Episodic Manifestations Research Articles

Cortical pain processing in migraine.

Among painful disorders, migraine is distinguishable by its chronic pathology and episodic clinical manifestation. Only a small percentage of patients with migraine progress to a chronic form of migraine. Both peripheral and central portions of the trigeminal system are involved in the pathophysiology of migraine pain, as they are involved in the processes of peripheral and central sensitization, alongside various subcortical and cortical brain structures. This review focuses on clinical, neurophysiological, and neuroimaging data underscoring cortical pain processing in migraine. Data obtained from quantitative sensory testings are inconclusive and support the involvement of the peripheral portion of the trigeminovascular system as indirect evidence of peripheral sensitization, solely during the headache phase. The assessment of subjective pain intensity in response to several painful modalities has not been conclusive for the clear state of central sensitization in between migraine attacks but for the subclinical allodynia state that defines the boundary between behavioural responses and an irritable nervous state. Modulation of the brainstem and midbrain pain pathways, in conjunction with the thalamic and thalamocortical pathways, may be critical for the initiation and maintenance of migraine attacks. Several studies using different neuroimaging techniques have demonstrated that brains experiencing migraine undergo plastic changes in both microstructure and macrostructure and in the functioning of cortical networks, which may manifest early in the life of a patient with migraine. Further studies are required to understand how specific these results are to migraine relative to other painful disorders.

Comprehensive approach to therapy of adaptation disorders associated with computer addiction

Background. In modern conditions there is a quick increase in non-chemical addictions, primarily computer addiction. Unfortunately, patients with non-chemical addictions do not fall into the field of view of doctors at the early stages of the development of the disease. They seek specialized help when addiction becomes a chronic process; due to disability, and delinquent behavior, which contributes to a violation of social functioning and quality of life of the patient and his family.
 Objective – to develop and evaluate the effectiveness of a comprehensive program for the treatment of adaptation disorders associated with computer addiction, based on the study of clinical, psychopathological and pathopsychological patterns of their formation.
 Materials and methods. The study involved 117 patients with signs of computer addiction according to the results of AUDIT-like tests and with adaptation disorders. The main group consisted of 66 patients who took part in the complex therapy program using the methods of pharmacotherapy, psychotherapy and psycho-education; control group – 51 patients who received standard regulated therapy in a medical institution. We used such study methods: clinical-anamnestic; clinical-psychopathological, using AUDIT-like tests for a comprehensive assessment of addictive status, psychodiagnostic using a hospital scale of anxiety and depression, Hamilton anxiety rating scale, Hamilton depression rating scale, the questionnaire of neuro-psychic tension according to T. A. Niemchyn; statistical.
 Results. The clinical picture of computer addiction noted: compulsive surfing in a computer network (45.8±1.6% of the examined), computer games (22.3±1.2%), virtual communication (5.8±0.4%), gambling on-line (14.1±1.1%), passion for porn sites (1.2±0.1%). All examined patients received pharmacotherapy – antidepressants (SSRI) and anxiolytic drugs. and anxiolytic drugs. The psychotherapeutic complex included the use of rational psychotherapy, personality-oriented psychotherapy, existential psychotherapy, art therapy (painting technique). Psycho-educational work included the use of information modules, motivational trainings, the formation of communicative skills, problem-oriented discussions and teaching coping skills. Psychotherapeutic and psycho-educational work was aimed at determining the patient’s resource in overcoming computer addiction and its occurrence. Due to effects of the developed comprehensive program for the treatment of adaptation disorders associated with computer addiction, positive dynamics of the emotional status of patients were achieved, reduction of manifestations of anxiety and depression by HADS, reduction of manifestations of severe depressive and anxious episodes according to the Hamilton scales as well as reduce neuropsychic stress on a scale of T. A. Niemchyn were indicated.
 Conclusions. A comprehensive system for the treatment of adaptation disorders associated with computer addiction should include a combination of pharmacotherapy, psychotherapy and psycho-education. Positive dynamics of the emotional status of patients, the predominance of subclinical manifestations or the absence of anxiety and depression on the HADS scale; mild depressive and anxious episodes or their absence according to the HAM-D and HAM-A scales; reduction of neuropsychic stress on a scale of T. A. Niemchyn as well as stability of the therapeutic effect during a two-year follow-up study indicates the effectiveness of the developed comprehensive therapy program.

