Longitudinal Study of Cognitive Functioning in Friedreich's Ataxia.

OBJECTIVE: Friedreich's ataxia (FRDA) is the most common hereditary ataxia. It is a neurodegenerative disorder, characterized by progressive ataxia. FRDA is also associated with cognitive impairments. To date, the evolution of cognitive functioning is unknown. Our aim was to investigate the changes in the cognitive functioning of FRDA patients over an average eight-year timeframe. In addition, we aimed to study the relationship between cognitive changes and clinical variables. METHODS: Twenty-nine FRDA patients who had been part of the sample of a previous study participated in the present study. The mean average time between the two assessments was 8.24 years. The participants completed an extensive battery of neuropsychological tests chosen to examine cognitive functioning in various cognitive domains: processing speed, attention, working memory, executive functions, verbal and visual memory, visuoperceptive and visuospatial skills, visuoconstructive functions and language. RESULTS: At follow-up, cerebellar symptoms had worsened, and patients presented greater disability. Differences between baseline and follow-up were observed in motor and cognitive reaction times, several trials of the Stroop test, semantic fluency, and block designs. No other cognitive changes were observed. Deterioration in simple cognitive reactions times and block designs performance correlated with the progression of cerebellar symptoms. CONCLUSIONS: Our study has demonstrated for the first time that patients with FRDA experience a significant decline over time in several cognitive domains. Specifically, after an eight-year period, FRDA patients worsened in processing speed, fluency, and visuoconstructive skills. This progression is unlikely to be due to greater motor or speech impairment.

Expanding the phenotypic and molecular spectrum of RNA polymerase III-related leukodystrophy.

OBJECTIVE: To expand the phenotypic spectrum of severity of POLR3-related leukodystrophy and identify genotype-phenotype correlations through study of patients with extremely severe phenotypes. METHODS: We performed an international cross-sectional study on patients with genetically proven POLR3-related leukodystrophy and atypical phenotypes to identify 6 children, 3 males and 3 females, with an extremely severe phenotype compared with that typically reported. Clinical, radiologic, and molecular features were evaluated for all patients, and functional and neuropathologic studies were performed on 1 patient. RESULTS: Each patient presented between 1 and 3 months of age with failure to thrive, severe dysphagia, and developmental delay. Four of the 6 children died before age 3 years. MRI of all patients revealed a novel pattern with atypical characteristics, including progressive basal ganglia and thalami abnormalities. Neuropathologic studies revealed patchy areas of decreased myelin in the cerebral hemispheres, cerebellum, brainstem, and spinal cord, with astrocytic gliosis in the white matter and microglial activation. Cellular vacuolization was observed in the thalamus and basal ganglia, and neuronal loss was evident in the putamen and caudate. Genotypic similarities were also present between all 6 patients, with one allele containing a POLR3A variant causing a premature stop codon and the other containing a specific intronic splicing variant (c.1771-7C>G), which produces 2 aberrant transcripts along with some wild-type transcript. CONCLUSIONS: We describe genotype-phenotype correlations at the extreme end of severity of the POLR3-related leukodystrophy spectrum and shed light on the complex disease pathophysiology.

Health-related quality of life and depressive symptoms in Friedreich ataxia.

PURPOSE: Friedreich ataxia (FRDA) is a chronic, progressive and highly disabling cerebellar degenerative disease. Despite this, little attention has been paid to the health-related quality of life (HRQOL) in this disease. The aim of the present study was to assess FRDA patients' perception of HRQOL and to determine the influence of depression, and demographic and clinical variables. METHOD: The sample consisted of 62 patients with genetically confirmed FRDA. The SF-36 Health Survey was used to assess HRQOL. Depressive symptoms were evaluated with the Beck Depression Inventory-II. RESULTS: FRDA patients' mean scores were significantly lower than the values for the Spanish population in all SF36 dimensions. Average z scores ranged from - 5.5 in physical functioning to - 0.48 in mental health. Age and clinical variables were significant predictors of HRQOL in only several dimensions, whereas BDI scores were able to predict a significant percentage of variance in all SF36 dimensions, except physical functioning. CONCLUSIONS: Our study demonstrates the high impact of Friedreich ataxia on quality of life. This impact does not only occur in those aspects most related to motor disability but it is also present in non-motor dimensions. Depressive symptomatology is the most relevant variable for predicting quality of life.

Cognitive characterization of SCAR10 caused by a homozygous c.132dupA mutation in the ANO10 gene.

