Real-life experiences with galcanezumab and predictors for treatment response in Turkey.

BACKGROUND: The complexity of clinical practice extends far beyond the controlled settings of trials, and there is a need for real-world studies aimed at identifying which patients will respond to anti-CGRP monoclonal antibodies in different countries. This study aimed to investigate the efficacy and safety of galcanezumab in treating migraine in a real-life setting in Turkey, as well as identify predictors of treatment response. METHODS: A total of 476 patients who diagnosed with migraine according to ICHD-3 criteria and treated with galcanezumab by headache specialists were voluntarily participated in this cross-sectional study. Galcanezumab is indicated for the prevention of migraine in adults who have at least 4 monthly migraine days in Turkey. All patients filled out a survey on Google Form that comprised 54 questions, addressing various aspects such as demographics, migraine characteristics, previous use of acute symptomatic medication, failures with preventive drug classes, comorbidities, most bothersome symptoms, as well as the interictal burden of migraine. RESULTS: Among the participants, 89.3% reported that galcanezumab treatment was beneficial for them. A decrease in the frequency (80.0%), severity (85.7%), and acute medication usage for migraine attacks (71.4%) was reported with galcanezumab treatment. An adverse effect related to galcanezumab was reported in 16.3% of cases, but no serious adverse reactions were observed. Remarkably, 14.3% of participants reported no longer experiencing any headaches, and 18.9% did not require any acute treatment while receiving galcanezumab treatment. A logistic regression model showed that male gender, lack of ictal nausea, and previous failure of more than 2 prophylactic agents may predict the non-responders. CONCLUSIONS: The first large series from Turkey showed that galcanezumab treatment is safe and effective in most of the patients diagnosed with migraine by headache experts in the real-life setting. Patients reported a significant decrease in both ictal and interictal burden of migraine and expressed satisfaction with this treatment.

COVID-19 vaccination-related headache showed two different clusters in the long-term course: a prospective multicenter follow-up study (COVA-Head Study).

BACKGROUND: Although acute headache following COVID-19 vaccination is widely acknowledged, the long-term progression of these headaches remains poorly understood. Our objective was to identify various phenotypes of prolonged or worsened headaches associated with COVID-19 vaccination and document any changes in these phenotypes over an extended period. Additionally, we aimed to document the diverse headache presentations among patients with pre-existing primary headaches. METHODS: A multinational, prospective observational study was conducted to investigate prolonged or worsened headaches associated with COVID-19 vaccination. Questionnaires assessing COVID-19 vaccination-related headaches at three time points (initial visit, 3rd month follow-up, and 6th month follow-up) were developed for the study. Headache specialists/clinicians evaluated patients using these questionnaires in a prospective manner. Repeated K-means cluster analysis was performed to identify patient profiles with prolonged or worsened headaches related to COVID-19 vaccination. RESULTS: Among the 174 patients included in the study, there was a female-to-male ratio of 128 (73.6%) to 46 (26.4%). The mean age of the patient group was 45.2 ± 13.3 years, and 107 patients (61.5%) had a pre-existing history of primary headaches. Through the analysis, two major clusters were identified based on headache characteristics at each visit. During the first visit (n = 174), Cluster 1 primarily comprised patients with a history of primary headaches, frontal localization of pain, throbbing pain type, more severe headaches accompanied by symptoms such as nausea, phonophobia, photophobia, and osmophobia, and worsened by physical activity. In contrast, Cluster 2 consisted of patients with longer headache durations (over one month) and a stabbing/pressing quality of pain. Patients in Cluster 1 had a higher prevalence of migraine as the pre-existing primary headache disorder compared to Cluster 2 (90.48% vs. 68.18%, respectively; p = 0.005). CONCLUSION: The identification of two distinct phenotypes of prolonged or worsened headaches related to COVID-19 vaccination can provide valuable clinical insights. Having an awareness of the potential worsening of headaches following COVID-19 vaccination, particularly in patients with a primary headache disorder such as migraine, can help clinicians and headache experts anticipate and adjust their treatment strategies accordingly. This knowledge can aid in preplanning treatment modifications and optimize patient care.

An invisible cause of disability: stigma in migraine and epilepsy.