Into the dark room: a predictive processing account of major depressive disorder

Major depression is a prevalent mental disorder that leads to persistent negative mood and tremendous suffering in affected individuals. However, the biological realization of this disorder and associated symptom clusters remain poorly understood. Recently, phenomenological accounts of major depressive disorder and contributions to the emerging predictive processing account have provided valuable insights into the phenomenological and neuro-functional components that lead to manifestations of major depressive episodes. The purpose of this paper is to weave together these different strands of research to develop a predictive processing account of major depressive disorder. In doing so, I will relate personal-level descriptions of associated phenomenal experiences to a sub-personal-level predictive processing account of the functional realization of major depression. I will argue that pervasive symptoms of the disorder, which include a diminished sense of agency, fatigue, social withdrawal, and rumination, are integrated by existential feelings of loss and impossibility. These phenomenal experiences, I will argue, are associated with dysfunctional processes of prediction error minimization, which are characterized by an overall decrease of the causal contributions of active inference and by distorted precision estimates. The emerging account promises to contribute to a better understanding of the complex processes that give rise to depressive experiences.

Sea food consumption for improving cardiac and cerebral manifestations of mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes.

Since the initial description >30 y ago, therapeutic options for mitochondrial encephalopathy, lactic acidosis, and stroke- like episodes (MELAS) syndrome, the most well-known of the mitochondrial disorders (MIDs), remain limited due to the complexity of its genetic background and its clinical manifestations (1,2).

The Effect of Bariatric Surgery on Migraine Headache in Morbid Obese Patients

Background: Migraine is a common and chronic neuro-inflammatory disease with progressive and episodic headache manifestation that leads to considerable disability. Many studies recognized that obesity is a risk factor for progression of migraine. Furthermore, both migraine and obesity is highly prevalent and important risk factors of chronic cardiovascular disease, stroke, and other inflammatory disease. Thus, it is very important if weight loss could alleviate the migraine headache and its related comorbidities. Aim: The present review article was conducted to assess the potential effect of Bariatric surgery on improvement of migraine headaches in morbid obese patients. Search Strategy: Scopus, PubMed and web of science electronic database were systematically searched with key words of “Bariatric surgery”, “gastric Bypass”; “Morbid Obesity” and “Migraine headache” for interventional studies investigated the impact of Bariatric surgery on migraine headache. Results: The findings suggest significant improvement in headache frequency, duration, migraine-induced discomfort and migraine derived symptoms (nausea, phono and photophobia and) occurs as early as 3 months after bariatric surgery. Moreover, patients who had higher weight loss were more likely to experience a 50% or higher reduction in headache frequency, duration and severity. Conclusions: The entire evidences suggest patients with indications of bariatric surgery will benefit from the improvements in the Migraine headache after surgery. However, it remains unclear whether Bariatric-induced endocrine, gut-brain axis alterations, or reduction in adipokine contribute to migraine improvement, so further studies are needed to confirm and clarify these findings.

Propranolol treatment prevents chronic central sensitization induced by repeated dural stimulation.

