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OBJECTIVE: To evaluate the frequency, distribution, and clinical associations of the dilated appearance of cerebral cortical veins, termed cortical veins sign on T2*-weighted gradient recalled-echo (T2*-GRE) in the acute setting of migraine with aura attack in adult patients. METHODS: We conducted a retrospective analysis of 60 consecutive patients admitted for acute neurological symptoms with a final diagnosis of migraine with aura (42%) or probable migraine with aura (58%) who underwent emergency brain magnetic resonance imaging and 60 non-migrainous control adults. The cortical veins sign was defined as a marked hypo-intensity and/or an apparent increased diameter of at least one cortical vein. We examined the prevalence, the spatial distribution, and the associations of cortical veins sign with clinical characteristics of migraine with aura. RESULTS: We detected the cortical veins sign in 25 patients (42%) with migraine with aura, compared to none in the control group (p < 0.0001). The spatial distribution of cortical veins sign was characterised by the predominantly bilateral and posterior location. Presence of cortical veins sign was associated with increased severity of aura (p = 0.05), and shorter delay to MRI (p = 0.02). CONCLUSION: In the setting of acute neurological symptoms, the presence of cortical veins sign is frequent in patients with migraine with aura and can be detected with good reliability. This imaging marker may help clinicians identify underlying migraine with aura.
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Epilepsia , Trastornos Migrañosos , Migraña con Aura , Adulto , Humanos , Imagen por Resonancia Magnética , Migraña con Aura/diagnóstico por imagen , Reproducibilidad de los Resultados , Estudios RetrospectivosRESUMEN
INTRODUCTION: The locus coeruleus (LC) is one of the brainstem nuclei that may be activated during migraine attack. As LC contains neuromelanin, a by-product of norepinephrine synthesis, it can be delineated in vivo using neuromelanin sensitive magnetic resonance imaging (MRI). The neuromelanin content in LC has been suggested to reflect previous LC activation. We investigated LC MRI contrast in patients with migraine with aura (MWA) and its correlation with migraine features. METHODS: This matched cohort study compared 23 MWA patients aged 30-55 and without comorbidity, to 23 sex- and age-matched healthy controls. The study was conducted in a University Hospital. LC contrast was measured with T1 neuromelanin-sensitive-weighted 3T MRI. Voxels were manually selected by 2 independent researchers and comparison was made twice using intersection and union of the voxels selected by the 2 observers. RESULTS: No difference was found in neuromelanin LC contrast between MWA patients and controls with both the INTER method (0.224 ± 0.042 vs 0.228 ± 0.048; difference: 0.0001 (95%CI: -0.032 to 0.026), P = .799) and UNION method (0.218 ± 0.043 vs 0.222 ± 0.047; difference: -0.0012 (95%CI: -0.031 to 0.026), P = .775). Global LC volume was also similar between the 2 groups with INTER method (15.087 ± 3.965 vs 13.739 ± 3.583; difference: 2 (95%CI: -1 to 4), P = .233) and UNION method (17.522 ± 4.440 vs 16.087 ± 4.274; difference: 1 (95%CI: -2 to 4), P = .270). Moreover, no correlations were found between neuromelanin LC contrast and migraine features (duration of migraine and frequency of attacks). CONCLUSION: These negative findings do not support the use of neuromelanin LC contrast as a biomarker of MA.
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Locus Coeruleus/metabolismo , Melaninas/metabolismo , Migraña con Aura/metabolismo , Adulto , Biomarcadores/metabolismo , Estudios de Cohortes , Medios de Contraste , Femenino , Humanos , Locus Coeruleus/diagnóstico por imagen , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Migraña con Aura/diagnóstico por imagenRESUMEN
BACKGROUND: The typical sign of intracranial hypotension (IH) is postural headache. However, IH can be associated with a large diversity of clinical or radiological signs leading to difficult diagnosis especially in case of coma. The association of cerebral venous thrombosis (CVT) and subdural hemorrhage is rare but should suggest the diagnosis of IH. METHODS: Case report. CASE DESCRIPTION: We report here a case of comatose patient due to spontaneous IH complicated by CVT and subdural hemorrhage. The correct diagnosis was delayed due to many confounding factors. IH was suspected after subdural hemorrhage recurrence and confirmed by magnetic resonance imaging (MRI). After 2 epidural patches with colloid, favorable outcome was observed. DISCUSSION: The most common presentation of IH is postural orthostatic headaches. In the present case report, the major clinical signs were worsening of consciousness and coma, which are a rare presentation. Diagnosis of IH is based on the association of clinical history, evocative symptomatology, and cerebral imaging. CVT occurs in 1-2% of IH cases and the association between IH, CVT, and subdural hemorrhage is rare. MRI is probably the key imaging examination. In the present case, epidural patch was performed after confounding factors for coma had been treated. Benefit of anticoagulation had to be balanced in this case with potential hemorrhagic complications, especially within the brain. CONCLUSION: Association of CVT and subdural hemorrhage should lead to suspect IH. Brain imaging can help and find specific signs of IH.
