ABSTRACT
Borderline Personality Disorder (BPD) is a severe mental disorder, characterized by deficits in emotion regulation, interpersonal dysfunctions, dissociation and impulsivity. Brain abnormalities have been generally explored; however, the specific contribution of different limbic structures to BPD symptomatology is not described. The aim of this study is to cover this gap, exploring functional and structural alterations of amygdala and insula and to highlight their contribution to neuropsychiatric symptoms. Twenty-eight BPD patients (23.7 ± 3.42 years; 6 M/22F) and twenty-eight matched healthy controls underwent a brain MR protocol (1.5 T, including a 3D T1-weighted sequence and resting-state fMRI) and a complete neuropsychiatric assessment. Volumetry, cortical thickness and functional connectivity of amygdala and insula were evaluated, along with correlations with the neuropsychiatric scales. BPD patients showed a lower cortical thickness of the left insula (p = 0.027) that negatively correlated with the Anger Rumination Scale (p = 0.019; r = - 0.450). A focused analysis on female patients showed a significant reduction of right amygdala volumes in BPD (p = 0.037), that correlate with Difficulties in Emotion Regulation Scale (p = 0.031; r = - 0.415), Beck Depression Inventory (p = 0.009; r = - 0.50) and Ruminative Response Scale (p = 0.045; r = - 0.389). Reduced functional connectivity was found in BPD between amygdala and frontal pole, precuneus and temporal pole. This functional connectivity alterations correlated with Anger Rumination Scale (p = .009; r = - 0.491) and Barratt Impulsiveness Scale (p = 0.020; r = - 0.447). Amygdala and insula are altered in BPD patients, and these two limbic structures are implicated in specific neuropsychiatric symptoms, such as difficulty in emotion regulation, depression, anger and depressive rumination.
Subject(s)
Borderline Personality Disorder , Humans , Female , Amygdala/diagnostic imaging , Anger , Brain , Magnetic Resonance Imaging/methods , Impulsive Behavior , EmotionsABSTRACT
INTRODUCTION: Charles Bonnet syndrome is characterized by simple or complex visual hallucinations (VH) due to damage along the visual pathways. We report a functional MRI study of brain correlates of VH in the context of a severe optic atrophy in a patient with Leber's Hereditary Optic Neuropathy (LHON). CASE REPORT: A 62-year-old man was diagnosed with LHON (11778/ND4 mtDNA mutation) after subacute visual loss in left eye (right eye was amblyopic). One month later, he experienced VH of a few seconds consisting in "moving red and blue miniature cartoons". One year later VH content changed in colored mosaic (10-15 s duration), usually stress-related, and blue and white flashes (2-5 s), triggered by unexpected auditory stimuli. Audiometry revealed mild sensorineural hearing loss. Three block design functional MRI paradigms were administrated: 1) random "clap", 2) "checkerboard" and 3) non-random "beep". After random "claps" simple flashes were evoked with bilateral activation of primary and secondary visual cortex, cuneus, precuneus and insula. Neither hallucinations nor cortex activation were registered after "checkerboard" stimulation, due to the severe visual impairment. Primary and secondary auditory cortices were "beep"-activated, without eliciting VH by non-random "beep". CONCLUSIONS: The peculiarity of our case is that VH were triggered by random auditory stimuli, possibly due to a cross-modal plasticity between visual and auditory networks, likely influenced by the sensorineural deafness. Functional alterations of both networks in resting conditions have been demonstrated in LHON patients, even without an auditory deficit. Finally, the absence of VH triggered by expected stimuli is consistent with the "expectation suppression theory", based on increased neural activations after unexpected but not by predicted events.
