Plasma cytokines profile in patients with Alzheimer's and Parkinson's Disease: a comparative study in terms of inflammation.

BACKGROUND: Neurodegenerative disorders such as Alzheimer's and Parkinson's disease inflict economic and health burdens on societies. Alzheimer's disease (AD), the most prevalent form of dementia, is accompanied by progressive degradation of memory, decision-making, and judgment. Parkinson's disease (PD) is characterized by resting tremor, rigidity, bradykinesia, and loss of balance. Extensive research has pinpointed inflammation as a cause of the onset and progression of both diseases. However, it has not been confirmed which one is more formidable in terms of inflammation. METHODS: To assess the extent of inflammation that is implicated in AD and PD and answer the question of which one is more inflammatory, serum levels of inflammatory biomarkers, including cytokines, chemokines, and prostaglandin E2 (PEG2), were measured in AD and PD patients as well as a healthy group. RESULTS: Our results showed a significant increase in IL-1α, IL-1ß, IL-4, IL-6, IL-10, IL-12p70, IP-10, MCP-1, PEG2, and TNF-α in AD and PD patients compared with the control. Interestingly, IFN-γ did not manifest any significant difference in AD or PD patients compared with the control. CONCLUSION: As a hallmark of our results, it could be inferred that inflammation, as the underlying etiological cause, plays a more crucial role in PD compared with AD. Based on our results, it is proposed that anti-inflammatory remedies would be putatively more effective in PD rather than AD.

Psychometric evaluation of Persian version of Seizure Severity Questionnaire.

BACKGROUND AND PURPOSE: Seizure severity has been increasingly gaining attention as a complementary assessment to seizure frequency for the measurement of treatment responses. This study aimed to assess the reliability and external validity and of the Persian version of the Seizure Severity Questionnaire (SSQ). METHODS: The study sample was recruited from 126 patients with epilepsy who attended the neurology outpatient clinic at Imam Khomeini and Roozbeh hospitals, Tehran, Iran. The Forward-Backward technique was applied to translate the questionnaire. The reliability of SSQ was assessed by Cronbach's alpha coefficient. The external validity of SSQ was assessed by correlating SSQ scores with Quality of Life in Epilepsy Inventory-31 (QOLIE-31) subscales. RESULTS: The sample comprised 63 women (50%) and 63 men (50%) aged 13-76 years. The mean scores of SSQ items ranged from 3.46 to 5.48. Distribution was skewed for all component scores, with a tendency for the item scores to concentrate toward the highest scores. Reliability for almost all domains were moderate to good, with Cronbach's alpha ranging from 0.615 to 0.770. Component B to D and total score of SSQ had weak-to-moderate inverse correlation with QOLIE-31 subscale scores. However, the result showed no significant correlation with age, sex, or education. CONCLUSION: With some limitations, the Persian version of the SSQ shows relatively good reliability and content validity, supporting its use as a specific measure of seizure severity in epilepsy in Iran.

Safety and efficacy of melatonin, clonazepam, and trazodone in patients with Parkinson's disease and sleep disorders: a randomized, double-blind trial.

BACKGROUND: Sleep disturbances are common non-motor symptoms of Parkinson's disease (PD). We aimed to compare the safety and efficacy of trazodone with melatonin and clonazepam in patients with PD and sleep complaints. METHODS: This single-center, double-blind, randomized clinical trial was conducted on PD patients with subjective sleep complaints. Eligible patients were randomized 1:1:1 to receive melatonin 3 mg/day, clonazepam 1 mg/day, or trazodone 50 mg/day for 4 weeks. The primary outcome measure was the changes in Pittsburgh Sleep Quality Index (PSQI) scores. The mean change in Epworth Sleepiness Scale (ESS) and RBD screening questionnaire (RBDSQ) was considered as the secondary outcome measures. RESULTS: A total of 112 eligible patients were randomized and 93 participants, melatonin (n = 31), trazodone (n = 31), and clonazepam (n = 31), completed the study. There was a significant decrease in PSQI scores after 4 weeks of treatment in all groups. The mean changes of PSQI from baseline were similar among the treatment arms (P = 0.325). Mean changes of RBDSQ and ESS from baseline were significantly different between study arms (P < 0.05). Melatonin intake was associated with a higher decrease in RBDSQ score compared to trazodone (P = 0.011) and clonazepam (P = 0.004). Trazodone intake was associated with a higher decrease in ESS score compared to clonazepam (P = 0.010). Mild adverse events were reported in three patients in the clonazepam, two patients in the trazodone group, and none in the melatonin group. CONCLUSIONS: Trazodone 50 mg/day, clonazepam 1 mg/day, and melatonin 3 mg/day were all tolerable and effective in improving sleep quality in patients with PD. TRIAL REGISTRATION: Iranian Registry of Clinical Trials (registration number; IRCT20170821035819N2).