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Coma/diagnóstico , Hematoma Subdural/diagnóstico , Hipotensión Intracraneal/diagnóstico , Trombosis Intracraneal/diagnóstico , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Tomografía Computarizada por Rayos XRESUMEN
BACKGROUND: Migraine with aura is independently associated with increased risk of ischemic stroke, especially in younger subjects. This association might be related to an impairment of cerebral autoregulation, which normally maintains cerebral blood flow independent of arterial blood pressure variations. METHODS: Patients aged 30-55, fulfilling ICHD-3 beta criteria for migraine with aura, were prospectively enrolled and compared with gender- and age-matched healthy controls without a history of migraine. Patients and controls with a history of stroke or any disease potentially impairing cerebral autoregulation were excluded. We assessed cerebral autoregulation with two different methods: Transfer function analysis, and the correlation coefficient index Mx. The transfer function phase and gain reflect responses of cerebral blood flow velocities to relatively fast fluctuations of arterial blood pressure, whereas Mx also reflects responses to slower arterial blood pressure fluctuations. RESULTS: A total of 22 migraine with aura patients (median age [IQR]: 39.5 [12.5] years) and 22 controls (39 [9.75] years) were included. Transfer function parameters and Mx were not different between patients and controls. However, Mx was inversely correlated with age in patients (ρ = -0.567, p = 0.006) and not in controls (ρ = -0.084, p = 0.509). Mx was also inversely correlated with migraine with aura duration (ρ = -0.617, p = 0.002), suggesting improvement of cerebral autoregulation efficiency with disease duration. CONCLUSIONS: Cerebral autoregulation did not differ between patients and controls aged 30-55. However, cerebral autoregulation efficiency was strongly correlated with migraine with aura duration. Further studies in younger patients are needed to determine whether cerebral autoregulation is impaired early in the course of disease. TRIAL REGISTRATION: NCT02708797.
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Encéfalo/irrigación sanguínea , Encéfalo/fisiopatología , Circulación Cerebrovascular/fisiología , Migraña con Aura/fisiopatología , Adulto , Presión Sanguínea/fisiología , Estudios de Casos y Controles , Femenino , Homeostasis/fisiología , Humanos , Masculino , Persona de Mediana Edad , Ultrasonografía Doppler TranscranealRESUMEN
OBJECTIVE: To investigate the functional connectivity of the hypothalamus in chronic migraine compared to interictal episodic migraine in order to improve our understanding of migraine chronification. METHODS: Using task-free fMRI and ROI-to-ROI analysis, we compared anterior hypothalamus intrinsic connectivity with the spinal trigeminal nucleus in patients with chronic migraine (n = 25) to age- and sex-matched patients with episodic migraine in the interictal phase (n = 22). We also conducted a seed-to-voxel analysis with anterior hypothalamus as a seed. RESULTS: All patients with chronic migraine had medication overuse. We found a significant connectivity (T = 2.08, p = 0.024) between anterior hypothalamus and spinal trigeminal nucleus in the chronic group, whereas these two regions were not connected in the episodic group. The strength of connectivity was not correlated with pain intensity (rho: 0.09, p = 0.655). In the seed-to-voxel analysis, three regions were more connected with the anterior hypothalamus in the chronic group: The spinal trigeminal nuclei (MNI coordinate x = 2, y = -44, z = -62), the right dorsal anterior insula (MNI coordinate x = 10, y = 10, z = 18), and the right caudate (MNI coordinate x = 12, y = 28, z = 6). However, these correlations were no longer significant after whole brain FWE correction. CONCLUSION: An increased functional connectivity between the anterior hypothalamus and the spinal trigeminal nucleus, as previously reported in preictal episodic migraine, was demonstrated in chronic migraine with medication overuse. This finding confirms a major role of the anterior hypothalamus in migraine and suggests that chronic migraineurs are locked in the preictal phase.
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Hipotálamo/fisiopatología , Trastornos Migrañosos/fisiopatología , Vías Nerviosas/fisiopatología , Uso Excesivo de Medicamentos Recetados , Núcleo Espinal del Trigémino/fisiopatología , Adulto , Femenino , Trastornos de Cefalalgia/fisiopatología , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVE: To describe a case series of 7 patients presenting cluster headache (CH) criteria and a substance use disorder, reported to a French Addictovigilance center. Then, to assess clinical, pharmacological, and neurobiological linkages between substance use and CH onset. BACKGROUND: CH patients are presenting a higher prevalence of comorbidities, among which the use of psychoactive substances, licit or illicit, have been explored by a few authors. Recently, 3 cases of CH in patients seen in the hospital-based addiction care center have been reported to the Toulouse addictovigilance center. METHODS: Other cases have been identified in the same tertiary hospital after a collaborative investigation done with the departments of neurology and psychiatry and included in the case series. A narrative review was performed to assess the potential of psychoactive substance consumption to induce or facilitate CH. RESULTS: From 2016 to 2018, 6 males and 1 female aged between 26 and 54 years old, presenting CH criteria and a substance use disorder, were included in our case series. Among substances used, there are: (1) daily use of tobacco and alcohol in 5/7 subjects; (2) daily or almost daily use of cocaine in 5/7 subjects; (3) regular use of cannabis before attacks beginning in 4/7 subjects; and (4) opioids, as a substitutive medication or abused, in 5/7 subjects. The intranasal route administration is reported by all the subjects and precedes the beginning of attacks for 5/7 subjects. CONCLUSIONS: We have found a CH prevalence of 0.9% in our studied population, while it is estimated at 0.1% in the general population. The coexistence of cluster headache and addiction behaviors reflects possible common neurobiological pathways, which would include the hypothalamus. Research could be conducted on the potential of hypothalamic therapeutic targets.
