Photobiomodulation's potential as a non-invasive therapy for alzheimer's disease and minimal cognitive impairment: A 12-week investigation.

BACKGROUND: Alzheimer's Disease (AD), undergoing a faster increase in occurrence than any other type of dementia, lacks a curative remedy despite advanced discoveries. To explore the realm of non-pharmacologic therapies, our study evaluates the 12-week impact of non-invasive Photobiomodulation (PBM) on cognitive and psychological aspects in individuals with AD and minimal cognitive impairment (MCI). The urgency of exploring innovative interventions is underscored by the rising occurrence of AD, particularly in regions with aging populations like Iran. METHOD: 13 patients (6 case patients and 7 control patients) participated in the study. Sham treatment was administered to seven individuals, while another six received PBM treatment over 12 weeks, with daily at-home LED (810 nm wavelength) device usage lasting 20 min. Initially, the patient and their caregiver participated in two hospital sessions to acquaint them with the device's operation. RESULTS: The mean reduction of Hamilton's anxiety questionnaire score was 3.33±6.08 in the intervention group and 2.00±3.46 in the control group (p-value=0.836). The mean score reduction of the Hamilton depression questionnaire was 3.16±3.86 in the intervention group and 4.85±6.20 in the control group (p-value=0.836). The mean score of the DAD questionnaire in the intervention group before the study was 25.50±13.13 and after the intervention was 29.83±12.12 (p-value=0.084) and in the control group it was 29.71±8.19 and after the study was 29±0.972 (p-value = 0.526). The mean changes in the DAD questionnaire score in the intervention group increased by 4.33±4.92 and decreased by 0.71±2.81 in the control group (p-value=0.041). CONCLUSION: In general, PBM appears to hold promise as a potentially safe method for enhancing the cognitive, functional, and psychological status of individuals with Alzheimer's disease, though further research with larger sample size and cautious interpretation are warranted.

Structural Analysis and Conformational Dynamics of Short Helical Hyperphosphorylated Segments of Tau Protein (Sequence 254-290) in Alzheimer's Disease: A Molecular Dynamics Simulation Study.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder whose early diagnosis leads to a chance for successful treatment and decreases the side effects. Hyperphosphorylation of tau proteins is a pathological hallmark of AD that causes it to lose its attachment ability to the microtubules. Alteration of tau structure due to its hyperphosphorylation is an exciting challenge regarding AD treatments. Here, we aimed to examine the structural alterations of short helical segments of tau protein with one to three phosphorylated sites by molecular dynamics simulation. Results indicated that the interaction of two similar segments with three phosphorylated sites (P-Ser262, 285, and 289) formed a compact and more stable structure than the one phosphorylated site complex (P-Ser262). Moreover, due to the high dynamics of the P-Ser262 complex, several structures were made with different conformational dynamics, but there was only one stable cluster of the P-Ser262, 285, and 289 complex during simulation. It seems that the P-Ser262, 285, and 289 complex plays an important role in the formation of paired helical filaments (PHFs) by forming a stable dimer. Generally, it is important to identify how structural features of segments in tau protein change when the phosphorylated sites increase from one to three sites and their effects on the formation of PHFs for drug design and diagnostic biomarkers.

Promising effects of corticosteroid treatment in combination with antifungal agents in a patient with Aspergillus meningitis.

Although Aspergillus meningitis is poorly responsive to current guidelines for treatment, we describe a dramatic response of Aspergillus meningitis in a patient to treatment using a combination of corticosteroids with guideline's suggested antifungal agents. Administration of corticosteroids in patients with Aspergillus meningitis is rarely reported in previous studies.

Clinical, Laboratory and Imaging Characteristics of Hospitalized COVID-19 Patients with Neurologic Involvement; a Cross-Sectional Study.

Introduction: Although neurologic involvement and neuroimaging abnormalities have been frequently identified in COVID-19 patients, the underlying factors remain unclear. In this study, we assessed the association of the neurological manifestations and neuroimaging features of hospitalized COVID-19 patients with their clinical, laboratory, and imaging characteristics. Methods: This multicenter cross-sectional study was conducted between September 2020 and March 2021 at two large academic hospitals in Tehran, Iran. We used census sampling from medical records to enroll hospitalized patients with a positive COVID-19 Polymerase chain reaction (PCR) test who underwent brain imaging due to presenting any acute neurologic symptom during hospital stay. Results: Of the 4372 hospitalized patients with COVID-19, only 211 met the inclusion criteria (35.5% with severe infection). Central nervous system and psychiatric manifestations were significantly more common in severe cases (p ≤ 0.044). Approximately, 30% had a new abnormality on their neuroimaging, with ischemic (38/63) and hemorrhagic (16/63) insults being the most common. The most frequent reasons that provoked cranial imaging were headache (27%), altered consciousness (25.6%), focal neurologic signs (19.9%), and delirium (18%). Analysis revealed a positive correlation for age, neutrophilia, lymphopenia, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) with the emergence of neuroimaging abnormalities (p ≤ 0.018). In addition, patients with new neuroimaging abnormalities had a significantly higher lung CT score than those without any pathologic findings (11.1 ± 4.8 vs. 5.9 ± 4.8, p < 0.001). Conclusion: Approximately 30% of the study population had various acute neuroimaging findings. The lung CT score, neutrophil count, and age were strong predictors of acute neuroimaging abnormalities in hospitalized COVID-19 patients.