Boswellia serrata extract shows cognitive benefits in a double-blind, randomized, placebo-controlled pilot clinical trial in individuals who suffered traumatic brain injury.

BACKGROUND: Traumatic brain injury (TBI) is a major cause of death and disability. TBI can result in neuropsychiatric and cognitive problems as well as neurodegenerative pathologies that can appear right after or develop and persist years after injury. METHOD: We conducted a double-blind, randomized, placebo-controlled clinical trial on patients who suffered from TBI three months to three years ago. The patients were randomized to placebo (n = 34) or K-Vie™ group (n = 46) for a treatment period of 3 months. The main primary outcomes include cognitive assessment in the Rey Auditory Verbal Learning Test-Recognition Test (RAVLT), Wechsler adult intelligence Digit Symbol Substitution Test (DSST) and trail-making test part B (TMT-B). Assessments were performed at baseline and at the month 3 follow-up visit. Linear mixed models were carried out to evaluate cognitive changes from baseline across all cognitive assessment tests. RESULT: The current study showed significant (p < 0.05) improvement in cognitive function of patients who were given K-Vie™ compared with placebo across the RAVLT, DSST and TMT-B performance assessments. A larger cohort would be beneficial to further confirm the clinical utility of K-Vie™ and assess its effects in acute phases of TBI.

Conformational change and GTPase activity of human tubulin: A comparative study on Alzheimer's disease and healthy brain.

In Alzheimer's disease (AD), the most common form of dementia, microtubules (MTs) play a pivotal role through their highly dynamic structure and instability. They mediate axonal transport that is crucial to synaptic viability. MT assembly, dynamic instability and stabilization are modulated by tau proteins, whose detachment initiates MT disintegration. Albeit extensive research, the role of GTPase activity in molecular mechanism of stability remains controversial. We hypothesized that GTPase activity is altered in AD leading to microtubule dynamic dysfunction and ultimately to neuronal death. In this paper, fresh tubulin was purified by chromatography from normal young adult, normal aged, and Alzheimer's brain tissues. Polymerization pattern, assembly kinetics and dynamics, critical concentration, GTPase activity, interaction with tau, intermolecular geometry, and conformational changes were explored via Förster Resonance Energy Transfer (FRET) and various spectroscopy methods. Results showed slower MT assembly process in samples from the brains of people with AD compared with normal young and aged brains. This observation was characterized by prolonged lag phase and increased critical and inactive concentration of tubulin. In addition, the GTPase activity in samples from AD brains was significantly higher than in both normal young and normal aged samples, concurrent with profound conformational changes and contracted intermolecular MT-tau distances as revealed by FRET. These alterations were partially restored in the presence of a microtubule stabilizer, paclitaxel. We proposed that alterations of both tubulin function and GTPase activity may be involved in the molecular neuropathogenesis of AD, thus providing new avenues for therapeutic approaches.

Functional improvement and immune-inflammatory cytokines profile of ischaemic stroke patients after treatment with boswellic acids: a randomized, double-blind, placebo-controlled, pilot trial.

