Search Results (22)

This narrative review examines the effects of caffeine on brain health in older adults, with particular attention to its potential for dependence—an often-overlooked issue in geriatric care. Caffeine acts on central adenosine, dopamine, and glutamate systems, producing both stimulating and rewarding effects that can foster tolerance and habitual use. Age-related pharmacokinetic and pharmacodynamic changes prolong caffeine’s half-life and increase physiological sensitivity in the elderly. While moderate consumption may enhance alertness, attention, and possibly offer neuroprotective effects—especially in Parkinson’s disease and Lewy body dementia—excessive or prolonged use may lead to anxiety, sleep disturbances, and cognitive or motor impairment. Chronic exposure induces neuroadaptive changes, such as adenosine receptor down-regulation, resulting in tolerance and withdrawal symptoms, including headache, irritability, and fatigue. These symptoms, often mistaken for typical aging complaints, may reflect a substance use disorder yet remain under-recognized due to caffeine’s cultural acceptance. The review explores caffeine’s mixed role in neurological disorders, being beneficial in some and potentially harmful in others, such as restless legs syndrome and frontotemporal dementia. Given the variability in individual responses and the underestimated risk of dependence, personalized caffeine intake guidelines are warranted. Future research should focus on the long-term cognitive effects and the clinical significance of caffeine use disorder in older populations. Full article

Topiramate evokes pharmacological activity via a blockade of voltage-dependent sodium channels, reduction in glutamate release, inhibition of AMPA receptors and kainate receptors, and potentiation of GABAergic neurotransmission. Therefore, it is used not only as an antiseizure drug but is also effective in migraine prophylaxis, cluster headaches, neuropathic pain, and alcohol dependence. The aim of this study was to investigate the effect of topiramate in morphine dependence in mice, particularly in terms of morphine tolerance, morphine withdrawal signs, and morphine sensitization. In these experiments, topiramate was administered both acutely and chronically. Topiramate significantly reduced the morphine tolerance in the hot-plate test and attenuated naloxone-induced morphine withdrawal signs. Its effect on morphine sensitization to the locomotor activity of mice was poor. The obtained results showed that topiramate might be an effective drug for reducing the physical symptoms of morphine dependence. Full article

Long COVID, also known as post-acute sequelae of SARS-CoV-2 infection (PASC), is increasingly recognized as a condition affecting not only adults but also children and adolescents. While children often experience milder acute COVID-19 symptoms compared to adults, some develop persistent physical, psychological, and neurological symptoms lasting for weeks or months after initial infection. The most commonly reported symptoms include debilitating fatigue, respiratory issues, headaches, muscle pain, gastrointestinal disturbances, and cognitive difficulties, which significantly impact daily activities, schooling, and social interactions. Additionally, many children with long COVID experience psychological symptoms, such as anxiety, depression, mood swings, and irritability, likely exacerbated by prolonged illness and lifestyle disruptions. Risk factors for long COVID in children include pre-existing health conditions such as asthma, obesity, and neurological disorders, with adolescents and females seemingly more affected. Hypothesized mechanisms underlying long COVID include chronic immune dysregulation, persistent viral particles stimulating inflammation, autonomic nervous system dysfunction, and mitochondrial impairment, which may collectively contribute to the variety of observed symptoms. Long-term outcomes remain uncertain; however, long COVID can lead to school absenteeism, social withdrawal, and psychological distress, potentially affecting cognitive development. Severe cases may develop chronic conditions such as postural orthostatic tachycardia syndrome (POTS) and reduced exercise tolerance. This review synthesizes the existing literature on long COVID in children, examining its prevalence, symptomatology, risk factors, and potential mechanisms, with an emphasis on the need for further clinical studies. While existing research largely relies on surveys and self-reported data, clinical assessments are essential to accurately characterize long COVID in pediatric populations and to guide effective management strategies. Full article