Subject(s)
Cerebral Cortex/physiopathology , Charles Bonnet Syndrome/complications , Charles Bonnet Syndrome/physiopathology , Optic Atrophy, Hereditary, Leber/complications , Acoustic Stimulation , Adult , DNA, Mitochondrial/genetics , Functional Neuroimaging , Hallucinations/complications , Hallucinations/physiopathology , Humans , Magnetic Resonance Imaging , Male , Middle Aged , NADH Dehydrogenase/genetics , Optic Atrophy, Hereditary, Leber/genetics , Vision Disorders/complicationsABSTRACT
BACKGROUND AND PURPOSE: Mitochondrial neurogastrointestinal encephalopathy is a rare disorder due to recessive mutations in the thymidine phosphorylase gene, encoding thymidine phosphorylase protein required for mitochondrial DNA replication. Clinical manifestations include gastrointestinal dysmotility and diffuse asymptomatic leukoencephalopathy. This study aimed to elucidate the mechanisms underlying brain leukoencephalopathy in patients with mitochondrial neurogastrointestinal encephalopathy by correlating multimodal neuroradiologic features to postmortem pathology. MATERIALS AND METHODS: Seven patients underwent brain MR imaging, including single-voxel proton MR spectroscopy and diffusion imaging. Absolute concentrations of metabolites calculated by acquiring unsuppressed water spectra at multiple TEs, along with diffusion metrics based on the tensor model, were compared with those of healthy controls using unpaired t tests in multiple white matters regions. Brain postmortem histologic, immunohistochemical, and molecular analyses were performed in 1 patient. RESULTS: All patients showed bilateral and nearly symmetric cerebral white matter hyperintensities on T2-weighted images, extending to the cerebellar white matter and brain stem in 4. White matter, N-acetylaspartate, creatine, and choline concentrations were significantly reduced compared with those in controls, with a prominent increase in the radial water diffusivity component. At postmortem examination, severe fibrosis of brain vessel smooth muscle was evident, along with mitochondrial DNA replication depletion in brain and vascular smooth-muscle and endothelial cells, without neuronal loss, myelin damage, or gliosis. Prominent periependymal cytochrome C oxidase deficiency was also observed. CONCLUSIONS: Vascular functional and histologic alterations account for leukoencephalopathy in mitochondrial neurogastrointestinal encephalopathy. Thymidine toxicity and mitochondrial DNA replication depletion may induce microangiopathy and blood-brain-barrier dysfunction, leading to increased water content in the white matter. Periependymal cytochrome C oxidase deficiency could explain prominent periventricular impairment.
Subject(s)
Cerebral Small Vessel Diseases/pathology , Leukoencephalopathies/pathology , Mitochondria/pathology , Mitochondrial Encephalomyopathies/pathology , Adult , Brain/metabolism , Brain/pathology , Cerebral Small Vessel Diseases/etiology , Cerebral Small Vessel Diseases/metabolism , Diffusion Magnetic Resonance Imaging , Female , Humans , Leukoencephalopathies/etiology , Leukoencephalopathies/metabolism , Male , Mitochondria/metabolism , Mitochondrial Encephalomyopathies/complications , Mitochondrial Encephalomyopathies/metabolismABSTRACT
BACKGROUND AND PURPOSE: Brain white matter is frequently affected in mitochondrial diseases; optic atrophy gene 1-autosomal dominant optic atrophy and Leber hereditary optic neuropathy are the most frequent mitochondrial monosymptomatic optic neuropathies. In this observational study, brain white matter microstructure was characterized by DTI in patients with optic atrophy gene 1-autosomal dominant optic atrophy and Leber hereditary optic neuropathy, in relation to clinical and genetic features. MATERIALS AND METHODS: Nineteen patients with optic atrophy gene 1-autosomal dominant optic atrophy and 17 with Leber hereditary optic neuropathy older than 18 years of age, all genetically diagnosed, and 19 healthy volunteers underwent DTI by using a 1.5T MR imaging scanner and neurologic and ophthalmologic assessments. Brain white matter DTI metrics were calculated for all participants, and, in patients, their correlations with genetics and clinical findings were calculated. RESULTS: Compared with controls, patients with optic atrophy gene 1-autosomal dominant optic atrophy had an increased mean diffusivity in 29.2% of voxels analyzed within major white matter tracts distributed throughout the brain, while fractional anisotropy was reduced in 30.3% of voxels. For patients with Leber hereditary optic neuropathy, the proportion of altered voxels was only 0.5% and 5.5%, respectively, of which half was found within the optic radiation and 3.5%, in the smaller acoustic radiation. In almost all regions, fractional anisotropy diminished with age in patients with optic atrophy gene 1-autosomal dominant optic atrophy and correlated with average retinal nerve fiber layer thickness in several areas. Mean diffusivity increased in those with a missense mutation. Patients with Leber hereditary optic neuropathy taking idebenone had slightly milder changes. CONCLUSIONS: Patients with Leber hereditary optic neuropathy had preferential involvement of the optic and acoustic radiations, consistent with trans-synaptic degeneration, whereas patients with optic atrophy gene 1-autosomal dominant optic atrophy presented with widespread involvement suggestive of a multisystemic, possibly a congenital/developmental, disorder. White matter changes in Leber hereditary optic neuropathy and optic atrophy gene 1-autosomal dominant optic atrophy may be exploitable as biomarkers.
