Francisco Navacerrada

Influence of age and gender in motor performance in healthy subjects

BACKGROUND/OBJECTIVES Slowing of motor performance in human aging is a well demonstrated clinical observation. Information on the influence of gender in motor performance is less well-established. With the aim of analyzing the possible influence of age and gender in motor performance, we studied basic motor function in a large series of healthy sex-matched individuals aged >40 years. METHODS We studied 246 subjects (123 males and 123 females; mean age 63.67 ± 10.79 and 63.61 ± 11.04 years, respectively), stratified by age in 7 groups for each gender. Evaluation included four timed tests (pronation-supination, finger tapping and movement between two points, all with both hands, and walking test), and the three tests performed on a personal computer (speed for pressing repetitively a key - frequency, visual reaction time and movement time, all with both hands). Statistical analysis included two-way analysis of variance (ANOVA) for two factors (age and gender) and Pearsons or Spearmans correlation tests where appropriate. RESULTS The analysis of motor performance between subgroups showed a clear influence of age on motor performance of all the tests, with the exception of the left visual reaction time. The results of all the motor tests performed were inversely correlated with age. Gender influenced the performance (the speed of motor performance was significantly better in males) of all the tasks with the exception of left pronation-supination, and left and right visual reaction time. CONCLUSION Our results confirm in a large series of healthy subjects that basic motor performance deteriorates with age and is influenced by gender.

Diamine Oxidase rs10156191 and rs2052129 Variants Are Associated With the Risk for Migraine

Histamine has been implicated in the pathogenesis of migraine. We investigated the possible association between functional single nucleotide polymorphisms (SNPs) in the diamine oxidase gene (DAO; chromosome 7q36.1, involved in histamine metabolism) and the risk for migraine.

Alcohol dehydrogenase 2 genotype and risk for migraine.

(Headache 2010;50:85‐91)

Histamine‐N‐Methyl Transferase Polymorphism and Risk for Migraine

Background/Objectives.— Histamine has been implicated in the pathogenesis of migraine. In the CNS, histamine is almost exclusively metabolized by the polymorphic enzyme histamine N‐methyltransferase (HNMT). The HNMT gene (chromosome 2q22.1), shows diverse single nucleotide polymorphisms. One of these, located in exon 4 C314T, causes the amino acid substitution Thr105Ile, related to decreased enzyme activity. The aim of this study was to investigate the possible association between HNMT polymorphism and the risk for migraine.

Heme Oxygenase-1 and 2 Common Genetic Variants and Risk for Restless Legs Syndrome.

AbstractSeveral neurochemical, neuropathological, neuroimaging, and experimental data, suggest that iron deficiency plays an important role in the pathophysiology of restless legs syndrome (RLS). Heme-oxygenases (HMOX) are an important defensive mechanism against oxidative stress, mainly through the degradation of heme to biliverdin, free iron, and carbon monoxide. We analyzed whether HMOX1 and HMOX2 genes are related with the risk to develop RLS.We analyzed the distribution of genotypes and allelic frequencies of the HMOX1 rs2071746, HMOX1 rs2071747, HMOX2 rs2270363, and HMOX2 rs1051308 SNPs, as well as the presence of Copy number variations (CNVs) of these genes in 205 subjects RLS and 445 healthy controls.The frequencies of rs2071746TT genotype and rs2071746T allelic variant were significantly lower in RLS patients than that in controls, although the other 3 studied SNPs did not differ between RLS patients and controls. None of the studied polymorphisms influenced the disease onset, severity of RLS, family history of RLS, serum ferritin levels, or response to dopaminergic agonist, clonazepam or GABAergic drugs.The present study suggests a weak association between HMOX1 rs2071746 polymorphism and the risk to develop RLS in the Spanish population.

Dopamine receptor D3 (DRD3) gene rs6280 variant and risk for restless legs syndrome

