herniation of the cerebellum, the caudal part of brain stem, and part of an occipital lobe into the cervical vertebral canal. The ultrasonographic diagnosis was confirmed as post mortem examination. This type of brain defect, associated with spina bifida, resembles the Arnold-Chiari malformation in humans.


Assuntos
Tronco Encefálico/anormalidades , Bovinos/anormalidades , Cerebelo/anormalidades , Meningomielocele/veterinária , Disrafismo Espinal/veterinária , Animais , Animais Lactentes , Malformação de Arnold-Chiari/complicações , Malformação de Arnold-Chiari/diagnóstico por imagem , Malformação de Arnold-Chiari/veterinária , Autopsia/veterinária , Tronco Encefálico/diagnóstico por imagem , Cerebelo/diagnóstico por imagem , Eutanásia Animal , Feminino , Meningomielocele/complicações , Meningomielocele/diagnóstico por imagem , Lobo Occipital/anormalidades , Lobo Occipital/diagnóstico por imagem , Disrafismo Espinal/complicações , Disrafismo Espinal/diagnóstico por imagem , Ultrassonografia
20.
Vet Radiol Ultrasound ; 51(6): 667-9, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-21158244

RESUMO

We describe the ultrasonographic diagnosis of diplomyelia in a 40-day-old calf. The acoustic window was the lumbosacral junction, which, in cattle, corresponds to the L6-S1 intervertebral space and enables the evaluation of approximately 1 cm of the length of the spinal cord. Despite this limited length, this acoustic window yields good anatomic details and can be helpful in assessing anomalies of the caudal aspect of the spinal cord.


Assuntos
Doenças dos Bovinos/congênito , Doenças dos Bovinos/diagnóstico por imagem , Bovinos/anormalidades , Medula Espinal/anormalidades , Medula Espinal/diagnóstico por imagem , Animais , Animais Lactentes , Eutanásia Animal , Feminino , Ultrassonografia
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