Semi-quantification and grading of amyloid PET: A project of the European Alzheimer's Disease Consortium (EADC).

BACKGROUND: amyloid-PET reading has been classically implemented as a binary assessment, although the clinical experience has shown that the number of borderline cases is non negligible not only in epidemiological studies of asymptomatic subjects but also in naturalistic groups of symptomatic patients attending memory clinics. In this work we develop a model to compare and integrate visual reading with two independent semi-quantification methods in order to obtain a tracer-independent multi-parametric evaluation. METHODS: We retrospectively enrolled three cohorts of cognitively impaired patients submitted to 18F-florbetaben (53 subjects), 18F-flutemetamol (62 subjects), 18F-florbetapir (60 subjects) PET/CT respectively, in 6 European centres belonging to the EADC. The 175 scans were visually classified as positive/negative following approved criteria and further classified with a 5-step grading as negative, mild negative, borderline, mild positive, positive by 5 independent readers, blind to clinical data. Scan quality was also visually assessed and recorded. Semi-quantification was based on two quantifiers: the standardized uptake value (SUVr) and the ELBA method. We used a sigmoid model to relate the grading with the quantifiers. We measured the readers accord and inconsistencies in the visual assessment as well as the relationship between discrepancies on the grading and semi-quantifications. CONCLUSION: It is possible to construct a map between different tracers and different quantification methods without resorting to ad-hoc acquired cases. We used a 5-level visual scale which, together with a mathematical model, delivered cut-offs and transition regions on tracers that are (largely) independent from the population. All fluorinated tracers appeared to have the same contrast and discrimination ability with respect to the negative-to-positive grading. We validated the integration of both visual reading and different quantifiers in a more robust framework thus bridging the gap between a binary and a user-independent continuous scale.

"Ears of the Lynx" MRI Sign Is Associated with SPG11 and SPG15 Hereditary Spastic Paraplegia.

BACKGROUND AND PURPOSE: The "ears of the lynx" MR imaging sign has been described in case reports of hereditary spastic paraplegia with a thin corpus callosum, mostly associated with mutations in the spatacsin vesicle trafficking associated gene, causing Spastic Paraplegia type 11 (SPG11). This sign corresponds to long T1 and T2 values in the forceps minor of the corpus callosum, which appears hyperintense on FLAIR and hypointense on T1-weighted images. Our purpose was to determine the sensitivity and specificity of the ears of the lynx MR imaging sign for genetic cases compared with common potential mimics. MATERIALS AND METHODS: Four independent raters, blinded to the diagnosis, determined whether the ears of the lynx sign was present in each of a set of 204 single anonymized FLAIR and T1-weighted MR images from 34 patients with causal mutations associated with SPG11 or Spastic Paraplegia type 15 (SPG15). 34 healthy controls, and 34 patients with multiple sclerosis. RESULTS: The interrater reliability for FLAIR images was substantial (Cohen κ, 0.66-0.77). For these images, the sensitivity of the ears of the lynx sign across raters ranged from 78.8 to 97.0 and the specificity ranged from 90.9 to 100. The accuracy of the sign, measured by area under the receiver operating characteristic curve, ranged from very good (87.1) to excellent (93.9). CONCLUSIONS: The ears of the lynx sign on FLAIR MR imaging is highly specific for the most common genetic subtypes of hereditary spastic paraplegia with a thin corpus callosum. When this sign is present, there is a high likelihood of a genetic mutation, particularly associated with SPG11 or SPG15, even in the absence of a family history.

Enfermedad de Alzheimer de inicio precoz y de inicio tardío: ¿son la misma entidad? / Early- and late-onset Alzheimer disease: Are they the same entity?

