The Interplay Between Neuroinfections, the Immune System and Neurological Disorders: A Focus on Africa

Neurological disorders related to neuroinfections are highly prevalent in Sub-Saharan Africa (SSA), constituting a major cause of disability and economic burden for patients and society. These include epilepsy, dementia, motor neuron diseases, headache disorders, sleep disorders, and peripheral neuropathy. The highest prevalence of human immunodeficiency virus (HIV) is in SSA. Consequently, there is a high prevalence of neurological disorders associated with HIV infection such as HIV-associated neurocognitive disorders, motor disorders, chronic headaches, and peripheral neuropathy in the region. The pathogenesis of these neurological disorders involves the direct role of the virus, some antiretroviral treatments, and the dysregulated immune system. Furthermore, the high prevalence of epilepsy in SSA (mainly due to perinatal causes) is exacerbated by infections such as toxoplasmosis, neurocysticercosis, onchocerciasis, malaria, bacterial meningitis, tuberculosis, and the immune reactions they elicit. Sleep disorders are another common problem in the region and have been associated with infectious diseases such as human African trypanosomiasis and HIV and involve the activation of the immune system. While most headache disorders are due to benign primary headaches, some secondary headaches are caused by infections (meningitis, encephalitis, brain abscess). HIV and neurosyphilis, both common in SSA, can trigger long-standing immune activation in the central nervous system (CNS) potentially resulting in dementia. Despite the progress achieved in preventing diseases from the poliovirus and retroviruses, these microbes may cause motor neuron diseases in SSA. The immune mechanisms involved in these neurological disorders include increased cytokine levels, immune cells infiltration into the CNS, and autoantibodies. This review focuses on the major neurological disorders relevant to Africa and neuroinfections highly prevalent in SSA, describes the interplay between neuroinfections, immune system, neuroinflammation, and neurological disorders, and how understanding this can be exploited for the development of novel diagnostics and therapeutics for improved patient care.

A decision support system for primary headache developed through machine learning

Background Primary headache is a disorder with a high incidence and low diagnostic accuracy; the incidence of migraine and tension-type headache ranks first among primary headaches. Artificial intelligence (AI) decision support systems have shown great potential in the medical field. Therefore, we attempt to use machine learning to build a clinical decision-making system for primary headaches. Methods The demographic data and headache characteristics of 173 patients were collected by questionnaires. Decision tree, random forest, gradient boosting algorithm and support vector machine (SVM) models were used to construct a discriminant model and a confusion matrix was used to calculate the evaluation indicators of the models. Furthermore, we have carried out feature selection through univariate statistical analysis and machine learning. Results In the models, the accuracy, F1 score were calculated through the confusion matrix. The logistic regression model has the best discrimination effect, with the accuracy reaching 0.84 and the area under the ROC curve also being the largest at 0.90. Furthermore, we identified the most important factors for distinguishing the two disorders through statistical analysis and machine learning: nausea/vomiting and photophobia/phonophobia. These two factors represent potential independent factors for the identification of migraines and tension-type headaches, with the accuracy reaching 0.74 and the area under the ROC curve being at 0.74. Conclusions Applying machine learning to the decision-making system for primary headaches can achieve a high diagnostic accuracy. Among them, the discrimination effect obtained by the integrated algorithm is significantly better than that of a single learner. Second, nausea/vomiting, photophobia/phonophobia may be the most important factors for distinguishing migraine from tension-type headaches.

Migraine

Migraine is the most common disabling brain disorder. Chronic migraine, a condition characterized by the experience of migrainous headache on at least 15 days per month, is highly disabling. Patients with chronic migraine present to primary care, are often referred for management to secondary care, and make up a large proportion of patients in specialist headache clinics. Many patients with chronic migraine also have medication overuse, defined as using a compound analgesic, opioid, triptan or ergot derivative on at least 10 days per month. All doctors will encounter patients with chronic headaches. A basic working knowledge of the common primary headaches, and a rational manner of approaching the patient with these conditions, allows a specific diagnosis of chronic migraine to be made quickly and safely, and by making this diagnosis one opens up a substantial number of acute and preventive treatment options. This article discusses the current state of management of chronic migraine.

How to Assess the Headache—Sleep Disorders Comorbidity in Children and Adolescents

Sleep disorders and primary headaches are frequent health problems in childhood, and they are often comorbid in an individual, linked by a mutual and complex relationship. This comorbidity is frequent and well-documented, but the available literature is usually biased in favor of one aspect or another, mainly depending on the expertise of the authors. The aim of this paper is to review existing literature on the diagnostic assessment of comorbid primary headaches and sleep disorders, so as to propose practical suggestions to accurately investigate the presence of comorbid conditions in children evaluated for primary headaches or for sleep disorders.

Migraine and Its Equivalents: What Do They Share? A Narrative Review on Common Pathophysiological Patterns

Migraine is the first in order of frequency of the neurological disorders, affecting both adult and paediatric populations. It is also the first cause of primary headaches in children. Migraine equivalents are periodic disorders that can be associated with migraine or considered as prognostic features of a future migraine manifestation. Despite the mechanisms underlying migraine and its equivalents are not entirely clear, several elements support the hypothesis of common pathophysiological patterns shared by these conditions. The aim of this review is thus to analyze the literature in order to highlight which currently known mechanisms may be common between migraine and its equivalents.

