Neuropeptides as a Marker for Chronic Headache

Abstract

Purpose of Review

The purpose of this review is to revise current evidence on trigemino-vascular system (TVS) neuropeptides as potential biomarkers for chronic primary headaches, mainly for chronic migraine (CM).

Recent Findings

Within sensory neuropeptides, released by an activated trigeminal nerve, calcitonin gene-related peptide (CGRP) levels seem to be a good biomarker of acute migraine and somewhat sensitive and specific for CM. CGRP, however, is not increased in 20–30% of CM patients, which suggests that CGRP is not the only neuropeptide involved in migraine pain generation and maintenance. Data for other sensory neuropeptides are inconsistent (neurokinin, substance P) or absent (amylin and cholecystokinin-8). Among parasympathetic neuropeptides, vasoactive intestinal polypeptide (VIP) is increased interictally in CM, and in at least some migraine cases ictally, pituitary adenylate cyclase-activating peptide (PACAP) has been shown to be increased ictally in jugular blood, but interictal, peripheral data do not indicate such an increase, and there are no data for other parasympathetic peptides. Finally, S100B, as a potential marker of glial TVS activation, has been studied with inconsistent results in migraine patients.

Summary

Current data on TVS neuropeptides as potential migraine biomarkers must be taken with caution, even for the promising case of CGRP. We do not know with certainty whether increased levels are the reflection of TVS activation, the reliability and homogeneity of the different laboratory tests, or what is the influence on these measurements of the short half-life of many of these peptides or of preventive treatments. One further limitation would be whether the described increases in levels of some neuropeptides such as CGRP are specific for migraine versus other headaches.

http://ift.tt/2mmkLH1

Recognizing CADASIL: a Secondary Cause of Migraine with Aura

Abstract

Purpose of Review

CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) is an important disease to consider in the differential diagnosis of migraine with aura. This review examines current literature regarding migraine in CADASIL, as well as diagnostic and treatment modalities.

Recent Findings

Recent studies have shown that smoking is a modifiable risk factor for progression of CADASIL (Chabriat et al. in Stroke 47:4–11, 2015). Specific imaging changes and findings on clinical exam can predict disease progression. However, migraine symptoms often precede MRI changes (Guey et al. in Cephalalgia 36:1038–47, 2015). A recent paper on migraine treatment in CADASIL reevaluates the prevailing belief that vasoconstrictive abortive medications are contraindicated in these patients (Tan and Markus in PLoS ONE 11:e0157613, 2016).

Summary

CADASIL is an autosomal dominantly inherited vasculopathy causing ischemic pathology in younger individuals due to a mutation in the NOTCH3 gene. The mutation results in impaired arterial contractility due to accumulation of granular osmiophilic extracellular material (GOM) in vascular smooth muscle cells (VSMCs). Clinical manifestations include migraine with and without aura, cognitive decline, ischemic events, and mood disorders. The presenting symptom is often migraine with aura. Characteristic MRI changes are often present. Genetic screening is available to confirm NOTCH3 mutation and pathognomic changes are often seen in skin biopsy. Treatment of migraine is similar to the general population, but with some notable and specific differences. Further studies in CADASIL, other small vessel arteriopathies, and migraine may help us understand more about the pathophysiology of these conditions and help with treatment development.

http://ift.tt/2mJSNaK

Cannabis for Pain and Headaches: Primer

Abstract

Purpose of Review

Marijuana has been used both medicinally and recreationally since ancient times and interest in its compounds for pain relief has increased in recent years. The identification of our own intrinsic, endocannabinoid system has laid the foundation for further research.

Recent Findings

Synthetic cannabinoids are being developed and synthesized from the marijuana plant such as dronabinol and nabilone. The US Food and Drug Administration approved the use of dronabinol and nabilone for chemotherapy-associated nausea and vomiting and HIV (Human Immunodeficiency Virus) wasting. Nabiximols is a cannabis extract that is approved for the treatment of spasticity and intractable pain in Canada and the UK. Further clinical trials are studying the effect of marijuana extracts for seizure disorders.

Summary

Phytocannabinoids have been identified as key compounds involved in analgesia and anti-inflammatory effects. Other compounds found in cannabis such as flavonoids and terpenes are also being investigated as to their individual or synergistic effects. This article will review relevant literature regarding medical use of marijuana and cannabinoid pharmaceuticals with an emphasis on pain and headaches.

http://ift.tt/2m6b3HN

Headache in Neuromyelitis Optica

Abstract

Purpose of Review

Neuromyelitis optica (NMO) classically features a clinical presentation that includes longitudinally extensive transverse myelitis and optic neuritis. However, many other pathognomonic phenomena have more recently been described in patients diagnosed with NMO, including intractable hiccups, vomiting, and painful tonic spasms, but less has been reported regarding the relationship between NMO and headache. Though headache is well established as both a symptom and comorbidity of multiple sclerosis (MS), it has been much less described thus far in the NMO literature and warrants more careful evaluation. Many questions remain unanswered about the relationship between NMO and headache, including headache prevalence in certain groups, distribution of primary and symptomatic headache disorders that are seen most frequently and the specific neuroimaging findings that are associated with an increased risk of headache.