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Cefalalgia Histamínica/epidemiología , Trastornos Relacionados con Sustancias/epidemiología , Adulto , Comorbilidad , Femenino , Francia/epidemiología , Humanos , Masculino , Persona de Mediana EdadRESUMEN
AIM: To assess the renal effects of chronic exposure to advanced glycation end-products (AGEs) in the absence of diabetes and the potential impact of concomitant treatment with the antioxidant N-acetyl cysteine (NAC). METHODS: Wistar rats received intraperitoneally 20 mg/kg/day of albumin modified (AlbAGE) or not (AlbC) by advanced glycation for 12 weeks and oral NAC (600mg/L; AlbAGE+NAC and AlbC+NAC, respectively). Biochemical, urinary and renal morphological analyses; carboxymethyl-lysine (CML, an AGE), CD68 (macrophage infiltration), and 4-hydroxynonenal (4-HNE, marker of oxidative stress) immunostaining; intrarenal mRNA expression of genes belonging to pathways related to AGEs (Ager, Ddost, Nfkb1), renin-angiotensin system (Agt, Ren, Ace), fibrosis (Tgfb1, Col4a1), oxidative stress (Nox4, Txnip), and apoptosis (Bax, Bcl2); and reactive oxidative species (ROS) content were performed. RESULTS: AlbAGE significantly increased urine protein-to-creatinine ratio; glomerular area; renal CML content and macrophage infiltration; expression of Ager, Nfkb1, Agt, Ren, Tgfb1, Col4a1, Txnip, Bax/Bcl2 ratio; and 4-HNE and ROS contents. Some of these effects were attenuated by NAC concomitant treatment. CONCLUSION: Because AGEs are highly consumed in modern diets and implicated in the progression of different kidney diseases, NAC could be a therapeutic intervention to decrease renal damage, considering that long-term restriction of dietary AGEs is difficult to achieve in practice.
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Acetilcisteína/farmacología , Diabetes Mellitus Experimental/patología , Productos Finales de Glicación Avanzada/toxicidad , Riñón/patología , Animales , Antioxidantes/farmacología , Regulación de la Expresión Génica/efectos de los fármacos , Riñón/efectos de los fármacos , Macrófagos/efectos de los fármacos , Macrófagos/patología , Masculino , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratas Wistar , Especies Reactivas de Oxígeno/metabolismo , Albúmina Sérica/metabolismoRESUMEN
BACKGROUND: Friedreich's ataxia usually occurs before the age of 25. Rare variants have been described, such as late-onset Friedreich's ataxia and very-late-onset Friedreich's ataxia, occurring after 25 and 40 years, respectively. We describe the clinical, functional, and molecular findings from a large series of late-onset Friedreich's ataxia and very-late-onset Friedreich's ataxia and compare them with typical-onset Friedreich's ataxia. METHODS: Phenotypic and genotypic comparison of 44 late-onset Friedreich's ataxia, 30 very late-onset Friedreich's ataxia, and 180 typical Friedreich's ataxia was undertaken. RESULTS: Delayed-onset Friedreich's ataxia (late-onset Friedreich's ataxia and very-late-onset Friedreich's ataxia) had less frequently dysarthria, abolished tendon reflexes, extensor plantar reflexes, weakness, amyotrophy, ganglionopathy, cerebellar atrophy, scoliosis, and cardiomyopathy than typical-onset Friedreich's ataxia, along with less severe functional disability and shorter GAA expansion on the smaller allele (P < 0.001). Delayed-onset Friedreich's ataxia had lower scale for the assessment and rating of ataxia and spinocerebellar degeneration functional scores and longer disease duration before wheelchair confinement (P < 0.001). Both GAA expansions were negatively correlated to age at disease onset (P < 0.001), but the smaller GAA expansion accounted for 62.9% of age at onset variation and the larger GAA expansion for 15.6%. In this comparative study of late-onset Friedreich's ataxia and very-late-onset Friedreich's ataxia, no differences between these phenotypes were demonstrated. CONCLUSION: Typical- and delayed-onset Friedreich's ataxia are different and Friedreich's ataxia is heterogeneous. Late-onset Friedreich's ataxia and very-late-onset Friedreich's ataxia appear to belong to the same clinical and molecular continuum and should be considered together as "delayed-onset Friedreich's ataxia." As the most frequently inherited ataxia, Friedreich's ataxia should be considered facing compatible pictures, including atypical phenotypes (spastic ataxia, retained reflexes, lack of dysarthria, and lack of extraneurological signs), delayed disease onset (even after 60 years of age), and/or slow disease progression.