La enfermedad de Alzheimer de inicio precoz (EAIP), definida como la que se manifiesta antes de los 65 años de edad, muestra ciertas características diferentes de la enfermedad de Alzheimer de inicio tardío (EAIT). Nuestro objetivo fue analizar los trabajos más actuales que comparan la clínica, la neuropsicología, la patología, la genética y la neuroimagen de la EAIP y la EAIT, para determinar si nos enfrentamos a dos enfermedades distintas o a variantes de una misma entidad. Como resultado, hallamos consistencia en algunas características diferenciales entre los 2 cuadros clínicos. Fundamentalmente, la EAIP comienza con mayor frecuencia con una clínica atípica; la valoración cognitiva muestra mayor afectación de las funciones ejecutiva y visuoespacial y de las praxias, y menor afectación de la memoria; la neuropatología evidencia mayor densidad y una distribución más difusa de la patología tipo Alzheimer; los estudios de neuroimagen estructural y funcional muestran una afectación cortical mayor y más difusa, afectando al neocórtex (especialmente el precuneus). En conclusión, las evidencias actuales hacen pensar que la EAIP y la EAIT son variantes clínicas de una misma entidad, que en el caso de la EAIT se ve influida probablemente por factores asociados al envejecimiento

Early-onset Alzheimer disease (EOAD), which presents in patients younger than 65 years, has frequently been described as having different features from those of late-onset Alzheimer disease (LOAD). This review analyses the most recent studies comparing the clinical presentation and neuropsychological, neuropathological, genetic, and neuroimaging findings of both types in order to determine whether EOAD and LOAD are different entities or distinct forms of the same entity. We observed consistent differences between clinical findings in EOAD and in LOAD. Fundamentally, the onset of EOAD is more likely to be marked by atypical symptoms, and cognitive assessments point to poorer executive and visuospatial functioning and praxis with less marked memory impairment. Alzheimer-type features will be more dense and widespread in neuropathology studies, with structural and functional neuroimaging showing greater and more diffuse atrophy extending to neocortical areas (especially the precuneus). In conclusion, available evidence suggests that EOAD and LOAD are 2 different forms of a single entity. LOAD is likely to be influenced by ageing-related processes

Early- and late-onset Alzheimer disease: Are they the same entity? / Enfermedad de Alzheimer de inicio precoz y de inicio tardío: ¿son la misma entidad?

Early-onset Alzheimer disease (EOAD), which presents in patients younger than 65 years, has frequently been described as having different features from those of late-onset Alzheimer disease (LOAD). This review analyses the most recent studies comparing the clinical presentation and neuropsychological, neuropathological, genetic, and neuroimaging findings of both types in order to determine whether EOAD and LOAD are different entities or distinct forms of the same entity. We observed consistent differences between clinical findings in EOAD and in LOAD. Fundamentally, the onset of EOAD is more likely to be marked by atypical symptoms, and cognitive assessments point to poorer executive and visuospatial functioning and praxis with less marked memory impairment. Alzheimer-type features will be more dense and widespread in neuropathology studies, with structural and functional neuroimaging showing greater and more diffuse atrophy extending to neocortical areas (especially the precuneus). In conclusion, available evidence suggests that EOAD and LOAD are 2 different forms of a single entity. LOAD is likely to be influenced by ageing-related processes.

Descripción de una serie de pacientes con diagnóstico de enfermedad priónica / Clinical and neuroimaging characteristics of 14 patients with prionopathy: A descriptive study

Introducción: Las prionopatías representan hasta el 62% de los casos de demencia rápidamente progresiva (DRP) en los que se alcanza un diagnóstico definitivo. La variabilidad de los síntomas y signos iniciales y las diferencias en su evolución dificultan el diagnóstico precoz. Métodos: Estudio retrospectivo en el que se incluye a pacientes con prionopatía probable o definitiva, que acudieron a la consulta de Neurología de nuestro centro durante el periodo 1999-2012. Se describen las características clínicas y los resultados de las exploraciones complementarias (proteína 14-3-3, EEG, RM, PET-FDG y análisis genético), con la finalidad de identificar qué marcadores permiten un diagnóstico precoz. Resultados: Se describe a 14 pacientes: 6 con enfermedad de Creutzfeldt-Jakob esporádica (ECJe) definitiva, 3 con ECJe probable, 4 con insomnio familiar fatal y uno con la nueva variante de la enfermedad de Creutzfeldt-Jakob. La mediana de edad al diagnóstico fue de 54 años y la mediana de supervivencia de 9,5 meses. El trastorno del ánimo fue el síntoma inicial más frecuente, seguido de inestabilidad de la marcha y deterioro cognitivo. La proteína 14-3-3 fue positiva en el líquido cefalorraquídeo en 7 de 11 pacientes y el EEG mostró signos típicos en 2 de 12 pacientes explorados. El estudio de neuroimagen mostró alteraciones en 13 de los 14 pacientes. Conclusiones: Además de la DRP, el trastorno conductual y de la marcha son síntomas iniciales frecuentes en las prionopatías. En nuestra serie, las pruebas complementarias más útiles para apoyar el diagnóstico fueron la RM y la PET-FDG