To the Editor Ondine’s curse is a failure of autonomic respiration when asleep, despite normal respiration while awake. It is reported in pathologic conditions which involve the brainstem or spinal cord. [1] Though diverse pathologies are known to cause this rare phenomenon, [2] there has been no reported case of paraneoplastic brainstem syndrome which manifested Ondine’s curse. A 54 year old woman with recurrent breast cancer insidiously developed stiffness of the trunk and arms, and trismus. Voluntary horizontal gaze was impossible with impaired vestibule–ocular reflex, although vertical eyeball movement was intact. Her brain and cervical spine MRI were normal. Anti-Ri antibody was positive in the patient’s serum and Anti-GAD antibody was negative. She had recurrent episodes of O2 desaturation (down to 49 mmHg), CO2 retention (up to 144 mmHg), and poor response to stimulation while asleep. Her awake O2 and CO2 values were normal. She was incubated and had mechanical ventilation. Even after a tracheostomy, she could not be weaned off from the ventilator due to persistent nocturnal respiratory failure. She continued to show decreased ventilator activity with a decrease in rate (down to six/minute) and tidal volume (300 ml) during sleep resulting in O2 desaturation and CO2 retention. Spontaneous breathing while awake was normal in a rate of (16–20/min) and tidal volume (400 ml). She was discharged with bi-level positive airway pressure, support. The pathology is believed to be in the pons causing horizontal gaze palsy and trismus, and to have extended downward to the medulla causing Ondine’s curse. Respiratory failure is reported in paraneoplastic brainstem syndrome, but the causes included laryngospasm or increased respiratory muscle spasm [3]. To our knowledge, this is the first report of Ondine’s curse as a neurologic complication of paraneoplastic syndrome.

Paraoxonase 1 (PON1) polymorphisms and risk for migraine

The polymorphic enzyme human serum paraoxonase 1 (PON1), encoded by the gene PON1 (chromosome 7q21.3) plays a role as an antioxidant molecule through several mechanisms. Because oxidative stress has been implicated in the pathogenesis of migraine, we have investigated the possible association between the nonsynonymous polymorphisms 55LM and 192QR in the PON1 and the risk for migraine. We studied the frequency of the PON1 genotypes and allelic variants in 197 patients with migraine and 220 healthy controls using a TaqMan single nucleotide polymorphism analysis. The frequencies of the PON1 genotypes and PON1 allelic variants did not differ significantly between patients with migraine and controls, and were unrelated with gender, family history of migraine, and presence or absence of aura. The frequencies of the genotype PON1 192QQ and the allelic variant PON1 192Q were significantly higher in patients with earlier onset of migraine. The results of the present study suggest that PON1 polymorphisms are not related with the risk for migraine in Caucasian Spanish people, although PON1 192Q/Q genotype and PON1 192Q allelic variant should be related with an earlier onset of migraine.

MAPT1 gene rs1052553 variant is unrelated with the risk for restless legs syndrome.

Mutations in the microtubule-associated protein tau gene (MAPT) can cause frontotemporal dementia with Parkinsonism linked to the chromosome 17, and are associated with the risk for progressive supranuclear palsy, Parkinson’s disease, corticobasal degeneration, and multiple system atrophy. We tried to establish, whether MAPT H1 discriminating haplotype single nucleotide polymorphisms (SNP) (rs1052553) is associated with the risk for restless legs syndrome (RLS). We studied the allelic and genotype frequencies of the SNP rs1052553 in 205 patients with RLS and 324 healthy controls using TaqMan genotyping. rs1052553 genotype and allelic frequencies did not differ significantly between patients with RLS and controls, and were unrelated with the age at onset of RLS, gender, family history of RLS, and severity of RLS. The results of the present study suggest that the SNP rs1052553 is not related with the risk for RLS.

Dopamine receptor 3(DRD3) polymorphism and risk for migraine.

Background/objectives:  Dopamine has been implicated in the pathogenesis of migraine. We investigated the possible association between the polymorphism 312G>A (rs6280) in the DRD3 gene(essential tremor 1‐ETM1‐ locus, chromosome 3q13) and the risk for migraine and for triggering migraine attacks by alcohol.

Neuronal nitric oxide synthase (nNOS, NOS1) rs693534 and rs7977109 variants and risk for restless legs syndrome

Several biochemical, neuropathological, and experimental data suggest a possible role of nitric oxide (NO) in the pathophysiology of restless legs syndrome (RLS). Two single nucleotide polymorphisms (SNPs) neuronal nitric oxide synthase (nNOS or NOS1) gene (rs7977109 and rs693534) have been found to be associated with the risk for RLS in Germans, although only one of them (rs7977109) remained as significant after multiple comparison tests. The aim of our study was to replicate the possible association between these SNPs and risk for RLS in the Spanish population. We studied the allelic and genotype frequencies of the SNPs rs7977109 and rs693534 in 205 patients with RLS and 328 healthy controls using TaqMan genotyping. The rs7977109 and rs693534 genotypes and allelic frequencies did not significantly differ between patients with RLS and controls and were unrelated with the age at onset of RLS, gender, ferritin levels, and response to dopaminergic or gabaergic agents. The rs7999109GA genotype was overrepresented in RLS patients with positive family history of RLS, and in patients with symptomatic response to clonazepam. The results of our study suggest that these two NOS1 SNPs are not related to the overall risk for RLS in the Spanish population.