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Ataxia de Friedreich/diagnóstico , Ataxia de Friedreich/genética , Repeticiones de Trinucleótidos/genética , Adolescente , Adulto , Edad de Inicio , Anciano , Cardiomiopatías/diagnóstico , Cardiomiopatías/etiología , Niño , Electrocardiografía , Femenino , Ataxia de Friedreich/sangre , Ataxia de Friedreich/fisiopatología , Genotipo , Hemoglobina Glucada/metabolismo , Humanos , Procesamiento de Imagen Asistido por Computador , Cooperación Internacional , Estimación de Kaplan-Meier , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Fenotipo , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Estadísticas no Paramétricas , Adulto JovenRESUMEN
BACKGROUND: Underreporting of adverse drug reactions is common but has been rarely studied in Parkinson's disease (PD). OBJECTIVE: To compare the prevalence of adverse events (AEs) in relation to antiparkinsonian drugs in PD patients using two different data collection methods: patient's spontaneous reporting versus a predefined investigator-driven structured interview. Secondary objectives were to assess factors related to spontaneous reporting and to compare the rate of AE reporting in PD patients with that of a group of non-parkinsonian post-stroke patients. STUDY DESIGN: Cross-sectional study. PATIENTS: Ambulatory, cognitively intact PD or post-stroke outpatients. INTERVENTIONS: None. OUTCOME MEASURES: Patients were first asked by means of an an open question to disclose any unpleasant effects in connection with their current medications that had occurred during the previous week. Afterwards, a predefined questionnaire listing the most common AEs known to be related to antiparkinsonian drugs was used to question the same patients in a systematic manner about the presence of any AE during the same week. Chronological and semiological criteria were used to classify the reported AEs as "unrelated" or "possibly/plausibly related" to the antiparkinsonian treatment. RESULTS: A total of 203 PD and 52 post-stroke patients of comparable age and sex were recruited. Eighty-five PD and five post-stroke patients reported spontaneously at least one AE (42 vs. 10%, p < 0.01), while 203 PD and 47 post-stroke patients reported at least one AE following the structured questionnaire (100 vs. 90%, p < 0.001). In PD patients, there were a total of 112 spontaneously reported AEs as compared with 1,574 according to the structured questionnaire (7%). Spontaneous disclosure of AEs was associated with experiencing >2 AEs [OR = 1.2 (1.1-3.2)], logistic regression). Seventy-four percent of PD patients had ≥1 AE possibly/plausibly related to antiparkinsonian drugs. CONCLUSIONS: Results showed that only 7% of AEs were reported spontaneously by patients, thus underscoring the importance of systematically asking about AEs in PD patients.
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Antiparkinsonianos/efectos adversos , Revelación , Enfermedad de Parkinson/tratamiento farmacológico , Anciano , Antiparkinsonianos/uso terapéutico , Estudios Transversales , Monitoreo de Drogas , Femenino , Francia , Hospitales Universitarios , Humanos , Entrevistas como Asunto , Masculino , Servicio Ambulatorio en Hospital , Encuestas y CuestionariosRESUMEN
BACKGROUND: Greater occipital nerve stimulation (ONS) has been recently proposed to treat severe chronic cluster headache patients (CCH) refractory to medical treatment. We report the results of a French multidisciplinary cohort study. METHODS: Thirteen CCH patients were operated and data were collected prospectively. All of them suffered from CCH according to the International Headache Society classification, lasting for more than 2 years, refractory to pharmacological prophylactic treatment with adequate trials, with at least one daily attack. Chronic ONS was delivered through a subcutaneous occipital electrode connected to an implanted generator, in order to induce paraesthesias perceived locally in the lower occipital region. RESULTS: After surgery (mean follow-up 14,6 months), the mean attack frequency and intensity decreased by 68% and 49%, respectively. At last follow-up, 10/13 patients were considered as responders (improvement >50%). Prophylactic treatment could be stopped or reduced in 8/13 cases. Local infection occurred in one patient, leading to hardware removal. CONCLUSIONS: Our data confirmed the results of the 36 similar cases reported in the literature, suggesting that ONS may act as a prophylactic treatment in chronic CH. Considering their respective risks, ONS should be proposed before deep brain stimulation in severe refractory CCH patients.
