Lucía Ayuso-Peralta

Symptomatic orthostatic tremor in pontine lesions

Orthostatic tremor (OT) is a rare movement disorder that consists of involuntary shaking of the legs and trunk present only on standing. Although the origin and the mechanism of this condition are not well understood, the neurophysiologic abnormalities and PET studies suggest a central origin. We describe the clinical and radiologic features of two patients with symptomatic OT and associated pontine lesions, and conclude that OT may arise from dysfunction of the cerebellum or related pontine structures.

Environmental risk factors for essential tremor.

We conducted a case-control study searching for a possible role of environment in the risk of essential tremor (ET). We interviewed 142 ET patients and 284 age- and sex-matched controls about a family history of ET, exposure to environmental products containing lead, mercury, manganese, solvents and β-carbolines, and exposure to agricultural work, well water, pesticides, and cigarette smoking and alcohol drinking habits. In a univariate study, reported family history of ET and exposure to agricultural work, pesticides, smelting, frosted glass, paintings, wheat, corn, and barley were more frequent in the ET patient group. With a multivariate study, only reported family history of ET and exposure to agricultural work and frosted glass remained significant. Time of exposure to agricultural work, wheat and barley was significantly higher in ET patients. Age at onset of ET was significantly lower in patients with a family history of tremor and higher in patients exposed to iron-manganese alloys and alcohol. Time of exposure, but not total consumption of alcohol and cigarettes, was correlated with age at onset of ET. In conclusion, our study shows that the association between ET and reported family history of ET was robust, and that there were also associations between ET and exposure to some environmental factors (agricultural work and frosted glass).

Vitamin D3 Receptor (VDR) Gene rs2228570 (Fok1) and rs731236 (Taq1) Variants Are Not Associated with the Risk for Multiple Sclerosis: Results of a New Study and a Meta-Analysis

Background Some epidemiological, genetic, and experimental data suggest a possible role of vitamin D in the pathogenesis of multiple sclerosis (MS) and in experimental autoimmune encephalomyelitis. Data on the possible contribution of several single nucleotide polymorphisms (SNP) in the vitamin D receptor (VDR) gene to the risk for MS are controversial. Several studies suggested an interaction between some SNPs in the VDR gene and HLADRB1*1501 in the risk for MS. Objectives The aim of this study was to investigate a possible influence of the SNPs rs2228570 and rs731236 in the VDR gene in the risk for MS. A secondary objective was to address the possible interactions between VDR genes and HLADRB1*1501. Methods We analyzed the allelic and genotype frequency of VDR rs2228570, rs731236, and HLADRB1*1501 (rs3135388) in 303 patients with MS and 310 healthy controls, using TaqMan Assays. We also conducted a meta-analysis, that was carried out by using the software Meta-Disc 1.1.1 (http://www.hrc.es/investigacion/metadisc.html; Unit of Clinical Statistics, Hospital Ramón y Cajal, Madrid, Spain). Heterogeneity between studies in terms of degree of association was tested using the Q-statistic. Results VDR rs2228570 and rs731236 allelic and genotype frequencies did not differ significantly between MS patients and controls, and were unrelated with the age of onset of MS, gender, and course of MS. HLADRB1*1501 showed a high association with the risk of developing MS 4.76(95% C.I.  = 3.14–7.27; p<0.0001). The meta-analysis, after excluding data of one study that was responsible of heterogeneity for rs731236 polymorphism, showed lack of relation of both SNPs with the risk for MS. HLADRB1*1501 showed lack of interaction with VDR rs2228570 and rs731236 in increasing MS risk. Conclusions These results suggest that VDR rs2228570 and rs731236 polymorphisms are not related with the risk for MS, and did not confirm interaction between these VDR SNPs and HLADRB1 in the risk for MS.

Drug-induced parkinsonism in a movement disorders unit: A four-year survey

UNLABELLED To establish the frequency of drug-induced parkinsonism (DIP) and the drugs responsible for this side-effect we reviewed the database of our Movement Disorders Unit during the first 4 years of its use. The diagnostic criteria for DIP included: (1) the presence of two or more cardinal symptoms of parkinsonism, (2) an absence of parkinsonian symptoms before the exposure to the offending drug, (3) a disappearance or significant improvement in parkinsonism after withdrawal of the offending drug, (4) no better explanation for the parkinsonism. One-hundred and five patients fulfilled the diagnostic criteria for DIP (16.3% of total patients referred and 33.8% of patients with parkinsonian syndromes). Drug-induced parkinsonism was related to 1, 2, 3, 4, 5 and 7 drugs in 62, 30, 9, 1, 2 and 1 patients, respectively. The most frequently offending drugs were: calcium-channel blockers (61 cases), antipsychotic drugs (29 cases), thiethylperazine (18 cases), clebopride (14 cases), and sulpiride (10 cases). When compared with idiopathic Parkinsons disease patients, DIP patients were predominantly female and showed an older age at the onset of parkinsonian signs. Parkinsonian signs only disappeared completely in 41 patients (39.0%). IN CONCLUSION (1) DIP was a frequent cause of parkinsonism in our Movement Disorder Unit, (2) calcium-channel blockers, and/or orthopramides and substituted benzamides were a frequent cause of DIP in our series, (3) old age and the female gender were frequent among DIP patients, (4) DIP is not always reversible.

