Association between COMMD1 gene polymorphism rs11125908 and rheumatoid arthritis in the Cuban population.

OBJECTIVE: To evaluate the association of the rs11125908 polymorphism in the COMMD1 gene in the Cuban population with rheumatoid arthritis (RA). METHODS: In this case-control study, 161 RA patients and 150 control subjects were genotyped for rs11125908 by the allele-specific polymerase chain reaction method. DNA sequencing was used to verify the assignation of the polymorphism. The odds ratios (OR) and their 95% confidence interval were calculated by logistic regression to determine the associations between genotypes and RA using the SNPStats software. RESULTS: An association of the single nucleotide polymorphism with the disease was found in the overdominant model (p=0.025; OR=1.91) for the AG genotype. Our analyses revealed an association between rs11125908 and the subgroup of patients with swollen joints < median under the codominant model for AG (p=0.034; OR=2.30) and GG genotype (p=0.034; OR=0.82) and with the overdominant model (p=0.01; OR=2.38). The subgroup of patients with an age of onset lower than the mean and AG genotype showed an association in the overdominant model (p=0.027; OR=2.27). Disease activity score 28 with erythrocyte sedimentation rate and disease duration variables were not associated with the rs11125908 polymorphism. CONCLUSIONS: rs11125908 was associated with RA and with the number of swollen joints and age of onset subgroup analyses. We provide concepts for treatments for RA, based on pharmacological management of COMMD1 expression.

Expanding the use of flow diverters beyond their initial indication: treatment of small unruptured aneurysms.

BACKGROUND: Experience with the endovascular treatment of unruptured small intracranial aneurysms by flow diverter devices is still limited. OBJECTIVE: To assess the safety and efficacy of the SILK flow diverter (SFD) in the treatment of small unruptured cerebral aneurysms (<10 mm). METHODS: We performed a retrospective review of a prospectively maintained database of patients treated with a SFD between July 2008 and December 2013 at 4 institutions in Spain to identify all patients with small unruptured aneurysms (<10 mm). Data for patient demographics, aneurysm characteristics, and technical procedures were analyzed. Angiographic and clinical findings were recorded during the procedure and at 6- and 12-month follow-ups. RESULTS: A total of 109 small aneurysms were treated with a SFD in 104 patients (78 women; 26 men; mean, median, and range of age: 55.2, 57.1, and 19-80 years, respectively). A total of 60 patients were asymptomatic (57.7%). All except 7 aneurysms (6.4%) arose from the anterior circulation. The mean size of the aneurysms was 4.7±1.9 mm. At 6 months, the neuromorbidity and neuromortality rates were 2.9% and 0.9%, respectively. Imaging at the 12-month follow-up showed complete occlusion, neck remnants, and residual aneurysm in 88.5% (69/78), 7.7% (6/78), and 3.3% (3/78) of cases, respectively. No delayed hemorrhage occurred. CONCLUSIONS: The findings suggest that the indications for SFD can be safely extended to small intracranial aneurysms.

Familial amyloidosis with polyneuropathy type 1 caused by transthyretin mutation Val50Met (Val30Met): 4 cases in a non-endemic area. / Polineuropatía amiloidótica familiar I por mutación Val50Met (Val30Met) en el gen de la transtiretina.

INTRODUCTION: Transthyretin-related familial amyloid polyneuropathy (TTR-FAP) typically arises as an autonomic neuropathy primarily affecting small fibres and it occurs in adult patients in their second or third decades of life. It progresses rapidly and can lead to death in approximately 10 years. Other phenotypes have been described in non-endemic areas. OBJECTIVES AND METHODS: We described 4 cases from the Spanish province of Guipuzcoa, a non-endemic area, to highlight the clinical variability of this disease. PATIENTS AND RESULTS: Three patients presented a late-onset form manifesting after the age of 50, featuring a predominantly motor polyneuropathy initially causing distal impairment of the lower limbs followed by the upper limbs. One patient suffered severe neuropathic pain. None showed signs of autonomic involvement. The fourth patient, of Portuguese descent, presented a typical form with onset in her thirties, neuropathic pain and dysautonomia. All patients carry the Val50Met mutation in the TTR gene. CONCLUSION: FAP is a pleomorphic disease even in patients carrying the same mutation. In non-endemic areas, its main form of presentation may resemble a predominantly motor polyneuropathy developing in the sixth decade of life with no signs of dysautonomia. Given this non-specific presentation and the widely available technical means of studying the TTR gene, we believe that the protocol for the aetiological diagnosis of any polyneuropathy should include genetic sequencing of TTR.