Background/Objectives: Chronic migraine with medication-overuse headache (CM-MOH) is neurophysiologically characterized by increased cortical excitability with sensitization at both the thalamocortical and the cortical levels. It is unclear whether the increased cortical excitability could be reverted by medication withdrawal (i.e., brain state) or whether it is a brain trait of individuals predisposed to medication overuse. In this study, we aim to investigate whether withdrawal from overused drugs can influence and restore these neurophysiological abnormalities. Methods: Somatosensory evoked potentials (SSEPs) were elicited by electrical stimulation of the median nerve (M), the ulnar nerve (U), and the simultaneous stimulation of both nerves (MU) in 14 patients with CM-MOH before (T₀) and after (T₁) a three-week withdrawal protocol and, for comparison, in 14 healthy volunteers (HVs) of a comparable age distribution. We measured the level of thalamocortical (pre-HFO) and cortical activation (post-HFO) by analyzing the high-frequency oscillations (HFOs) embedded in parietal N20 median SSEPs. Furthermore, we calculated the habituation and the degree of cortical lateral inhibition (dLI) of N20-P25 low-frequency SSEPs. Results: After the three-week withdrawal protocol (T₁), we observed a normalization of the baseline habituation deficit (T₀: +0.10 ± 0.54; T₁: −0.53 ± 0.8; p = 0.040) and a reduction in the amplitude for both pre-HFO (p < 0.009) and post-HFO (p = 0.042), with values comparable to those of the HVs. However, no effects were observed on the dLI (p = 0.141). Conclusions: Our findings showed that withdrawal from overused drugs could affect the increased excitability of the non-painful somatosensory system in patients with CM-MOH, reducing the level of sensitization at both the thalamocortical and the cortical levels. Full article

Background: Fibromyalgia (FM) is characterized by chronic pain, significantly affecting the quality of life and functional capabilities of patients. In addition to pain, patients may experience insomnia, chronic fatigue, depression, anxiety, and headaches, further complicating their overall well-being. The Transient Receptor Potential Vanilloid 1 (TRPV1) receptor responds to various noxious stimuli and plays a key role in regulating pain sensitivity and inflammation. Thus, targeting TRPV1 may provide analgesic and anti-inflammatory benefits. This study investigates the efficacy of electroacupuncture (EA) in alleviating chronic pain in FM through TRPV1 and its downstream molecules in the central nervous system (CNS). Methods: To model FM, we subjected mice to intermittent cold stress (ICS) for three days. The study comprised five rodent groups: Control (CON), ICS, ICS + EA, ICS + Sham EA, and ICS + KO (TRPV1 knockout mice). Results: Our findings revealed that ICS induced allodynia and hyperalgesia in mice by day four, persisting until day 21. EA at 2 Hz and TRPV1 KO significantly decreased both mechanical and thermal hypersensitivity (Withdrawal—Day 14: 2.43 ± 0.19 g; Day 21: 5.88 ± 0.47 g, n = 6, p < 0.05; Latency—Day 14: 2.77 ± 0.22 s; Day 21: 5.85 ± 0.41 s, n = 6, p < 0.05). In contrast, sham EA did not produce significant effects. Additionally, TRPV1 and several pain-related proteins were significantly elevated in the thalamus, somatosensory cortex (SSC), medial prefrontal cortex (mPFC), hippocampus, hypothalamus, cerebellum regions V (CB V), VI (CB VI) and VII (CB VII) after the ICS model. Both EA at the ST36 acupoint and TRPV1 KO mice showed diminished overexpression of pain-related proteins, with the sham EA group showing no significant changes compared to the ICS group. Conclusions: Chronic widespread pain was reduced by EA and TRPV1 KO, with the effects of EA on the TRPV1 pain pathway clearly evident in the CNS after 21 days. Full article