Recent Findings

Various types of headache, such as cervicogenic headache and trigeminal autonomic cephalalgia-like headache, have been reported as the initial clinical presentation of NMO. Other publications have emphasized the association of NMO and other etiologies of headache, such as trigeminal neuralgia, PRES, and preeclampsia. Certain MR imaging findings such as medullary lesions in patients with NMO have also been associated with headache.

Summary

The link between headache and NMO is evident not only in limited case reports and clinical studies but also with both MR imaging and even with some potential common underlying biomarkers such as pentraxin-3 and interleukin-6. Developing a further understanding in the association between these two diseases may lead to better management of headache in patients with NMO and potentially lead to earlier diagnosis of NMO in whom headache may serve as an initial presenting symptom and may even herald a disease exacerbation.

http://ift.tt/2lHcel0

Condylar geometry variation is associated with ENPP1 variant in a population of patients with dento-facial deformities

Publication date: Available online 8 March 2017
Source:Journal of Cranio-Maxillofacial Surgery
Author(s): Marion Constant, Romain Nicot, Alexandre R. Vieira, Gwenael Raoul, James J. Sciote, Joel Ferri
PurposeBone remodeling is essential in maintaining bone health. Considering that ENPP1 contributes to bone geometry and bone mineralization, the aim of our study was to analyze the association between single-nucleotide polymorphisms (SNPs) of ENPP1 and condylar remodeling.Materials and MethodsA total of 156 patients undergoing orthodontic and maxillofacial surgery treatment for correction of malocclusion were included in this prospective study. Saliva samples from all subjects were used for DNA extraction and genotyping. Four ENPP1 SNPs were selected and tested to determine whether specific allelic variants are correlated with condylar remodeling. The criteria of condylar remodeling chosen were the ratio between each side of condylar height or surface differences on a dental panoramic of each patient. A diagnostic threshold was set at 15% difference between both sides.ResultsThe ENPP1 SNP rs9373000 showed a statistically significant association with condylar height ratio > 15% (p=0.012). The GG genotype was found to be a protective factor against condylar height decrease (p=0.003).ConclusionThis study identifies the genetic variant rs9373000 as a potentially causal variant for mandibular condyle geometry variation for patients presenting with dento-facial deformities.



http://ift.tt/2n2JF1v

A Novel ABCA4 Mutation Associated with a Late-Onset Stargardt Disease Phenotype: A Hypomorphic Allele?

Background: Stargardt disease (STGD) is the most common juvenile hereditary macular dystrophy. In the majority of cases, the diagnosis is made prior to 20 years of age and usually leads to loss of central vision. Late-onset STGD affects a smaller number of patients. Identifying genetic changes which could be associated with clinically important differences in severity or presentation of the disease is important for understanding the mechanisms of visual loss and for planning future therapeutic approaches. Methods: We report a patient with the classic phenotype of STGD with late-onset mild disease exhibiting a slow clinical progression over 14 months of follow-up. Results: A 37-year-old man presented with STGD and good vision of 6/24 in the right eye and of 6/6 in the left eye as well as typical electrophysiology findings. Objective and subjective visual deterioration was not noted over a period of 14 months. Macular genetic testing revealed a novel missense mutation in ABCA4 (Thr829Met) combined with Gly1961Glu, a classic STGD mutation usually associated with a moderately severe phenotype. Conclusions: It is suggested that the Thr829Met mutation could give rise to a hypomorphic allele of the ABC transporter with a resultant phenotype of comparatively mild STGD.
Case Rep Ophthalmol 2017;8:180–184

http://ift.tt/2ni3Nsr

Usefulness of Intravitreal Bevacizumab for Retinopathy of Prematurity with Severely Dilated Tunica Vasculosa Lentis and Poor Mydriasis

Background: Laser therapy has been the gold standard treatment for retinopathy of prematurity (ROP), while intravitreal bevacizumab (IVB) is reported to be of significant benefit for zone I ROP. A problem with laser therapy is that it is difficult to administer in ROP patients with severely dilated tunica vasculosa lentis and poor mydriasis. However, although IVB treatment has been performed in such severe ROP cases, only 1 report has discussed its usefulness. Case 1: A male infant was born with a birth weight of 382 g at 23 weeks' gestation. As visualization was poor and laser therapy could not be performed due to dilated tunica vasculosa lentis and poor mydriasis, IVB (0.625 mg/0.025 mL) was administered to both eyes. Following treatment, the ROP gradually improved, with regression of the dilated tunica vasculosa lentis and improvement of the mydriasis in both eyes. Case 2: A male infant was born with a birth weight of 698 g at 25 weeks' gestation. As laser therapy could not be performed due to severely dilated tunica vasculosa lentis and poor mydriasis, IVB (0.625 mg/0.025 mL) was administered to both eyes. Following treatment, the ROP gradually improved, with regression of the dilated tunica vasculosa lentis and improvement of the mydriasis in both eyes. Conclusions: IVB is potentially more useful than laser therapy for the treatment of severe ROP with dilated tunica vasculosa lentis and poor mydriasis.
Case Rep Ophthalmol 2017;8:173–179

http://ift.tt/2moP0hX