Migraine is currently conceptualized as a chronic disease with episodic manifestations. In some patients, migraine attack frequency increases, leading to chronic migraine. Daily preventive therapy is initiated to decrease attack frequency. Propranolol, a first-line medication for migraine prophylaxis, reduces attack frequency in nearly 50% of patients receiving it. However, the mechanisms of its antimigraine action are unclear. We examined the effect of daily propranolol treatment (10 mg·kg per os, 8 days) in a rat model of recurrent activation of dural nociceptors (repeated infusion of an inflammatory soup (IS) on the dura through a cannula every 2-3 days). Propranolol does not abort IS-induced acute cephalic mechanical allodynia but blocks the development of a chronic cutaneous hypersensitivity upon repeated IS injections. Furthermore, propranolol prevents (1) the elevated touch-evoked Fos expression within the trigeminocervical complex, (2) enhanced both spontaneous activity, and evoked responses of second-order trigeminovascular neurons, (3) elevated touch-evoked rostral ventromedial medulla and locus coeruleus Fos expression and (4) diffuse noxious inhibitory controls impairment, induced by repeated IS injections. Our results suggest that propranolol exerts its prophylactic action, at least in part, by blocking the chronic sensitization of descending controls of pain, arising from the rostral ventromedial medulla and locus coeruleus, and in turn preventing the maintenance of a state of facilitated trigeminovascular transmission within the trigeminocervical complex. Assessing changes in these brain areas has the potential to elucidate the mechanisms for migraine transformation and to reveal novel biological and molecular targets for specific migraine-preventive therapies.

The Potential Role of Store-Operated Calcium Entry (SOCE) Pathways in the Pathophysiology of Epilepsy and Migraine-Like Headaches in Patients with Neurocysticercosis

Cysticercosis is the most common helminthic disease of the nervous system in humans. The clinical presentation of neurocysticercosis (NCC) is nonspecifi c and can mimic a wide array of primary central nervous system (CNS) disorders, making its diagnosis a challenge especially in endemic areas. The pathophysiology of episodic CNS manifestations of NCC is not well understood.

P015. Externalizing behaviours in children with headache and epilepsy: a case-control study.

Background Epilepsy and migraine are chronic neurological disorders with episodic manifestations that are commonly treated in neurological practice and frequently occur together [1]. These two disorders share several pathophysiological mechanisms. These mechanisms especially involve neurotransmitter and ion channel dysfunctions [2]. Children with epilepsy or headache are at risk of behavioural disorders that can affect their quality of life. Aim of this study was to analyze the possible correlation between externalizing problems and migraine or epilepsy in children.

Host directed therapies (HDTs) and immune response signatures: insights into a role for interleukin-32.

The clinical manifestations of recurrent episodes of TB reflect the complex interaction between Mycobacterium tuberculosis ( M.tb ) and the host immune response (1). There are an estimated 2 billion people in the world who have latent M.tb infection (LTBI) with no symptoms and signs of ill health. Co-evolution between M.tb and humans over centuries has established a delicate, balanced liaison between the host and pathogen (2). The clinical outcome of the encounter with M.tb in immune-competent individuals is apparently a success story: more than 90% of individuals exposed to M.tb (3) do not develop clinical TB. Therefore, TB provides a highly relevant paradigm of how optimally-activated and balanced host response networks tailor the outcome of an infection, which leads either to latent LTBI or to a life-threatening disease (4). Despite some advances in defining clinically relevant markers of immune protection against M.tb (5), the identification of host factors which enable protection to clinical TB remain elusive. Increasing evidence shows that biomarkers present in individuals with latent LTBI may represent components that orchestrate complex host anti- M.tb immune response networks and ultimately determine protection from expression of clinical TB disease. Contrary to this, M.tb infection can lead to intense immune and inflammatory responses which result in severe pulmonary pathology, eventually resulting in death. The paradigm that limiting overt inflammation in infectious diseases may result in benefit to the patient has been shown in settings of several infectious diseases, for example, the use of cytotoxic drugs such as etoposide and cyclosporine A, or limiting excessive inflammation and removing regulatory T cells (Tregs) in severe avian influenza A (H5N1) infection by (6), and use corticosteroids for the treatment of community—acquired pneumonia (7). The strength of inflammation is not only determined by the pathogen type [e.g., infection with the M.tb Beijing lineage that results in stronger pro-inflammatory responses (8)], but also by the host genetic background e.g., determined by SNPs associated with arachidonic acid metabolism, and pro-inflammatory cytokine receptors (8).