Autosomal recessive spinocerebellar ataxia type 10 (SCAR10) caused by a homozygous c.132dupA mutation in the anoctamin 10 gene is infrequent and little is known about its cognitive profile. Three siblings (1 male) with this mutation were assessed with a neuropsychological battery measuring multiple cognitive domains. The deficits observed in one patient were in executive functions whereas the other two patients showed deficits in practically all the functions. Cognitive impairment seems to be a characteristic of the SCAR10 produced by this mutation, with a range from mild impairment, especially involving prefrontal systems, to a severe cognitive impairment suggesting widespread cerebral involvement.

The influence of Parkinson's disease on the functional connectivity of the motor loop of human basal ganglia.

Current basal ganglia models integrate information obtained from humans and animals to explain motor disorders in Parkinson's disease. These models explain some motor disturbances of Parkinson's disease (PD), but different clinical observations which remain unexplained have promoted the development of new basal ganglia (BG) models. The present study uses the time-relationship (partial correlation) of the BOLD-signal fluctuations to study the influence of PD on BG interactions of 17 age-matched controls (58.7 ±â€¯5.3 years of age) and 24 PD patients (56.7 ±â€¯8.4 years of age). Controls showed a complex functional connectivity of BG with a positive correlation between some nuclei (synchrony) and a negative correlation between other nuclei (anti-synchrony). This functional connectivity was different in PD-patients who showed: 1. an increased synchrony between the primary motor cortex(M1)-external pallidum(GPe), putamen(Put)-GPe, Put-subthalamic nucleus (STN), STN-internal pallidum (GPi), STN-motor thalamus (Tal), STN-GPi substantia nigra (SN) and SN-Tal, 2. a decreased synchrony between Put-GPi, GPe-STN, GPe-SN, STN-SN and GPi-SN, and 3. an increased anti-synchrony between GPe-SN and GPi-Tal. In control subjects, the motor-task increased the Put-Tal, GPi-SN and STN-Tal synchrony, decreased the STN-GPi and STN-SN synchrony and decreased the M1-GPe and the GPe-GPi anti-synchrony. The effect of the motor-task was very different in PD-patients, in whom it induced a decrease of the M1-GPe, STN-GPi and SN-Tal synchrony and a decrease of the GPe-Tal and GPe-SN anti-synchrony. Functional connectivity imaging methods may provide data that cannot be obtained by other methods in humans, and that may help to understand the physiology of BG and its deterioration in PD.

Depressive symptoms in Friedreich ataxia.

Background/Objective: Almost no attention has been paid to depression in Friedreich ataxia (FRDA), a highly disabling cerebellar degenerative disease. Our aim was to study the presence and the profile of depressive symptoms in FRDA and their relationship with demographic-disease variables and cognitive processing speed. Method: The study groups consisted of 57 patients with a diagnosis of FRDA. The Beck Depression Inventory-II was used to assess symptoms of depression. Speed of information processing was measured with a Choice Reaction time task. Results: The mean BDI score for patients was significantly higher than the mean score in the general population. Twenty one percent of participants scored in the moderate/severe range. A Cognitive-Affective score and a Somatic-Motivational score was calculated for each patient. Patients' scores in both dimensions were significantly higher than the scores in the general population. Demographic and disease variables were not related with symptoms of depression, except for severity of ataxia. Depressive symptoms predict cognitive reaction times. The greater proportion of variance was explained by the Cognitive-Affective dimension. Conclusions: Our data show that both somatic-motivational and cognitive affective symptoms of depression are frequent in individuals with FRDA. In addition, depressive symptoms may influence cognition, especially, the cognitive and affective symptoms.

Antecedentes/Objetivo: La depresión en la ataxia de Friedreich (FRDA), una enfermedad degenerativa cerebelosa altamente incapacitante, ha recibido poca atención. Nuestro objetivo es evaluar la presencia y el perfil de los síntomas depresivos en FRDA y su relación con variables clínico-demográficas y la velocidad de procesamiento cognitivo. Método: Se estudiaron 57 pacientes con diagnóstico de FRDA. Se usó el Inventario de Depresión de Beck-II para evaluar los síntomas de depresión. La velocidad de procesamiento se midió con una tarea de tiempos de reacción. Resultados: La puntuación media de los pacientes en el BDI fue significativamente mayor que en la población general. El 21% de los participantes obtuvo puntuaciones en el rango moderado/grave. Se calculó una puntuación cognitiva-afectiva y una puntuación somática-motivacional para cada paciente. Las puntuaciones en ambas dimensiones fueron significativamente mayores que en la población general. Las variables clínico-demográficas no estaban relacionadas con los síntomas de depresión, a excepción de la gravedad de la ataxia. Los síntomas depresivos predicen los tiempos de reacción cognitivos. Conclusiones: Nuestros datos muestran que en la FRDA son frecuentes los síntomas de depresión, tanto los síntomas somático-motivacionales como los cognitivo-afectivos. Además, los síntomas de depresión pueden influir en la cognición, especialmente, los de tipo cognitivo-afectivo.