OBJECTIVE: Our purpose was to identify the ratio and severity of stigmatization in patients with migraine and epilepsy. We also collected demographic and clinical data to search for possible facilitators. METHODS: In total, 196 patients with migraine and 60 patients with epilepsy were enrolled. Neuro-QoL Stigma Scale was applied in an office setting by a neurologist in 3 different centers. Stigma scores were calculated as standardized T scores (total, enacted, and internalized). Demographics, clinical characteristics, and treatment status of the patients were also compared in terms of stigma scores. Kruskal-Wallis test or Mann-Whitney U tests were applied for comparisons. Spearman's correlation analysis was used for the evaluation of inter-parameter correlations. RESULTS: Eighty-one percent of the patients with epilepsy and 72% of the patients with migraine reported being stigmatized. Total T scores were significantly higher in the epilepsy group (50.78 ± 9.1) than the patients with migraine (44.9 ± 7.62), also than the chronic (45.86 ± 8.76) and episodic (44.7 ± 7.27) migraine subgroups (p < 0.05). T scores increased as the duration of disease increased; however, this correlation was significant for the epilepsy group only (p < 0.05). Migraine group with prophylactic treatment had significantly higher scores than the migraineurs without preventive therapy (p < 0.05). Enacted T scores were higher than internalized T scores in all analyzed groups and subgroups (p < 0.05). CONCLUSION: Patients with migraine and epilepsy are subjected to stigma. The ratio and intensity can change in different countries. We need to increase the awareness and search for better solutions. The standardized tests are important to compare results between studies.

Headache onset after vaccination against SARS-CoV-2: a systematic literature review and meta-analysis.

BACKGROUND: Vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are used to reduce the risk of developing Coronavirus Disease 2019 (COVID-19). Despite the significant benefits in terms of reduced risk of hospitalization and death, different adverse events may present after vaccination: among them, headache is one of the most common, but nowadays there is no summary presentation of its incidence and no description of its main features. METHODS: We searched PubMed and EMBASE covering the period between January 1st 2020 and August 6th, 2021, looking for record in English and with an abstract and using three main search terms (with specific variations): COVID-19/SARS-CoV-2; Vaccination; headache/adverse events. We selected manuscript including information on subjects developing headache after injection, and such information had to be derived from a structured form (i.e. no free reporting). Pooled estimates and 95% confidence intervals were calculated. Analyses were carried out by vaccine vs. placebo, by first vs. second dose, and by mRNA-based vs. "traditional" vaccines; finally, we addressed the impact of age and gender on post-vaccine headache onset. RESULTS: Out of 9338 records, 84 papers were included in the review, accounting for 1.57 million participants, 94% of whom received BNT162b2 or ChAdOx1. Headache was generally the third most common AE: it was detected in 22% (95% CI 18-27%) of subjects after the first dose of vaccine and in 29% (95% CI 23-35%) after the second, with an extreme heterogeneity. Those receiving placebo reported headache in 10-12% of cases. No differences were detected across different vaccines or by mRNA-based vs. "traditional" ones. None of the studies reported information on headache features. A lower prevalence of headache after the first injection of BNT162b2 among older participants was shown. CONCLUSIONS: Our results show that vaccines are associated to a two-fold risk of developing headache within 7 days from injection, and the lack of difference between vaccine types enable to hypothesize that headache is secondary to systemic immunological reaction than to a vaccine-type specific reaction. Some descriptions report onset within the first 24 h and that in around one-third of the cases, headache has migraine-like features with pulsating quality, phono and photophobia; in 40-60% of the cases aggravation with activity is observed. The majority of patients used some medication to treat headache, the one perceived as the most effective being acetylsalicylic acid.

Olfactory and Gustatory Dysfunctions in COVID-19 Patients: From a Different Perspective.