Ischaemic stroke represents one of the main causes of disability. According to the broad investigations, it is widely assumed that the contribution of inflammatory mediators is strongly involved in its pathogenesis. Hence, it seems that stroke treatment needs more efficient and inflammatory-targeted compounds to modulate inflammatory-related pathways. Such strategies paved the way to achieve better clinical outcomes along with conventional therapies. Boswellic acids (BAs), the main bioactive compounds of Boswellia sp. resin; are triterpenoids with well-documented anti-inflammatory properties. Compared with NSAIDs, BAs cross blood-brain barrier yet they do not cause serious gastrointestinal adverse effects. Considering BAs anti-inflammatory features, we conducted a randomized double-blind placebo-controlled pilot trial of these compounds as a supplementary therapy. This trial randomized 80 ischaemic stroke patients (40-80-years old) with a 4-20 score according to the National Institutes of Health Stroke Scale (NIHSS), within 72 h of neurological sign onset, in 1-month follow-up period. We assessed NIHSS as primary and plasma levels of TNF-α, IL-1α, IL-1ß, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IFN-γ, IP-10, MCP-1, 8-isoprostane, and PGE2 as secondary outcomes. According to NIHSS evaluation, patients who were allocated to BA group had a significant recovery in neurological function during the 1-month follow-up, compared with the placebo. The levels of plasma inflammatory markers were significantly decreased in BA group after 7 days of intervention in TNF-α, IL-1ß, IL-6, IL-8, and PGE2. As a preliminary controlled trial in ischaemic stroke, BAs could improve clinical outcome in the early phases of stroke along with promising changes in plasma inflammatory factors.Clinical trial registrationhttps://www.irct.ir Unique identifier: IRCT20170315033086N5. IRCT is a primary registry in the WHO registry network (https://www.who.int/ictrp/network/primary/en/).

PTRHD1 (C2orf79) mutations lead to autosomal-recessive intellectual disability and parkinsonism.

INTRODUCTION: Atypical parkinsonism is a neurodegenerative disease that includes diverse neurological and psychiatric manifestations. OBJECTIVES: We aimed to identify the disease-cauisng mutations in a consanguineous family featuring intellectual disability and parkinsonism. METHODS: Full phenotypic characterization, followed by genome-wide single-nucleotide polymorphism genotyping and whole-genome sequencing, was carried out in all available family members. RESULTS: The chromosome, 2p23.3, was identified as the disease-associated locus, and a homozygous PTRHD1 mutation (c.157C>T) was then established as the disease-causing mutation. The pathogenicity of this PTRHD1 mutation was supported by its segregation with the disease status, its location in a functional domain of the encoding protein, as well as its absence in public databases and ethnicity-matched control chromosomes. CONCLUSION: Given the role of 2p23 locus in patients with intellectual disability and the previously reported PTRHD1 mutation (c.155G>A) in patients with parkinsonism and cognitive dysfunction, we concluded that the PTRHD1 mutation identified in this study is likely to be responsible for the phenotypic features of the family under consideration. © 2016 International Parkinson and Movement Disorder Society.

Memantine for Prophylactic Treatment of Migraine Without Aura: A Randomized Double-Blind Placebo-Controlled Study.

