Agustín Oterino

Cough, exertional, and sexual headaches An analysis of 72 benign and symptomatic cases

We analyzed our experience with cough, exertional, and vascular sexual headaches, evaluated the interrelationships among them, and examined the possible symptomatic cases.Seventy-two patients consulted us because of headaches precipitated by coughing (n = 30), physical exercise (n = 28), or sexual excitement (n = 14). Thirty (42%) were symptomatic. The 17 cases of symptomatic cough headache were secondary to Chiari type I malformation, while the majority of cases of symptomatic exertional headaches and the only case of symptomatic sexual headache were secondary to subarachnoid hemorrhage. Although the precipitant was the same, benign and symptomatic headaches differed in several clinical aspects, such as age at onset, associated clinical manifestations, or response to pharmacologic treatment. Although sharing some properties, such as male predominance, benign cough headache and benign exertional headache are clinically separate conditions. Benign cough headache began significantly later, 43 years on average, than benign exertional headache. By contrast, our findings suggest that there is a close relationship between benign exertional headache and benign vascular sexual headache. We conclude that benign and symptomatic cough headaches are different from both benign and symptomatic exertional and sexual headaches. NEUROLOGY 1996;46: 1520-1524

Headache in type I Chiari malformation

We analyzed the headaches in 50 patients with type I Chiari malformation. Of the 50, 14 (28%) had a rather specific, usually protracted, suboccipital-occipital headache of variable quality and duration that was aggravated by Valsalvas maneuver, effort, cough, or postural changes and relieved by occipital-suboccipital craniectomy. Only the degree of tonsillar herniation significantly correlated with the presence of this pain. Both migraine and tension-type headache occurred with the expected frequency for the general population.

MTHFR T677 homozygosis influences the presence of aura in migraineurs.

It has been suggested that folate metabolism could be involved in migraine pathogenesis. We analysed the 5′, 10′ -methylenetetrahydrofolate reductase (MTHFR) genotypic distribution in a large migraine sample. We genotyped 230 migraine patients (152 migraine without aura (MO) and 78 migraine with aura (MA)) and 204 nonheadache controls. The incidence of TT homozygosis for migraine in general (12%), MO (9%) and MA (18%) did not significantly differ from that found in healthy controls (13%). Differences were significant when the frequency of TT homozygosis between MA and MO (P = 0.03, OR = 2.34, 95% CI = 1.04-5.26) was compared. There was a tendency for a higher frequency of the MTHFR T allele in the MA group (42%) as compared to MO (29%) and controls (36%). These differences were significant only in the case of MA vs. MO (P = 0.006, OR = 1.75, 95% CI = 1.15-2.65). These results could indicate that the MTHFR C677T polymorphism, causing mild hyperhomocystinaemia, might be a genetic risk factor for experiencing aura among migraineurs. Overall, however, there was no association between migraine and the C677T MTHFR polymorphism.

LRRK2 G2019S is a common mutation in Spanish patients with late-onset Parkinson's disease

Mutations in the leucine-rich repat kinase 2 (LRRK2) gene have been shown to cause both autosomal dominant and sporadic Parkinsons disease (PD). The common G2019S mutation shows wide geographical distribution while R1441G has been only reported in Northern Spain. The overall frequency of these mutations remains to be established. To determine the prevalence of G2019S and R1441G mutations in our population of Cantabria (Northern Spain), we recruited 105 consecutive PD patients and 310 controls and conducted genetic analysis of these mutations. G2019S was detected in eight late-onset patients (7.6%). Five of them had no relevant family history. R1441G was not detected in any of our study subjects. The prevalence of G2019S mutation in unselected late-onset PD patients might be higher than previously reported: 3/16 (18.7%) of familial PD and 5/82 (6.1%) of sporadic PD.

