Association of RAMP1†rs7590387 with the risk of migraine transformation into medication overuse headache.

OBJECTIVES/BACKGROUND: We herein investigated the role of polymorphisms in calcitonin gene-related peptide (CGRP)-related genes looking at the association of rs3781719 (T > C) in the calcitonin gene-related polypeptide-alpha (CALCA) gene and of rs3754701 (T > A) and rs7590387 (C > G) at the receptor activity modifying 1 (RAMP1) locus with triptan response in patients with migraine without aura (MwoA). In addition, their role was evaluated as risk factors for transformation of episodic migraine into medication overuse headache (MOH). The CGRP has a central role in the pathogenesis of migraine; however, little information is currently available concerning the role of polymorphisms in CGRP-related genes as determinants of clinical response to anti-migraine drugs or as risk factors for migraine chronification. METHODS: Genotyping was conducted retrospectively by real-time polymerase chain reaction allelic discrimination assay in 219 patients with MwoA and 130 with MOH in whom migraine was the primary headache type. Gene variants association was evaluated by logistic regression analysis adjusted by confounding factors. The threshold of statistical significance was set according to the total number of polymorphisms analyzed in the current study and in previous publications arising from overlapping datasets. RESULTS: No evidence of association was found between the three polymorphisms tested and triptan response in MwoA patients. Conversely, carriers of RAMP1 rs7590387GG displayed a lower risk of episodic migraine transformation into MOH (vs C allele carriers, odds ratio [OR]: 0.27, 95% confidence interval [CI]: 0.13-0.57, P = 0.0002; threshold of significance set at P < 0.0029). When genotype distribution for RAMP1 rs7590387 was compared between healthy controls (n = 209) and MOH patients, carriers of rs7590387GG were found at lower risk of developing MOH (OR: 0.43, 95%CI: 0.22-0.85, P = 0.011). CONCLUSION: These results suggest that RAMP1 rs7590387 may have a role in the transformation of episodic migraine into MOH.

Lack of association between GRIA1 polymorphisms and haplotypes with migraine without aura or response to triptans.

The present study was designed to replicate previous findings reporting a significant association between the rs548294 polymorphism at the glutamate receptor subunit GluR1 gene (GRIA1) and migraine without aura, either as a single marker or in haplotype combination with rs2195450. In addition, the role of GRIA1 polymorphisms and haplotypes was evaluated in migraine patients without aura as predictive factors for consistency in headache response to triptans. Analysis of rs548294 and rs2195450 polymorphisms of GRIA1 was conducted by Real-time PCR allelic discrimination assay in 186 migraine patients without aura and 312 healthy controls, respectively. In the logistic regression analysis adjusted for gender and age, genotype and haplotype frequencies for the two polymorphisms did not significantly differ between migraine patients without aura and controls. In addition, no evidence of association was found between GRIA1 polymorphisms/haplotypes and consistent response to triptans. This study failed to replicate previously reported association between GRIA1 rs548294 and migraine without aura, either as single marker or when analyzed in haplotype combination with rs2195450. In addition, no evidence was found for a relevant role of GRIA1 polymorphisms and haplotypes as modulating factors of headache response to triptans.

Occipital Neuralgia in Chiari I Malformation: Two Different Events or Two Different Faces of the Same Event?

Occipital neuralgia (ON) is characterized by severe pain in the occipital region due to an irritation of the occipital nerves. Traumatic injuries, mass or vascular compression, and infective and inflammatory processes could cause ON. The dislocation of a nerve/muscle/tendon, as can happen in malformations such as the Chiari I malformation (CIM), also can be responsible. Usually, headaches associated with CIM and ON are distinguishable based on specific features of pain. However, the diagnosis is not easy in some cases, especially if a clear medical history cannot be accurately collected. Determining if the pain is related to ON rather than to CIM is important because the treatments may be different.

Impaired visual inhibition in migraine with aura.

OBJECTIVE: The pathophysiology of migraine with or without aura (MA, MO) is still a matter of debate. We thus studied patients with MA and MO by means of paired-pulse flash-visual evoked potentials (paired F-VEPs). This technique, recently revived, analyses the overall excitability of visual system as detected from the cortical occipital signal. METHODS: We enrolled 13 adult patients with MO and 13 with MA. Twenty-two normal subjects of similar age and sex acted as controls. Stimuli were single flashes, intermingled at random to flash pairs at critical interstimulus intervals (ISIs, 16.5-125ms) with closed and open eyes. The "single"(unconditioned) F-VEP was split into a "main complex" (50-200ms after the flash) and a "late response" (200-400ms). As for paired stimulation, the "test" F-VEP emerged from electronic subtraction of the "single" F-VEP to the "paired" F-VEP. Its size was expressed as "test"/"single"F-VEP∗100. RESULTS: As for paired F-VEPs, the "main complex" of the "test" F-VEP in the MA group did not show the size reduction (at ISIs 50-62.5ms) which was typical among the control and MO groups (p⩽0.016) in the "eyes-closed" state. CONCLUSIONS: Paired F-VEPs document a defective neural inhibition in the visual system of patients with MA. SIGNIFICANCE: Paired F-VEPs may warrant inclusion in future preclinical/clinical studies, to evaluate its potential role in the pathophysiology and management of MA.

An opposite-direction modulation of the COMT Val158Met polymorphism on the clinical response to intrathecal morphine and triptans.