Аllergies in Families of Moscow (Russia) Newborns: Suspected Cases within Three Generations Framework

Background: Allergy prevalence in parents of newborns is an indicator of allergic diseases in children, which is split upon parent’s gender and allergic conditions. Objective: to find out gender patterns within a larger framework of allergies in grandparents, aunts, uncles of newborns in maternal and paternal families. Methods: In 2011 13 visits to the Postnatal Department of Moscow No.1 Maternity Hospital were carried out. All women delivered within the preceding 48 hours were interviewed. Mothers provided us with information on relatives of a newborn in regards to clinical manifestations of food allergies, atopic dermatitis, eczema, urticaria, angioedema, allergic rhinitis, allergic conjunctivitis, asthma and episodes of drug allergy. Information on 3534 relatives from 393 newborns was collected. Results: The rate of suspected allergic conditions in grandfathers is the same in both maternal and paternal families (4,35% 95%CI 1,99-6,70 and 4,62% 95%CI 2,12-7,12 respectively), but in grandmothers and aunts the rate of suspected allergic incidence is increased in maternal family (11,54% 95%CI 8,58-14,50) over paternal (6,80% 95%CI 4,46-9,14). The cumulative rate of suspected allergies in grandfathers+fathers+uncles (i.e. in male relatives of two preceding the newborns generations) is significantly lower (8,57% 95%CI 7,03-10,11) than in grandmothers+mothers+aunts (i.e. in female relatives of two preceding the newborns generations) (13,28% 95%CI 11,44-15,13) (p < .05). Conclusion: There are clear gender differences with increased prevalence of suspected allergic conditions in female relatives of two preceding the newborn generations compared with male relatives. There is a tendency to increased suspected allergic manifestations among women of maternal relatives in comparison to paternal relatives.

General trigeminospinal central sensitization and impaired descending pain inhibitory controls contribute to migraine progression

Migraine is a chronic disease with episodic manifestations. In a subgroup, attack frequency increases over time, leading to chronic migraine. One of the most important risk factors for migraine progression is frequency of headache attacks at baseline. Unfortunately, the actual effects of repeated activation of dural nociceptors are poorly known. We investigated the behavioral, anatomical, and electrophysiological changes induced by repeated low- and high-intensity stimulation of meningeal nociceptor by injecting an inflammatory soup in rats. Single high-intensity, but not low-intensity, stimulation produces a reversible cephalic allodynia. Upon repetition, however, low-intensity stimulation, too, induces a reversible cephalic allodynia, and high-intensity, reversible cephalic and extracephalic allodynia. Moreover, cephalic allodynia becomes, in part, persistent upon repeated high-intensity stimulation. Fos expression reveals that a single high-intensity stimulation already leads to widespread, trigeminal, and spinal central sensitization, and that such general central sensitization potentiates upon repetition. Trigeminovascular nociceptive neurons become persistently sensitized and their diffuse noxious inhibitory controls (DNIC) concomitantly impaired. Thus, compared with single stimulation, repeated dural nociceptor activation specifically leads to: 1) a gradual worsening of cutaneous hypersensitivity and general neuronal hyperexcitability and 2) spreading of cutaneous hypersensitivity superimposed on 3) persistent cephalic cutaneous hypersensitivity and trigeminal central sensitization. Such repetition-induced development of central sensitization and its consequence, cutaneous allodynia, may arise from both the general neuronal hyperexcitability that results from DNIC impairment and hyperexcitability that likely develops in trigeminal nociceptive neurons in response to their repetitive activation. These neuronal changes may in turn elevate the risk for developing chronic migraine.

PReS-FINAL-2236: Continuous autoinflammatory syndromes: a single-center experience in Argentina

Patients with autoinflammatory syndromes may present a clinical course characterized by recurrent, episodic manifestations (such as fever, skin rash or visceral involvement) or they may show a continuous, unremitting disease course with persistent clinical manifestations. Patients with certain diseases, such as CAPS or Blau syndrome, usually present this type of course.

Malária em Gestantes Atendidas no Hospital da Mulher Mãe Luzia, em Macapá, Amapá, Brasil

A malária é uma doença infecciosa e parasitária com manifestações episódicas de caráter agudo e de evolução crônica, causada por um protozoário do gênero Plasmodium e transmitida ao homem pela picada do mosquito fêmea do gênero Anopheles. As mulheres grávidas são vulneráveis à malária porque o seu estado de imunidade se modifica durante a gestação, tornando-a mais suscetível às alterações no curso da gravidez.