Subject(s)
Diffusion Tensor Imaging , Optic Atrophy, Autosomal Dominant/pathology , Optic Atrophy, Hereditary, Leber/pathology , White Matter/pathology , Adult , Female , Humans , Male , Middle AgedABSTRACT
INTRODUCTION: MRI, proton magnetic resonance spectroscopy (¹H-MRS), and diffusion tensor imaging (DTI) have been shown to be of great prognostic value in term newborns with moderate-severe hypoxic-ischemic encephalopathy (HIE). Currently, no data are available on ¹H-MRS and DTI performed in the subacute phase after hypothermic treatment. The aim of the present study was to assess their prognostic value in newborns affected by moderate-severe HIE and treated with selective brain cooling (BC). METHODS: Twenty infants treated with BC underwent conventional MRI and (1)H-MRS at a mean (SD) age of 8.3 (2.8) days; 15 also underwent DTI. Peak area ratios of metabolites and DTI variables, namely mean diffusivity (MD), axial and radial diffusivity, and fractional anisotropy (FA), were calculated. Clinical outcome was monitored until 2 years of age. RESULTS: Adverse outcome was observed in 6/20 newborns. Both ¹H-MRS and DTI variables showed higher prognostic accuracy than conventional MRI. N-acetylaspartate/creatine at a basal ganglia localisation showed 100% PPV and 93% NPV for outcome. MD showed significantly decreased values in many regions of white and gray matter, axial diffusivity showed the best predictive value (PPV and NPV) in the genu of corpus callosum (100 and 91%, respectively), and radial diffusivity was significantly decreased in fronto white matter (FWM) and fronto parietal (FP) WM. The decrement of FA showed the best AUC (0.94) in the FPWM. CONCLUSION: Selective BC in HIE neonates does not affect the early and accurate prognostic value of ¹H-MRS and DTI, which outperform conventional MRI.
Subject(s)
Brain/metabolism , Brain/pathology , Cryotherapy/methods , Diffusion Tensor Imaging/methods , Hypoxia-Ischemia, Brain/diagnosis , Hypoxia-Ischemia, Brain/therapy , Magnetic Resonance Imaging/methods , Biomarkers/analysis , Female , Humans , Hypoxia-Ischemia, Brain/metabolism , Infant, Newborn , Male , Prognosis , Protons , Reproducibility of Results , Sensitivity and Specificity , Treatment OutcomeABSTRACT
BACKGROUND AND PURPOSE: The aim of this study was to evaluate the presence of abnormalities in the brain of patients with restless legs syndrome (RLS) using voxel-based morphometry and diffusion tensor imaging (DTI). METHODS: Twenty patients and twenty controls were studied. Voxel-based morphometry analysis was performed using statistical parametric mapping (SPM8) and FSL-VBM software tools. For voxel-wise analysis of DTI, tract-based spatial statistics (TBSS) and SPM8 were used. RESULTS: Applying an appropriate threshold of probability, no significant results were found either in comparison or in correlation analyses. CONCLUSIONS: Our data argue against clear structural or microstructural abnormalities in the brain of patients with idiopathic RLS, suggesting a prevalent role of functional or metabolic impairment.