UNLABELLED: Genetic variation in the COMT gene is thought to have clinical implications for pain perception and pain treatment. In the present study, we first evaluated the association between COMT rs4680 and the analgesic response to intrathecal morphine in patients with chronic low back pain to provide confirmation of previously reported positive findings. Next, we assessed the relationship between rs4680 and headache response to triptans in 2 independent cohorts of migraine patients. In patients with chronic low back pain (n = 74), logistic stepwise regression analysis showed that age (odds ratio [OR]: .90, 95% confidence interval [CI]: .85-.96, P = .002) and the presence of the COMT Met allele (vs Val/Val, OR: .21, 95% CI: .04-.98, P = .048) were predictive factors for lower risk of poor analgesic response to intrathecal morphine. Intriguingly, in migraine patients, the COMT rs4680 polymorphism influenced headache response to triptans in the opposite direction. Indeed, in an exploratory cohort of migraine patients without aura (n = 75), homozygous carriers of the COMT 158Met allele were found at increased risk to be poor responders to frovatriptan when compared to homozygous patients for the Val allele (OR: 5.20, 95% CI: 1.25-21.57, P = .023). In the validation cohort of migraine patients treated with triptans other than frovatriptan (n = 123), logistic stepwise regression analysis showed that use of prophylactic medications (OR: .43, 95% CI: .19-.99, P = .048) and COMT Met/Met genotype (vs Val/Val, OR: 4.29, 95% CI: 1.10-16.71, P = .036) were independent risk factors for poor response to triptans. PERSPECTIVE: This study highlights the importance of COMT rs4680 in influencing the clinical response to drugs used for chronic pain, including opioid analgesics and triptans. These findings also underline a complex relationship between COMT genotypes and pain responder status.

A case of cranial multinevritis: from the onset to the diagnosis of primary neurolymphomatosis.

Neurolymphomatosis (NL) is a rare peripheral or cranial neuropathy caused by non-Hodgkin's lymphoma (NHL). Diagnosis is often delayed and prognosis is poor. The authors described a woman in her 70s with a facial left peripheral palsy, complete right abducent palsy, left hypoacusia and balance deficit. Then she presented with low progressive hyposthenia at four limbs and cognitive impairment, sudden facial right peripheral palsy and complete left abducent palsy. The authors performed brain and spinal MRI, cerebrospinal fluid (CSF) analysis and extensive haematological examinations for infections, autoimmune and neoplastic diseases. All the results were not diagnostic. Only repeating for the third time a spinal tap, CSF presented neoplastic B cells suggestive for large B-NHL. The authors diagnosed primary NL. The patient was treated with R-CHOP but she died 2 months later. In front of rapidly progressive neuropathy, a NL has to be considered performing different examinations, especially and repeating them after a short period.

Posterior alien hand in a left-handed person.

Posterior alien hand syndrome usually involves the non-dominant hand with lesions usually in the right hemisphere. This is the first case in a left-handed person, involving the dominant hand.

The serotonin transporter gene polymorphism STin2 VNTR confers an increased risk of inconsistent response to triptans in migraine patients.

The aim of the present observational study was to assess the value of the C825T polymorphism of the beta-3 subunit of G proteins (GNB3) as well as of variants in the SLC6A4 gene (5HTTLPR and STin2 VNTR) and DRD2 gene (TaqI A and NcoI) as predictive markers for consistency in headache response to triptans in migraine patients. Consistent responders to triptans were defined as the migraineurs who experienced a > or =2 point reduction in a 4-point scale intensity of pain from 3 (severe) to 0 (absent) 2h after triptan administration, in at least two attacks out of the three. Genotyping was performed by PCR and PCR-RFLP on genomic DNA extracted from peripheral blood. The impact of clinical and biological variables on consistency status of headache response to triptans was evaluated by using a binary logistic regression model with stepwise selection. Forty-three (33%) of the 130 migraine patients included in the study did not consistently respond to triptan administration. In a binary logistic regression model, STin 2.12/12 genotype (OR=3.363, 95% CI: 1.262-8.966, P=0.005) and non-use of migraine prophylactic medications (OR=2.848, 95% CI: 1.019-7.959, P=0.010) were found as significant factors increasing the odds of achieving inconsistent response to triptans. The analysis of classificatory power of the model showed moderate values of sensitivity (0.56), high specificity (0.87), and an overall prediction correctness (0.77). These results support the role of STin2 VNTR polymorphism of serotonin transporter gene as a relevant genetic factor conferring a higher risk of inconsistent response to triptans in migraine patients.

Cluster-like headache and idiopathic intracranial hypertension: a case report.

Cluster headache (CH) is a well-defined primary headache syndrome, but cases of symptomatic headache with clinical features of CH have been previously reported. Idiopathic Intracranial Hypertension (IIH) is a secondary headache disorder characterized by headache and visual symptoms, without clinical, radiological or laboratory evidence of intracranial pathology. Both papilloedema and IIH-related headache are typically bilateral, however asymmetrical or even unilateral localizations are described in literature. We report the case of a previously headache-free woman who presented cluster-like headache and asymmetrical papilloedema related to IIH. In our opinion the asymmetrical presentation supports, in this case, the hypothesis of cavernous sinus involvement in the IIH-related cluster-like headache pathogenesis.