RESUMEN
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.
Asunto(s)
Trastorno de Personalidad Limítrofe , Humanos , Femenino , Amígdala del Cerebelo/diagnóstico por imagen , Ira , Encéfalo , Imagen por Resonancia Magnética/métodos , Conducta Impulsiva , EmocionesRESUMEN
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.
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Corteza Cerebral/fisiopatología , Síndrome de Charles Bonnet/complicaciones , Síndrome de Charles Bonnet/fisiopatología , Atrofia Óptica Hereditaria de Leber/complicaciones , Estimulación Acústica , Adulto , ADN Mitocondrial/genética , Neuroimagen Funcional , Alucinaciones/complicaciones , Alucinaciones/fisiopatología , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , NADH Deshidrogenasa/genética , Atrofia Óptica Hereditaria de Leber/genética , Trastornos de la Visión/complicacionesRESUMEN
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.
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Enfermedades de los Pequeños Vasos Cerebrales/patología , Leucoencefalopatías/patología , Mitocondrias/patología , Encefalomiopatías Mitocondriales/patología , Adulto , Encéfalo/metabolismo , Encéfalo/patología , Enfermedades de los Pequeños Vasos Cerebrales/etiología , Enfermedades de los Pequeños Vasos Cerebrales/metabolismo , Imagen de Difusión por Resonancia Magnética , Femenino , Humanos , Leucoencefalopatías/etiología , Leucoencefalopatías/metabolismo , Masculino , Mitocondrias/metabolismo , Encefalomiopatías Mitocondriales/complicaciones , Encefalomiopatías Mitocondriales/metabolismoRESUMEN
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.
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Imagen de Difusión Tensora , Atrofia Óptica Autosómica Dominante/patología , Atrofia Óptica Hereditaria de Leber/patología , Sustancia Blanca/patología , Adulto , Femenino , Humanos , Masculino , Persona de Mediana EdadAsunto(s)
Deficiencia Múltiple de Acil Coenzima A Deshidrogenasa/diagnóstico , Deficiencia Múltiple de Acil Coenzima A Deshidrogenasa/terapia , Encéfalo/patología , Cuidados Críticos , Diagnóstico Diferencial , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Deficiencia Múltiple de Acil Coenzima A Deshidrogenasa/complicaciones , Insuficiencia Multiorgánica/etiología , Insuficiencia Multiorgánica/terapiaRESUMEN
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.
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Encéfalo/metabolismo , Encéfalo/patología , Crioterapia/métodos , Imagen de Difusión Tensora/métodos , Hipoxia-Isquemia Encefálica/diagnóstico , Hipoxia-Isquemia Encefálica/terapia , Imagen por Resonancia Magnética/métodos , Biomarcadores/análisis , Femenino , Humanos , Hipoxia-Isquemia Encefálica/metabolismo , Recién Nacido , Masculino , Pronóstico , Protones , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Resultado del TratamientoRESUMEN
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.
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Mapeo Encefálico/métodos , Imagen de Difusión Tensora/métodos , Síndrome de las Piernas Inquietas/patología , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Síndrome de las Piernas Inquietas/epidemiologíaRESUMEN
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.
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Catarata , Corteza Cerebral/patología , Cara/anomalías , Enfermedades del Nervio Facial , Fibras Nerviosas Mielínicas/patología , Catarata/complicaciones , Catarata/congénito , Catarata/patología , Niño , Enfermedades del Nervio Facial/complicaciones , Enfermedades del Nervio Facial/congénito , Enfermedades del Nervio Facial/patología , Humanos , Imagen por Resonancia Magnética/métodos , MasculinoRESUMEN
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.
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Cerebelo/patología , Temblor Esencial/patología , Análisis de Varianza , Anisotropía , Cerebelo/citología , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/patología , Valores de Referencia , Reproducibilidad de los ResultadosRESUMEN
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.
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Enfermedades Cerebelosas/fisiopatología , Músculo Esquelético/fisiopatología , Adulto , Enfermedades Cerebelosas/metabolismo , Enfermedades Cerebelosas/patología , Cerebelo/metabolismo , Cerebelo/patología , Cerebelo/fisiopatología , Imagen de Difusión por Resonancia Magnética , Femenino , Humanos , Migraña con Aura/metabolismo , Migraña con Aura/patología , Migraña con Aura/fisiopatología , Músculo Esquelético/metabolismo , Músculo Esquelético/patologíaRESUMEN
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.
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Ácido Aspártico/análogos & derivados , Encéfalo , Colina/metabolismo , Creatina/metabolismo , Espectroscopía de Resonancia Magnética/métodos , Adulto , Ácido Aspártico/metabolismo , Encéfalo/anatomía & histología , Encéfalo/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Procesamiento de Señales Asistido por Computador , Agua/metabolismo , Adulto JovenRESUMEN
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.