BACKGROUND: Uncontrolled studies in human have suggested that memantine might be a suitable option for migraine prophylaxis. OBJECTIVE: To assess the efficacy and tolerability of memantine for migraine prophylaxis. METHODS: This was a 12-week randomized double-blind placebo-controlled parallel-group study. Sixty patients with migraine without aura were randomized using a computer-generated list to receive memantine (10 mg/day) or placebo for 12 weeks. The primary outcome was the difference in change from baseline in the monthly attack frequency at week 12 between the two groups (using migraine diary). Secondary efficacy measures were assessed using several clinical, functional, and psychological instruments. We performed both complete case (CC) and intention-to-treat analyses (ITT). RESULTS: Twenty-five patients in the memantine group and 27 patients in the placebo group completed the study. Patients in the memantine group showed significantly greater reduction (mean change; 3.4; 95%CI, 2.3-4.4) in the monthly attack frequency than the placebo group (mean change, 1.0; 95%CI, 0.3-1.7) (mean difference [MD], 2.3; 95%CI, 1.1-3.5, P < .001). Both CC (MD, 4.9; 95%CI, 2.6-7.2 days), and ITT analyses (MD, 5.2; 95%CI, 2.0-8.5) showed significantly higher reduction in the mean number of migraine days in the memantine group than the placebo group (P < .01). Patients in the memantine group experienced greater reduction in the number of work absence days, severity, and disability score than the patients in the placebo group in both ITT and CC analyses. Changes in quality of life, sleep, depression, and anxiety did not differ between the two groups. Three patients in the memantine group complained of sedation, mild vertigo and nausea, and drowsiness. In the placebo group, one patient complained of nausea and another patient discontinued treatment after 2 weeks due to vertigo. CONCLUSION: Memantine might be a tolerable and efficacious option for prophylaxis in patients with migraine without aura. Tolerability, short duration required for titration, and safety profile in pregnancy might give memantine an advantage over other antimigraine medications. The study was registered in the Iranian Registry of Clinical Trials (Registration number: IRCT2013120115616N1).

From a simple chronic headache to neurobrucellosis: a case report.

Brucellosis is an infectious disease with high incidence in Iran. Neurobrucellosis is a focal complication of brucellosis affecting both central and peripheral nervous system presenting with a varieties of signs and symptoms. The most reported manifestations are meningitis and meningoencephalitis. In this report, we will describe a case of a young woman affected by neurobrucellosis presenting with chronic progressive headache and papilledema.

Depression is associated with the nonmotor symptoms of Parkinson's disease: A comparative analysis.

Background and aims: The nonmotor symptoms (NMS) of Parkinson's disease (PD) and their potential role in early diagnosis are recent debates. Herein, we aimed to investigate the association between depression and NMS of PD including sleep disorders, hyposexuality, hyposmia, constipation, and orthostatic hypotension. Methods: A total of 93 PD patients with depression and 67 PD patients without depression were included in the study, and NMS were compared between the two groups. Furthermore, the possible associations between depression severity measured by Beck Depression Inventory (BDI) and NMS were investigated using linear regression or binary logistic regression models controlled for possible confounders. Eventually, we performed a subgroup analysis in each mild, moderate, and severe depression group. Results: Orthostatic hypotension, constipation, and hyposexuality showed a significant difference between PD patients with and without depression (p < 0.001, p = 0.029, and p < 0.001, respectively). The BDI score was significantly associated with hyposexuality, Montreal cognitive assessment (MoCA), and Pittsburgh Sleep Quality (p = 0.016, p = 0.010, and p = 0.011, respectively); however, after adjustments for possible confounders, the associations of the BDI score with the MoCA score and hyposexuality remained significant (p = 0.015 and p = 0.019, respectively). Considering subgroup analysis, a similar pattern of significant results was observed particularly in the severe group. Conclusions: This study suggests a possible association between depression in PD patients and some NMS observed in the course of PD. These findings could be beneficial for early diagnosis of the disease, which eventually could make a considerable difference in the management of PD patients. Additional interventional longitudinal studies are warranted to explore how controlling depression could impact the NMS of patients with PD.

Therapeutic Potential of the Ketogenic Diet: A Metabolic Switch with Implications for Neurological Disorders, the Gut-Brain Axis, and Cardiovascular Diseases.