Depressive symptoms in Friedreich ataxia / Síntomas depresivos en la ataxia de Friedreich

Background/Objective: Almost no attention has been paid to depression in Friedreich ataxia (FRDA), a highly disabling cerebellar degenerative disease. Our aim was to study the presence and the profile of depressive symptoms in FRDA and their relationship with demographic-disease variables and cognitive processing speed. Method: The study groups consisted of 57 patients with a diagnosis of FRDA. The Beck Depression Inventory-II was used to assess symptoms of depression. Speed of information processing was measured with a Choice Reaction time task. Results: The mean BDI score for patients was significantly higher than the mean score in the general population. Twenty one percent of participants scored in the moderate/ severe range. A Cognitive-Affective score and a Somatic-Motivational score was calculated for each patient. Patients' scores in both dimensions were significantly higher than the scores in the general population. Demographic and disease variables were not related with symptoms of depression, except for severity of ataxia. Depressive symptoms predict cognitive reaction times. The greater proportion of variance was explained by the Cognitive-Affective dimension. Conclusions: Our data show that both somatic-motivational and cognitive affective symptoms of depression are frequent in individuals with FRDA. In addition, depressive symptoms may influence cognition, especially, the cognitive and affective symptoms (AU)

Antecedentes/Objetivo: La depresión en la ataxia de Friedreich (FRDA), una enfermedad degenerativa cerebelosa altamente incapacitante, ha recibido poca atención. Nuestro objetivo es evaluar la presencia y el perfil de los síntomas depresivos en FRDA y su relación con variables clínico-demográficas y la velocidad de procesamiento cognitivo. Método: Se estudiaron 57 pacientes con diagnóstico de FRDA. Se usó el Inventario de Depresión de Beck-II para evaluar los síntomas de depresión. La velocidad de procesamiento se midió con una tarea de tiempos de reacción. Resultados: La puntuación media de los pacientes en el BDI fue significativamente mayor que en la población general. El 21% de los participantes obtuvo puntuaciones en el rango moderado/grave. Se calculó una puntuación cognitiva-afectiva y una puntuación somática-motivacional para cada paciente. Las puntuaciones en ambas dimensiones fueron significativamente mayores que en la población general. Las variables clínico-demográficas no estaban relacionadas con los síntomas de depresión, a excepción de la gravedad de la ataxia. Los síntomas depresivos predicen los tiempos de reacción cognitivos. Conclusiones: Nuestros datos muestran que en la FRDA son frecuentes los síntomas de depresión, tanto los síntomas somáticomotivacionales como los cognitivo-afectivos. Además, los síntomas de depresión pueden influir en la cognición, especialmente, los de tipo cognitivo-afectivo (AU)

External conditions inversely change the RNA polymerase II elongation rate and density in yeast.

Elongation speed is a key parameter in RNA polymerase II (RNA pol II) activity. It affects the transcription rate, while it is conditioned by the physicochemical environment it works in at the same time. For instance, it is well-known that temperature affects the biochemical reactions rates. Therefore in free-living organisms that are able to grow at various environmental temperatures, such as the yeast Saccharomyces cerevisiae, evolution should have not only shaped the structural and functional properties of this key enzyme, but should have also provided mechanisms and pathways to adapt its activity to the optimal performance required. We studied the changes in RNA pol II elongation speed caused by alternations in growth temperature in yeast to find that they strictly follow the Arrhenius equation, and that they also provoke an almost inverse proportional change in RNA pol II density within the optimal growth temperature range (26-37 °C). Moreover, we discovered that yeast cells control the transcription initiation rate by changing the total amount of available RNA pol II.

A cocoa peptide protects Caenorhabditis elegans from oxidative stress and ß-amyloid peptide toxicity.