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Cefalalgia Histamínica/terapia , Terapia por Estimulación Eléctrica/métodos , Adulto , Terapia por Estimulación Eléctrica/efectos adversos , Electrodos Implantados/efectos adversos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
Deep brain stimulation of the posterior hypothalamus is a therapeutic approach to the treatment of refractory chronic cluster headache, but the precise anatomical location of the electrode contacts has not been clearly assessed. Our aim was to study the location of the contacts used for chronic stimulation, projecting each contact centre on anatomic atlases. Electrodes were implanted in a series of 10 patients (prospective controlled trial) in the so-called 'posteroinferior hypothalamus' according to previously described coordinates, i.e. 2 mm lateral, 3 mm posterior and 5 mm below the mid-commissural point. The coordinates of the centre of each stimulating contact were measured on postoperative computed tomography or magnetic resonance imaging scans, taking into account the artefact of the electrode. Each contact centre (n=10; left and right hemispheres pooled) was displayed on the Schaltenbrand atlas and a stereotactic three dimensional magnetic resonance imaging atlas (4.7 tesla) of the diencephalon-mesencephalic junction for accurate anatomical location. Of the 10 patients with 1-year follow-up, 5 responded to deep brain stimulation (weekly frequency of attacks decrease >50%). In responders, the mean (standard deviation) coordinates of the contacts were 2.98 (1.16) mm lateral, 3.53 (1.97) mm posterior and 3.31 (1.97) mm below the mid-commissural point. All the effective contacts were located posterior to the hypothalamus. In responders, structures located <2 mm from the centres of effective contacts were: the mesencephalic grey substance (5/5), the red nucleus (4/5), the fascicle retroflexus (4/5), the fascicle longitudinal dorsal (3/5), the nucleus of ansa lenticularis (3/5), the fascicle longitudinal medial (1/5) and the thalamus superficialis medial (1/5). The contact coordinates (Wilcoxon test) and the structures (Fisher's exact test) were not significantly different between responders and non-responders. These findings suggest that failure of deep brain stimulation treatment in cluster headache may be due to factors unrelated to electrode misplacement. They also suggest that the therapeutic effect is probably not related to direct hypothalamic stimulation. Deep brain stimulation might modulate either a local cluster headache generator, located in the hypothalamus or in the mesencephalic grey substance, or non-specific anti-nocioceptive systems.
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Encéfalo/anatomía & histología , Cefalalgia Histamínica/patología , Cefalalgia Histamínica/terapia , Estimulación Encefálica Profunda/instrumentación , Estimulación Encefálica Profunda/métodos , Adolescente , Adulto , Anciano , Electrodos Implantados , Estudios de Seguimiento , Humanos , Persona de Mediana Edad , Estudios Prospectivos , Adulto JovenRESUMEN
Advanced glycation end products (AGEs) play an important role in oxidative stress and inflammation, processes implicated in the development and progression of kidney dysfunction. In the present study, we investigated the participation of the pro-oxidant protein thioredoxin-interacting protein (TXNIP) and of epigenetic mechanisms on kidney tissue (in vivo, in non-diabetic rats) and on terminally differentiated glomerular podocytes (in vitro) chronically exposed to AGEs. AGEs induced total kidney and glomerular TXNIP expression and decreased H3K27me3 content. Concomitant treatment with the antioxidant N-acetyl-cysteine (NAC) reversed only the increased TXNIP expression. TXNIP expression positively correlated with proteinuria and negatively correlated with H3K27me3 content. In vitro studies in podocytes showed that 72 h exposure to AGEs decreased nephrin expression and increased Txnip, Nox4, Col4a1, and epithelial-to-mesenchymal transition (EMT) markers (Acta2, Snail1, and Tgfb1). Podocytes treatment with NAC reversed Nox4, Col4a1, Acta2, and Tgfb1 increased expression but did not abrogate the reduced expression of nephrin. MiR-29a expression was downregulated by AGEs in vivo, but not in vitro. In conclusion, treatment of non-diabetic rats with AGEs induced TXNIP expression and decreased the contents of the repressive epigenetic mark H3K27me3 and of miR-29a, potentially driving injury to glomerular filtration barrier and podocytes dysfunction.
