José Salas-Pacheco

Diagnoses behind patients with hard-to-classify tremor and normal DaT-SPECT: a clinical follow up study

The [123I]ioflupane—a dopamine transporter radioligand—SPECT (DaT-SPECT) has proven to be useful in the differential diagnosis of tremor. Here, we investigate the diagnoses behind patients with hard-to-classify tremor and normal DaT-SPECT. Therefore, 30 patients with tremor and normal DaT-SPECT were followed up for 2 years. In 18 cases we were able to make a diagnosis. The residual 12 patients underwent a second DaT-SPECT, were then followed for additional 12 months and thereafter the diagnosis was reconsidered again. The final diagnoses included cases of essential tremor, dystonic tremor, multisystem atrophy, vascular parkinsonism, progressive supranuclear palsy, corticobasal degeneration, fragile X–associated tremor ataxia syndrome, psychogenic parkinsonism, iatrogenic parkinsonism and Parkinsons disease. However, for 6 patients the diagnosis remained uncertain. Larger series are needed to better establish the relative frequency of the different conditions behind these cases.

Detrimental role of prolonged sleep deprivation on adult neurogenesis

Adult mammalian brains continuously generate new neurons, a phenomenon called adult neurogenesis. Both environmental stimuli and endogenous factors are important regulators of adult neurogenesis. Sleep has an important role in normal brain physiology and its disturbance causes very stressful conditions, which disrupt normal brain physiology. Recently, an influence of sleep in adult neurogenesis has been established, mainly based on sleep deprivation studies. This review provides an overview on how rhythms and sleep cycles regulate hippocampal and subventricular zone neurogenesis, discussing some potential underlying mechanisms. In addition, our review highlights some interacting points between sleep and adult neurogenesis in brain function, such as learning, memory, and mood states, and provides some insights on the effects of antidepressants and hypnotic drugs on adult neurogenesis.

Polymorphisms in the GSTT1 and GSTM1 genes are associated with increased risk of preeclampsia in the Mexican mestizo population.

Preeclampsia is a pregnancy-specific disorder in humans and a major cause of maternal and neonatal morbidity and mortality. Increasing evidence suggests that oxidative stress plays an important role in the pathogenesis of preeclampsia. The aim of this study was to investigate the relationship between null alleles of the glutathione S-transferases (GST) M1 and T1 genes and the risk of preeclampsia. This case-control study involved 112 preeclamptic and 233 normoevolutive pregnant women. The null polymorphisms were genotyped by multiplex polymerase chain reaction (PCR). Our results showed an increased risk of preeclampsia in patients with the GSTT1 null genotype [odds ratio (OR) = 2.21; 95% confidence interval (CI) = 1.14-4.27; P = 0.018]. Our data further showed that a combination of deletion genotypes of the GSTM1 and GSTT1 genes conferred an even higher risk of preeclampsia (OR = 4.56, 95%CI = 1.59-13.09; P = 0.005). Our results provide the first evidence suggesting that a GSTT1 null polymorphism might be associated with preeclampsia in the Mexican mestizo population, and that this risk increases with the combination of both GSTT1 and GSTM1 null polymorphisms.

MTA index: a simple 2D-method for assessing atrophy of the medial temporal lobe using clinically available neuroimaging

Background and purpose: Despite a strong correlation to severity of AD pathology, the measurement of medial temporal lobe atrophy (MTA) is not being widely used in daily clinical practice as a criterion in the diagnosis of prodromal and probable AD. This is mainly because the methods available to date are sophisticated and difficult to implement for routine use in most hospitals—volumetric methods—or lack objectivity—visual rating scales. In this pilot study we aim to describe a new, simple and objective method for measuring the rate of MTA in relation to the global atrophy using clinically available neuroimaging and describe the rationale behind this method. Description: This method consists of calculating a ratio with the area of 3 regions traced manually on one single coronal MRI slide at the level of the interpeduncular fossa: (1) the medial temporal lobe (MTL) region (A); (2) the parenchima within the medial temporal region, that includes the hippocampus and the parahippocampal gyrus—the fimbria taenia and plexus choroideus are excluded—(B); and (3) the body of the ipsilateral lateral ventricle (C). Therefrom we can compute the ratio “Medial Temporal Atrophy index” at both sides as follows: MTAi = (A − B)× 10/C. Conclusions: The MTAi is a simple 2D-method for measuring the relative extent of atrophy in the MTL in relation to the global brain atrophy. This method can be useful for a more accurate diagnosis of AD in routine clinical practice. Further studies are needed to assess the usefulness of MTAi in the diagnosis of early AD, in tracking the progression of AD and in the differential diagnosis of AD with other dementias.