Inflammatory profile discriminates clinical subtypes in LRRK2-associated Parkinson's disease.

BACKGROUND AND PURPOSE: The presentation of Parkinson's disease patients with mutations in the LRRK2 gene (PDLRRK2 ) is highly variable, suggesting a strong influence of modifying factors. In this context, inflammation is a potential candidate inducing clinical subtypes. METHODS: An extensive battery of peripheral inflammatory markers was measured in human serum in a multicentre cohort of 142 PDLRRK2 patients from the MJFF LRRK2 Consortium, stratified by three different subtypes as recently proposed for idiopathic Parkinson's disease: diffuse/malignant, intermediate and mainly pure motor. RESULTS: Patients classified as diffuse/malignant presented with the highest levels of the pro-inflammatory proteins interleukin 8 (IL-8), monocyte chemotactic protein 1 (MCP-1) and macrophage inflammatory protein 1-ß (MIP-1-ß) paralleled by high levels of the neurotrophic protein brain-derived neurotrophic factor (BDNF). It was also possible to distinguish the clinical subtypes based on their inflammatory profile by using discriminant and area under the receiver operating characteristic curve analysis. CONCLUSIONS: Inflammation seems to be associated with the presence of a specific clinical subtype in PDLRRK2 that is characterized by a broad and more severely affected spectrum of motor and non-motor symptoms. The pro-inflammatory metabolites IL-8, MCP-1 and MIP-1-ß as well as BDNF are interesting candidates to be included in biomarker panels that aim to differentiate subtypes in PDLRRK2 and predict progression.

Punción transcraneal arterial microselectiva e inyección de Onyx para el cierre endovascular de fístula arteriovenosa dural / Transcranial puncture using Onyx for endovascular embolisation of dural arteriovenous fistula

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Cognitive dysfunction in Parkinson's disease related to the R1441G mutation in LRRK2.

OBJECTIVE: The neuropsychological characteristics of patients with Parkinson's Disease (PD) associated with R1441G mutation in the LRRK2 gene (R1441G-PD) are not well known. The aim of this study was to examine the cognitive status and mood of R1441G-PD patients. METHODS: Thirty patients with R1441G-PD were compared with thirty idiopathic PD (i-PD) patients who were matched by age, sex, education, disease onset age and duration, using a comprehensive battery of neuropsychological test, and considering the Movement Disorder Society (MDS) criteria for the diagnosis of Mild Cognitive Impairment (PD-MCI) and dementia (PD-Dementia). RESULTS: The mean scores in the depression and anxiety scales were similar in the two groups. Depressive symptoms were detected in 31.8% of R1441G-PD and 25% of i-PD patients and anxiety symptoms were evident in 4.5% and 15%, respectively, but the differences were not significant. The only neuropsychological test on which there was a significantly worse performance in the R1441G-PD group was the Boston naming test but the difference became not significant when Bonferroni's correction was applied. The prevalence of PD-MCI was 30% in both R1441G-PD and i-PD, with no differences in the number and type of domains altered given that executive function, memory and attention were mainly affected. PD-Dementia was diagnosed in 13.3% (n = 4) of R1441G-PD and 26.7% (n = 8) of i-PD patients (difference was not significant). CONCLUSION: In conclusion, significant differences were not detected between R1441G-PD and i-PD in cognitive, depression and anxiety scales, or PD-MCI and PD-Dementia prevalence, and the cognitive profile was identical in the two groups.