Introduction: Prionopathy is the cause of 62% of the rapidly progressive dementias (RPD) in which a definitive diagnosis is reached. The variability of symptoms and signs exhibited by the patients, as well as its different presentation, sometimes makes an early diagnosis difficult. Methods: Patients withdiagnosis of definite or probable prionopathy during the period 1999-2012 at our hospital were retrospectively reviewed.The clinical features and the results of the complementary tests (14-3-3 protein, EEG, MRI, FDG-PET, and genetic analysis) were evaluated in order to identify some factors that may enable an earlier diagnosis to be made. Results: A total of 14 patients are described: 6 with definite sporadic Creutzfeldt-Jakob (sCJD) disease, 3 with probable sCJD, 4 with fatal familial insomnia, and 1 with the new variant. The median age at diagnosis was 54 years old. The mean survival was 9.5 months. Mood disorder was the most common feature, followed by instability and cognitive impairment. 14-3-3 protein content in the cerebrospinal fluid was positive in 7 of 11 patients, and the EEG showed typical signs in 2 of 12 patients. Neuroimaging (FDG-PET, MRI) studies suggested the diagnosis in 13 of the 14 patients included. Conclusions: Most patients presenting with RPD suffer from a prion disease. In our series the most useful complementary tests were MRI and FDG-PET, being positive in 13 of the 14 patients studied

Clinical and neuroimaging characteristics of 14 patients with prionopathy: a descriptive study.

INTRODUCTION: Prionopathy is the cause of 62% of the rapidly progressive dementias (RPD) in which a definitive diagnosis is reached. The variability of symptoms and signs exhibited by the patients, as well as its different presentation, sometimes makes an early diagnosis difficult. METHODS: Patients withdiagnosis of definite or probable prionopathy during the period 1999-2012 at our hospital were retrospectively reviewed.The clinical features and the results of the complementary tests (14-3-3 protein, EEG, MRI, FDG-PET, and genetic analysis) were evaluated in order to identify some factors that may enable an earlier diagnosis to be made. RESULTS: A total of 14 patients are described: 6 with definite sporadic Creutzfeldt-Jakob (sCJD) disease, 3 with probable sCJD, 4 with fatal familial insomnia, and 1 with the new variant. The median age at diagnosis was 54 years old. The mean survival was 9.5 months. Mood disorder was the most common feature, followed by instability and cognitive impairment. 14-3-3 protein content in the cerebrospinal fluid was positive in 7 of 11 patients, and the EEG showed typical signs in 2 of 12 patients. Neuroimaging (FDG-PET, MRI) studies suggested the diagnosis in 13 of the 14 patients included. CONCLUSIONS: Most patients presenting with RPD suffer from a prion disease. In our series the most useful complementary tests were MRI and FDG-PET, being positive in 13 of the 14 patients studied.

[Correction: Incorrect spelling of last author name in Neuropsychological profile of frontotemporal lobar degeneration]. / Perfil neuropsicológico de la degeneración lobar frontotemporal.

This corrects the article on p. 79 in volume 38(1), PMID 25963461.

Neuroimagen estructural y funcional en las enfermedades priónicas humanas / Structural and functional neuroimaging in human prion diseases