BACKGROUND: Cocoa and cocoa-based products contain different compounds with beneficial properties for human health. Polyphenols are the most frequently studied, and display antioxidant properties. Moreover, protein content is a very interesting source of antioxidant bioactive peptides, which can be used therapeutically for the prevention of age-related diseases. METHODOLOGY/PRINCIPAL FINDINGS: A bioactive peptide, 13L (DNYDNSAGKWWVT), was obtained from a hydrolyzed cocoa by-product by chromatography. The in vitro inhibition of prolyl endopeptidase (PEP) was used as screening method to select the suitable fraction for peptide identification. Functional analysis of 13L peptide was achieved using the transgenic Caenorhabditis elegans strain CL4176 expressing the human Aß1₋42 peptide as a pre-clinical in vivo model for Alzheimer's disease. Among the peptides isolated, peptide 13L (1 µg/mL) showed the highest antioxidant activity (P≤0.001) in the wild-type strain (N2). Furthermore, 13L produced a significant delay in body paralysis in strain CL4176, especially in the 24-47 h period after Aß1₋42 peptide induction (P≤0.0001). This observation is in accordance with the reduction of Aß deposits in CL4176 by western blot. Finally, transcriptomic analysis in wild-type nematodes treated with 13L revealed modulation of the proteosomal and synaptic functions as the main metabolic targets of the peptide. CONCLUSIONS/SIGNIFICANCE: These findings suggest that the cocoa 13L peptide has antioxidant activity and may reduce Aß deposition in a C. elegans model of Alzheimer's disease; and therefore has a putative therapeutic potential for prevention of age-related diseases. Further studies in murine models and humans will be essential to analyze the effectiveness of the 13L peptide in higher animals.

Cognition in late-onset Friedreich ataxia.

Friedreich ataxia (FRDA) is the most common hereditary ataxia. Since the discovery of the genetic cause of this disease, the phenotypic spectrum seems to be wider, including late-onset forms such as late-onset Friedreich ataxia--LOFA (25-39 years at onset). The neuropathological and clinical patterns in patients with LOFA are similar to those in patients with typical FRDA, but LOFA patients tend to have an overall milder, slowly evolving disease. Given the lack of data about cognitive performance of LOFA, we aimed to investigate whether differences in age at disease onset may be related also to differences at a cognitive level. Twenty-nine typical FRDA and seven LOFA patients were administered a comprehensive neuropsychological battery measuring multiple domains: processing speed, attention, working memory, executive functions, verbal and visual memory, visuoperceptive and visuospatial skills, visuoconstructive functions, and language. There were no significant differences in disease duration between the two groups of patients. Every patient group was matched in gender, age, years of education, and estimated IQ with a healthy-participant control group. Results indicate that both patient groups shared slowed motor processing speed and impaired conceptual thinking and verbal fluency. However, only typical FRDA patients showed a diminished cognitive processing speed and impaired visuoperceptive and visuoconstructive abilities. This pattern indicates that a later disease onset is associated to a milder cognitive impairment. Thus, our findings are in concordance with those related to clinical differences between typical FRDA and LOFA.

Caenorhabditis elegans as a model to study the effectiveness and metabolic targets of dietary supplements used for obesity treatment: the specific case of a conjugated linoleic acid mixture (Tonalin).

The antiobesity effect of conjugated linoleic acid (CLA) has previously been described in different animal models. The aim of the present study was to investigate the effect of a commercial mixture (Tonalin) on Caenorhabditis elegans to assess their potential use for functional ingredient screenings. Body-fat reduction with Tonalin was demonstrated in wild-type strain N2. The 1 µg/mL dose was the most effective, either alone or added to a food matrix, and also significantly decreased triglyceride content in nematodes fed on the CLA mixture. Furthermore, the antiobesity effect was related to the CLA isomer trans-10, cis-12. Finally, the transcriptional study showed C. elegans fed with Tonalin (1 µg/mL) underwent an upregulation of energy metabolism, reproduction, protein metabolism and oxidative stress processes. In conclusion, the results presented here clearly correlate well with other animal studies, demonstrating the value of C. elegans as a useful model to evaluate antiobesity compounds/ingredients.

Cognition in Friedreich ataxia.