The Ketogenic Diet (KD) is a dietary regimen that is low in carbohydrates, high in fats, and contains adequate protein. It is designed to mimic the metabolic state of fasting. This diet triggers the production of ketone bodies through a process known as ketosis. The primary objective of KD is to induce and sustain ketosis, which has been associated with numerous health benefits. Recent research has uncovered promising therapeutic potential for KD in the treatment of various diseases. This includes evidence of its effectiveness as a dietary strategy for managing intractable epilepsy, a form of epilepsy that is resistant to medication. We are currently assessing the efficacy and safety of KD through laboratory and clinical studies. This review focuses on the anti-inflammatory properties of the KD and its potential benefits for neurological disorders and the gut-brain axis. We also explore the existing literature on the potential effects of KD on cardiac health. Our aim is to provide a comprehensive overview of the current knowledge in these areas. Given the encouraging preliminary evidence of its therapeutic effects and the growing understanding of its mechanisms of action, randomized controlled trials are warranted to further explore the rationale behind the clinical use of KD. These trials will ultimately enhance our understanding of how KD functions and its potential benefits for various health conditions. We hope that our research will contribute to the body of knowledge in this field and provide valuable insights for future studies.

Lysine ε-aminolysis and incorporation of sulfhydryl groups into human brain tau 4R/1N and 306VQIVYK311 enhances the formation of beta structures and toxicity.

In the present study, we investigated the effects of N-homocysteine thiolactone (tHcy) modification on expressed and purified tau protein and the synthesized VQIVYK target peptide. The modified constructs were subjected to comprehensive validation using various methodologies, including mass spectrometry. Subsequently, in vivo, in vitro, and in silico characterizations were performed under both reducing and non-reducing conditions, as well as in the presence and absence of heparin as a cofactor. Our results unequivocally confirmed that under reducing conditions and in the presence of heparin, the modified constructs exhibited a greater propensity for aggregation. This enhanced aggregative behavior can be attributed to the disruption of lysine positive charges and the subsequent influence of hydrophobic and p-stacking intermolecular forces. Notably, the modified oligomeric species induced apoptosis in the SH-SY5Y cell line, and this effect was further exacerbated with longer incubation times and higher concentrations of the modifier. These observations suggest a potential mechanism involving reactive oxygen species (ROS). To gain a deeper understanding of the molecular mechanisms underlying the neurotoxic effects, further investigations are warranted. Elucidating these mechanisms will contribute to the development of more effective strategies to counteract aggregation and mitigate neurodegeneration.

The effect of cannabidiol on seizure features and quality of life in drug-resistant frontal lobe epilepsy patients: a triple-blind controlled trial.

Background: Treatment-resistant epileptic seizures are associated with reduced quality of life (QoL). As polypharmacy with routine antiseizure medications has many side effects, novel add-on treatments are necessary. Recent research showed the efficacy of add-on therapy by cannabidiol (CBD) on refractory epilepsy. We attempted to extend data on the efficacy and safety profile of CBD in patients with frontal lobe treatment-resistant epilepsy. Methods: A total of 27 patients were recruited into two CBD (n = 12) and placebo (n = 15) groups. The CBD group received a highly purified liposomal preparation of the drug in addition to routine antiseizure medications. The placebo group only received antiseizure medications. This experiment followed a triple-blinding protocol. Outcome measures were seizure frequency, the Chalfont seizure severity scale (CSSS), and the quality of life questionnaire score (QOLIE-31) assessed at baseline, 4 weeks, and 8 weeks. Results: At 4 weeks, results indicated that a higher fraction of patients in the CBD group (66.67%) showed improvement in seizure, compared to the placebo group (20.00%). Before-after comparison revealed that CBD, unlike routine ADEs, was effective in reducing the occurrence of seizures at the study's final timepoint [mean difference 45.58, 95% CI (8.987 to 82.18), p = 0.009]. Seizure severity was not affected by study groups or time intervals (repeated-measures ANOVA p > 0.05). Post-hoc tests found that the QoLI-31 score was improved at 8 weeks compared to baseline [mean diff. -5.031, 95% CI (-9.729 to -0.3328), p = 0.032]. The difference in cases who experienced enhanced QoL was meaningful between the CBD and placebo groups at 8 weeks [RR: 2.160, 95% CI (1.148 to 4.741), p = 0.018] but not at 4 weeks (p = 0.653). A positive finding for QoL improvement was associated with a positive finding for seizure frequency reduction [r = 0.638, 95% CI (0.296 to 0.835), p = 0.001]. Interestingly, limiting the correlation analysis to cases receiving CBD indicated that QoL improvement was not linked with seizure parameters such as severity and frequency (p > 0.05). Conclusion: The present study suggests the benefit of a purified and highly efficient preparation of CBD for seizure frequency reduction and improvement of QoL in refractory frontal lobe epilepsy. Further study with longer follow-ups and larger sample size is advised. Clinical trial registration: https://www.irct.ir/trial/56790, identifier: IRCT20210608051515N1.

