Daniela Mittino

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.

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.

Churg-Strauss syndrome associated with the leukotriene antagonist montelukast

Abstract.Churg-Strauss syndrome (CSS) is a disseminated small vessel vasculitis characterized by late-onset asthma, upper airways disease, eosinophilia and late neurological manifestations such as peripheral neuropathy. Recently, several cases of CSS have been reported in patients treated with leukotriene antagonists after weaning corticosteroids. We describe a case of CSS developed while the patient was receiving montelukast for asthma treatment, after corticosteroids withdrawal. A causal relationship between montelukast therapy and CSS is hypothesized.

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.

Association of RAMP1 rs7590387 With the Risk of Migraine Transformation Into Medication Overuse Headache

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.

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.

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.

SLE-related longitudinal myelitis with favorable outcome.

disease with multi-organ involvement, defined by its clinical features and the presence in the blood of antibodies against one or more components of cell nuclei1. Neurological and psychiatric complications of SLE include seizures, psychosis, cerebrovascular disease, cognitive dysfunction2 and headache3, described in up to 75% of patients4,5. In general terms, any part of the nervous system6,7 may be involved, however, central nervous system (CNS) complications are of relevance because can significantly affect prognosis and mortality. Different pathogenetic mechanisms have been claimed to play a relevant role in CNS complications of SLE such as vasculitis, antibodies against brain tissues, deposition of immunocomplex, overproduction of cytokines, thrombosis, and hemorrhage8. Myelopathy is one of 19 possible syndromes described by the American College of Rheumatology9, with transverse myelitis (TM) being a rare but serious neurologic complication. It presents as a rapidly progressive motor, sensory and autonomic dysfunction10-12, with uncertain pathophysiology, whose prevalence seems to be in the region of 1-2% among SLE patients10,13-16. Since the initial description of the first nine cases in 196817, SLE-related TM is now a well-known clinical entity and a number of authors pointed out the close relationships with antiphospholipid antibodies (aPL) syndrome. In fact, from 55% to 64% of SLE-related TM present high levels of aPL, which is higher than that reported in the general SLE population (3050%)18-19. Different authors, therefore, speculated that the pathogenesis of TM may be related to a vascular thrombosis or to a direct interaction between aPL and membrane phospholipids at the spinal cord level14. A rare variant of the SLE-related myelopathy is longitudinal myelitis (LM), which is defined by the continuous involvement of more than four spinal cord segments20-23. In fact, one to four spinal segments are generally involved in SLE-related TM20,23. Longitudinal myelitis needs to be promptly diagnosed and recognized because it is characterized by an acute catastrophic onset and an unfavorable prognosis, and a closer association with aPL syndrome has been suggested when compared to TM20. Here, we describe a patient presenting with LM and peripheral neuropathy as early manifestations of SLE, with negative aPL and a favorable outcome. Clinical, electrophysiological and radiological features at the onset and during the follow-up are discussed.

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.

Headache in immigrant patients: similarities and differences with Italian population

Headache is one of the most common neurological diseases. It is well known that there are differences in the perception and in the management of pain in various populations. Immigrants represent a growing portion between neurology outpatients. We analyzed the epidemiological characteristic of headache in immigrants come to our attention, in comparison with Italians. Data collected included age at immigration, age of onset of headache, headache’s type (HIS criteria), and psychiatric comorbidities. There were not substantial differences in the incidence of headache subtypes: migraine was the most frequent diagnosis in both groups, followed by tension-type headache. The incidence of depression was similar, while anxiety was significantly less frequent in immigrants. Studies on neurological diseases in immigrants are few. The data available seem to show no differences in the incidence, but rather in treatment. Our study confirms the evenness of two populations, local and foreign, afferent in a Headache Unit, according to the single similar study, except for anxiety, maybe related to language difficulties or cultural background.