Subject(s)
Brain Mapping/methods , Diffusion Tensor Imaging/methods , Restless Legs Syndrome/pathology , Adult , Female , Humans , Male , Middle Aged , Restless Legs Syndrome/epidemiologyABSTRACT
In this study we assessed ΔG'(ATP) hydrolysis, cytosolic [ADP], and the rate of phosphocreatine recovery using Phosphorus Magnetic Resonance Spectroscopy in the calf muscle of a group of patients affected by glycogen myo-phosphorylase deficiency (McArdle disease). The goal was to ascertain whether and to what extent the deficit of the glycogenolytic pathway would affect the muscle energy balance. A typical feature of this pathology is the lack of intracellular acidosis. Therefore we posed the question of whether, in the absence of pH decrease, the rate of phosphocreatine recovery depends on the amount of phosphocreatine consumed during exercise. Results showed that at the end of exercise both [ADP] and ΔG'(ATP) of patients were significantly higher than those of matched control groups reaching comparable levels of phosphocreatine concentration. Furthermore, in these patients we found that the rate of phosphocreatine recovery is not influenced by the amount of phosphocreatine consumed during exercise. These outcomes provide experimental evidence that: i) the intracellular acidification occurring in exercising skeletal muscle is a protective factor for the energy consumption; and ii) the influence of pH on the phosphocreatine recovery rate is at least in part related to the kinetic mechanisms of mitochondrial creatine kinase enzyme.
Subject(s)
Muscles/metabolism , Phosphorylases/metabolism , Adult , Female , Humans , Hydrogen-Ion Concentration , Kinetics , Magnetic Resonance Spectroscopy , Male , Middle Aged , Muscles/enzymology , Phosphorus Isotopes , ThermodynamicsABSTRACT
Slowly progressive aphemia (SPA) is a rare focal degenerative disorder characterized by severe dysarthria, frequent orofacial apraxia, dysprosody, phonetic and phonemic errors without global cognitive deterioration for many years. This condition is caused by a degeneration of anterior frontal lobe regions, mainly of the left frontal operculum. We report a case of SPA with a course of 8 years, evaluated by repeated neuropsychological, conventional, and functional MRI examinations. In our case, neuropsychological examinations showed a progressive impairment of speech articulation including dysprosody, phonetic and phonemic errors, and slight writing errors. No global cognitive deterioration was detected and the patient is still completely autonomous. Morphological and functional investigations showed, respectively, a progressive atrophy and progressive impairment of the left frontal region, confirming the role of the opercular region in determining this rare syndrome. During verbal task generation as the cortical activation of this region gradually decreased, the language articulation worsened.
Subject(s)
Apraxias/diagnosis , Apraxias/physiopathology , Magnetic Resonance Imaging , Neuropsychological Tests , Aged , Brain/blood supply , Brain/pathology , Disease Progression , Humans , Image Processing, Computer-Assisted , Language Tests , Longitudinal Studies , Male , Mental Status Schedule , Oxygen/bloodABSTRACT
Congenital Cataracts with Facial Dysmorphisms and Neuropathy (CCFDN) is a complex autosomal recessive disorder characterized by bilateral congenital cataracts, developmental delay, peripheral; hypo-demyelinating neuropathy, mild facial dysmorphisms, and other rare signs. Cerebral and spinal cord atrophy is the main neuroimaging finding but other less common abnormalities have been previously described. We describe progressive focal lesions of supratentorial white matter in a 10-year-old boy affected by CCFDN. Other etiologies have been excluded and these lesions can be considered a new finding of the disease. We discuss a possible demyelinating mechanism affecting both peripheral and central myelin.