PURPOSE: The prevalence of sensory disorders (smell and/or taste) in affected patients has shown a high variability of 5% to 98% during the COVID-19 outbreak, depending on the methodology, country, and study. Loss of smell and taste occurring in COVID-19 cases are now recognized by the international scientific community as being among the main symptoms of the disease. This study investigates loss of smell and taste in outpatients and hospitalized patients with laboratory-confirmed COVID-19 infection. METHODS: Enrolled in the study were patients with a positive PCR test for COVID-19. Excluded were patients with chronic rhinosinusitis, nasal polyposis, common cold, influenza, and olfactory/gustatory dysfunction predating the pandemic. Patients were asked about changes in their sense of smell and taste by structured questionnaire. Their status was classified according to severity of the symptoms. RESULTS: A total of 217 patients were included in the study, of whom 129 received outpatient treatment, whereas 88 were hospitalized; mean age was 41.74 years (range18-76), 59.4% were male. At evaluation for olfactory dysfunction, 53.9% of the patients were found to be normal, whereas 33.2% were anosmic. No gustatory dysfunction was found in 49.8% of patients, whereas in those with loss of taste, the most commonly recorded symptom was ageusia. Anosmia was significantly more common in outpatients (P = 0.038). Presentation of chemosensorial symptoms in women was higher than in men (P = 0.009). No correlation was found between olfactory and gustatory dysfunction and age (P = 0.178). CONCLUSIONS: About one-half of our patients presented olfactory and/or gustatory deficits, and loss of smell was more common in mild cases. It should be considered; a sudden, severe, and isolated loss of smell and/or taste may also be present in COVID-19 patients who are otherwise asymptomatic. We suggest that identification of persons with these signs and early isolation could prevent spread of the disease in the community.

The frequency of complementary and integrative medicine methods in headache patients and their spending habits.

BACKGROUND: It is known that complementary and integrative medicine (CIM) methods are especially used by patients with chronic headaches. The aim of our study is to increase the knowledge on this topic, to provide objective data about use in Turkish headache patients. METHODS: This study included 425 patients with headache. The survey form prepared was filled in under the supervision of a health professional. The questionnaire included 2 items, about CIM methods and finance. RESULTS: Among the patients evaluated, 316 were female, and 109 were male. All of 52% answered yes to the question "did you ever use any CIM treatment method for headaches during your life?". The most frequently used methods were combined (herbal+one or more other method) (29.6%), herbal (9.4%) and cupping therapy (4.2%). Among the patients that used combined methods, 26.9% had spent 30-100TL (5-25euro), 20.6% had spent 100-300TL (25-70euro), 26.9% had spent 300-500TL (70-120euro) and the last two groups that formed 12.6% had spent 500-1000 (120-250euro) and >1000TL (>250euro). CONCLUSION: Half of the patients that applied to outpatient clinic with headaches use one or more of these methods and make budgets in accordance with their income levels. Physicians should have sufficient knowledge and clinical opinions about the CIM methods used by headache patients.

Does migraine affect central auditory processing abilities?

OBJECTIVE: Migraine is a neurological disease associated with an altered cortical excitability level. Several studies have investigated the relationship between migraine and central auditory processing (CAP), with deficits in CAP being common among migraine patients. However, studies on the factors affecting these CAP changes observed in migraine patients are still few and controversial. This study aims to investigate CAP changes in migraine patients with Duration Pattern Test (DPT) and Frequency Pattern Test (FPT), which have not been used in previous studies. METHODS: Sixty subjects were divided into two groups and one migraine subgroup: control group, twenty normal healthy subjects, fourty subjects diagnosed with migraine. They were evaluated using the CAP test including DPT and FPT. To identify the variables and possible effects of the variables, a questionnaire describing the characteristics of migraine features was administered to participants with migraine. RESULTS: No significant difference was found the between the control and study group in CAP tests scores. No significant correlation was found between migraine characteristics and CAP tests scores. Males had significantly higher FPT scores in both ears than females (p<0.05). Significant statistical negative correlation was found between age and FPT scores for both ears and left DPT scores (p<0.05). CONCLUSION: Although migraine patients generally showed lower CAP ability than the control group, no significant difference was observed between them. This was also valid for subgroups of migraine. However, as age increased in the migraine group, a significant decrease in CAP performance was observed. It was observed that male migraine patients had better CAP ability, especially FPT scores. Migraine may affect performance in CAP depending on gender and age factors.

Can Auditory and Vestibular Findings Differentiate Vestibular Migraine and Meniere's Disease?