Respuesta al tratamiento con corticoides en un caso de angiopatía amiloide inflamatoria sin realización de biopsia / Response to treatment with corticoids in a case of inflammatory amyloid angiopathy without performing a biopsy

Introducción. La angiopatía amiloide inflamatoria (AAI) es una forma de presentación infrecuente de la angiopatía amiloide cerebral recientemente reconocida y cuyo diagnóstico definitivo es anatomopatológico. Objetivo. Se presenta un paciente con AAI con buena respuesta clínica, neuropsicológica y de neuroimagen al tratamiento con corticoides y en el que no se consideró necesario practicar biopsia cerebral. Caso clínico. Varón de 68 años con diagnóstico de enfermedad de Alzheimer que sufrió una crisis convulsiva generalizada seguida de trastorno del lenguaje y hemiparesia derecha. La resonancia magnética mostró una lesión de comportamiento infiltrante hemisférica izquierda y múltiples microsangrados. La clínica y radiología fueron sugestivas de AAI y se instauró tratamiento corticoideo. La neuroimagen y los tests neuropsicológicos mostraron una notable mejoría a los 30 días del inicio del tratamiento inmunosupresor. El genotipo fue ApoE ε4/ε4. Se desestimó la realización de biopsia cerebral. Conclusiones. El caso descrito sugiere la posibilidad de, en casos individualizados con clínica y radiología características de AAI, instaurar tratamiento empírico con corticoides con diagnóstico de probabilidad y realizar biopsia cerebral en caso de que no haya respuesta al tratamiento (AU)

Introduction. Inflammatory amyloid angiopathy (IAA) is an infrequent presenting symptom of the recently recognised cerebral amyloid angiopathy and its definitive diagnosis is reached by means of pathological analyses. Aim. We report the case of a male patient with IAA and good clinical, neuropsychological and neuroimaging response to treatment with corticoids; a biopsy of brain tissue was not considered necessary. Case report. The patient, 68 years old and diagnosed with Alzheimer’s disease, suffered from generalised seizures followed by a language disorder and hemiparesis of the right-hand side. A magnetic resonance imaging scan showed a lesion displaying infiltrating behaviour in the left hemisphere and multiple instances of microbleeding. Clinical and radiological features suggested IAA and treatment was established with corticoids. Neuroimaging and neuropsychological tests revealed a notable improvement at 30 days after beginning treatment with immunosuppressants. The genotype was ApoE ε4/ε4. The need to perform a biopsy of brain tissue was ruled out. Conclusions. The case described here suggests that, in individualised cases with clinical and radiological features that are characteristic of IAA, it may be possible to establish an empirical treatment with corticoids with a probability diagnosis and perform a biopsy of brain tissue in the event of a lack of response to treatment (AU)

[Sleep disorders in Parkinson's disease: insomnia and sleep fragmentation, daytime hypersomnia, alterations to the circadian rhythm and sleep apnea syndrome]. / Trastornos del sueño en la enfermedad de Parkinson: insomnio y fragmentación del sueño, hipersomnia diurna, alteraciones del ritmo circadiano y síndrome de apnea del sueño.

INTRODUCTION: Sleep disorders in Parkinson's disease are present in 60-98% of patients and reduce their quality of life. AIMS: To review the pathophysiology, diagnostic approach and management of the different sleep disorders. DEVELOPMENT: We describe the pathophysiology associated with neurodegeneration, due to symptoms (motor and nonmotor) and drug therapies. This article reviews insomnia, excessive daytime sleepiness, circadian sleep disorders and sleep apnea. CONCLUSIONS: Subjective or objective sleepiness assessment should routinely be performed by physicians looking after Parkinson's disease patients. Management is difficult and should be targeted to the specific sleep disorder and its likely cause.

Cognitive/personality pattern and triplet expansion size in adult myotonic dystrophy type 1 (DM1): CTG repeats, cognition and personality in DM1.

