CGRP receptor antagonists (gepants).

Small molecule calcitonin gene-related peptide (CGRP) receptor antagonists are commonly referred to as gepants. The first generation of gepants provided the first line of evidence of CGRP-mediated antimigraine medication in 2004-2011. However, further development was halted due to either lack of oral availability or concerns of hepatotoxicity. More than 15 years later, the first second generation of gepants, ubrogepant and rimegepant, are now approved for the acute treatment of migraine with or without aura. Furthermore, a novel and promising third-generation gepant, zavegepant, has recently been approved as well. In this chapter, we review the evidence supporting the effectiveness, safety, and tolerability of gepants for the acute treatment of migraine. Furthermore, we discuss the potential limitations and future directions of this class of migraine-specific medication.

Perspectives on Neuronutrition in Prevention and Treatment of Neurological Disorders.

The term neuronutrition has been proposed as part of nutritional neuroscience, studying the effects of various dietary components on behavior and cognition. Other researchers underline that neuronutrition includes the use of various nutrients and diets to prevent and treat neurological disorders. The aim of this narrative review was to explore the current understanding of the term neuronutrition as the key concept for brain health, its potential molecular targets, and perspectives of its nutritional approach to the prevention and treatment of Alzheimer's and Parkinson's diseases, multiple sclerosis, anxiety, depressive disorders, migraine, and chronic pain. Neuronutrition can be defined as a part of neuroscience that studies the influence of various aspects of nutrition (nutrients, diet, eating behavior, food environment, etc.) on the development of nervous disorders and includes nutrition, clinical dietetics, and neurology. There is evidence that the neuronutritional approach can influence neuroepigenetic modifications, immunological regulation, metabolic control, and behavioral patterns. The main molecular targets in neuronutrition include neuroinflammation, oxidative/nitrosative stress and mitochondrial dysfunction, gut-brain axis disturbance, and neurotransmitter imbalance. To effectively apply neuronutrition for maintaining brain health, a personalized approach is needed, which includes the adaptation of the scientific findings to the genetic, biochemical, psycho-physiological, and environmental features of each individual.

Migraine and light: A narrative review.

OBJECTIVE: In this narrative review, we summarize clinical and experimental data on the effect of light in migraine and discuss future prospects. BACKGROUND: Effective nonpharmacological treatment of hypersensitivity to light in migraine is an unmet clinical need. Current management strategies primarily consist of seeking a dark room and avoiding light exposure. Advances in the past 2 decades have improved our understanding of the underlying pathophysiology of how migraine is influenced by light. This may provide promising avenues for novel approaches in clinical management. METHODS: We searched MEDLINE for articles published from database inception up to September 1, 2021. We used the search term "migraine" with the search terms "light," "photophobia," "treatment," "trigger," "circadian rhythm," "environment," and/or "pathophysiology." RESULTS: Light is commonly reported as a trigger factor of migraine attacks, however, early manifestation of photophobia and false attribution is likely the actual cause based on data deriving from retrospective, prospective, and experimental studies. The most common photophobia symptoms in migraine are exacerbation of headache by light and abnormal sensitivity to light with the underlying neural pathways likely being dependent on ongoing activity in the trigeminovascular system. Clinical studies and experimental models have identified mediators of photophobia and uncovered narrow wavebands of the light spectrum that may reduce pain intensity during a migraine attack. Consequently, novel devices have undergone exploratory clinical trials with promising results. CONCLUSION: False attribution is likely the reason why light is commonly reported as a trigger factor of migraine attacks, and a prospective confirmation is required to prevent unnecessary avoidance. The observation that individuals with migraine are not equally photophobic to all wavebands of the light spectrum opens the potential for innovative pain management strategies. In this context, using human-centric lighting (also called integrative lighting) to mimic the natural daylight cycle and avoid harmful wavebands through modern technology may prove beneficial. Future research should identify direct and indirect consequences of light and other environmental factors in migraine to fill out knowledge gaps and enable evidence-based care strategies within institutions, work environments, and other settings.

Safety and Efficacy of Melatonin in Chronic Tension-Type Headache: A Post-Marketing Real-World Surveillance Program.