Subject(s)
Cataract , Cerebral Cortex/pathology , Face/abnormalities , Facial Nerve Diseases , Nerve Fibers, Myelinated/pathology , Cataract/complications , Cataract/congenital , Cataract/pathology , Child , Facial Nerve Diseases/complications , Facial Nerve Diseases/congenital , Facial Nerve Diseases/pathology , Humans , Magnetic Resonance Imaging/methods , MaleABSTRACT
OBJECTIVE: The aim of our study was to investigate the microstructural integrity of brain regions functionally involved in the tremor loop in patients with familial essential tremor (FET), using diffusion tensor imaging (DTI). METHODS: Twenty-five patients with FET, 15 patients with Parkinson disease (PD), and 15 healthy subjects were studied. DTI was performed to measure fractional anisotropy (FA) and mean diffusivity (MD) in various regions of interest: red nucleus, dentate nucleus (DN), cerebellar white matter, middle (MCP) and superior cerebellar peduncle (SCP), and ventrolateral thalamus. RESULTS: In patients with FET, FA values in the DN (median 0.19, range 0.13-0.23) were reduced (p < 0.001) compared with patients with PD (median 0.37, range 0.32-0.58) and healthy controls (median 0.36, range 0.33-0.40). In patients with FET, FA was also reduced (p = 0.003) and MD values increased (p < 0.001) in the SCP compared with patients with PD and healthy controls. Among patients with FET, those with longer disease duration showed FA values in the DN lower than those with shorter disease duration (p = 0.018). Patients with FET could be completely distinguished from both patient with PD and healthy controls using FA values of the DN alone. CONCLUSION: Neuroimaging evidence of microstructural changes consistent with neurodegeneration was found in the dentate nucleus (DN) and SCP of patients with familial essential tremor. This suggests that neurodegenerative pathology of cerebellar structures may play a role in essential tremor. Further studies are needed to assess the role of fractional anisotropy and mean diffusivity changes in DN and SCP in the differential diagnosis of essential tremor and Parkinson disease, which may present similar clinical signs at the onset of disease.
Subject(s)
Cerebellum/pathology , Essential Tremor/pathology , Analysis of Variance , Anisotropy , Cerebellum/cytology , Female , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Parkinson Disease/pathology , Reference Values , Reproducibility of ResultsABSTRACT
We used multimodal magnetic resonance (MR) techniques [brain diffusion-weighted magnetic resonance imaging, diffusion-weighted imaging (DWI), proton MR spectroscopy (MRS), (1)H-MRS; and skeletal muscle phosphorous MRS, (31)P-MRS] to investigate interictal brain microstructural changes and tissue energy metabolism in four women with genetically determined familial hemiplegic migraine type 2 (FHM2), belonging to two unrelated families, compared with 10 healthy women. Brain DWI revealed a significant increase of the apparent diffusion coefficient median values in the vermis and cerebellar hemispheres of FHM2 patients, preceding in two subjects the onset of interictal cerebellar deficits. (31)P-MRS revealed defective energy metabolism in skeletal muscle of FHM2 patients, while brain (1)H-MRS showed a mild pathological increase in lactate in the lateral ventricles of one patient and a mild reduction of cortical N-acetyl-aspartate to creatine ratio in another one. Our MRS results showed that a multisystem energy metabolism defect in FHM2 is associated with microstructural cerebellar changes detected by DWI, even before the onset of cerebellar symptoms.
Subject(s)
Cerebellar Diseases/physiopathology , Muscle, Skeletal/physiopathology , Adult , Cerebellar Diseases/metabolism , Cerebellar Diseases/pathology , Cerebellum/metabolism , Cerebellum/pathology , Cerebellum/physiopathology , Diffusion Magnetic Resonance Imaging , Female , Humans , Migraine with Aura/metabolism , Migraine with Aura/pathology , Migraine with Aura/physiopathology , Muscle, Skeletal/metabolism , Muscle, Skeletal/pathologyABSTRACT
The study concerns 130 Staphylococcus aureus strains isolated from different raw-milk dairy products (122 isolates) and human samples (eight isolates). Four different typing techniques were applied: biochemical profiles (Biolog GP), restriction fragment length polymorphism of coagulase gene (coaRFLP), random amplified polymorphic DNA (RAPD) and multilocus variable number tandem repeat analysis (MLVA). Moreover multiplex-PCR was used to study the distribution of genes encoding staphylococcal enterotoxins. The results of this study reveal marked genomic and phenotypic variability among the tested S. aureus. The considered techniques were all found useful for strain typing, but, based on discriminatory power as the key parameter of the typing system, MLVA and Biolog GP were found to be the most powerful techniques. The methods showed little concordance in terms of discerning the clusters of related strains.