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Encéfalo/patología , Síndrome de Creutzfeldt-Jakob/patología , Imagen de Difusión por Resonancia Magnética/métodos , Adulto , Anciano , Autopsia , Ganglios Basales/patología , Ganglios Basales/fisiopatología , Encéfalo/fisiopatología , Mapeo Encefálico/métodos , Corteza Cerebral/patología , Corteza Cerebral/fisiopatología , Síndrome de Creutzfeldt-Jakob/fisiopatología , Progresión de la Enfermedad , Femenino , Gliosis/patología , Gliosis/fisiopatología , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , Masculino , Persona de Mediana Edad , Degeneración Nerviosa/patología , Degeneración Nerviosa/fisiopatología , Valor Predictivo de las Pruebas , Tálamo/patología , Tálamo/fisiopatologíaRESUMEN
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.
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ADN Mitocondrial/genética , Metabolismo Energético/genética , Predisposición Genética a la Enfermedad/genética , Mutación/genética , Mioclonía/genética , Atrofia Óptica Hereditaria de Leber/genética , Adenosina Trifosfato/deficiencia , Adulto , Análisis Mutacional de ADN , Electroencefalografía , Electromiografía , Femenino , Frecuencia de los Genes , Pruebas Genéticas , Genotipo , Humanos , Patrón de Herencia/genética , Espectroscopía de Resonancia Magnética , Masculino , Persona de Mediana Edad , Mitocondrias/genética , Mitocondrias/metabolismo , Mitocondrias/patología , Mioclonía/fisiopatología , Atrofia Óptica Hereditaria de Leber/complicaciones , Atrofia Óptica Hereditaria de Leber/fisiopatología , Linaje , RecurrenciaRESUMEN
BACKGROUND: Overlapping phenotypes including LHON, MELAS, and Leigh syndrome have recently been associated with numerous mtDNA point mutations in the ND5 gene of complex I, now considered a mutational hot spot. OBJECTIVE: To identify the mtDNA defect in a family with a prevalent ocular phenotype, including LHON-like optic neuropathy, retinopathy, and cataract, but characterised also by strokes, early deaths, and miscarriages on the maternal line. RESULTS: Sequencing of the entire mitochondrial genome from the proband's muscle DNA identified the heteroplasmic 13042G-->A transition, which was previously described only once in a patient with a different mitochondrial disease. This mutation fulfils the major pathogenic criteria, inducing an amino acid change (A236T) at an invariant position in a highly conserved domain of the ND5 gene. Phosphorus magnetic resonance spectroscopy in the proband disclosed an in vivo brain and skeletal muscle energy metabolism deficit. CONCLUSIONS: These findings conclusively establish the pathogenic role of the 13042G-->A mutation and underscore its variable clinical expression.
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ADN Mitocondrial/genética , Oftalmopatías/genética , Polimorfismo de Nucleótido Simple , Disparidad de Par Base , Encéfalo/patología , Humanos , Espectroscopía de Resonancia Magnética , Mutación , Reacción en Cadena de la Polimerasa , PrevalenciaRESUMEN
Over the last two decades magnetic resonance spectroscopy has been extensively used to investigate the role of energy metabolism impairment in the physiopathology of migraine. In this paper we review the studies performed on migraine sufferers during headache attacks as well as interictally. Overall there is currently evidence that migraine is associated with a generalised disorder of energy metabolism and that this, in association with other susceptibility factors, may be an important feature that lowers the threshold for triggering migraine attacks.
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Metabolismo Energético/fisiología , Trastornos Migrañosos/fisiopatología , Humanos , Isquemia/complicaciones , Espectroscopía de Resonancia Magnética/métodos , Trastornos Migrañosos/etiologíaRESUMEN
In children, narcolepsy may be the symptom of a brain lesion or genetic disease. The authors report two cases with severe narcolepsy-cataplexy emerging in childhood in close temporal association with obesity and precocious puberty.