Valproic acid-induced hyperammonemia in neuropsychiatric disorders: a 2-year clinical survey.

INTRODUCTION: Valproic acid (VPA)-induced hyperammonemia (HA) is a rare adverse effect reported even at therapeutic VPA levels. The present study aimed to investigate the characteristics of VPA-induced HA and its association with the total dose, duration, and level of VPA. This study also investigated whether the use of VPA in combination with other medications has any effect on elevating serum ammonia levels. METHODS: A total of 316 patients with a history of VPA prescribed for underlying neuropsychiatric disorders were found eligible for the study. Data including demographic information, medical history and diagnosis, VPA dosage, VPA treatment duration, VPA level, and ammonia serum level were extracted and reviewed from our hospital records. The history of other neuropsychiatric medications was also included. RESULTS: Among 316 patients receiving VPA, HA was observed in 54 (17%) patients, and 15 patients were symptomatic among them. There was no significant difference in demographics between symptomatic and asymptomatic HA groups except for the number of co-administrated medications (p = 0.044). Besides, VPA duration and dose did not show a significant difference between the two groups. Additionally, the VPA level was significantly higher in patients who used risperidone in addition to VPA (p = 0.019). Eventually, VPA level showed a significant association with ammonia level (p = 0.025) and symptomatic HA (p = 0.033) after adjusting for possible confounders. CONCLUSION: VPA level showed a significant association with ammonia level and symptomatic HA. Moreover, co-administrated medications such as risperidone might have an impact on the serum level of VPA. Further studies are recommended to confirm these findings.

Thyroid hormone levels in Alzheimer disease: a systematic review and meta-analysis.

BACKGROUND AND OBJECTIVE: Thyroid hormone (TH) disturbances are perceived to contribute to cognitive impairment and dementia. However, there is no consensus on the association between TH levels and Alzheimer Disease (AD). In this study, we aimed to compare serum and cerebrospinal fluid (CSF) TH levels in AD patients to controls by performing a meta-analysis. METHODS: We systematically searched online databases for papers comparing CSF or serum TH levels in AD patients to controls, and performed a meta-analysis on the extracted data. RESULTS: Out of 1604 records identified, 32 studies were included. No significant difference in serum TSH (standardized mean difference (SMD): -0.03; 95% confidence interval (CI): -0.22-0.16), total T4 (SMD: 0.10; 95% CI: -0.29-0.49), and free T4 (SMD: 0.25; 95% CI: -0.16-0.69) levels were observed. However, there was significantly lower serum total T3 (SMD: -0.56; 95%CI: -0.97 to -0.15) and free T3 (SMD: -0.47; 95%CI: -0.89 to -0.05) levels in AD group compared to controls. Subgroup analyses on studies including only euthyroid patients did not show any significant difference in either of the thyroid hormone levels. Also, no significant difference in CSF total T4 and total T3/total T4 ratios but significantly lower CSF total T3 (SMD: -2.45; 95% CI: -4.89 to -0.02) in AD group were detected. CONCLUSION: Serum total and free T3 and CSF total T3 levels are significantly lower in AD patients compared to controls. The temporality of changes in thyroid hormone levels and AD development should be illustrated by further longitudinal studies.

Psychosis of Epilepsy: A 10-Year Iranian Clinical Survey.

