Lluisa Rubio

Impairment of rapid repetitive finger movements and visual reaction time in patients with essential tremor

Background and purpose:  The question whether patients with essential tremor (ET) have slowed movements as part of their clinical manifestations is still a matter of controversy. We analyzed basic motor function in patients with ET and in healthy matched controls.

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.

Most of the Quality of Life in Essential Tremor Questionnaire (QUEST) psychometric properties resulted in satisfactory values

OBJECTIVE This study sought to assess the psychometric attributes of the Quality of Life in Essential Tremor Questionnaire (QUEST) by undertaking an independent validation. STUDY DESIGN AND SETTING This was an observational, multicenter, cross-sectional study carried out in Neurology Departments of general hospitals. The following assessments were applied: Louis Rating Scale, Clinical Assessment of Tremor, Clinical Global Impression of Severity (CGI-ET), Hospital Anxiety and Depression Scale (HADS), EQ-5D, and QUEST (Spanish version). RESULTS One hundred and eighteen consecutive patients were included. According to the CGI-ET, most of patients had mild (42.4%) or moderate (43.2%) impact of tremor on performing daily activities. Fully computable QUEST data were 60.2%. The QUEST Summary Index (QUEST-SI) displayed marginal floor or ceiling effect. On the whole, QUEST internal consistency and reproducibility were satisfactory (Cronbachs alpha values: 0.73-0.86; QUEST-SI intraclass correlation coefficient: 0.77). Factor analysis identified eight factors (73.6% of the variance) that could be grouped into six, relatively coincident with the questionnaires dimensions. The QUEST-SI correlated moderately with the EQ-5D index (r(S)=-0.40), HADS-Depression (r(S)=0.39), and CGI-ET (r(S)=0.39), and strongly with the QUEST scale for self-evaluation of tremor severity (r(S)=0.63). The standard error of measurement was 8.00. CONCLUSION Apart from a substantial problem of acceptability, most of the tested psychometric attributes of the QUEST resulted satisfactory.

Gamma-aminobutyric acid (GABA) receptor rho (GABRR) polymorphisms and risk for essential tremor

Some clinical and experimental data suggest a possible role of gamma-aminobutyrate (GABA)-ergic mechanisms in the pathophysiology of essential tremor (ET), such as the improvement of ET with some GABAergic drugs and the development of an experimental model of ET in GABA A receptor alpha-1 knockout mice (postural and kinetic tremor and motor incoordination similar to human ET). To investigate the possible association between the GABA receptor subtype rho1, rho2, and rho3 (GABRR1, GABRR2, and GABRR3) genotypes and allelic variants of the single nucleotide polymorphisms GABRR1-M26V (Met26Val, rs12200969), GABRR1-H27R (His26Arg, rs1186902), GABRR2-T455M (Thr55Met, rs282129), and GABRR3-Y205X (Tyr205X, rs832032), and the risk for ET, we studied the frequency of the previously mentioned GABRR genotypes and allelic variants in 200 patients with ET and 250 healthy controls using TaqMan genotyping. The frequencies of the GABBR1 genotypes and allelic variants of the studied polymorphisms did not differ significantly between patients with ET and controls, and were unrelated with the age at onset of tremor, gender, localization of tremor, and response of tremor to ethanol. These data suggest that the single nucleotide polymorphisms studied in the GABBR genes are not related to the risk for ET.

Gamma-aminobutyric acid GABRA4, GABRE, and GABRQ receptor polymorphisms and risk for essential tremor.

Some clinical and experimental data suggest a possible role of &ggr;-aminobutyrate (GABA)-ergic mechanisms in the pathophysiology of essential tremor (ET). We studied the allelic and genotype frequencies of the single nucleotide polymorphisms, such as GABRA4-L26M (Leu26Met, rs2229940), GABRE-S102A (Ser26Ala, rs1139916), and GABRQ-I478F (Ile26Phe, rs3810651), in 200 patients with familial ET and 250 healthy controls using TaqMan genotyping. GABRA4-L26M, GABRE-S102A, and GABRQ-I478F genotype and allelic frequencies did not differ significantly between patients with ET and controls, and were unrelated to the age at onset of tremor or sex. The GABRQ-478F allele seemed to be related to improvement of tremor with ethanol use among men (odds ratio=2.32, 95% confidence interval=0.26–4.3, P=0.007, Pc=0.021). The results of this study suggest that the single nucleotide polymorphisms studied in the GABRA4, GABRE, and GABRQ genes are not related to the risk for familial ET.

Refractory hiccup: successful treatment with gabapentin.

Objective: To report a patient with intractable hiccup which improved with gabapentin. Case Report: A 69-year-old woman diagnosed with refractory hiccup that started 50 years before improved dramatically after a trial of gabapentin for essential tremor. Gabapentin withdrawal led to reappearance of hiccup, which improved again after its reintroduction. Conclusions: Gabapentin should be considered as a possible therapy for refractory hiccup.

Dopamine receptor D3 (DRD3) genotype and allelic variants and risk for essential tremor

To investigate the possible association between dopamine receptor D3 genotype (DRD3) and allelic variants and the risk for developing essential tremor (ET). Leukocytary DNA from 201 patients with ET and 282 healthy controls was studied for the genotype DRD3 and the occurrence of DRD3 allelic variants by using allele‐specific PCR amplification and MslI‐RFLPs analyses. A meta‐analysis of previous studies was performed. The frequencies of the DRD3Ser/Gly genotype and of the allelic variant DRDGly were significantly higher in patients with ET than in controls (P < 0.017 and <0.005, respectively), These findings were especially relevant in women (OR = 1.73, 95% CI: 1.15–2.59, P = 0.008), and in patients with earlier onset of the disease with (P = 0.014). The frequencies of the DRD3Ser/Gly and DRD3Gly/Gly genotypes and of the allelic variant DRD3Gly in patients were significantly higher in patients with voice tremor, but not with head, tongue, or chin tremor, than in controls. The meta‐analysis indicated association of variant genotypes with ET risk (OR = 1.18, 95% CI 1.01–1.38). These results suggest that DRD3 genotype and the variant DRD3Gly allelic variant is associated with the risk for and age at onset of ET, and with the risk for voice tremor, in Caucasian Spanish people.

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.

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.