Background/Objectives: Habituation and sensitization are opposite phenomena that play a role in the pathophysiology of episodic migraine and its progression to chronic migraine (CM). There have been just a few studies that have investigated these phenomena in patients with medication overuse headache (MOH) in comparison to those with chronic migraine (CM) and healthy controls (HCs), and the findings have been inconsistent. Methods: We measured and examined visual evoked potentials (VEPs) in 81 patients with MOH and 24 patients with CM, as well as 24 HCs. The VEPs were used to assess sensitization by analysing the amplitude of the first block (100 sweeps) and to evaluate habituation by measuring the amplitude response decrement after six blocks. We further examined patients diagnosed with MOH based on their acute medication type and after a 3-week acute medication withdrawal program. Results: There were no significant differences between groups in terms of the first N1-P1 VEP amplitude block and its habituation. It was found that patients with MOH had a greater drop in the amplitude of the VEP P1-N2 complex after repeated stimulation than patients with CM or HC. The VEP parameters showed no significant differences based on the specific overused drug and after a 3-week acute medication withdrawal. Conclusions: We propose that the results obtained in patients with MOH indicate an abnormal activation of inhibitory circuits in the parieto-occipital region in response to repeated modulatory stimuli. Full article

Long-term frequent use of acute pain medication for the treatment of headaches has paradoxically been shown to increase the frequency of headaches. So-called medication-overuse headache (MOH) is particularly problematic in patients with migraine who overuse triptans and opioids. Prevention through education remains the most important management strategy. Once established, MOH can be difficult to treat. Although complete or near-complete withdrawal of acute pain medication for 8–12 weeks has been shown to benefit most patients, this can be hard to achieve. The use of OnabotulinumtoxinA and drugs that target the calcitonin gene-related peptide system for the prevention of migraines have been shown to benefit patients with MOH. Furthermore, the use of novel acute pain medication for migraines, including Gepants and Ditans, which do not cause MOH, are likely to improve patient outcomes. In this review article we examine the following: the burden of MOH; who develops MOH; the pathophysiological mechanisms; and the treatment strategies. Full article

Many patients with cluster headaches report that their relatives do not understand what they are going through. This qualitative study aimed to collect patients’ recommendations and wishes on how others should respond to those suffering from cluster headaches. We recruited 22 patients with episodic or chronic cluster headaches for this cross-sectional study. They responded to seven questions that assessed the disease’s impact on their relationships with relatives and their wishes for others’ behaviour towards them. Seven recommendations for relatives emerged: (i) withdraw during attacks, (ii) respect post-ictal exhaustion, (iii) do not insist on discussing the disorder, (iv) help the patient to lead a “normal” life, (v) support preserving social contacts, (vi) show being aware of the disease severity, and (vii) expect the disease to take up space in patients’ lives and minds. Two recommendations for the interictal period indicate avoidance, which is considered a negative coping strategy. Conversely, the suggestion to support preserving social contacts might mean confronting the disease, which is likely associated with more favourable outcomes. Still, adhering to all patients’ requests might increase suffering instead of reducing it. Thus, further research is needed to develop strategies suited to improve well-being. Full article

Consumption of caffeine in the diet, both daily and occasional, has a significant biological effect on the nervous system. Caffeine, through various and not yet fully investigated mechanisms, affects headaches. This is especially noticeable in migraine. In other headaches such as hypnic headache, post-dural puncture headache and spontaneous intracranial hypotension, caffeine is an important therapeutic agent. In turn, abrupt discontinuation of chronically used caffeine can cause caffeine-withdrawal headache. Caffeine can both relieve and trigger headaches. Full article

A 27-year-old Han Chinese woman presented with fever, headache, lethargy, and difficulty in expression. Magnetic resonance imaging (MRI) detected extensive hyperintensity of the left-sided frontoparietal, temporal, occipital, and insular cortices via fluid-attenuated inversion recovery (FLAIR) imaging. Post-contrast MRI revealed linear enhancement in the frontoparietal, temporal, and occipital sulci bilaterally. The detection of anti-myelin oligodendrocyte glycoprotein (MOG) was positive in the cerebrospinal fluid (CSF) and serum. The patient was diagnosed with anti-MOG antibody-associated unilateral cortical encephalitis with bilateral meningeal involvement. The patient received low doses of intravenous dexamethasone followed by oral prednisone, which was tapered until withdrawal. The treatment significantly improved the patient’s symptoms. A one-month follow-up showed that the patient gradually resumed her normal lifestyle. No further relapse was recorded after a one-year follow-up. MRI performed almost a year after the initial symptom onset showed that the FLAIR signal had decreased in the left insular lobe, and the abnormal cortical signal of the FLAIR in the original left frontotemporal occipital lobe had disappeared. Thus, we report a rare case of anti-MOG antibody encephalitis (unilateral cortical encephalitis with bilateral meningeal involvement) in an adult patient. This study provides a reference for the clinical diagnosis and treatment of MOG antibody-associated unilateral cortical encephalitis. Full article