The Holistic Phase Model of Early Adult Crisis

The objective of the current study was to explore the structural, temporal and experiential manifestations of crisis episodes in early adulthood, using a holistic-systemic theoretical framework. Based on an analysis of 50 interviews with individuals about a crisis episode between the ages of 25 and 35, a holistic model was developed. The model comprises four phases: (1) Locked-in, (2) Separation/Time-out, (3) Exploration and (4) Rebuilding, which in turn have characteristic features at four levels—person-in-environment, identity, motivation and affect-cognition. A crisis starts out with a commitment at work or home that has been made but is no longer desired, and this is followed by an emotionally volatile period of change as that commitment is terminated. The positive trajectory of crisis involves movement through an exploratory period towards active rebuilding of a new commitment, but ‘fast-forward’ and ‘relapse’ loops can interrupt Phases 3 and 4 and make a positive resolution of the episode less likely. The model shows conceptual links with life stage theories of emerging adulthood and early adulthood, and it extends current understandings of the transitional developmental challenges that young adults encounter.

Towards dynamical network biomarkers in neuromodulation of episodic migraine.

Computational methods have complemented experimental and clinical neurosciences and led to improvements in our understanding of the nervous systems in health and disease. In parallel, neuromodulation in form of electric and magnetic stimulation is gaining increasing acceptance in chronic and intractable diseases. In this paper, we firstly explore the relevant state of the art in fusion of both developments towards translational computational neuroscience. Then, we propose a strategy to employ the new theoretical concept of dynamical network biomarkers (DNB) in episodic manifestations of chronic disorders. In particular, as a first example, we introduce the use of computational models in migraine and illustrate on the basis of this example the potential of DNB as early-warning signals for neuromodulation in episodic migraine.

Panic Disorder and Migraine: Comorbidity, Mechanisms, and Clinical Implications

A growing body of literature suggests that comorbid anxiety disorders are more common and more prognostically relevant among migraine sufferers than comorbid depression. Panic disorder (PD) appears to be more strongly associated with migraine than most other anxiety disorders. PD and migraine are both chronic diseases with episodic manifestations, involving significant functional impairment and shared symptoms during attacks, interictal anxiety concerning future attacks, and an absence of identifiable secondary pathology. A meta-analysis of high-quality epidemiologic study data from 1990 to 2012 indicates that the odds of PD are 3.76 times greater among individuals with migraine than those without. This association remains significant even after controlling for demographic variables and comorbid depression. Other less-rigorous community and clinical studies confirm these findings. The highest rates of PD are found among migraine with aura patients and those presenting to specialty clinics. Presence of PD is associated with greater negative impact of migraine, including more frequent attacks, increased disability, and risk for chronification and medication overuse. The mechanisms underlying this common comorbidity are poorly understood, but both pathophysiological (eg, serotonergic dysfunction, hormonal influences, dysregulation of the hypothalamic-pituitary-adrenal axis) and psychological (eg, interoceptive conditioning, fear of pain, anxiety sensitivity, avoidance behavior) factors are implicated. Means of assessing comorbid PD among treatment-seeking migraineurs are reviewed, including verbal screening for core PD symptoms, ruling out medical conditions with panic-like features, and administering validated self-report measures. Finally, evidence-based strategies for both pharmacologic and behavioral management are outlined. The first-line migraine prophylactics are not indicated for PD, and the selective serotonin re-uptake inhibitors used to treat PD are not efficacious for migraine; thus, separate agents are often required to address each condition. Core components of behavioral treatments for PD are reviewed, and their integration into clinical headache practice is discussed.

