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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Challenges in corticosteroid dose regulation in a patient with autoimmune thyroid disease and neuropsychiatric syndrome: A running commentary.

In the following, we report a therapeutic challenge faced by reduction in corticosteroid therapeutic dosage in a patient diagnosed with Hashimoto's encephalopathy (HE), which is equivalent to corticosteroid-responsive encephalopathy related to autoimmune thyroiditis and often misdiagnosed as neuropsychiatric status. The patient developed psychiatric symptoms.

Cognitive Impairment in Opium Use Disorder.

This cross-sectional study is aimed at assessing the effects of opium use disorder (OUD) on attention, working memory, and information-processing speed. Thirty outpatients with OUD and 20 healthy controls (HCs) were assessed using a neuropsychological battery consisted of Auditory Verbal Learning Test-Revised (AVLT-R), Brief Visuospatial Memory Test-Revised (BVMT-R), Digit Forward and Backward Tests (DFT and DBT), and WAIS-R Digit Symbol Substitution Test (DSST). The most affected cognitive functions in patients with OUD were detected by DBT and DSST. However, we found no significant difference between patients according to the route of administration. Within patients with OUD, DBT score was associated with opium use quantity (OUQ) (r = -0.385), and DBT (r = 0.483) and DSST (r = 0.542) scores were correlated with duration of use. Our findings indicated that working memory and information-processing speed are the most affected domains of cognitive functioning. DBT and DSST could be used as brief assessments in clinical settings to screen for cognitive deficits in patients with OUD.

Idiopathic superficial siderosis of the central nervous system.

BACKGROUND: Regardless of the cause of the superficial siderosis (SS) disease, which is bleeding, the source of bleeding cannot be found in some cases. CASE PRESENTATION: In this article, we report two cases with idiopathic SS. Case 1 presented with bilateral hearing loss, cognitive impairment, sleep disturbances, and tremors. Case 2 presented with sensory neural hearing loss, ataxia, and spastic paraparesis. In both cases, brain MRI indicated evidence of SS. CT myelogram and SPECT with labeled RBC couldn't help finding the source of occult bleeding. CONCLUSION: SS is a rare central nervous system disease caused by the deposition of hemosiderin in the brain and spinal cord, which results in the progression of neurological deficits. The cause of this hemorrhage is often subarachnoid haemorrhage, intracranial surgery, carcinoma, arteriovenous malformation, nerve root avulsion, and dural abnormality. The condition progresses slowly and, by the time diagnosis is confirmed, the damage is often irreversible. In our cases, brain MRI clarified the definitive diagnosis, but we could not find the source of bleeding. SS should be considered in cases with ataxia and hearing loss, even if no source of bleeding is found.

Chronic neurological diseases and COVID-19: Associations and considerations.

The 2019 novel coronavirus pandemic, severe acute respiratory syndrome CoV-2 (COVID-19), has been a worldwide urgent public health threat, resulting in six-hundred seventy thousand deaths to date. The COVID-19 pandemic has led to a series of public health challenges. One such challenge is the management of diseases such as chronic neurological diseases during an epidemic event. COVID-19 affects all kinds of people, including older people with chronic underlying diseases, who are particularly at risk of severe infection or even death. Chronic neurological diseases such as epilepsy, dementia, Parkinson's disease (PD), and multiple sclerosis (MS) are frequently associated with comorbidities; thus, these patients are in the high-risk category. Therefore, in this article, we review associations and challenges the people with epilepsy, dementia, PD, and MS faces during the COVID-19 pandemic and suggest approaches to provide consensus recommendations on how to provide the best possible care.

Evaluating Executive Functions in Patients with Juvenile Myoclonic Epilepsy Using Frontal Assessment Battery.

OBJECTIVE: In this study, we aimed to evaluate the executive profile of juvenile myoclonic epilepsy (JME) patients using the Frontal Assessment Battery (FAB) as a bedside screening tool and investigate its association with seizure proximity, family history of epilepsy, and polytherapy/monotherapy with antiepileptic drugs (AEDs). BACKGROUND: JME patients have deficits in various aspects of executive functions. FAB has proved to be a useful tool for evaluating executive functions in clinical settings. METHODS: Thirty-one JME patients and 110 healthy controls (HCs) were enrolled in this study. The participants were assessed using six subsets of FAB, including conceptualization, mental flexibility, motor programming, sensitivity to interference, inhibitory control, and environmental autonomy. RESULTS: Compared to HCs, JME patients showed lower scores in conceptualization, mental flexibility, programming, sensitivity to interference, and total FAB. The number of AEDs (polytherapy versus monotherapy) and duration of time since the last seizure had no significant effect on FAB scores in JME patients. We found significant associations between disease duration and conceptualization, mental flexibility, inhibitory control, and total FAB score only in JME patients with recent seizure. Finally, receiver operating characteristic (ROC) analysis showed area under the curve (AUC) of 0.971 (95% confidence interval (CI): 0.947-0.994) for FAB total score, 0.933 for conceptualization (95% CI: 0.973-894), and 0.836 for mental flexibility (95% CI: 0.921-751). CONCLUSIONS: In summary, JME patients had deficits in different aspects of executive functions. FAB is a useful clinical tool for evaluation of executive functions in JME patients.