BACKGROUND AND OBJECTIVES: Besides evaluating the auditory and vestibular systems of patients with vestibular migraine (VM) and Meniere's disease (MD), this study aimed to examine the clinical overlaps between these two conditions by detailed evaluation of the patient's symptoms. Subjects and. METHODS: The ears of the patients with VM and MD were evaluated and patients' vestibular and auditory complaints were questioned particularly. Pure tone audiometry, vestibular evoked myogenic potential (VEMP) responses, and caloric test results were evaluated for objective measurements. RESULTS: The VM group had better air-conduction and boneconduction threshold and speech reception threshold and speech discrimination score test values (p<0.05). Regarding the interaural N1-P1 asymmetry ratio, the cervical VEMP between the groups had significant differences (p=0.019). The MD group had more unilateral tinnitus and ear fullness complaints and canal paresis results (p<0.01). The VM group had more motion sickness complaints (p<0.01). CONCLUSIONS: If only ears with hearing loss are evaluated; there was no significant difference between VM and MD, but regardless of hearing level or only the patients with normal hearing were evaluated, the VM group had better hearing levels. It should be considered that patients with VM may have VM-independent hearing loss, and patient complaints should be sufficiently detailed to make an accurate distinction from MD.

Cerebral proliferative angiopathy accompanied by cerebral cavernous malformation: A case report.

Cerebral Proliferative Angiopathy (CPA) is a rare vascular malformation that is distinguished from classical brain arteriovenous malformations (AVM) in its imaging findings and clinical progression but more importantly in its pathophysiology. Here we report the case of a 37-year-old male patient with CPA accompanied by Cerebral Cavernous Malformation (CCM) in hopes to expand the inquiry into the pathophysiology of this rare lesion. A patient with progressive headache, right-sided weakness, and impaired speech were evaluated at our medical center. Neuroimaging studies were performed, and the patient was diagnosed with CPA. The patient has been followed up with conservative management and periodic neuroradiological evaluation for 5 years. Digital subtraction angiography (DSA) showed a vascular malformation diffusely covering the left hemisphere that is consistent with CPA. In addition, 2 sequential CCMs were detected in the right hemisphere. Also, the patients' familial history included two brothers with CCMs. The coexistence of CPA with CCM and patients' familial history of CCM could suggest the possibility of a common pathophysiological element.

The Relationship Between Pain, and Freezing of Gait and Falls in Parkinson's Disease.

INTRODUCTION: To investigate the relationship between pain, freezing of gait (FOG) and falls in Parkinson's Disease (PD). METHODS: The study included 110 PD patients. The Unified PD Rating Scale (UPDRS) and Hoehn and Yahr Scale were used to evaluate disease severity. The patients self-reported occurrence of FOG and falls, and the FOG Questionnaire was administered to evaluate the severity of FOG. A visual analog scale (VAS) was used to measure the severity of pain and pain localization was self-reported by the patients. RESULTS: Fifty-eight of the patients had FOG and 43 experienced falls. Among the patients, 42 had no pain, whereas 35 had lower extremity pain. Higher UPDRS motor and FOG scores, and advanced-stage disease were noted in significantly more of the patients with FOG and falls. VAS scores were not affected by the presence of FOG or falls. There was a positive correlation between the severity of FOG and VAS score in the male patients (r=0.308; p=0.010). More patients with falls had lower extremity pain than those without falls (r=0.308; p=0.010). DISCUSSION: Patients with FOG and falls had more severe motor findings. Pain is correlated with both FOG and falls. Further investigations should be done to understand the mechanism of this relationship to prevent the motor complications in advanced PD.

Accelerated long-term forgetting after amygdalohippocampectomy in temporal lobe epilepsy.

AIM OF THE STUDY: Temporal lobe epilepsy (TLE) has been associated with the phenomenon of accelerated long-term forgetting (ALF). In this study, we aimed to demonstrate the effect of surgery on the ALF phenomena thus contributing to potential explanation of the causal mechanism. MATERIALS AND METHODS: We evaluated 51 patients with TLE related to hippocampal sclerosis who had amygdalohippocampectomy and had remained seizure-free after surgery. A control group consisted of 24 healthy individuals. All were given a verbal learning test assessing recall after 30 min, 1 week and 6 weeks. RESULTS: In our study, the Left-TLE (L-TLE) group showed a statistically significant reduction in the performance at all assessment intervals from 30 min to 1 week compared to the Right-TLE and control groups regarding verbal learning memory test (VLMT) as well as for logical memory. The forgetting rates in the VLMT from 30 min to 1 week were not statistically significantly different between all 3 groups. The logical memory test results equally showed no statistically significant difference in the forgetting rates for the 3 groups between 30 min and 1 week. CONCLUSIONS AND CLINICAL IMPLICATIONS: These results may support ongoing debates assuming the initial low performance in the memory of L-TLE patients to be directly related with left hippocampal-temporal tissue loss irrespective of epileptic activity. The discovery of the ALF phenomenon explains that standard memory tests are unable to detect memory loss in some patients who are experiencing a significant level of problems with forgetfulness in their daily lives.