Introducción: Las prionopatías son un conjunto de enfermedades neurodegenerativas producidas por el acúmulo de una isoforma anormal de la proteína priónica celular (PrPc). Se clasifican en adquiridas, hereditarias y esporádicas. Aunque son muchas las características clí- nicas, evolutivas y anatomopatológicas que las diferencian, todas ellas tienen en común un curso desfavorable y un pronóstico fatal. Desarrollo: Si bien algunos tipos como el kuru, prácticamente han desaparecido, otras formas como la variante de la enfermedad de Creutzfeldt-Jakob (vECJ) o la iatrogénica siguen vigentes y suponen un reto en la medicina actual. El diagnóstico de certeza se realiza postmortem, salvo en el caso de la vECJ en la que la biopsia amigdalar puede detectar el 100% de los casos. Ello ha supuesto que se definan criterios diagnósticos en función de una probabilidad estadística, que precisa la realización de exámenes complementarios tales como el estudio electroencefalográ- fico y la detección de la proteína 14-3-3 en el líquido cefalorraquídeo (LCR). Solamente la vECJ ha llegado a incluir en los criterios diagnósticos de la OMS el «signo del pulvinar» en resonancia magnética cerebral(RM). En este artículo se revisan los hallazgos de neuroimagen que han sido descritos para cada tipo de prionopatía en pacientes con un diagnóstico de certeza. Conclusiones: La finalidad es definir la utilidad de estas pruebas complementarias como una herramienta de apoyo para el diagnóstico de este conjunto de enfermedades neurodegenerativas (AU)

Introduction: Prion diseases are neurodegenerative disorders resulting from the accumulation of a misfolded isoform ofthe cellular prion protein (PrPc). They can occur as acquired, sporadic, or hereditary forms. Although prion diseases show a wide range of phenotypic variations, pathological features and clinical evolution, they are all characterised by a common unfavourable course and a fatal outcome. Review summary: Some variants, such as kuru, have practically disappeared, while others, for example the variant Creutzfeldt-Jakob (vCJD) or those attributable to iatrogenic causes, are still in force and pose a challenge to current medicine. There are no definitive pre-mortem diagnostic tests, except for vCJD, where a tonsil biopsy detects 100% of the cases. For this reason, diagnostic criteria dependent on statistical probability have had to be created. These require complementary examinations, such as an electroencephalogram (EEG) orthe detection of 14-3-3 protein in cerebrospinal fluid (CSF).Only the pulvinar sign in magnetic resonance imaging (MRI) has been included as a vCJD diagnostic criterion. The presentreview discusses neuroimaging findings for each type of prion disease in patients with a definitive histopathological diagnosis. Conclusions: The aim is to define the usefulness of these complementary examinations as a tool for the diagnosis of this family of neurodegenerative diseases (AU)

Automated analysis of FDG PET as a tool for single-subject probabilistic prediction and detection of Alzheimer's disease dementia.

PURPOSE: To introduce, evaluate and validate a voxel-based analysis method of ¹8F-FDG PET imaging for determining the probability of Alzheimer's disease (AD) in a particular individual. METHODS: The subject groups for model derivation comprised 80 healthy subjects (HS), 36 patients with mild cognitive impairment (MCI) who converted to AD dementia within 18 months, 85 non-converter MCI patients who did not convert within 24 months, and 67 AD dementia patients with baseline FDG PET scan were recruited from the AD Neuroimaging Initiative (ADNI) database. Additionally, baseline FDG PET scans from 20 HS, 27 MCI and 21 AD dementia patients from our institutional cohort were included for model validation. The analysis technique was designed on the basis of the AD-related hypometabolic convergence index adapted for our laboratory-specific context (AD-PET index), and combined in a multivariable model with age and gender for AD dementia detection (AD score). A logistic regression analysis of different cortical PET indexes and clinical variables was applied to search for relevant predictive factors to include in the multivariable model for the prediction of MCI conversion to AD dementia (AD-Conv score). The resultant scores were stratified into sixtiles for probabilistic diagnosis. RESULTS: The area under the receiver operating characteristic curve (AUC) for the AD score detecting AD dementia in the ADNI database was 0.879, and the observed probability of AD dementia in the six defined groups ranged from 8% to 100% in a monotonic trend. For predicting MCI conversion to AD dementia, only the posterior cingulate index, Mini-Mental State Examination (MMSE) score and apolipoprotein E4 genotype (ApoE4) exhibited significant independent effects in the univariable and multivariable models. When only the latter two clinical variables were included in the model, the AUC was 0.742 (95% CI 0.646 - 0.838), but this increased to 0.804 (95% CI 0.714 - 0.894, bootstrap p=0.027) with the addition of the posterior cingulate index (AD-Conv score). Baseline clinical diagnosis of MCI showed 29.7% of converters after 18 months. The observed probability of conversion in relation to baseline AD-Conv score was 75% in the high probability group (sixtile 6), 34% in the medium probability group (merged sixtiles 4 and 5), 20% in the low probability group (sixtile 3) and 7.5% in the very low probability group (merged sixtiles 1 and 2). In the validation population, the AD score reached an AUC of 0.948 (95% CI 0.625 - 0.969) and the AD-Conv score reached 0.968 (95% CI 0.908 - 1.000), with AD patients and MCI converters included in the highest probability categories. CONCLUSION: Posterior cingulate hypometabolism, when combined in a multivariable model with age and gender as well as MMSE score and ApoE4 data, improved the determination of the likelihood of patients with MCI converting to AD dementia compared with clinical variables alone. The probabilistic model described here provides a new tool that may aid in the clinical diagnosis of AD and MCI conversion.