INTRODUCTION: Tension-type headache (TTH) is the most prevalent primary headache. Every year, about 2-3% of patients with TTH progress to chronic TTH with daily or near-daily headache, warranting preventive treatment. The treatment of chronic TTH is complex and very often associated with significant tolerability issues. To date, melatonin has been studied in only a few small uncontrolled trials. The aim of this surveillance program was to evaluate the efficacy of melatonin (Melaxen®) in patients with TTH and disruption of circadian rhythms in real-world practice. METHODS: Sixty-one patients with chronic TTH were enrolled. After the 30-day baseline period, patients took 3 mg of melatonin at bedtime for 30 days with a follow-up period of another 30 days. VAS pain intensity assessments, Hamilton Anxiety Rating Scale (HAM-A), Hamilton Depression Rating Scale (HAM-D), HIT-6 and Levin sleep quality scores were obtained at the baseline visit, at month 1, and month 2. RESULTS: A significant decrease in the number of headache days per month, VAS pain intensity, HAM-A, HAM-D and HIT-6 scores, and an improvement in sleep quality were observed throughout the study. No treatment-emergent adverse events were reported. CONCLUSIONS: Melatonin is an effective and safe alternative for the treatment of chronic TTH.

Sleep Disorders and Headache: A Review of Correlation and Mutual Influence.

The review is devoted to the complex relationship between headache and sleep disorders. The shared neuroanatomical structures of the nervous system involved in pain perception and sleep are shown, and mechanisms of comorbidity between headaches and sleep disorders are considered. Various types of headaches in the continuum of the sleep-wake cycle are described. Both pharmacological and non-pharmacological approaches to treatment are examined in detail, with the biochemical basis of the drug action.

Cognitive impairment in chronic migraine: a cross-sectional study in a clinic-based sample.

Cognitive impairment has been described in all phases of a migraine attack and interictally. However, the prevalence and phenotype of such impairment in chronic migraine (CM) have not yet been studied. OBJECTIVES: The aim of this study was to evaluate both the prevalence of the objective cognitive deficit in patients with CM and the factors underlying its etiology. METHODS: 144 patients with CM and 44 age-matched patients with low-frequency episodic migraine (EM) (a maximum of 4 headache days per month) participated in this study. Neuropsychiatric characteristics were measured with the HADS Hospital Anxiety and Depression Scale. Cognitive function was assessed with the Montreal Cognitive Assessment (MoCA), Digit Symbol Substitution Test (DSST), Rey Auditory Verbal Learning Test (RAVLT), and the Perceived Deficits Questionnaire (PDQ-20). RESULTS: Compared to EM, CM subjects demonstrated higher subjective and objective cognitive impairment across all tests. CM patients had 4 times higher odds of achieving a RAVLT score in the lower quartile range compared to EM (Odds Ratio [OR] 3.8; 95% confidence interval [95%CI] 1.5‒9.6; р=0.005). In the MoCA, CM patients demonstrated the most striking impairment in memory/delayed recall (65.3%), attention (46.5%), abstraction (30.6%), and language (27.1%). Chronic headache and level of education, but not gender, depression or anxiety, were independent predictors of cognitive impairment. CONCLUSIONS: Cognitive impairment is prevalent in the CM population during their mildest possible pain and may be caused by a central sensitization. Timely preventive treatment of EM is warranted.

Cognitive impairment in chronic migraine: a cross-sectional study in a clinic-based sample / Comprometimento cognitivo na enxaqueca crônica: um estudo transversal em uma amostra clínica

Abstract Cognitive impairment has been described in all phases of a migraine attack and interictally. However, the prevalence and phenotype of such impairment in chronic migraine (CM) have not yet been studied. Objectives: The aim of this study was to evaluate both the prevalence of the objective cognitive deficit in patients with CM and the factors underlying its etiology. Methods: 144 patients with CM and 44 age-matched patients with low-frequency episodic migraine (EM) (a maximum of 4 headache days per month) participated in this study. Neuropsychiatric characteristics were measured with the HADS Hospital Anxiety and Depression Scale. Cognitive function was assessed with the Montreal Cognitive Assessment (MoCA), Digit Symbol Substitution Test (DSST), Rey Auditory Verbal Learning Test (RAVLT), and the Perceived Deficits Questionnaire (PDQ-20). Results: Compared to EM, CM subjects demonstrated higher subjective and objective cognitive impairment across all tests. CM patients had 4 times higher odds of achieving a RAVLT score in the lower quartile range compared to EM (Odds Ratio [OR] 3.8; 95% confidence interval [95%CI] 1.5‒9.6; р=0.005). In the MoCA, CM patients demonstrated the most striking impairment in memory/delayed recall (65.3%), attention (46.5%), abstraction (30.6%), and language (27.1%). Chronic headache and level of education, but not gender, depression or anxiety, were independent predictors of cognitive impairment. Conclusions: Cognitive impairment is prevalent in the CM population during their mildest possible pain and may be caused by a central sensitization. Timely preventive treatment of EM is warranted.

