Behavioral therapy in migraine: Expanding the therapeutic arsenal.

BACKGROUND AND PURPOSE: The US Headache Consortium developed evidence-based guidelines for the treatment of migraine and found grade A evidence in support of behavior therapy (BT). Understanding the mechanisms of BT may improve the management of migraine and reduce its burden. METHODS: We performed a narrative review to define the current evidence of BT and determine its usefulness in migraine management. RESULTS: The information was obtained from 116 publications, with 56 of them retrieved through direct searches in PubMed (2011-2020) and the remainder selected by the authors to complete the content. BT might reduce migraine impact by decreasing the sympathetic nervous system's response to stress and increasing pain tolerance. Acting in headache-related surroundings can be improved, together with headache duration and self-efficacy. Applications such as mobile health and electronic health applications can help to carry out healthier lifestyle patterns. Regarding medication overuse, BT seems to be a good choice, with similar results to pharmacological prophylaxis. Advantages of using BT are the lack of adverse effects and the unrestricted use in children, where BT is postulated to be even more effective than the standardized pharmacopeia. CONCLUSIONS: BT is an interesting tool that can be used as an add-on therapy in migraine. Through BT, the autonomy and empowerment of migraine patients is enhanced. BT may not cure migraine, but it could help to reduce pain severity perception, disability, and migraine impact, adding an emotive and cognitive approach to the perceptive role of pharmacopeia. Thus, a better approach in migraine, implementing specific therapeutic management, can improve migraine control.

Co-occurrence of four nucleotide changes associated with an adult mitochondrial ataxia phenotype.

BACKGROUND: Mitochondrial DNA maintenance disorders are an important cause of hereditary ataxia syndrome, and the majority are associated with mutations in the gene encoding the catalytic subunit of the mitochondrial DNA polymerase (DNA polymerase gamma), POLG. Mutations resulting in the amino acid substitutions A467T and W748S are the most common genetic causes of inherited cerebellar ataxia in Europe. METHODS: We report here a POLG mutational screening in a family with a mitochondrial ataxia phenotype. To evaluate the likely pathogenicity of each of the identified changes, a 3D structural analysis of the PolG protein was carried out, using the Alpers mutation clustering tool reported previously. RESULTS: Three novel nucleotide changes and the p.Q1236H polymorphism have been identified in the affected members of the pedigree. Computational analysis suggests that the p.K601E mutation is likely the major contributing factor to the pathogenic phenotype. CONCLUSIONS: Computational analysis of the PolG protein suggests that the p.K601E mutation is likely the most significant contributing factor to a pathogenic phenotype. However, the co-occurrence of multiple POLG alleles may be necessary in the development an adult-onset mitochondrial ataxia phenotype.

Sustained response to botulinum toxin in SUNCT syndrome.

INTRODUCTION: Short-lasting, unilateral, neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) is a rare condition grouped in the category of trigeminal autonomic cephalalgia. The syndrome is characterized by very frequent, unilateral attacks of pain in the ocular and periocular region accompanied by ipsilateral conjunctival injection and lacrimation. The aetiology is unknown, although there have been reports of cases secondary to structural lesions, and treatment is usually ineffective. PATIENTS AND METHODS: We present the case of a patient diagnosed with SUNCT refractory to pharmacological treatment; duration of the SUNCT was 20 years. OnabotulinumtoxinA was infiltrated at four points around the orbit. RESULTS: The pain showed a dramatic response to onabotulinumtoxinA infiltration. Efficacy has been maintained for 18 months with 3-monthly infiltrations, with no adverse effects. CONCLUSIONS: OnabotulinumtoxinA should be added to the limited therapeutic arsenal available for the treatment of refractory cases of SUNCT.

Clinical and myopathological evaluation of early- and late-onset subtypes of myofibrillar myopathy.

Myofibrillar myopathies (MFM) are a group of disorders associated with mutations in DES, CRYAB, MYOT, ZASP, FLNC, or BAG3 genes and characterized by disintegration of myofibrils and accumulation of degradation products into intracellular inclusions. We retrospectively evaluated 53 MFM patients from 35 Spanish families. Studies included neurologic exam, muscle imaging, light and electron microscopic analysis of muscle biopsy, respiratory function testing and cardiologic work-up. Search for pathogenic mutations was accomplished by sequencing of coding regions of the six genes known to cause MFM. Mutations in MYOT were the predominant cause of MFM in Spain affecting 18 of 35 families, followed by DES in 11 and ZASP in 3; in 3 families the cause of MFM remains undetermined. Comparative analysis of DES, MYOT and ZASP associated phenotypes demonstrates substantial phenotypic distinctions that should be considered in studies of disease pathogenesis, for optimization of subtype-specific treatments and management, and directing molecular analysis.

Mutations in progranulin gene: clinical, pathological, and ribonucleic acid expression findings.

BACKGROUND: There is an increasing interest in the clinico-pathological correlation of mutations in progranulin (PGRN) and frontotemporal lobar degeneration (FTLD) complex diseases. We aim to study the PGRN expression variability in patients with different clinical features for a better understanding of its roles in FTLD disease. METHODS: We sequenced the PGRN gene in 72 patients suffering from FTLD (25 familial and 47 sporadic cases) and in 24 asymptomatic at-risk relatives. We also analyzed PGRN expression in blood by quantitative real-time polymerase chain reaction from 37 patients, 8 asymptomatic mutation carriers, and 10 control subjects as well as in brain tissue from 16 patients and 9 control subjects. RESULTS: Four novel mutations were associated with familial and sporadic FTLD and familial dementia associated with amyotrophic lateral sclerosis. We identified a close association between the IVS6-1G>A mutation in PGRN and corticobasal syndrome. Brain tissue was available for carriers of two of the four mutations (IVS6-1 G>A and P357HfsX3). Immunohistochemical analysis revealed ubiquitin- and TDP-43positive and tau/alpha-synuclein negative immunoreactive neuronal intranuclear inclusions. The relative expression of PGRN in the clinical sample was significantly lower in carriers of the IVS6-1 G>A than in control subjects. CONCLUSIONS: Progranulopathies are a major cause of the main phenotypes included in the FTLD complex. According to our results, the level of expression of PGRN in blood could be a useful marker both for diagnostics of part of the spectrum of FTLD conditions and for monitoring future treatments that might boost the level of PGRN in this disorder.