High risk of severe cardiac adverse events in patients with mitochondrial m.3243A&gt;G mutation

To determine the long-term incidence of cardiac life-threatening complications and death in patients with the m.3243A>G mutation, and to identify cardiac prognostic factors. We retrospectively included patients carrying the m.3243A>G mutation who were admitted to the Neuromuscular Disease Clinic of Pitié Salpêtrière Hospital between January 1992 and December 2010. We collected information relative to their yearly neurologic and cardiac investigations, their mutation load in blood, urine, and muscle at initial admission, and the occurrence of cardiac life-threatening adverse events and death during follow-up. Forty-one patients (median age = 47 years [36-55 years], men = 13) were included, of whom 38 had clinical manifestations of mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) and 3 were asymptomatic. One patient had a personal history of cardiac transplantation. Cardiac investigations displayed left ventricular hypertrophy, left ventricular dysfunction, or both abnormalities in 18 patients, along with Wolff-Parkinson-White syndrome in 7, conduction system disease in 4, and atrial fibrillation in 1. Over a median 5-year (3-9 years) follow-up period, 11 patients died, including 3 due to heart failure; 7 had life-threatening adverse events, including 6 hospitalizations for severe heart failure and 1 resuscitated cardiac arrest. By multivariate analysis, left ventricular hypertrophy was the only parameter independently associated with occurrence of cardiac adverse events. Patients with the m.3243A>G mutation have a high incidence of cardiac death and life-threatening adverse events. Left ventricular hypertrophy was the only parameter independently associated with occurrence of these events.

Polytherapy for migraine prophylaxis

Migraine is a chronic neurological disorder with episodic manifestations, progressive in some individuals. Preventive treatment is recommended for patients with frequent or disabling attacks. A sizeable proportion of migraineurs in need of preventive treatment does not significantly benefit from monotherapy. This short review evaluates the role of pharmacological polytherapy in migraine prevention.

Ictal epileptic headache as “subtle” symptom in generalized idiopathic epilepsy

Epilepsy and migraine are common neurologic chronic disorders with episodic manifestations characterized by recurrent attacks and a return to baseline conditions between attacks. Epilepsy and migraine are frequently observed in comorbidity, with the occurrence of one disorder increasing the probability of the other: Migraine occurs in about one-fourth of patients with epilepsy, whereas epilepsy is present in 8-15% of patients with migraine. The link between headache and seizures is controversial and multifactorial. In epilepsy, headache can be seen as a preictal, ictal, or postictal phenomenon. In this report, we describe a case of a 37-year-old patient, affected by both drug-resistant generalized idiopathic epilepsy and headache, who displayed the sudden onset of a headache attack referred during a 24-h electroencephalography (EEG). The EEG tracing during this event revealed the activation of subcontinuous epileptic activity consisting of generalized spike-wave discharges (GSWDs) and generalized polyspike and wave discharges (GPSWDs) that persisted for 60 min, that is, until the disappearance of the headache. The case we describe appears to be original in that it represents one of the few EEG-documented ictal epileptic headaches in generalized idiopathic epilepsy.

Strategic decisions as drivers of innovation: the case of MicroLink

PurposeThe purpose of this paper is to find out how strategic decisions have resulted in innovation in the context of the organizational environment. The author studies connections between strategic decision making and innovation to find out what kinds of factors of the organizational environment influence strategic decisions that lead an organization to innovate.Design/methodology/approachThe theoretical and empirical part proceeds from dividing strategic decisions into proactive and reactive; the environment into internal and external, including primary and secondary environment, and dynamic capabilities; and innovation into product, process, marketing and organizational innovation. The study uses qualitative research and case study methodologies to analyse the case of an Estonian IT company, MicroLink.FindingsThe results show that even if innovation is not strategically managed in a company, it can still be innovative. However, the potential for different types of innovation at the organizational and local and global market level is very often determined by the company's general strategic vision and its proactive nature, which should be supported by its dynamic capabilities.Practical implicationsBased on the results, some conclusions are also presented for other Estonian IT companies in terms of what aspects they should keep in mind when making strategic decisions and implementing innovation.Originality/valueThe paper contributes to the understanding of how innovation evolves and it is presumed that innovation is not always a purposeful, but rather an episodic manifestation that could be a result of strategic decisions. Besides, product and process innovation, this study also helps to highlight the role of marketing and organizational innovation, which have gained much less attention in the literature.