Resumo O comprometimento cognitivo foi descrito em todas as fases de um ataque de enxaqueca, de maneira intermitente. Entretanto, a prevalência e o fenótipo desse comprometimento na enxaqueca crônica (EC) não foram estudados. Objetivos: O objetivo deste estudo foi avaliar a prevalência do déficit cognitivo objetivo em pacientes com EC e fatores subjacentes à sua etiologia. Métodos: 144 pacientes com CM e 44 pacientes pareados por idade com enxaqueca episódica (EE) de baixa frequência (máximo de 4 dias de dor de cabeça por mês) foram incluídos. As características neuropsiquiátricas foram medidas pela Hospital Anxiety and Depression Scale (HADS). A função cognitiva foi avaliada por meio da Montreal Cognitive Assessment (MoCA), o Digit Symbol Substitution Test (DSST), o Rey Auditory Verbal Learning Test (RAVLT) e o Perceived Deficits Questionnaire (PDQ-20). Resultados: Em comparação com a EE, os indivíduos com EC demonstraram um comprometimento cognitivo subjetivo e objetivo maior em todos os testes. Os pacientes com CM tiveram 4 vezes mais chances de alcançar um escore RAVLT na faixa quartil inferior, em comparação com EE (Odds Ratio [OR] 3,8; intervalo de confiança de 95% [IC95%] 1,5‒9,6; p=0,005). No MoCA, os pacientes com EC demonstraram o maior prejuízo na memória/atraso na recordação (65,3%), atenção (46,5%), abstração (30,6%) e linguagem (27,1%). Dor de cabeça crônica e nível de escolaridade, mas não o sexo, depressão ou ansiedade, foram preditores independentes de comprometimento cognitivo. Conclusões: O comprometimento cognitivo é prevalente na população com enxaqueca crônica mesmo durante uma dor muito leve e pode ser causado pela sensibilização central. O tratamento preventivo oportuno da enxaqueca episódica se faz necessário.

Psychogenic Seizure Imitating Narcolepsy.

Psychogenic or functional neurological disorders (FND) often occur in the practice of a neurologist. Diagnosis of FND usually causes significant difficulties. Among FND, psychogenic non-epileptic seizures (PNES) comprise around 40% cases. Sometimes it is necessary to differentiate PNES from narcolepsy. We describe a 55-year-old man with frequent brief and sudden sleep-like attacks in combination with nocturnal sleep disturbance. During attacks he was unresponsive, snoring but maintained posture. He resisted passive eye opening but with rolling eyes. The patient was confused on waking. In the interictal period, there were FND signs including give-way weakness of the left hand, typical functional "leg-dragging" gait, mistake in the finger-to-nose test. Video-electroencephalogram monitoring did not detect specific epileptic activity or sleep pattern during the attacks. Polysomnography showed multiple waking episodes during the night, but no typical pattern of narcolepsy was found in the multiple sleep latency test. The patient had frequent urgent hospitalizations due to different diseases and numerous invasive procedures. Six month later, the patient obtained state related disability financial benefit, after which hospitalizations in various hospitals continued, and PNES became shorter and less pronounced.

Assessment of copper, iron, zinc and manganese status and speciation in patients with Parkinson's disease: A pilot study.

BACKGROUND: The objective of this pilot study was to assess iron (Fe), copper (Cu), zinc (Zn), and manganese (Mn) status (hair, serum, and urine) and speciation (serum) in Parkinson's disease (PD) patients. METHODS: A pilot study involving a total of 27 subjects (13 PD patients, 14 controls) was performed. Serum, urine, and hair metal content was assessed using ICP-MS. Speciation analysis of Cu, Zn, Fe, and Mn was performed using a hybrid HPLC-ICP-MS system. RESULTS: Group comparisons did not reveal any significant group difference in serum Cu, Zn, Fe, and Mn total metal level between PD patients and controls. Speciation analysis revealed a significant decrease in Cu/ceruloplasmin copper in association with elevation of low-molecular weight species (amino acids)-bound copper. It is proposed that in PD, binding of Cu(II) ions to ceruloplasmin is reduced and free copper ions coordinate with low molecular weight ligands. The level of Mn-albumin complexes in PD patients was more than 4-fold higher as compared to the respective value in the control group. The observed difference may be considered as a marker of redistribution between high and low molecular weight ligands. CONCLUSIONS: Metal speciation is significantly affected in serum of PD-patients. These findings are indicative of the potential role of metal metabolism and PD pathogenesis, although the exact mechanisms of such associations require further detailed studies.