Blink Reflex in Episodic and Chronic Migraine.

INTRODUCTION: Activation of the trigeminovascular system and sensitization of brainstem trigeminal nuclei play a significant role in the physiopathology of migraine. Our aim was to investigate blink reflex (BR) and its recovery in episodic and chronic migraine patients. METHODS: Twenty-eight chronic migraine patients, thirty-two episodic migraine without aura patients and thirty healthy controls were included in the study. The study was performed using a portable electromyography device with a software specifically prepared for BR. Blink reflex assessments were performed in patients during the pain-free period and in healthy controls using the 'standard method - double stimulation' technique in 200 ms, 500 ms, 1000 ms, 2000 ms, and 5000 ms intervals. RESULTS: Blink reflex recovery was significantly increased in both patient groups as compared to the control group in 200 ms interstimulus interval (ISI) on both sides (p<0.005). Moreover, when it was compared to the control group, recovery was also significantly increased in the chronic migraine group in 2000 ms ISI on the right side and in 5000 ms ISI on the left side as well as in 500 and 1000 ms ISIs on the left side in the migraine without aura group (p<0.002, p<0.003). R2 recovery curve was noted to be higher in both patient groups as compared to the control group, although could not be demonstrated statistically in all intervals. A statistically significant increase was observed in the migraine group without auras compared with the controls (p <0,037, p <0,011) in the left side at 500 and 1000 ms ISIs. For all intervals in our study, although the increase in recovery was not statistically significant, it was noted that the R2 recovery curve was higher in the patient groups, with respect to the normals. The increase in R2 recovery noted in both patient groups suggested increased sensitization of the trigeminal structures. Significantly increased recovery in low ISI (200 ms) in the two patient groups as compared to the control group raised the thought that the migraine brain goes through two different excitability periods (ictal and interictal). CONCLUSION: In conclusion, similar to the previous studies, the findings of this study suggested that there was a reduction in central inhibitory mechanisms during interictal period in migraine patients.

Beyond The Therapeutic Effect of rTMS in Alzheimer's Disease: A Possible Neuroprotective Role of Hippocampal BDNF? : A Minireview.

Repetitive transcranial magnetic stimulation (rTMS) is a well known non-invasive brain stimulation procedure which is capable of inducing the expression of the hippocampal BDNF that has been already shown to exert significant neuroprotective and pro-cognitive effects in AD. However, it is nearly impossible directly to evaluate the BDNF expression in humans after rTMS application. Here we summarized the underlying mechanisms of the neuroprotective and procognitive effect of BDNF that can be induced through a region-specific rTMS approach. Additionally, we have also evaluated the role of Magnetic Resonance Spectroscopy in monitoring the BDNF response after rTMS application in Alzheimer's Disease. We have provided strong evidence that rTMS exerts significant neuroprotective and pro-cognitive effects through the expression of hippocampal BDNF. Furthermore, Magnetic Resonance Spectroscopy might play a critical role in monitoring the BDNF response after rTMS application in AD patients. Such a sophisticated approach might be able to enlighten us on the time-dependent cognitive and neuroprotective correlates of the rtMS application in AD patients.

Human Herpesvirus 6 encephalitis in an immunocompetent pregnant patient and review of the literature.

Central nervous system infection caused by Human Herpesvirus 6 (HHV-6) is well known in immunocompromised; however, data regarding immunocompetent patients is limited to case series. We describe a 29-year-old immunocompetent pregnant woman with meningoencephalitis due to HHV-6 and review current literature. HHV-6 should be kept in mind in patients with meningoencephalitis of unknown etiology.

Transcranial Direct Current Stimulation in the Treatment of Essential Tremor: An Open-Label Study.