Structural and functional neuroimaging in human prion diseases.

INTRODUCTION: Prion diseases are neurodegenerative disorders resulting from the accumulation of a misfolded isoform of the cellular prion protein (PrPc). They can occur as acquired, sporadic, or hereditary forms. Although prion diseases show a wide range of phenotypic variations, pathological features and clinical evolution, they are all characterised by a common unfavourable course and a fatal outcome. REVIEW SUMMARY: Some variants, such as kuru, have practically disappeared, while others, for example the variant Creutzfeldt-Jakob (vCJD) or those attributable to iatrogenic causes, are still in force and pose a challenge to current medicine. There are no definitive pre-mortem diagnostic tests, except for vCJD, where a tonsil biopsy detects 100% of the cases. For this reason, diagnostic criteria dependent on statistical probability have had to be created. These require complementary examinations, such as an electroencephalogram (EEG) or the detection of 14-3-3 protein in cerebrospinal fluid (CSF). Only the pulvinar sign in magnetic resonance imaging (MRI) has been included as a vCJD diagnostic criterion. The present review discusses neuroimaging findings for each type of prion disease in patients with a definitive histopathological diagnosis. CONCLUSIONS: The aim is to define the usefulness of these complementary examinations as a tool for the diagnosis of this family of neurodegenerative diseases.

Brown-sequard syndrome after endovascular embolization of vertebral hemangioma.

STUDY DESIGN: Several causes of Brown-Sequard syndrome have been described. Endovascular embolization can be used to treat symptomatic vertebral hemangiomas. We describe a previously undocumented case of Brown-Sequard syndrome followed by endovascular embolization with microcoils of a vertebral hemangioma. We also provide a clinical-radiological correlation of this finding and review the relevant literature. CASE REPORT: A 39-year-old male was referred to our hospital for endovascular treatment of a right T9 hemivertebral hemangioma with compromise of the spinal canal. Fifteen minutes after the procedure, the patient developed right lower limb weakness and numbness on the left leg. The emergency magnetic resonance imaging (MRI) of the spine showed no abnormalities. Five days later, a new spinal MRI revealed an infarction in the right half of the spinal cord at T6 and T7 level. This stroke was probably caused by a microcoil ended up in the right sulcocommisural artery. One week after surgery, the patient was able to raise the right leg against gravity, but sensory deficit showed no improvement. CONCLUSIONS: To the best of our knowledge this is the first case of a Brown-Sequard syndrome related to vertebral hemangioma embolization, a relatively safe technique with no important complications made known until this report. Clinicians should always weight the benefits with the potential devastating complications of this therapeutic option.

Analysis of the GIGYF2 gene in familial and sporadic Parkinson disease in the Spanish population.

BACKGROUND AND PURPOSE: Linkage analysis in familial Parkinson's disease (PD) identified a locus in 2q36-37 (PARK11). Sequencing of GIGYF2 identified several variants only present amongst PD individuals. METHODS: We analyzed the presence of disease-associated GIGYF2 variants in familial and sporadic PD from Spanish origin by sequencing of 147 PD individuals. The entire GIGYF2 coding sequence was analyzed in 122 familial PD individuals and exons 2, 4, 8-11, 14 and 25-26 were sequenced in 25 sporadic PD to identify disease-associated variants. RESULTS: We found no variants associated with PD and failed to identify any of previously PD-associated GIGYF2 variants in our sample. We identified four novel missense changes in GIGYF2. p.Met48Ile was found in a PD individual who also was a carrier of two PARKIN mutations. p.Q1244_Q1247del variant was present only in one PD individual but not found in 70 controls. However, its location in the highly polymorphic GIGYF2 glutamine/proline-rich region does not support a role in PD. Two variants (p.P1238insAGC and p.Q1249del) were present both in PD subjects and in controls. Additionally, the p.L1230_Q1237del variant, which was previously considered as a PD-associated change, was found in one control. CONCLUSION: Our findings suggest that GIGYF2 mutations are not a frequent cause of PD in the Spanish population, since we found no clearly segregating variants. We propose further analyses in PD subjects from different populations to define the role of GIGYF2. A clear pathogenic mutation in other gene at 2q36-37 in the PARK11-linked PD families would definitively disprove GIGYF2 as the responsible gene.