Subject(s)
Bacterial Typing Techniques/methods , Dairy Products/microbiology , Polymorphism, Restriction Fragment Length , Staphylococcus aureus/genetics , Animals , Cattle , Coagulase/genetics , DNA Fingerprinting/methods , Female , Humans , Milk/microbiology , Polymerase Chain Reaction/methods , Polymorphism, Restriction Fragment Length/genetics , Random Amplified Polymorphic DNA Technique/methods , Restriction Mapping/methods , Sheep , Sheep Diseases/microbiology , Staphylococcal Infections/diagnosis , Staphylococcal Infections/veterinary , Staphylococcus aureus/enzymology , Staphylococcus aureus/isolation & purification , Tandem Repeat Sequences/geneticsABSTRACT
This study extensively investigates different strategies for the absolute quantitation of N-acetyl aspartate, creatine and choline in white and grey matter by (1)H-MRS at 1.5 T. The main focus of this study was to reliably estimate metabolite concentrations while reducing the scan time, which remains as one of the main problems in clinical MRS. Absolute quantitation was based on the water-unsuppressed concentration as the internal standard. We compared strategies based on various experimental protocols and post-processing strategies. Data were obtained from 30 control subjects using a PRESS sequence at several TE to estimate the transverse relaxation time, T(2), of the metabolites. Quantitation was performed with the algorithm QUEST using two different metabolite signal basis sets: a whole-metabolite basis set (WhoM) and a basis set in which the singlet signals were split from the coupled signals (MSM). The basis sets were simulated in vivo for each TE used. Metabolites' T(2)s were then determined by fitting the estimated signal amplitudes of the metabolites obtained at different TEs. Then the absolute concentrations (mM) of the metabolites were assessed for each subject using the estimated signal amplitudes and either the mean estimated relaxation times of all subjects (mean protocol, MP) or the T(2) estimated from the spectra derived from the same subject (individual protocol, IP). Results showed that MP represents a less time-consuming alternative to IP in the quantitation of brain metabolites by (1)H-MRS in both grey and white matter, with a comparable accuracy when performed by MSM. It was also shown that the acquisition time might be further reduced by using a variant of MP, although with reduced accuracy. In this variant, only one water-suppressed and one water-unsuppressed spectra were acquired, drastically reducing the duration of the entire MRS examination. However, statistical analysis highlights the reduced accuracy of MP when performed using WhoM, particularly at longer echo times.
Subject(s)
Aspartic Acid/analogs & derivatives , Brain , Choline/metabolism , Creatine/metabolism , Magnetic Resonance Spectroscopy/methods , Adult , Aspartic Acid/metabolism , Brain/anatomy & histology , Brain/metabolism , Female , Humans , Male , Middle Aged , Signal Processing, Computer-Assisted , Water/metabolism , Young AdultABSTRACT
OBJECTIVE: The cause of hyperintense magnetic resonance changes and reduced apparent diffusion coefficient (ADC) in specific brain regions of patients with Creutzfeldt-Jakob disease (CJD) is unknown. Our aim was to determine the neuropathologic correlates of antemortem water ADC and normalized T2-weighted changes in patients with CJD. METHOD: Ten patients with CJD and 10 sex- and age-matched healthy controls were studied by DWI and T2-weighted echoplanar MRI. At postmortem, patients with CJD were evaluated for semiquantitative assessment of gliosis and neuronal loss, spongiform changes, and abnormal PrP protein deposition in four cortical regions (occipital, parietal, and temporal cortex, and cingulate gyrus), thalamus, and striatum for a total of 60 regions of interest (ROI). RESULTS: Gliosis and neuronal loss correlated very highly with each other in the 60 ROIs. Where status spongiosus was absent, spongiform change correlated very highly with gliosis and neuronal loss in the cortex, but not in deep gray matter. Spongiform change was also significantly correlated with PrPSc load in both cortical and deep gray ROIs. In deep gray matter, ADC decreased with increasing spongiform change (R2 = 0.78; p < 0.001) and PrPSc load (R2 = 0.51; p = 0.003). In the cortex, ADC decreased with increases in all three, highly correlated, pathologic scores. CONCLUSION: Antemortem reductions in ADC values, typically found in patients with Creutzfeldt-Jakob disease (CJD), are correlated with spongiform changes seen at autopsy. This could be clearly established in the striatum and thalamus of our patients with CJD where the extent of spongiform change was not significantly correlated with gliosis or neuronal loss.