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Cataplejía/complicaciones , Hipotálamo/fisiopatología , Péptidos y Proteínas de Señalización Intracelular/fisiología , Narcolepsia/complicaciones , Neuropéptidos/fisiología , Pubertad Precoz/complicaciones , Ácido Aspártico/análogos & derivados , Ácido Aspártico/análisis , Compuestos de Bencidrilo/uso terapéutico , Cataplejía/diagnóstico , Cataplejía/tratamiento farmacológico , Niño , Creatina/análisis , Ciclohexanoles/uso terapéutico , Trastornos de Somnolencia Excesiva/etiología , Femenino , Alucinaciones/etiología , Educación en Salud , Humanos , Hipotálamo/química , Péptidos y Proteínas de Señalización Intracelular/deficiencia , Masculino , Modafinilo , Narcolepsia/diagnóstico , Narcolepsia/tratamiento farmacológico , Neuropéptidos/deficiencia , Terrores Nocturnos/etiología , Obesidad/complicaciones , Orexinas , Polisomnografía , Pubertad Precoz/fisiopatología , Televisión , Clorhidrato de VenlafaxinaRESUMEN
The authors used 1H-MRS to investigate hypothalamic metabolism in 26 patients with cluster headache (CH) and 12 healthy subjects. Hypothalamic N-acetylaspartate/creatine was reduced in patients with CH vs controls (p < 0.01). Dividing the patients into episodic CH outside- and in-cluster periods and chronic CH, the hypothalamic N-acetylaspartate/creatine in all three subgroups of patients was reduced. The reduction of the neuronal marker N-acetylaspartate is consistent with hypothalamic neuronal dysfunction in patients with CH.
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Cefalalgia Histamínica/metabolismo , Hipotálamo/metabolismo , Espectroscopía de Resonancia Magnética , Enfermedad Aguda , Adulto , Anciano , Ácido Aspártico/análogos & derivados , Ácido Aspártico/antagonistas & inhibidores , Ácido Aspártico/metabolismo , Biomarcadores/metabolismo , Corteza Cerebral/metabolismo , Corteza Cerebral/patología , Enfermedad Crónica , Cefalalgia Histamínica/patología , Creatina/antagonistas & inhibidores , Creatina/metabolismo , Femenino , Humanos , Hipotálamo/patología , Espectroscopía de Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Neuronas/metabolismo , Neuronas/patología , Lóbulo Occipital/metabolismo , Lóbulo Occipital/patología , Lóbulo Parietal/metabolismo , Lóbulo Parietal/patología , ProtonesRESUMEN
A dysfunction of the orexin (hypocretin) system in the hypothalamus has recently been linked to the pathogenesis of narcolepsy. The authors used in vivo proton MR spectroscopy to assess the N-acetylaspartate (NAA) content in the hypothalamus of narcoleptic patients. Hypothalamic NAA/creatine-phosphocreatine was reduced in narcoleptic patients compared with control subjects (p < 0.01). Hypothalamic neuronal loss/damage is a central pathogenetic feature in narcolepsy.
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Atrofia/diagnóstico , Hipotálamo/patología , Narcolepsia/diagnóstico , Degeneración Nerviosa/diagnóstico , Neuronas/patología , Adolescente , Adulto , Anciano , Ácido Aspártico/análogos & derivados , Ácido Aspártico/análisis , Ácido Aspártico/deficiencia , Ácido Aspártico/metabolismo , Atrofia/metabolismo , Atrofia/fisiopatología , Cataplejía/etiología , Cataplejía/patología , Cataplejía/fisiopatología , Creatina/metabolismo , Femenino , Humanos , Hipotálamo/metabolismo , Hipotálamo/fisiopatología , Péptidos y Proteínas de Señalización Intracelular/deficiencia , Imagen por Resonancia Magnética , Espectroscopía de Resonancia Magnética , Masculino , Persona de Mediana Edad , Narcolepsia/metabolismo , Narcolepsia/fisiopatología , Degeneración Nerviosa/metabolismo , Degeneración Nerviosa/fisiopatología , Neuronas/metabolismo , Neuropéptidos/deficiencia , Orexinas , PolisomnografíaRESUMEN
BACKGROUND: Brain edema and increased intracranial pressure worsen prognosis in patients with end-stage chronic cirrhosis. OBJECTIVE: To use diffusion-weighted imaging (DWI) to quantify water apparent diffusion coefficient (ADC) in different brain regions of patients with chronic liver failure with or without hepatic encephalopathy. METHODS: The authors studied 14 patients with viral liver cirrhosis and 12 sex- and age-matched healthy volunteers. Seven patients had no clinical evidence of hepatic encephalopathy; six had grade I hepatic encephalopathy; and one had grade II hepatic encephalopathy. Brain DWI was obtained using a single-shot echo-planar imaging sequence, and four gradient strengths (b values = 0, 300, 600, and 900 s/mm(2)) were applied to calculate the average diffusivity maps. RESULTS: Mean ADC values in the brains of patients with cirrhosis were significantly increased in all selected regions of interest (caudate, putamen, and pallidus nuclei; occipital, parietal, and frontal lobe white matter) except in the thalamus. Venous ammonia was linearly related to ADC values in deep gray and white matter regions of interest. CONCLUSIONS: Brain water apparent diffusion coefficient is increased in patients with chronic liver disease and may be useful in monitoring patients with hepatic encephalopathy.