Dietary fibre intake is inversely associated with carotid intima-media thickness: a cross-sectional assessment in the PREDIMED study.

OBJECTIVE: To assess the association between the intake of dietary fibre and carotid intima-media thickness (IMT) in a Mediterranean population at high cardiovascular risk. METHODS: Baseline cross-sectional assessment of 457 men and women (average age 67 years) from two different Spanish centres of the PREDIMED trial. A previously validated food frequency questionnaire (137 food items) was administered by trained dieticians in a face-to-face interview. Mean common carotid IMT was measured using B-mode ultrasound imaging of the right and left carotid arteries by four certified sonographers who used a common protocol. Anthropometric and blood pressure measurements were performed and samples of fasting blood were obtained. Participants were categorized into four groups (roughly quartiles: < or =21; >21 to < or =25; >25 to < or =31 and >31 g/day) of energy-adjusted intake of dietary fibre. Multiple linear regression models were used to adjust for age, sex, centre, smoking, body mass index, diabetes, blood pressure, lipid levels and statin use. RESULTS: In the crude analyses, energy-adjusted fibre intake showed a significant inverse correlation with IMT (r=-0.27, P<0.001). In multivariate analyses, a modest, though statistically significant (P=0.03) inverse association between energy-adjusted fibre intake and IMT was also found. The multivariate-adjusted difference in average IMT was -0.051 mm (95% confidence interval: -0.094 to-0.009, P=0.02) for participants whose intake was >35 g/day, (n=47) when compared with those whose intake was <25 g/day (n=224). CONCLUSIONS: Our results suggest that high fibre intake is inversely associated with carotid atherosclerosis.

New MRI, 18F-DOPA and 11C-(+)-alpha-dihydrotetrabenazine templates for Macaca fascicularis neuroimaging: advantages to improve PET quantification.

Normalization of neuroimaging studies to a stereotaxic space allows the utilization of standard volumes of interest (VOIs) and voxel-based analysis (SPM). Such spatial normalization of PET and MRI studies requires a high quality template image. The aim of this study was to create new MRI and PET templates of (18)F-DOPA and (11)C-(+)-alpha-dihydrotetrabenazine ((11)C-DTBZ) of the Macaca fascicularis brain, an important animal model of Parkinson's disease. MRI template was constructed as a smoothed average of the scans of 15 healthy animals, previously transformed into the space of one representative MRI. In order to create the PET templates, (18)F-DOPA and (11)C-DTBZ PET of the same subjects were acquired in a dedicated small animal PET scanner and transformed to the created MRI template space. To validate these templates for PET quantification, parametric values obtained with a standard VOI-map applied after spatial normalization to each template were statistically compared to results computed using individual VOIs drawn for each animal. The high correlation between both procedures validated the utilization of all the templates, improving the reproducibility of PET analysis. To prove the utility of the templates for voxel-based quantification, dopamine striatal depletion in a representative monkey treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was assessed by SPM analysis of (11)C-DTBZ PET. A symmetric reduction in striatal (11)C-DTBZ uptake was detected in accordance with the induced lesion. In conclusion, templates of M. fascicularis brain have been constructed and validated for reproducible and automated PET quantification. All templates are electronically available via the internet.

Forceps minor region signal abnormality "ears of the lynx": an early MRI finding in spastic paraparesis with thin corpus callosum and mutations in the spatacsin gene (SPG11) on chromosome 15.