Discovery of Entamoeba histolytica hexokinase 1 inhibitors through homology modeling and virtual screening

Abstract Entamoeba histolytica, the parasite which causes amebiasis is responsible for 110 000 deaths a year. Entamoeba histolytica depends on glycolysis to obtain ATP for cellular work. According to metabolic flux studies, hexokinase exerts the highest flux control of this metabolic pathway; therefore, it is an excellent target in the search of new antiamebic drugs. To this end, a tridimensional model of E. histolytica hexokinase 1 (EhHK1) was constructed and validated by homology modeling. After virtual screening of 14 400 small molecules, the 100 with the best docking scores were selected, purchased and assessed in their inhibitory capacity. The results showed that three molecules (compounds 2921, 11275 and 2755) inhibited EhHK1 with an I50 of 48, 91 and 96 µM, respectively. Thus, we found the first inhibitors of EhHK1 that can be used in the search of new chemotherapeutic agents against amebiasis.

Magnetic Resonance Techniques Applied to the Diagnosis and Treatment of Parkinson's Disease.

Parkinson’s disease (PD) affects at least 10 million people worldwide. It is a neurodegenerative disease, which is currently diagnosed by neurological examination. No neuroimaging investigation or blood biomarker is available to aid diagnosis and prognosis. Most effort toward diagnosis using magnetic resonance (MR) has been focused on the use of structural/anatomical neuroimaging and diffusion tensor imaging (DTI). However, deep brain stimulation, a current strategy for treating PD, is guided by MR imaging (MRI). For clinical prognosis, diagnosis, and follow-up investigations, blood oxygen level-dependent MRI, DTI, spectroscopy, and transcranial magnetic stimulation have been used. These techniques represent the state of the art in the last 5 years. Here, we focus on MR techniques for the diagnosis and treatment of Parkinson’s disease.

Association of COMT G675A and MTHFR C677T polymorphisms with hypertensive disorders of pregnancy in Mexican mestizo population

OBJECTIVE To investigate the relationship between COMT G675A and MTHFR C677T polymorphisms and hypertension disorders of pregnancy (HDP) in a Mexican mestizo population. DESIGN AND METHODS This case-control study involved 194 HDP and 194 normoevolutive pregnant women. The polymorphisms were genotyped by real time PCR. RESULTS Our results showed that the COMT AA genotype increases the risk to HDP (OR: 2.67; 95% CI 1.33-5.35), preeclampsia (OR: 2.69; 95% CI 1.00-7.22) and gestational hypertension (OR: 3.87; 95% CI 1.25-12.0). Furthermore, the double mutant genotype (COMTAA/MTHFRTT) potency the risk to HDP more than two times (OR: 5.21; 95% CI 1.12-24.3, p=0.019). CONCLUSION Our work provides evidence that COMT 675AA genotype is a risk factor for HDP and that this risk is increased by the presence of MTHFR 677TT genotype in a Mexican mestizo population.