Pain catastrophizing and cutaneous allodynia are commonly altered in patients with chronic migraine associated with medication overuse headache (CM-MOH) and tend to improve in parallel with clinical improvement. The relation between pain catastrophizing and cutaneous allodynia is poorly understood in patients with CM-MOH receiving OnabotulinumtoxinA therapy. In this single-arm open-label longitudinal observational study, patients with CM-MOH were assigned to structured withdrawal and then administered OnabotulinumtoxinA (5 sessions on a three-month basis, 195 UI per 31 sites). Headache frequency, medication intake, disability, impact, cutaneous allodynia and pain catastrophizing were evaluated with specific questionnaires. In total, 96 patients were enrolled and 79 completed the 12-month follow-up. With the exclusion of cutaneous allodynia and the magnification subscale of the pain catastrophizing questionnaire, all variables showed significant improvement by the sixth month, which was maintained at 12 months. Reduction of pain catastrophizing, and particularly of its helplessness subscale, was a significant predictor of reduction in headache frequency and medication intake. Pain catastrophizing is often implicated in the clinical improvement in patients with CM-MOH receiving behavioral treatments, but, in this study, also showed a role in patients receiving OnabotulinumtoxinA; combining OnabotulinumtoxinA and behavioral treatments specifically addressing pain catastrophizing might further enhance patients’ clinical outcome. Full article

This preliminary analysis of a single-blind phase-III RCT aims to compare the feasibility and short-term efficacy of mindfulness as an add-on to treatment as usual (TaU) in the management of patients with chronic migraine (CM) and medication overuse headache (MOH). Patients were randomized to either TaU (structured withdrawal of overused drugs, patient education and pharmacological prophylaxis) or TaU + MIND, wherein patients additionally received six 90 min weekly group sessions of mindfulness-based therapy. Repeated measures analyses were used to test whether patients in the two arms showed different course with regard to headache frequency and medication intake over a three-month period. Drop-out rates were not different between the two groups: 6/89 (6.7%) and 9/88 (10.2%) among those in TaU and TaU + MIND, respectively. A significant effect of time for all variables was shown, together with a significant effect of time by group, favoring TaU + MIND condition for headache frequency (p = 0.025) and NSAID intake (p = 0.007), controlling for age and CM duration. In total, 45/83 (54.2%) and 69/79 (75.9%) of the patients allocated to TaU and TaU + MIND, respectively, achieved 50% or more headache-day reduction (chi-squared 8.38, p = 0.004). Our preliminary analysis indicates that adding six mindfulness-based sessions to TaU was feasible and showed short-term efficacy in the treatment of patients with CM and MOH. Full article

Background: Idiopathic generalized epilepsies (IGEs) represent 15–20% of all cases of epilepsy in children. This study explores predictors of long-term outcome in a sample of children with childhood absence epilepsy (CAE). Methods: The medical records of patients with CAE treated at a university paediatric hospital between 1995 and 2022 were systematically reviewed. Demographics and relevant clinical data, including electroencephalogram, brain imaging, and treatment outcome were extracted. Outcomes of interest included success in seizure control and seizure freedom after anti-seizure medication (ASM) discontinuation. An analysis of covariance using the diagnostic group as a confounder was performed on putative predictors. Results: We included 106 children (age 16.5 ± 6.63 years) with CAE with a mean follow-up of 5 years. Seizure control was achieved in 98.1% (in 56.6% with one ASM). Headache and generalized tonic-clonic seizures (GTCS) were more frequent in children requiring more than one ASM (p < 0.001 and p < 0.002, respectively). Of 65 who discontinued ASM, 54 (83%) remained seizure-free, while 11 (17%) relapsed (mean relapse time 9 months, range 0–18 months). Relapse was associated with GTCS (p < 0.001) and number of ASM (p < 0.002). Conclusions: A history of headache or of GTCS, along with the cumulative number of ASMs utilized, predicted seizure recurrence upon ASM discontinuation. Withdrawing ASM in patients with these characteristics requires special attention. Full article