Subject(s)
Brain/pathology , Creutzfeldt-Jakob Syndrome/pathology , Diffusion Magnetic Resonance Imaging/methods , Adult , Aged , Autopsy , Basal Ganglia/pathology , Basal Ganglia/physiopathology , Brain/physiopathology , Brain Mapping/methods , Cerebral Cortex/pathology , Cerebral Cortex/physiopathology , Creutzfeldt-Jakob Syndrome/physiopathology , Disease Progression , Female , Gliosis/pathology , Gliosis/physiopathology , Humans , Image Processing, Computer-Assisted/methods , Male , Middle Aged , Nerve Degeneration/pathology , Nerve Degeneration/physiopathology , Predictive Value of Tests , Thalamus/pathology , Thalamus/physiopathologyABSTRACT
AIM: This study investigated the fate of the stent inner surface in carotid artery stenting (CAS). In addition, the occurrence of late cerebral micro-embolism after CAS has been studied in order to identify predictors and correlate it with a possible neo-intimal layer. METHODS: A series of patients were evaluated before CAS through aortic arch trans-oesophageal echocardiography. Six months after CAS, the stent coverage by neo-intima and the possible presence of uncovered plaques were determined by high-resolution duplex scanning (5-17-Hz probe and 3D reconstruction). Possible micro-embolic signals (MESs) were evaluated through transcranial duplex scanning (30-min analysis of ipsilateral middle cerebral artery with a 1-4-Hz probe) and correlated with patients' characteristics, intimal media thickness (IMT) (>0.9mm vs. <0.9mm) and uncovered proximal plaques, type of stent (closed vs. open cells) and aortic arch complicated plaques (>4mm). Fisher's and Wilcoxon tests were used to evaluate differences across groups for categorical and continuous variables, respectively. RESULTS: In the 68 CASs examined (40 closed cells and 28 open cells), the stent was completely covered by neo-intima in 52 cases (76.4%). Complete coverage was significantly correlated with IMT<0.9mm and the absence of a proximal plaque uncovered by the stent (100% vs. 0%, p<0.001). Hypertension was an independent predictor of complete intimal coverage (p=0.002), while the stent type did not influence this process. The MESs were significantly more frequent in patients with complicated aortic arch plaques (62.5% vs. 23.8%, p<0.012), independently from all other factors. CONCLUSIONS: The extent of the stent neo-intimal formation is independent of stent type, but it is correlated with proximal plaque coverage. Six months after CAS, MESs are still possible and are not prevented by complete neo-intimal stent coverage. Complicated aortic arch atherosclerosis is an independent predictor of late MES, thus underlying its importance in cerebral ischaemia onset.