Parkinsonism unmasked by verapamil.

We report the case of a 55-year-old man who had a parkinsonian syndrome unresponsive to levodopa for 5 years and had been taking verapamil during the past 8 years. Parkinsonian signs improved markedly after withdrawal of verapamil, suggesting its role in unmasking the parkinsonism. To our knowledge, this side effect of verapamil has not been described previously.

Peripheral iron metabolism in patients with Parkinson's disease

To elucidate the possible role of peripheral metabolism of iron in the risk for developing Parkinsons disease (PD), we compared serum levels of iron, transferrin and ferritin, and 24-h iron excretion in urine after a single intramuscular dose of 1 mg/kg desferrioxamine, in 68 PD patients and their spouses as the control group. All these values did not differ significantly between the groups, they were not influenced by antiparkinsonian therapy, and they did not correlate with age, age at onset and duration of the disease, scores of the Unified PD Rating Scale or the Hoehn and Yahr staging in the PD group, with the exception of the 24-h urinary iron excretion with the duration of the disease (r = 0.32, p < 0.05). These results suggest that peripheral metabolism of iron is apparently unrelated to the risk of developing PD.

Orthostatic Tremor: Successful Treatment With Phenobarbital

This article describes two patients with orthostatic tremor. The tremor affected the legs while standing and had a frequency of 14-16 Hz. We remark on the success of therapy with phenobarbital.

Functional assessment of the visual pathway with multifocal visual evoked potentials, and their relationship with disability in patients with multiple sclerosis.

Objective: To objectively evaluate the visual function, and the relationship between disability and optic nerve dysfunction, in patients with multiple sclerosis (MS) and optic neuritis (ON), using multifocal visual evoked potentials (mfVEP). Methods: This observational, cross-sectional study assessed 28 consecutive patients with clinically definite MS, according to the McDonald criteria, and 19 age-matched healthy subjects. Disability was recorded using the Expanded Disability Status Scale (EDSS) score. The patients’ mfVEP were compared to their clinical, psychophysical (Humphrey perimetry) and structural (optic coherence tomography (OCT)) diagnostic test data. Results: We observed a significant agreement between mfVEP amplitude and Humphrey perimetry/OCT in MS-ON eyes, and between mfVEP amplitude and OCT in MS but non-ON eyes. We found significant differences in EDSS score between patients with abnormal and normal mfVEP amplitudes. Abnormal mfVEP amplitude defects (from interocular and monocular probability analysis) were found in 67.9% and 73.7% of the MS-ON and MS-non-ON group eyes, respectively. Delayed mfVEP latencies (interocular and monocular probability analysis) were seen in 70.3% and 73.7% of the MS-ON and MS-non-ON groups, respectively. Conclusions: We found a significant relationship between mfVEP amplitude and disease severity, as measured by EDSS score, that suggested there is a role for mfVEP amplitude as a functional biomarker of axonal loss in MS.

Evaluation of visual structural and functional factors that predict the development of multiple sclerosis in clinically isolated syndrome patients.

PURPOSE To evaluate visual pathway structure and function in patients with clinical isolated syndrome (CIS) by using spectral-domain optical coherence tomography (OCT) and multifocal visual-evoked potentials (mfVEP), predicting CIS conversion to clinically definite multiple sclerosis (MS). METHODS This observational, longitudinal study assessed the eyes with no previous history of optic neuritis of 29 consecutive patients with CIS according to the McDonald criteria. The relationships of the mfVEP results with the clinical findings, and psychophysical (Humphrey perimetry) and structural (OCT) diagnostic test data were investigated. RESULTS The mfVEP amplitude responses (interocular and monocular probability analysis) showed abnormal cluster visual field defects in 48.3% of the CIS eyes, whereas mfVEP latency analysis showed significant delays in 20.7%. The OCT average retinal nerve fiber layer thickness (RNFLT) was significantly reduced compared with the control group (P = 0.02). Significant differences between CIS eyes with abnormal and normal mfVEP latencies were found for the OCT RNFLT (P < 0.001) with a longer latency being linked to more severe axonal damage. Using multivariate logistic regression analysis, OCT average RNFLT was found to be an independent predictor of clinically definitive MS diagnosis at 12 months. CONCLUSIONS The combined use of OCT and mfVEP is helpful to detect significant subclinical visual pathway abnormalities and axonal loss in CIS patients. Retinal axonal loss measured by OCT is an important prognostic factor of conversion to MS in patients with CIS in absence of symptomatic optic neuritis.

Plasma levels of nitrates in patients with Parkinson's disease

It has been suggested that nitric oxide (NO) could be implicated in the neuronal degeneration of substantia nigra compacta in patients with Parkinsons disease (PD). To ascertain the possible role of NO as risk factor for PD, we studied the plasma levels of nitrate (oxidation product that provides an indirect estimation of NO), in 68 PD patients and 68 matched-controls. The plasma levels of nitrate did not differ significantly between PD patient and control groups (44.5 +/- 2.46 and 44.8 +/- 2.67 mumol/l, respectively). They were not influenced by antiparkinsonian drug and they did not correlate with age at onset, duration, scores of the Unified Parkinsons Disease Rating scales and Hoehn and Yahr staging in the PD group. These data suggest that plasma levels of nitrate are apparently unrelated to the risk for PD.