INTRODUCTION: Pharmacotherapy and thalamic stimulation are the most accepted methods used for the treatment of essential tremor (ET). Transcranial direct current stimulation (tDCS) is a noninvasive method for brain stimulation, especially to treat pain, cerebrovascular disease, and depression. tDCS applied to the cerebellar region has been shown to exhibit a modulating effect on the excitability of Purkinje cells and to cause primary motor cortex inhibition through the regulation of synaptic dentato-thalamo-cortical excitability. There is only 1 trial that studied the effect of tDCS on ET with 8 patients, and the results were not satisfactory. CASE SERIES: Six ET patients were administered the Essential Tremor Rating Assessment Scale (TETRAS) and Activities of Daily Living (ADL). We applied tDCS to the dorsolateral prefrontal areas (anode) and to inion (inion at 2 mA for 20 min in 10 consecutive sessions with a 2-d break between the first and the second 5-d sessions). One month after the initial course of therapy, 5 more tDCS sessions were administered in an every-other-day manner. TETRAS and ADL scales were readministered. The Friedman test was used to assess differences in TETRAS scores and ADL over the whole time course. CONCLUSIONS: A significant improvement was observed in TETRAS and ADL scores at the end of 50 days (P=0.015, 0.024). We concluded that although our sample group is small, tDCS might be an alternative therapy for patients with ET.

The Neuroprotective Role of Repetitive Transcranial Magnetic Stimulation (rTMS) for Neurodegenerative Diseases: A Short Review on Experimental Studies.

There are rapidly replicating human data suggesting the therapeutic and neurorestorative role of transcranial magnetic stimulation in various neurological and psychiatric disorders. However there are only limited experimental studies in the literature enlighting the neurobiological mechanisms of this technique. In the light of these findings, we aimed to review the neuroprotective effect of rTMS in various animal studies. We have shown that rTMS may exert significant neuroprotective effect through acting on the neuroinflammation, excitotoxicity, oxidative stress and Aß aggregation.

Therapeutic Effects of Rivastigmine and Alfa-Lipoic Acid Combination in the Charles Bonnet Syndrome: Electroencephalography Correlates.

BACKGROUND: Charles Bonnet Syndrome (CBS) is a rare clinical condition which is characterized by complex hallucinations in visually impaired patients. The pathophysiology of this disorder remains largely unknown, and there is still no proven treatment for this disease. In our study, we aimed to investigate the neural activity through Electroencephalography (EEG) power and evaluate the effect of rivastigmine in combination with alpha-lipoic acid on hallucination in two CBS patients with diabetic retinopathy. METHODS: EEG data was recorded with standard routine EEG protocols for both patients in our electrophysiological research laboratory (REMER Clinical Electrophysiology and Neuromodulation Research and Application Laboratory) with Brain Vision Recorder (Brainproduct, Munich, Germany). All spectral analyses were processed by BrainVision Analyzer 2 (Brainproduct, Munich, Germany, 2.0.4 Version) in 128 Hz sample rates and the EEG recording and analysis was performed before the administration of rivastigmine (4.5 mg/daily and five patch daily for the first and second patients, respectively) in combination with alpha-lipoic acid (600 mg/daily) for both patients while they were not hallucinated during the time period recordings. Based on our measurement protocol, we have compared the patients in the study group with the three control subjects who were found to be normal except of visual disturbances secondary to significant diabetic retinopathy. RESULTS: Highest theta power values were found in right occipital and left temporo-parietal regions for first and second CBS patients, respectively. Additionally, power spectra were lower in two cases as compared to their control groups in the alpha band for all electrodes. We have also shown that acid rivastigmine in combination with alpha-lipoic exerted significant anti-hallucinatory efficiency. CONCLUSION: Our present findings could support the hypothesis that increased activation of specific areas in the source monitoring system plays an important role in the pathogenesis of CBS. In addition, rivastigmine in combination with alpha-lipoic acid could be a new valuable option for CBS patients.

Surgical approaches used in the reconstruction of the eyelids after excision of malignant tumors.

The choice of reconstructive technique for eyelid defects after malignant tumors was based on tumor location and defect size after tumor excision. Treatments included direct closure for defects measuring less than 25%, Tenzel flap for defects measuring 25-50%, lid-sharing procedures for defects measuring more than 50%, skin grafts for tumors affecting the inner canthus advancement flap for outer canthus tumors, and orbital exenteration for malignant tumors demonstrating orbital invasion.