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Proteínas de Ciclo Celular/genética , Nefropatías Diabéticas/metabolismo , Productos Finales de Glicación Avanzada/farmacología , Animales , Antioxidantes/metabolismo , Proteínas de Ciclo Celular/metabolismo , Diabetes Mellitus Experimental/metabolismo , Nefropatías Diabéticas/genética , Epigénesis Genética/genética , Células Epiteliales/metabolismo , Expresión Génica/genética , Regulación de la Expresión Génica/efectos de los fármacos , Productos Finales de Glicación Avanzada/metabolismo , Histonas , Riñón/citología , Riñón/metabolismo , Glomérulos Renales/metabolismo , Masculino , Proteínas de la Membrana , Estrés Oxidativo , Podocitos/metabolismo , Ratas , Ratas Wistar , Especies Reactivas de Oxígeno/metabolismoAsunto(s)
Antagonistas de los Receptores CCR5/uso terapéutico , Linfocitos T CD8-positivos/metabolismo , Ciclohexanos/uso terapéutico , Síndrome Inflamatorio de Reconstitución Inmune/tratamiento farmacológico , Leucoencefalopatía Multifocal Progresiva/tratamiento farmacológico , Receptores CCR5/biosíntesis , Triazoles/uso terapéutico , Antirretrovirales/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Humanos , Síndrome Inflamatorio de Reconstitución Inmune/metabolismo , Leucoencefalopatía Multifocal Progresiva/inmunología , Leucoencefalopatía Multifocal Progresiva/metabolismo , Maraviroc , Microscopía Confocal , Receptores CCR5/análisisRESUMEN
OBJECTIVE: Photophobia is an abnormal sensitivity to light experienced by migraineurs and is perhaps caused by cortical hyperexcitability. In clinical studies, an inter-relation between light perception and trigeminal nociception has been demonstrated in migraineurs but not in controls. The purpose of the study was to verify this interaction by functional imaging. METHODS: The authors used H(2)O(15) positron emitting tomography (PET) to study the cortical responses of seven migraineurs between attacks and the responses of seven matched control subjects to luminous stimulations at three luminance intensities: 0, 600 and 1800 Cd/m(2). All three intensities were both with and without concomitant trigeminal pain stimulation. In order to facilitate habituation, the stimulations were started 30 s before PET acquisitions. RESULTS: When no concomitant pain stimulation was applied, luminous stimulations activated the visual cortex bilaterally in migraineurs (specifically in the cuneus, lingual gyrus and posterior cingulate cortex) but not in controls. Concomitant pain stimulation allowed visual cortex activation in control subjects and potentiated its activation in migraineurs. These activations by luminous stimulations were luminance-intensity-dependent in both groups. Concomitant stimulation by pain was associated with activation of the posterior parietal cortex (BA7) in migraineurs and controls. INTERPRETATION: The study shows the lack of habituation and/or cortical hyperexcitability to light in migraineurs. Moreover, the activation by light of several visual cortex areas (including the primary visual cortex) was potentiated by trigeminal pain, demonstrating multisensory integration in these areas.
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Trastornos Migrañosos/fisiopatología , Dolor/fisiopatología , Lóbulo Parietal/fisiopatología , Fotofobia/fisiopatología , Corteza Visual/fisiopatología , Adulto , Femenino , Humanos , Trastornos Migrañosos/complicaciones , Trastornos Migrañosos/diagnóstico por imagen , Radioisótopos de Oxígeno , Dolor/diagnóstico por imagen , Dimensión del Dolor/métodos , Lóbulo Parietal/diagnóstico por imagen , Estimulación Luminosa/métodos , Fotofobia/complicaciones , Fotofobia/diagnóstico por imagen , Tomografía de Emisión de Positrones , Corteza Visual/diagnóstico por imagenRESUMEN
Chronic cluster headache (CCH) is a disabling primary headache, considering the severity and frequency of pain attacks. Deep brain stimulation (DBS) has been used to treat severe refractory CCH, but assessment of its efficacy has been limited to open studies. We performed a prospective crossover, double-blind, multicenter study assessing the efficacy and safety of unilateral hypothalamic DBS in 11 patients with severe refractory CCH. The randomized phase compared active and sham stimulation during 1-month periods, and was followed by a 1-year open phase. The severity of CCH was assessed by the weekly attacks frequency (primary outcome), pain intensity,sumatriptan injections, emotional impact (HAD) and quality of life (SF12). Tolerance was assessed by active surveillance of behavior, homeostatic and hormonal functions.During the randomized phase, no significant change in primary and secondary outcome measures was observed between active and sham stimulation. At the end of the open phase, 6/11 responded to the chronic stimulation(weekly frequency of attacks decrease [50%), including three pain-free patients. There were three serious adverse events, including subcutaneous infection, transient loss of consciousness and micturition syncopes. No significant change in hormonal functions or electrolytic balance was observed. Randomized phase findings of this study did not support the efficacy of DBS in refractory CCH, but open phase findings suggested long-term efficacy in more than 50% patients, confirming previous data, without high morbidity. Discrepancy between these findings justifies additional controlled studies (clinicaltrials.gov number NCT00662935).
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Cefalalgia Histamínica/terapia , Estimulación Encefálica Profunda/métodos , Adulto , Cefalalgia Histamínica/psicología , Estudios Cruzados , Método Doble Ciego , Electrodos Implantados/efectos adversos , Femenino , Estudios de Seguimiento , Lateralidad Funcional/fisiología , Humanos , Hipotálamo/fisiología , Masculino , Persona de Mediana Edad , Dimensión del Dolor/métodos , Calidad de Vida , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: Whereas the clinical features of pure triptan overuse headache (TOH) are well known, there are insufficient data regarding the semiological pattern of headaches when triptan overuse is associated with other types of medication overuse. OBJECTIVE: To investigate and compare the clinical characteristics of patients with pure TOH and those with medication overuse headaches associating triptan and other medication overuses (combined TOH). METHODS: This cross-sectional, observational study was conducted in 7 tertiary-care headache centers participating in the French Observatory of Migraine and Headaches. From 2004 to 2006, data from 163 patients with TOH were collected in face-to-face structured interviews (according to the International Classification of Headache Disorders, 2nd edition criteria). RESULTS: Eighty-two patients fulfilled criteria for pure TOH (pTOH patients) and 81 for combined TOH (cTOH) patients. Continuous headaches were reported in 76% of cTOH patients compared with 32% of pTOH patients. Significantly more frequent and severe headaches and more intense phono-/photophobia between attacks were noted in cTOH patients. More cTOH than pTOH patients reported a history of tension-type headaches and a long-standing history of chronic headaches. Finally, compared with pTOH patients, cTOH patients were characterized by stronger dependence on acute treatments of headaches according to the DSM-IV criteria. CONCLUSIONS: Combined therapy with analgesics and/or the total number of drug units taken per day may cause a shift from a pattern of clear-cut headache attacks in patients with pTOH toward more severe clinical presentation in patients with cTOH. These patients should receive more intensive prophylactic therapy and specific behavioral management.