Friedreich ataxia (FRDA) is the most frequent of the inherited ataxias. However, very few studies have examined the cognitive status of patients with genetically defined FRDA. Our aim was to study cognitive performance of FRDA patients taking into account the motor problems characteristic of this clinical population. Thirty-six FRDA patients were administered a comprehensive neuropsychological battery measuring multiple domains: processing speed, attention, working memory, executive functions, verbal and visual memory, visuoperceptive and visuospatial skills, visuoconstructive functions, and language. Thirty-one gender, age, years of education, and estimated IQ-matched healthy participants served as control subjects. All participants were native Spanish speakers. Patients showed decreased motor and mental speed, problems in conceptual thinking, a diminished verbal fluency, deficits in acquisition of verbal information and use of semantic strategies in retrieval, visuoperceptive and visuoconstructive problems, and poor action naming. Scores on the depression inventory were significantly higher in patients than controls, but depression did not account for group differences in cognitive performance. The observed pattern of neuropsychological impairment is indicative of executive problems and parieto-temporal dysfunction. Neuropathological and neuroimaging studies with FRDA patients have reported only mild anomalies in cerebral hemispheres. Thus, cognitive impairment in FRDA is probably caused by the interruption of the cerebro-cerebellar circuits that have been proposed as the anatomical substrate of the cerebellar involvement in cognition.

Use of Saccharomyces cerevisiae and Caenorhabditis elegans as model organisms to study the effect of cocoa polyphenols in the resistance to oxidative stress.

Developing functional foods to improve the quality of life for elderly people has great economic and social impact. Searching for and validating ingredients with in vivo antioxidant effects is one of the key steps in developing this kind of food. Here we describe the combined use of simple biological models and transcriptomics to define the functional intracellular molecular targets of a polyphenol-enriched cocoa powder. Cocoa powder supplemented culture medium led to increased resistance to oxidative stress, in both the budding yeast Saccharomyces cerevisiae and the nematode Caenorhabditis elegans, and, in the latter, lifespan was also increased. These effects are fully dependent on the polyphenols present in the cocoa powder and on the sirtuins Hst3 (yeast) and SIR-2.1 (worm). The transcription factor DAF-16 also plays an important role in the case of the nematode, indicating that the insulin/IGF-1 (insulin-like growth factor) signaling pathway is related with the antioxidative effect of cocoa polyphenols. All in all, these results confirm that this polyphenol-enriched cocoa powder, with antioxidant activity, has great potential use as a functional food ingredient for elderly people. Furthermore, this work reveals the value of using simple biological models to screen for compounds that are of interest for the food and pharmacological industry.

Multilocus analyses reveal involvement of the ESR1, ESR2, and FSHR genes in migraine.

OBJECTIVE: Female hormone genes have been investigated in migraine in recent years. Research in this field has been controversial, especially in regard to ESR1 gene findings. None of the reports have yet to approach the problem from a multigenic point of view. METHODS: We investigated 5 polymorphisms implicated in female hormone metabolism (FSHR, CYP19A1, ESR1, NRIP1, and ESR2) in a cohort of 730 subjects matched for age and sex. The effect of gene-gene interaction was assessed using the set association approach, and the corresponding haplotypes were studied with PM Plus software. To corroborate initial results, we analyzed the selected markers using a cohort of 134 families in which 168 trios were suitable for transmission-disequilibrium test (TDT) analysis under the migraine with aura (MA) phenotype. RESULTS: A total of 356 consecutive migraine patients (198 with MA [76% females] and 158 migraine without aura [MO, 74% females], and 374 matched controls [71% females]) were genotyped. In the 2-point analyses, the ESR1 and ESR2 polymorphisms showed nominal association under MA/MO phenotype, and this association was higher with the FSHR polymorphism in MA females (P = .004, uncorrected). Using the SUMSTAT program, we observed ESR2-ESR1-FSHR significant gene-gene interaction, suggesting association with the MA/MO phenotype (P = .005; P = .003 in females), and with MA alone (P = .021; P = .030 for females).We corroborated that ESR2-ESR1-FSHR haplotypes interacted for migraine under a model-free hypothesis (empirical P = .010 for the whole sample; P = .001 for females), and the association was stronger for the MA phenotype alone (empirical P = 5.0e-4, under the heterogeneity model; P = .001 for females). These results were corroborated using family-based association approaches. We observed nominal association for ESR2 and ESR1 (P = .031 and .034, respectively) in the TDT study, and significant association for ESR1 using family-based association test statistics. Haplotype-TDT analyses showed further significant gene-gene interaction for ESR1-ESR2 (global P = .009), ESR2-FSHR (global P = .011), and nominally significant interaction for ESR2-ESR1-FSHR genes (global P = .037). CONCLUSION: We found significant association of female hormone metabolism polymorphisms under the perspective of multigene approach.

Lack of association of endothelial nitric oxide synthase polymorphisms and migraine.