Objective: Psychoses of epilepsy usually have an acute onset, accompanied by brief symptom duration and a risk of recurrence. Managing these conditions can be challenging due to the potential for seizures associated with certain antipsychotic medications, as well as exacerbating psychosis resulting from some antiepileptic medications. Our objective in this study was to assess the occurrence of psychosis among patients with epilepsy, as well as identify the factors linked to the presence and severity of psychosis in this population. Method : In this study, we included a total of 514 subjects diagnosed with epilepsy referring to our neuropsychiatry clinic affiliated with Tehran University of Medical Sciences from April 2011 to December 2021, among whom 57 patients showed psychotic presentations. We compared baseline and clinical characteristics between patients with psychosis of epilepsy and non-psychosis patients who also had epilepsy. Results: Marital status was the sole demographic factor that displayed a statistically significant difference between the psychosis and non-psychosis groups (P = 0.019). There was no significant difference observed between the two groups regarding family history of epilepsy and age at the onset of the epilepsy. Patients with psychosis experienced significantly more frequent seizures and generalized type (P < 0.001). Participants were matched for demographics and other clinical factors between the refractory and controlled psychosis groups, except for the psychosis frequency (P = 0.007). The type of epilepsy was significantly associated with psychosis when adjusted for the covariates (P < 0.001). Conclusion: Patients with psychosis of epilepsy experienced more episodes of epilepsy than non-psychotics. We identified generalized epilepsy as an independent risk factor for the development of psychosis. Additional cohorts are warranted to explore the factors associated with epilepsy-related psychosis across diverse populations.

Trail Making Test Could Predict Impairment in Cognitive Domains in Patients with Multiple Sclerosis: A Study of Diagnostic Accuracy.

OBJECTIVE: Cognitive impairment (CI) and executive dysfunction (ED) are prevalent in patients with multiple sclerosis (PwMS). The Minimal Assessment of Cognitive Function in Multiple Sclerosis (MACFIMS) is the gold standard neuropsychological battery (NPB) for detecting CI. Delis-Kaplan Executive Function System (DKEFS) NPB evaluates ED. We aimed to find practical test(s) from DKEFS with acceptable diagnostic utility for early detection of impairment in cognitive and executive domains. METHODS: Cognitive and executive tasks, physical disability, and depression scores of 30 PwMS were assessed (17 women, age: 38.1). Symbol Digit Modalities Test (SDMT), Paced Auditory Serial Addition Test (PASAT), and Controlled Oral Word Association Test (COWAT) from MACFIMS and Trail Making Test (TMT), Design Fluency Test (DFT), and Verbal Fluency Test (VFT) from DKEFS were selected. The association between patients' characteristics and performance in tests, and diagnostic accuracy of DKEFS tests in detecting impairment in cognitive tasks were evaluated, using Pearson correlation and receiver operator characteristic curve analyses, respectively. RESULTS: A significant correlation was found between disease duration and SDMT and TMT subtests. Expanded Disability Status Scale was significantly related to SDMT, VFT-switching, and TMT subtests. Beck Depression Inventory was significantly related to DFT. TMT-switching detected abnormalities in SDMT and PASAT with 100% sensitivity, 93.3% (for SDMT), and 85.7% specificity (for PASAT). TMT-letter showed 100% sensitivity and 90% specificity in identifying abnormalities in COWAT. CONCLUSIONS: TMT, particularly the switching condition, is a practical paper-based test that could predict impairment in cognitive tasks. Clinicians may use TMT as a screening tool among PwMS.

Boswellic Acids Improve Clinical Cognitive Scores and Reduce Systemic Inflammation in Patients with Mild to Moderate Alzheimer's Disease.