This paper examines evidence implicating migraine headache as a withdrawal symptom of excessive sodium chloride intake. Emerging research in food addiction posits that food and drug addictions share common features, such as withdrawal symptoms. Salt (sodium chloride) meets the criteria for the diagnosis of substance dependence, including withdrawal in which the substance is used to relieve withdrawal symptoms. The premonitory symptoms of migraine include food cravings for salty foods, which can alleviate migraine pain. Edema, possibly related to large amounts of salt consumed in binge eating, can cause approximately four pounds of retained fluid. This amount of fluid is similar to the fluid retained before the onset of migraine headache, which may be accompanied by polyuria. This paper proposes that inhibited withdrawal from highly processed food intake, rich in salt, mediates an association between increased sodium chloride intake and relief from migraine headache pain. The relief from withdrawal symptoms could also be a mediating factor that explains the controversial findings inversely associating dietary sodium intake with migraine history. Moreover, the withdrawal of retained sodium and edema related to the use of nonsteroidal anti-inflammatory drugs may elucidate a potential mechanism in medication overuse headache. Further research is needed to investigate the pain experienced from sodium chloride withdrawal in migraine headache. Full article

Autism spectrum disorder (ASD) is a neurodevelopmental disorder affecting approximately 2% of children in the United States. Growing evidence suggests that immune dysregulation is associated with ASD. One immunomodulatory treatment that has been studied in ASD is intravenous immunoglobulins (IVIG). This systematic review and meta-analysis examined the studies which assessed immunoglobulin G (IgG) concentrations and the therapeutic use of IVIG for individuals with ASD. Twelve studies that examined IgG levels suggested abnormalities in total IgG and IgG 4 subclass concentrations, with concentrations in these IgGs related to aberrant behavior and social impairments, respectively. Meta-analysis supported possible subsets of children with ASD with low total IgG and elevated IgG 4 subclass but also found significant variability among studies. A total of 27 publications reported treating individuals with ASD using IVIG, including four prospective, controlled studies (one was a double-blind, placebo-controlled study); six prospective, uncontrolled studies; 2 retrospective, controlled studies; and 15 retrospective, uncontrolled studies. In some studies, clinical improvements were observed in communication, irritability, hyperactivity, cognition, attention, social interaction, eye contact, echolalia, speech, response to commands, drowsiness, decreased activity and in some cases, the complete resolution of ASD symptoms. Several studies reported some loss of these improvements when IVIG was stopped. Meta-analysis combining the aberrant behavior checklist outcome from two studies demonstrated that IVIG treatment was significantly associated with improvements in total aberrant behavior and irritability (with large effect sizes), and hyperactivity and social withdrawal (with medium effect sizes). Several studies reported improvements in pro-inflammatory cytokines (including TNF-alpha). Six studies reported improvements in seizures with IVIG (including patients with refractory seizures), with one study reporting a worsening of seizures when IVIG was stopped. Other studies demonstrated improvements in recurrent infections, appetite, weight gain, neuropathy, dysautonomia, and gastrointestinal symptoms. Adverse events were generally limited but included headaches, vomiting, worsening behaviors, anxiety, fever, nausea, fatigue, and rash. Many studies were limited by the lack of standardized objective outcome measures. IVIG is a promising and potentially effective treatment for symptoms in individuals with ASD; further research is needed to provide solid evidence of efficacy and determine the subset of children with ASD who may best respond to this treatment as well as to investigate biomarkers which might help identify responsive candidates. Full article