Headache provocation by nitric oxide in men who have never experienced a headache

Introduction In the general population 4% have never experienced a headache. Freedom from headache could be due to distinctive protective mechanisms or a lack of environmental risk factors for headache. Isosorbide-5-mononitrate is an organic nitrate which in the body is metabolised to nitric oxide. The nitric oxide pathway plays a crucial role in the primary headaches. We hypothesized that people who are free from headache are protected by distinctive mechanisms in the nitric oxide pathway. Methods We performed an observer blinded case-control study using nitric oxide to provoke a headache. 32 headache free male participants and 26 randomly selected male controls received 60 mg Isosorbide-5-mononitrate orally on the study day. Participants fill out a headache diary with headache intensity and characteristics until 12 hours after administration of Isosorbide-5-mononitrate. Primary endpoint were areas under the curve of headache intensity score. Results All 58 participants completed the study. There was no significant difference in headache incidence, headache intensity score or migraine-like attack between headache free participants and controls. Conclusion We show that men who have never experienced a headache develop a headache when provoked with Isosorbide-5-mononitrate. This indicates that freedom from headache in men is not related to the nitric oxide pathway which is involved in the primary headache disorders.

Sleep disturbance management in patients with trigeminal autonomic cephalalgias

Trigeminal autonomic cephalalgias (TACs) are rare but are the most intense primary headaches that severely limit patients’ ability to work and be socially active. This article reviews the modern classification of TACs, based on the International Classification of Headache Disorders-3, and the key differences between TAC types, as well as the pathophysiological mechanisms – the role of the trigeminovascular system, autonomic nervous system, hypothalamus and vagus nerve – and their relation to circadian rhythms. The sleep disturbances that can occur in patients with TACs, exacerbating the course of the disease, and the role of melatonin, hypothalamus and suprachiasmatic nucleus in these conditions are also discussed. In addition, current therapies for cluster headache are described, which include acute therapy and prophylactic therapy, with recommendations regarding the timing of prophylactic therapy discontinuation. The review also includes the available data on melatonin as well as new therapies such as CGRP monoclonal antibodies and neuromodulation, which includes the two most promising techniques: non-invasive vagus nerve stimulation and sphenopalatine ganglion microstimulation. Furthermore, the authors present the clinical case of a patient with chronic cluster headache, which was significantly reduced in frequency and intensity when melatonin was added to the therapy.

Correlation between depression level and headache severity: A study among medical students during the COVID-19 pandemic

Headache is the most prevailing disorder and the third leading cause of disability worldwide. The prevalence of primary headaches has been reported to increase by 2-4 times in patients with psychiatric comorbidities, including depression. This study sought to assess the correlation between depression level and headache severity among medical students. To the best of our knowledge, this is the first study to evaluate the correlation between depression level and headache severity in Indonesia. A cross-sectional study was conducted among students of Airlangga University in 2021. To evaluate the level of depression and the severity of headache, Depression Anxiety Stress Scales (DASS-42) and Headache Impact Test 6 (HIT-6) were used, respectively. A set of validated questionnaires were used to assess students’ demographic characteristics. A total of 82 medical students were included in this study and most of them were female (86.6%). The third-semester students represented the highest proportion (45.2%) of subjects. The mean age and body mass index (BMI) were 19.88 ± 1.03 and 22.55±4.44, respectively. The average DASS-42 score was 10.98±11.47 which indicated a mild depression level. The average HIT-6 score was 45.74±6.130 which revealed a mild impact. The data of Spearman correlation suggested that headache severity was significantly correlated with depression level (r=0.396, p<0.001). This study provides insights on the importance of stress management and depression prevention to decrease the risk of headache, and vice versa.

Relation of hypertension with episodic primary headaches and chronic primary headaches in population of Rafsanjan cohort study

Headache has a variety of types, such as episodic primary headaches (EPH) and chronic primary headache (CPH) in its primary form. There is a positive correlation between these two types of headaches and hypertension (HTN), but in some works this correlation has been reported negatively. Therefore, we planned to study HTN-CPH as well as HTN-EPH correlation in our population. A sample of Rafsanjan population (10,000 individuals) entered the cohort study, as one of the Prospective Epidemiological Research Studies in Iran (PERSIAN). We compared the frequency of HTN categories in CPH and EPH cases with a normal population. Out of 9933 participants (46.6% males and 53.4% females) about 29% had EPH and 7.5% had CPH. HTN was found in 24.27% of EPH cases and 31.98% of CPH cases. HTN was also found to be associated with EPH and CPH in the crude model. Two Categories of HTN (Long controlled and uncontrolled) were not associated with EPH. On the other hand, CPH showed associations with all of the HTN categories. After included all variables and confounders, EPH and CPH had association with HTN without any considerable changes. There is strong HTN-EPH as well as HTN-CPH correlations in the studied population.

Immunological findings in patients with migraine and other primary headaches: a narrative review

Experimental findings suggest an involvement of neuroinflammatory mechanisms in the pathophysiology of migraine. Specifically, preclinical models of migraine have emphasized the role of neuroinflammation following the activation of the trigeminal pathway at several peripheral and central sites including dural vessels, the trigeminal ganglion and the trigeminal nucleus caudalis. The evidence of an induction of inflammatory events in migraine pathophysiological mechanisms has prompted researchers to investigate the Human leukocyte antigen (HLA) phenotypes as well as cytokine genetic polymorphisms in order to verify their potential relationship with migraine risk and severity. Furthermore, the role of neuroinflammation in migraine seems to be supported by evidence of an increase in pro-inflammatory cytokines, both ictally and interictally, together with the prevalence of Th1 lymphocytes and a reduction in regulatory lymphocyte subsets in peripheral blood of migraineurs. Cytokine profiles of cluster headache patients and those of tension-type headache patients further suggest an immunological dysregulation in the pathophysiology of these primary headaches, although evidence is weaker than for migraine. The present review summarizes available findings to date from genetic and biomarker studies that have explored the role of inflammation in primary headaches.