BACKGROUND AND PURPOSE: A thin corpus callosum on magnetic resonance imaging (MRI) characterizes a type of autosomal recessive disorder with progressive spastic paraparesis and cognitive impairment. Known as Hereditary Spastic Paraparesis with Thin Corpus Callosum (HSP-TCC), it has been associated with mutations of the SPG11 gene. No other specific MRI findings have been reported. METHODS: We studied with MRI four patients from three families with HSP-TCC who had identified causal mutations in the SPG11 gene. RESULTS: In all individuals studied the region of the forceps minor of the corpus callosum, corresponding to the genu fibers, appeared bright on T2-weighted and dark on T1-weighted images. On axial sections, the frontal horn region bore a remarkable resemblance to the ears of a lynx, with the areas of abnormal signal reminiscent of the tufts of hair crowning the tips of the ears of this animal. Less specific findings included a box-shape appearance of the calloso-caudate angle and diffusely increased signal in the hemispheric white matter. CONCLUSION: Abnormal MRI signal in the region of the forceps minor of the corpus callosum is a characteristic early imaging finding of HSP-TCC with SPG11 mutations.

[Headache in the emergency department]. / Cefalea en urgencias.

Headache is among the most frequent neurological symptoms in the Emergency department. Although most of the patients suffer from primary headaches (migraine), an acute headache might be the only symptom of a serious disease, such as subarachnoid haemorrhage. The physician's task is to make the diagnosis, carry out an appropriate selection of the patients who require further diagnostic evaluation and relieve the pain. An accurate history will identify most of the patients with secondary headaches. Clinicians should suspect secondary causes in sudden onset headache, headache in patients aged over 50 years, and also in those patients with abnormalities on neurological examination.

SPG11 compound mutations in spastic paraparesis with thin corpus callosum.

BACKGROUND: Autosomal recessive hereditary spastic paraparesis with thin corpus callosum (ARHSP-TCC) is being increasingly recognized as a variety of spastic paraplegia with mental retardation. SPG11 gene mutations have been reported to be associated with ARHSP-TCC. METHODS: As an independent group, we investigated SPG11 gene involvement in four individuals not previously described with either recessive or sporadic HSP-TCC presentation. RESULTS: Chromosome 15q13-15 segregating autosomal disease haplotypes were different across the kindreds and sequencing of SPG11 identified four novel frameshift/nonsense segregating mutations and the R2034X mutation, which were in heterozygous compound status. The affected examined had decreased thalamic and bilateral paracentral frontal lobe metabolism on (18)F-flurodeoxyglucose PET. CONCLUSIONS: Loss-of-function SPG11 mutations are the major cause of autosomal recessive hereditary spastic paraparesis with thin corpus callosum in Southern Europe, even in apparently sporadic cases. Decreased thalamic metabolism was consistently a phenotypical SPG11 mutation hallmark.

Cefalea en urgencias / Headache in the emergency department

Las cefaleas son un motivo común de consulta en los servicios de urgencias. La mayoría de los pacientes presentan cefaleas primarias (migraña y cefalea tensional), pero el dolor de cabeza puede ser el síntoma de una enfermedad que comprometa la vida del individuo como la hemorragia subaracnoidea. El abordaje diagnóstico del paciente con cefalea consiste en diferenciar los pacientes con cefalea primaria de los que presentan una etiología secundaria, valorar la necesidad de solicitar exploraciones complementarias y tratar adecuadamente el dolor. La anamnesis permite diferenciar las cefaleas primarias de las secundarias en la mayoría de los casos. Existen una serie de síntomas de alarma que obligan a excluir causas secundarias. En los pacientes con cefalea de inicio súbito, cuando se inicia por encima de los 50 años o en aquellos pacientes con exploración neurológica anormal, debe sospecharse una etiología secundaria (AU)

Headache is among the most frequent neurological symptoms in the Emergency department. Although most of the patients suffer from primary headaches (migraine), an acute headache might be the only symptom of a serious disease, such as subarachnoid haemorrhage. The physician’s task is to make the diagnosis, carry out an appropriate selection of the patients who require further diagnostic evaluation and relieve the pain. An accurate history will identify most of the patients with secondary headaches. Clinicians should suspect secondary causes in sudden onset headache, headache in patients aged over 50 years, and also in those patients with abnormalities on neurological examination (AU)