OBJECTIVE: The aim of this study was to evaluate if 2 functional endothelial nitric oxide synthase (eNOS) gene polymorphisms might be risk factors for migraine. BACKGROUND: Nitric oxide synthase promotes the synthesis of nitric oxide (NO). NO is a potent vasodilator and mediates several processes involved in migraine pathophysiology. Only one study has suggested an association with migraine with aura. METHODS: We performed a sex- and age-matched case-control study using 2 eNOS polymorphisms (rs1800779 and rs1799983), which are in linkage disequilibrium. Genotypes were obtained with allele-specific probes in a real-time polymerase chain reaction assay. Genotypic and allelic distributions were compared with chi(2) method. We also estimated the reconstructed haplotypes and calculated ORs for individual haplotypes. RESULTS: A total of 337 migraine patients (188 with aura) and 341 healthy controls were recruited. We found no significant differences in the distribution of genotypes and alleles for either polymorphism among clinical subgroups. Neither rs1800779 nor rs1799983 polymorphisms increased the risk for suffering from migraine aura. CONCLUSIONS: As others have previously reported, we failed to demonstrate genetic association of the eNOS gene with migraine.

SUNCT and trigeminal neuralgia attributed to meningoencephalitis.

We describe a 46-year-old female with viral meningoencephalitis (likely varicella-zoster virus) who developed a SUNCT syndrome followed a few days later by trigeminal neuralgia. Both disorders resolved in parallel with the resolution of encephalitis, which suggests a causal link. In conclusion, headache attributed to intracranial infection may have the clinical features of SUNCT or TN.

Differential impairment in semantic, phonemic, and action fluency performance in Friedreich's ataxia: possible evidence of prefrontal dysfunction.

This study examined phonemic (letters), semantic (animals) and action verbal fluency cues in twenty-four patients with FRDA, and twenty matched healthy control subjects. The Action Fluency Test (AFT) is a newly-developed verbal fluency cue that consists in asking the subject to rapidly generate verbs. Given the high presence of dysarthria and cognitive slowness in FRDA patients, control tasks were administered in order to dissociate motor/articulatory impairment and cognitive slowness from verbal fluency deficit. Results showed that patients and control subjects performed similarly on the semantic fluency task. In contrast, patients performed significantly poorer on phonemic and action fluency tests. Correlational analyses showed that the deficits cannot be attributed to dysarthria or cognitive slowness. Although executive processes are necessary for initiating and monitoring all verbal fluency tasks, phonemic and action fluency may place a greater burden on strategic processes, given that they require a more unusual type of lexicon search. Thus, the deficits found occur in tasks that require greater executive/prefrontal control. This impairment might be the result of an affectation of cerebellum-prefrontal cortex connections, although the possibility of a primary prefrontal dysfunction remains to be investigated.

Genetic association study and meta-analysis of the HTR2C Cys23Ser polymorphism and migraine.

The objectives of this study were to determine if the HTR2C Cys23Ser polymorphism is associated with migraine in a case-control study, and to perform a meta-analysis with present and previous available studies. The HTR2C gene is located at the Xq24-q28 chromosomal band. This band was linked to migraine with aura (MA) in two Australian families. Using the HTR2C Cys23Ser allelic variant, this gene has been ruled out as a migraine gene in 3 out of 4 studies. Only the Japanese study reported a higher risk for MA (OR=6.11; 95% CI=1.70-21.97, p trend<0.01). We performed a case-control study with 335 migraine subjects and 335 sex- and age-matched controls, and a meta-analysis pooling the results of the available data from MA subsets of patients. In the association study we found no significant differences among migraine and MA patients for this polymorphism. In the meta-analysis, under the fixed-effect model, the Ser allele did not confer higher risk for suffering MA (pooled OR=1.1; 99% CI=0.8-1.5, p=0.499). Our study did not confirm the HTR2C Cys23Ser polymorphism as a risk factor for migraine and MA.

The value of diffusion-weighted MRI in the diagnosis of cerebral fat embolism.

Fat embolism syndrome complicates open fractures involving long bones, although it occasionally follows nontraumatic conditions. Incomplete forms of the syndrome (ie, cerebral fat embolism) represent a challenge to diagnosis, and brain MRI represents a valuable diagnostic tool. We describe a patient who had a fat embolism to the brain after an isolated traumatic open fracture of the tibia. MRI with T2 and diffusion-weighted images revealed multiple, reversible brain lesions, suggesting vasogenic edema and consistent with this entity. At present, MR imaging is the most sensitive technique to evaluate cerebral fat embolism.