Auditory- and Vestibular-Evoked Potentials Correlate with Motor and Non-Motor Features of Parkinson’s Disease

Degeneration of several brainstem nuclei has been long related to motor and non-motor symptoms (NMSs) of Parkinson’s disease (PD). Nevertheless, due to technical issues, there are only a few studies that correlate that association. Brainstem auditory-evoked potential (BAEP) and vestibular-evoked myogenic potential (VEMP) responses represent a valuable tool for brainstem assessment. Here, we investigated the abnormalities of BAEPs, ocular VEMPs (oVEMPs), and cervical VEMPs (cVEMPs) in patients with PD and its correlation to the motor and NMSs. Fifteen patients diagnosed as idiopathic PD were evaluated by Unified Parkinson’s Disease Rating Scale and its subscores, Hoehn and Yahr scale, Schwab and England scale, and Non-Motor Symptoms Scale. PD patients underwent pure-tone, speech audiometry, tympanometry, BAEP, oVEMPs, and cVEMPs, and compared to 15 age-matched control subjects. PD subjects showed abnormal BAEP wave morphology, prolonged absolute latencies of wave V and I–V interpeak latencies. Absent responses were the marked abnormality seen in oVEMP. Prolonged latencies with reduced amplitudes were seen in cVEMP responses. Rigidity and bradykinesia were correlated to the BAEP and cVEMP responses contralateral to the clinically more affected side. Contralateral and ipsilateral cVEMPs were significantly correlated to sleep (p = 0.03 and 0.001), perception (p = 0.03), memory/cognition (p = 0.025), and urinary scores (p = 0.03). The oVEMP responses showed significant correlations to cardiovascular (p = 0.01) and sexual dysfunctions (p = 0.013). PD is associated with BAEP and VEMP abnormalities that are correlated to the motor and some non-motor clinical characteristics. These abnormalities could be considered as potential electrophysiological biomarkers for brainstem dysfunction and its associated motor and non-motor features.

Implications of DNA Methylation in Parkinson’s Disease

It has been 200 years since Parkinson’s disease (PD) was first described, yet many aspects of its etiopathogenesis remain unclear. PD is a progressive and complex neurodegenerative disorder caused by genetic and environmental factors including aging, nutrition, pesticides and exposure to heavy metals. DNA methylation may be altered in response to some of these factors; therefore, it is proposed that epigenetic mechanisms, particularly DNA methylation, can have a fundamental role in gene–environment interactions that are related with PD. Epigenetic changes in PD-associated genes are now widely studied in different populations, to discover the mechanisms that contribute to disease development and identify novel biomarkers for early diagnosis and future pharmacological treatment. While initial studies sought to find associations between promoter DNA methylation and the regulation of associated genes in PD brain tissue, more recent studies have described concordant DNA methylation patterns between blood and brain tissue DNA. These data justify the use of peripheral blood samples instead of brain tissue for epigenetic studies. Here, we summarize the current data about DNA methylation changes in PD and discuss the potential of DNA methylation as a potential biomarker for PD. Additionally, we discuss environmental and nutritional factors that have been implicated in DNA methylation. Although the search for significant DNA methylation changes and gene expression analyses of PD-associated genes have yielded inconsistent and contradictory results, epigenetic modifications remain under investigation for their potential to reveal the link between environmental risk factors and the development of PD.

The yearly rate of Relative Thalamic Atrophy (yrRTA): a simple 2D/3D method for estimating deep gray matter atrophy in Multiple Sclerosis

Despite a strong correlation to outcome, the measurement of gray matter (GM) atrophy is not being used in daily clinical practice as a prognostic factor and monitor the effect of treatments in Multiple Sclerosis (MS). This is mainly because the volumetric methods available to date are sophisticated and difficult to implement for routine use in most hospitals. In addition, the meanings of raw results from volumetric studies on regions of interest are not always easy to understand. Thus, there is a huge need of a methodology suitable to be applied in daily clinical practice in order to estimate GM atrophy in a convenient and comprehensive way. Given the thalamus is the brain structure found to be more consistently implied in MS both in terms of extent of atrophy and in terms of prognostic value, we propose a solution based in this structure. In particular, we propose to compare the extent of thalamus atrophy with the extent of unspecific, global brain atrophy, represented by ventricular enlargement. We name this ratio the “yearly rate of Relative Thalamic Atrophy” (yrRTA). In this report we aim to describe the concept of yrRTA and the guidelines for computing it under 2D and 3D approaches and explain the rationale behind this method. We have also conducted a very short crossectional retrospective study to proof the concept of yrRTA. However, we do not seek to describe here the validity of this parameter since these researches are being conducted currently and results will be addressed in future publications.