Genetic factors associated with drug-resistance of epilepsy: Relevance of stratification by patient age and aetiology of epilepsy

Epilepsy drug-resistance may depend on the metabolism of antiepileptic drugs (AEDs), transport to the epileptic focus and/or target sensitivity. Furthermore, drug response depends on multiple characteristics of the patient, the epilepsy, and the antiepileptic drugs used. We have investigated the association between polymorphisms related to antiepileptic drug metabolism (CYP2C9, CYP2C19, and UGT), transport (ABCB1), and targets (SCN1A) both in a crude analysis and after adjusting by clinical factors associated with drug-resistance, and stratifying by patient age or aetiology of epilepsy. Caucasian outpatients (N=289), children (N=80) and adolescent-adults (N=209), with idiopathic (N=69), cryptogenic (N=97) or symptomatic epilepsies (N=123) were selected when they had either drug-resistance (with at least four seizures over the previous year after treatment with more than three appropriate AEDs at appropriate doses) or drug responsiveness (without seizures for at least a year). Samples were genotyped by allelic discrimination using TaqMan probes. No significant association between polymorphisms and drug-resistance was found either in the crude analysis or in the adjusted analysis. However, adults with the ABCB1_3435TT or 2677TT genotypes had a lower risk of drug-resistance than those with the CC or the GG genotypes. Furthermore, patients with symptomatic epilepsies with the ABCB1_3435CT or TT genotypes had a lower risk of drug-resistance than those with the CC genotype. An opposite but insignificant tendency was found in children and in idiopathic epilepsies. Although replication studies will be needed to confirm our results, they suggest that stratification by patient age and by the aetiology of epilepsy could contribute to unmask the association between ABCB1 polymorphisms and drug-resistance of epilepsy.

UGT2B7_-161C>T polymorphism is associated with lamotrigine concentration-to-dose ratio in a multivariate study.

Lamotrigine (LTG) is metabolized by UGT1A4 but UGT2B7 also contributes to its glucuronidation. The aim of this study was to determine whether UGT2B7_− 161C>T and UGT2B7_372A>G polymorphisms contribute to the intersubject variability in LTG concentration-to-dose ratio (LTG-CDR) in epileptic patients. Fifty-three white epileptic patients attending the Neuropediatric and Neurology Services at the Marqués de Valdecilla University Hospital, in whom LTG serum concentration was to be measured for pharmacokinetic monitoring, were selected according to predefined criteria for LTG-CDR evaluation. All patients had at least one steady-state LTG serum concentration obtained before the first dose in the morning. Patients were classified in 3 groups of comedication: (1) LTG in combination with metabolism-inducer anticonvulsants (n = 22), (2) LTG in combination with valproate (n = 13), and (3) LTG as monotherapy (n = 16) or in combination with valproate and inducers (n = 2). Genotypes were determined by Applied Biosystems Genotyping Assays with TaqMan probes. A significant association was found between LTG-CDR and UGT2B7_−161C>T polymorphism (P = 0.021) when patient age and concomitant antiepileptic drugs were taken into account. Comedication explained 70% of the LTG-CDR variability, patient age 24%, and UGT2B7_−161C>T 12%. In contrast, a significant association between LTG-CDR and this polymorphism was not found in the bivariate study when age and comedication groups were not considered. A significant association between UGT2B7_372A>G and LTG-CDR was not found in the bivariate or the multivariate studies. UGT2B7_−161C>T polymorphism is significantly associated with LTG-CDR when comedication with other antiepileptic drugs and patient age are taken into account in a multivariate analysis.

Multilocus analyses reveal involvement of the ESR1, ESR2, and FSHR genes in migraine.

Objective.— Female hormone genes have been investigated in migraine in recent years. Research in this field has been controversial, especially in regard to ESR1 gene findings. None of the reports have yet to approach the problem from a multigenic point of view.

The Relationship Between Homocysteine and Genes of Folate-Related Enzymes in Migraine Patients

(Headache 2010;50:99‐168)

Poly (ADP-ribose) polymerase-1 (PARP-1) genetic variants are protective against Parkinson's disease

Poly (ADP-ribose) polymerase-1 (PARP-1) is involved in crucial pathogenic events in Parkinsons disease (PD). We studied the effect of promoter variations of PARP-1 gene on the risk for PD in a case-control association study comprising 146 PD patients and 161 controls from Northern Spain. Three polymorphisms from the promoter region of PARP-1 gene were analyzed: -410C/T, -1672G/A, and a (CA)n microsatellite. A protective effect against PD was found for heterozygosity at (-410) (OR 0.44) and (CA)n microsatellite (OR 0.53) polymorphisms, and heterozygosity at (-1672) polymorphism delayed by 4 years on the onset age of PD. Variations in the regulatory region of PARP-1 gene might modify the risk for PD.

Lack of Association of Endothelial Nitric Oxide Synthase Polymorphisms and Migraine

Objective.— The aim of this study was to evaluate if 2 functional endothelial nitric oxide synthase (eNOS) gene polymorphisms might be risk factors for migraine.