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Cefalea/inducido químicamente , Cefalea/clasificación , Agonistas de Receptores de Serotonina/efectos adversos , Triptaminas/efectos adversos , Adulto , Anciano , Estudios Transversales , Femenino , Cefalea/epidemiología , Cefalea/psicología , Humanos , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Observación , Estudios Retrospectivos , Adulto JovenRESUMEN
OBJECTIVE: The aim of this study was to assess behavioral dependence on migraine abortive drugs in medication-overuse headache (MOH) patients and identify the predisposing factors. BACKGROUND: It is common occurrence that MOH patients relapse after medication withdrawal. Behavioral determinants of medication overuse should therefore be identified in MOH patients. METHODS: This was a cross-sectional, multicenter study that included 247 MOH patients (according to International Classification of Headache Disorders, 2nd edition criteria) consulting in French headache specialty centers. Face-to-face interviews were conducted by senior neurologists using a structured questionnaire including the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) criteria for the evaluation of dependence, Hospital Anxiety and Depression Scale for the evaluation of anxiety and depression, and 6-item short-form Headache Impact Test scale for the determination of functional impact. RESULTS: Most MOH patients had pre-existing primary migraine (87.4%) and current migraine-type headaches (83.0%). Treatments overused included triptans (45.8%), opioid analgesics alone or in combination (43.3% of patients), and analgesics (27.9%). Nonmigraine abortive substances (tobacco, caffeine, sedatives/anxiolytics) were overused by 13.8% of patients. Two-thirds of MOH patients (66.8%) were considered dependent on acute treatments of headaches according to the DSM-IV criteria. Most dependent MOH patients had migraine as pre-existing primary headache (85.7%) and current migraine-type headaches (87.9%), and most of them overused opioid analgesics. More dependent than nondependent MOH patients were dependent on psychoactive substances (17.6% vs 6.1%). Multivariate logistic analysis indicated that risk factors of dependence on acute treatments of headaches pertained both to the underlying disease (history of migraine, unilateral headaches) and to drug addiction (opioid overuse, previous withdrawal). Affective symptoms did not appear among the predictive factors of dependence. CONCLUSION: In some cases, MOH thus appears to belong to the spectrum of addictive behaviors. In clinical practice, behavioral management of MOH should be undertaken besides pharmacological management.
Asunto(s)
Analgésicos/efectos adversos , Conducta Adictiva/psicología , Manual Diagnóstico y Estadístico de los Trastornos Mentales , Cefaleas Secundarias/psicología , Trastornos Relacionados con Sustancias/psicología , Adulto , Conducta Adictiva/clasificación , Conducta Adictiva/diagnóstico , Estudios Transversales , Femenino , Cefaleas Secundarias/clasificación , Cefaleas Secundarias/diagnóstico , Humanos , Masculino , Persona de Mediana Edad , Trastornos Relacionados con Sustancias/clasificación , Trastornos Relacionados con Sustancias/diagnósticoRESUMEN
Little is known about advanced glycation end products (AGEs) participation in glucose homeostasis, a process in which skeletal muscle glucose transporter GLUT4 (Scl2a4 gene) plays a key role. This study investigated (1) the in vivo and in vitro effects of AGEs on Slc2a4/GLUT4 expression in skeletal muscle of healthy rats, and (2) the potential involvement of endoplasmic reticulum and inflammatory stress in the observed regulations. For in vivo analysis, rats were treated with advanced glycated rat albumin (AGE-albumin) for 12 weeks; for in vitro analysis, soleus muscles from normal rats were incubated with bovine AGE-albumin for 2.5 to 7.5 hours. In vivo, AGE-albumin induced whole-body insulin resistance; decreased (~30%) Slc2a4 mRNA and GLUT4 protein content; and increased (~30%) the nuclear content of nuclear factor NF-kappa-B p50 subunit (NFKB1), and cellular content of 78 kDa glucose-regulated protein (GRP78). In vitro, incubation with AGE-albumin decreased (~50%) the Slc2a4/GLUT4 content; and increased cellular content of GRP78/94, phosphorylated-IKK-alpha/beta, nuclear content of NFKB1 and RELA, and the nuclear protein binding into Slc2a4 promoter NFKB-binding site. The data reveal that AGEs impair glucose homeostasis in non-diabetic states of increased AGEs concentration; an effect that involves activation of endoplasmic reticulum- and inflammatory-stress and repression of Slc2a4/GLUT4 expression.