BACKGROUND: Recent therapeutic approaches for Alzheimer's disease (AD) have had limited success. Considering the association of neuroinflammation with AD symptoms as demonstrated in multiple studies, assessment of the clinical efficacy of molecules that reduce systemic or brain inflammation is warranted. OBJECTIVE: This clinical trial assessed whether boswellic acids can improve cognitive and neuropsychiatric symptoms while reducing inflammation in AD patients. METHODS: A double-blind, placebo-controlled, study was conducted on 85 AD patients randomized to boswellic acids (K-Vie™ as the main ingredient in Memowell™) or placebo for 6 months. Clinical Dementia Rating-Sum of Boxes (CDR-SOB) and Mini-Mental State Examination (MMSE) scores were compared to baseline and between groups and constituted the co-primary clinical efficacy endpoints. Secondary outcomes included neuropsychiatric assessment (Neuropsychiatric Inventory-Questionnaire, NPI-Q) and assessment of AD and inflammation biomarkers. RESULTS: Patients on K-Vie™ showed a 3.1- and 1.6-unit improvement in MMSE and CDR-SOB scores, respectively, when compared to patients on placebo. NPI-Q analysis revealed significant improvement in the K-Vie™ but not in the placebo group. Only mild gastrointestinal side effects were reported in a few patients. Patients on K-Vie™ showed improvement in plasma AD biomarkers and reduction of key inflammatory cytokines including IL-6 and TNF. CONCLUSION: Our results support the positive cognitive effects of boswellic acids by reducing the systemic inflammation.

The potential role of the cardiac MIBG scan in differentiating the drug-induced Parkinsonism from Parkinson's disease.

INTRODUCTION: Considering the difficulties of differentiating Parkinson's disease (PD) from drug-induced Parkinsonism (DIP) in patients receiving antipsychotics, developing robust diagnostic tools is essential. Herein, we used the metaiodobenzylguanidine (MIBG) scan to assess its diagnostic accuracy for this purpose. METHODS: 44 DIP patients and 32 patients with PD as controls were enrolled. All the participants underwent a cardiac 131I-MIBG scan. Statistical analysis was conducted to determine the significance of the results, and accuracy analyses were conducted to calculate the related sensitivity and specificity of the MIBG scan. RESULTS: The mean age of PD and DIP groups were 62.6 ± 5.9 and 51.5 ± 10.8 years, respectively. The mean duration of drug consumption in the DIP group was 52.2 ± 29.4 days (the mean interval between drug initiation and DIP onset was 28.5 ± 20.5). Symptoms relief occurred 40 ± 24.2 days after drug discontinuation. In the PD group, 15.6% showed negative and 84.4% positive results on the MIBG scan. In the DIP group, 86.4% were negative, and the remaining were positive. The difference in MIBG uptake between the two groups was statistically significant (P-value < 0.001). The sensitivity and specificity of the MIBG scan were 84.4% (CI: 84.0-84.8) and 86.36% (CI: 86.0-86.7) for the diagnosis of PD, respectively. CONCLUSION: Our results indicated more positive MIBG scans in the PD group than the DIP. Also, the MIBG scan's sensitivity and specificity in differentiating the PD are acceptable. Future works should assess these findings and the role of the MIBG scan in prognosis assessment of DIP and better allocation of the patients to related disciplines.

A systematic review of resting-state and task-based fmri in juvenile myoclonic epilepsy.

Functional neuroimaging modalities have enhanced our understanding of juvenile myoclonic epilepsy (JME) underlying neural mechanisms. Due to its non-invasive, sensitive and analytical nature, functional magnetic resonance imaging (fMRI) provides valuable insights into relevant functional brain networks and their segregation and integration properties. We systematically reviewed the contribution of resting-state and task-based fMRI to the current understanding of the pathophysiology and the patterns of seizure propagation in JME Altogether, despite some discrepancies, functional findings suggest that corticothalamo-striato-cerebellar network along with default-mode network and salience network are the most affected networks in patients with JME. However, further studies are required to investigate the association between JME's main deficiencies, e.g., motor and cognitive deficiencies and fMRI findings. Moreover, simultaneous electroencephalography-fMRI (EEG-fMRI) studies indicate that alterations of these networks play a role in seizure modulation but fall short of identifying a causal relationship between altered functional properties and seizure propagation. This review highlights the complex pathophysiology of JME, which necessitates the design of more personalized diagnostic and therapeutic strategies in this group.