Subject(s)
Aorta, Thoracic , Aortic Diseases/surgery , Atherosclerosis/surgery , Intracranial Embolism/etiology , Stents/adverse effects , Aged , Aortic Diseases/diagnosis , Atherosclerosis/diagnosis , Disease Progression , Echocardiography, Transesophageal , Female , Follow-Up Studies , Humans , Imaging, Three-Dimensional , Incidence , Intracranial Embolism/diagnostic imaging , Intracranial Embolism/epidemiology , Italy/epidemiology , Male , Middle Cerebral Artery/diagnostic imaging , Prognosis , Prospective Studies , Prosthesis Failure , Risk Factors , Tunica Intima/diagnostic imaging , Ultrasonography, Doppler, Duplex , Ultrasonography, Doppler, Transcranial/methodsABSTRACT
OBJECTIVE: To investigate the mechanisms underlying myoclonus in Leber hereditary optic neuropathy (LHON). METHODS: Five patients and one unaffected carrier from two Italian families bearing the homoplasmic 11778/ND4 and 3460/ND1 mutations underwent a uniform investigation including neurophysiologic studies, muscle biopsy, serum lactic acid after exercise, and muscle ((31)P) and cerebral ((1)H) magnetic resonance spectroscopy (MRS). Biochemical investigations on fibroblasts and complete mitochondrial DNA (mtDNA) sequences of both families were also performed. RESULTS: All six individuals had myoclonus. In spite of a normal EEG background and the absence of giant SEPs and C reflex, EEG-EMG back-averaging showed a preceding jerk-locked EEG potential, consistent with a cortical generator of the myoclonus. Specific comorbidities in the 11778/ND4 family included muscular cramps and psychiatric disorders, whereas features common to both families were migraine and cardiologic abnormalities. Signs of mitochondrial proliferation were seen in muscle biopsies and lactic acid elevation was observed in four of six patients. (31)P-MRS was abnormal in five of six patients and (1)H-MRS showed ventricular accumulation of lactic acid in three of six patients. Fibroblast ATP depletion was evident at 48 hours incubation with galactose in LHON/myoclonus patients. Sequence analysis revealed haplogroup T2 (11778/ND4 family) and U4a (3460/ND1 family) mtDNAs. A functional role for the non-synonymous 4136A>G/ND1, 9139G>A/ATPase6, and 15773G>A/cyt b variants was supported by amino acid conservation analysis. CONCLUSIONS: Myoclonus and other comorbidities characterized our Leber hereditary optic neuropathy (LHON) families. Functional investigations disclosed a bioenergetic impairment in all individuals. Our sequence analysis suggests that the LHON plus phenotype in our cases may relate to the synergic role of mtDNA variants.
Subject(s)
DNA, Mitochondrial/genetics , Energy Metabolism/genetics , Genetic Predisposition to Disease/genetics , Mutation/genetics , Myoclonus/genetics , Optic Atrophy, Hereditary, Leber/genetics , Adenosine Triphosphate/deficiency , Adult , DNA Mutational Analysis , Electroencephalography , Electromyography , Female , Gene Frequency , Genetic Testing , Genotype , Humans , Inheritance Patterns/genetics , Magnetic Resonance Spectroscopy , Male , Middle Aged , Mitochondria/genetics , Mitochondria/metabolism , Mitochondria/pathology , Myoclonus/physiopathology , Optic Atrophy, Hereditary, Leber/complications , Optic Atrophy, Hereditary, Leber/physiopathology , Pedigree , RecurrenceABSTRACT
AIMS: To verify to what degree reducing capacity is a characterizing parameter of a species, and of the strains themselves within a given species, of lactic acid bacteria. METHODS AND RESULTS: Eighty-eight strains belonging to 10 species of lactic acid bacteria (LAB) isolated from traditional Italian cheeses were studied for their reduction activity: Enterococcus faecalis, Enterococcus faecium, Enterococcus durans, Streptococcus thermophilus, Lactococcus lactis ssp. lactis, Lactobacillus paracasei ssp. paracasei, Lactobacillus plantarum, Lactobacillus delbrueckii ssp. bulgaricus, Lactobacillus helveticus and Pediococcus pentosaceus. It was observed that the lactococci reached minimum redox potential before the lactobacilli. The reduction rate of Enterococcus spp. and L. lactis ssp. lactis was higher than that of the streptococci and Lactobacillus spp. All the P. pentosaceus strains had poor reduction activity compared with the other species. CONCLUSIONS: The evolution of the redox potential in milk over a time span of 24 h has been found to be a parameter that characterizes a species: the different courses corresponding to the species in question are clearly evident, and interesting differences can also be noted within the same species. SIGNIFICANCE AND IMPACT OF THE STUDY: The reduction aptitude of strains might be used to select and adapt appropriate strains for use as starters for dairy products.