Asunto(s)
Regulación de la Expresión Génica/efectos de los fármacos , Transportador de Glucosa de Tipo 4/genética , Productos Finales de Glicación Avanzada/farmacología , Resistencia a la Insulina , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/metabolismo , Animales , Biomarcadores/metabolismo , Retículo Endoplásmico/efectos de los fármacos , Retículo Endoplásmico/metabolismo , Glucosa/metabolismo , Homeostasis/efectos de los fármacos , Masculino , FN-kappa B/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratas , Ratas WistarRESUMEN
Because of the paucity of information regarding metabolic effects of advanced glycation end products (AGEs) on liver, we evaluated effects of AGEs chronic administration in (1) insulin sensitivity; (2) hepatic expression of genes involved in AGEs, glucose and fat metabolism, oxidative stress and inflammation and; (3) hepatic morphology and glycogen content. Rats received intraperitoneally albumin modified (AlbAGE) or not by advanced glycation for 12 weeks. AlbAGE induced whole-body insulin resistance concomitantly with increased hepatic insulin sensitivity, evidenced by activation of AKT, inactivation of GSK3, increased hepatic glycogen content, and decreased expression of gluconeogenesis genes. Additionally there was reduction in hepatic fat content, in expression of lipogenic, pro-inflamatory and pro-oxidative genes and increase in reactive oxygen species and in nuclear expression of NRF2, a transcription factor essential to cytoprotective response. Although considered toxic, AGEs become protective when administered chronically, stimulating AKT signaling, which is involved in cellular defense and insulin sensitivity.
Asunto(s)
Productos Finales de Glicación Avanzada/farmacología , Hormesis/efectos de los fármacos , Resistencia a la Insulina , Hígado/metabolismo , Albúminas/farmacología , Animales , Núcleo Celular/efectos de los fármacos , Núcleo Celular/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Gluconeogénesis/efectos de los fármacos , Gluconeogénesis/genética , Productos Finales de Glicación Avanzada/administración & dosificación , Glucógeno/metabolismo , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Proteína HMGB1/metabolismo , Mediadores de Inflamación/metabolismo , Inyecciones Intraperitoneales , Lipogénesis/efectos de los fármacos , Lipogénesis/genética , Hígado/efectos de los fármacos , Masculino , Modelos Biológicos , Factor 2 Relacionado con NF-E2/metabolismo , Oxidación-Reducción , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratas Wistar , Especies Reactivas de Oxígeno/metabolismo , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/metabolismoRESUMEN
Background: Advanced glycation endproducts elicit inflammation. However, their role in adipocyte macrophage infiltration and in the development of insulin resistance, especially in the absence of the deleterious biochemical pathways that coexist in diabetes mellitus, remains unknown. We investigated the effect of chronic administration of advanced glycated albumin (AGE-albumin) in healthy rats, associated or not with N-acetylcysteine (NAC) treatment, on insulin sensitivity, adipose tissue transcriptome and macrophage infiltration and polarization. Methods: Male Wistar rats were intraperitoneally injected with control (C) or AGE-albumin alone, or, together with NAC in the drinking water. Biochemical parameters, lipid peroxidation, gene expression and protein contents were, respectively, determined by enzymatic techniques, reactive thiobarbituric acid substances, RT-qPCR and immunohistochemistry or immunoblot. Carboxymethyllysine (CML) and pyrraline (PYR) were determined by LC/mass spectrometry (LC-MS/MS) and ELISA. Results: CML and PYR were higher in AGE-albumin as compared to C. Food consumption, body weight, systolic blood pressure, plasma lipids, glucose, hepatic and renal function, adipose tissue relative weight and adipocyte number were similar among groups. In AGE-treated animals, insulin resistance, adipose macrophage infiltration and Col12a1 mRNA were increased with no changes in M1 and M2 phenotypes as compared to C-albumin-treated rats. Total GLUT4 content was reduced by AGE-albumin as compared to C-albumin. NAC improved insulin sensitivity, reduced urine TBARS, adipose macrophage number and Itgam and Mrc mRNA and increased Slc2a4 and Ppara. CD11b, CD206, Ager, Ddost, Cd36, Nfkb1, Il6, Tnf, Adipoq, Retn, Arg, and Il12 expressions were similar among groups. Conclusions: AGE-albumin sensitizes adipose tissue to inflammation due to macrophage infiltration and reduces GLUT4, contributing to insulin resistance in healthy rats. NAC antagonizes AGE-albumin and prevents insulin resistance. Therefore, it may be a useful tool in the prevention of AGE action on insulin resistance and long-term complications of DM.