BACKGROUND: Although central nervous system (CNS) involvement in adult myotonic dystrophy type 1 (DM1) was described long ago, the large number of variables affecting the cognitive and personality profile have made it difficult to determine the effect of DM1 on the brain. The aim of this study was to define the cognitive and personality patterns in adult DM1 patients, and to analyse the relationship between these clinical patterns and their association with the underlying molecular defect. METHOD: We examined 121 adult DM1 patients with confirmed molecular CTG repeat expansion and 54 control subjects using comprehensive neuropsychological tests and personality assessments with the Millon Clinical Multiaxial Inventory (MCMI)-II. We used a multiple linear regression model to assess the effect of each variable on cognition and personality adjusted to the remainders. RESULTS: Patients performed significantly worse than controls in tests measuring executive function (principally cognitive inflexibility) and visuoconstructive ability. In the personality profile, some paranoid and aggressive traits were predominant. Furthermore, there was a significant negative correlation between the CTG expansion size and many of the neuropsychological and personality measures. The molecular defect also correlated with patients' daytime somnolence. CONCLUSIONS: Besides muscular symptomatology, there is significant CTG-dependent involvement of the CNS in adult DM1 patients. Our data indicate that the cognitive impairment predominantly affects the fronto-parietal lobe.

"Frontotemporoparietal" dementia: clinical phenotype associated with the c.709-1G>A PGRN mutation.

BACKGROUND: Mutations in the progranulin gene (PGRN) are a major cause of frontotemporal lobar degeneration with tau-negative and ubiquitin-positive neuronal inclusions. Most previous studies aimed at characterizing the clinical and neuropsychological phenotype of PGRN mutation carriers included patients with different PGRN mutations, assuming that the common proposed pathogenetic mechanism of haploinsufficiency will lead to a comparable phenotype. METHODS: We studied 21 patients with a single pathogenic splicing mutation in the PGRN gene (c.709-1G>A) in the same tertiary referral center using homogenous diagnostic criteria and protocols. All patients were of Basque descent. RESULTS: Patients exhibited a variable phenotype both in age at onset and initial symptoms. Behavioral variant frontotemporal dementia (52.4%) and progressive nonfluent aphasia (23.8%) were the most common presenting syndromes. Apathy was the most common behavioral symptom. Patients developed a relatively rapidly progressive dementia with features that led to a secondary diagnosis in 61.9% of cases 2 years after primary diagnosis. Notably, this secondary or tertiary diagnosis was corticobasal syndrome in 47.6% of cases, which confirmed the neuropsychological features of parietal lobe dysfunction seen at the initial assessment in 81.8% of patients. CONCLUSIONS: Patients carrying the c.709-1G>A mutation in the PGRN gene showed heterogeneous clinical and neuropsychological features and commonly developed corticobasal syndrome as the disease progressed.

[Tremor: update and controversy]. / El temblor: actualidad y controversias.

INTRODUCTION: Tremor is the most common movement disorder. The differential diagnosis on its origin is sometimes difficult and the number of conditions that include this symptom as part of their clinical spectrum continues to increase. AIMS: To provide an update on aspects that may help in the process of diagnosis, to review the main lines of therapy and to reflect on tremor within the context of Parkinson's disease. DEVELOPMENT: Complementary techniques in the study of Parkinson's disease, such as DaT-SCAN or the study of the cardiac sympathetic pathway by means of cardiac scintigraphy with meta-iodobenzylguanidine (MIBG), have helped in the aetiological diagnosis of this symptom; nevertheless, the patient's clinical history continues to be the main source of information for an accurate diagnosis. Pharmacologically, the therapeutic approach has varied very little and the outcomes of surgical procedures are still described as an alternative in medication-resistant cases. In Parkinson's disease, tremor at rest is a characteristic clinical sign that comprises a series of peculiarities, and the interrelation between essential tremor and this disease is always a controversial issue. The appearance of cases that have been diagnosed as Parkinson's disease, but in which the nigrostriatal pathway remains intact, opens up the spectrum even wider. CONCLUSIONS: In this paper we review the data available today that help in the differential diagnosis of tremor; the particularities concerning Parkinson's disease from the diagnostic, therapeutic and genotypic point of view are also discussed.