Dementia as a core clinical feature of a patient with aceruloplasminemia.

Aceruloplasminemia is an autosomal recessive disease, caused by systemic iron accumulation due to mutations in the Ceruloplasmin gene. We report two Iranian siblings who have been diagnosed with aceruloplasminemia. Although dementia has not been published as the first neurological feature, one of our cases was presented with pure dementia.

Deep brain stimulation of anteromedial globus pallidus internus improved OCD rather than tics in a Gilles de la Tourette syndrome patient.

A 32-year-old gentleman with refractory Gilles de la Tourette syndrome went on a DBS procedure on anteromedial globus pallidus internus. At the most suitable adjustment, the OCD component of his disease improved almost completely while his tics remained unchanged which was in contrast with other previous studies. Moreover, variations in symptoms were seen in response to different adjustments. We discuss that these variations and fluctuations in the therapeutic outcomes may be due to differences in physiological conditions of tic- or OCD-specified pathways and areas including distinct stimulation threshold and occurrence of neuroplasticity in neural circuits which may determine the responsiveness of each pathway or circuit to a specific stimulus. At last, we suggest that pathways and circuits should be targeted for DBS rather than single components; as these components may be involved in multiple pathways, related to different pathophysiological states.

Combining cell therapy with human autologous Schwann cell and bone marrow-derived mesenchymal stem cell in patients with subacute complete spinal cord injury: safety considerations and possible outcomes.

BACKGROUND: Cellular transplantations have promising effects on treating spinal cord injury (SCI) patients. Mesenchymal stem cells (MSCs) and Schwann cells (SCs), which have safety alongside their complementary characteristics, are suggested to be the two of the best candidates in SCI treatment. In this study, we assessed the safety and possible outcomes of intrathecal co-transplantation of autologous bone marrow MSC and SC in patients with subacute traumatic complete SCI. METHODS: Eleven patients with complete SCI (American Spinal Injury Association Impairment Scale (AIS); grade A) were enrolled in this study during the subacute period of injury. The patients received an intrathecal autologous combination of MSC and SC and were followed up for 12 months. We assessed the neurological changes by the American Spinal Injury Association's (ASIA) sensory-motor scale, functional recovery by spinal cord independence measure (SCIM-III), and subjective changes along with adverse events (AE) with our checklist. Furthermore, electromyography (EMG), nerve conduction velocity (NCV), magnetic resonance imaging (MRI), and urodynamic study (UDS) were conducted for all the patients at the baseline, 6 months, and 1 year after the intervention. RESULTS: Light touch AIS score alterations were approximately the same as the pinprick changes (11.6 ± 13.1 and 12 ± 13, respectively) in 50% of the cervical and 63% of the lumbar-thoracic patients, and both were more than the motor score alterations (9.5 ± 3.3 in 75% of the cervical and 14% of the lumbar-thoracic patients). SCIM III total scores (21.2 ± 13.3) and all its sub-scores ("respiration and sphincter management" (15 ± 9.9), "mobility" (9.5 ± 13.3), and "self-care" (6 ± 1.4)) had statistically significant changes after cell injection. Our findings support that the most remarkable positive, subjective improvements were in trunk movement, equilibrium in standing/sitting position, the sensation of the bladder and rectal filling, and the ability of voluntary voiding. Our safety evaluation revealed no systemic complications, and radiological images showed no neoplastic overgrowth, syringomyelia, or pseudo-meningocele. CONCLUSION: The present study showed that autologous SC and bone marrow-derived MSC transplantation at the subacute stage of SCI could reveal statistically significant improvement in sensory and neurological functions among the patients. It appears that using this combination of cells is safe and effective for clinical application to spinal cord regeneration during the subacute period.

Parkinson's disease patients may have higher rates of Covid-19 mortality in Iran.

BACKGROUND: Parkinson's disease (PD) patients may be at increased risk of Covid-19 mortality due to the nature of their disease or underlying conditions. METHOD: The information of 12,909 Covid-19 patients who were hospitalized during the last eleven months were collected from the data depository of two referral university hospitals. Eighty-seven of these patients were diagnosed with PD, and thirty-one of these PD patients died because of Covid-19. 2132 other deaths occurred in these centers, related to Covid-19 of non-PD patients. Fisher exact test, Chi-square test, and Principle component analysis were used for statistical analysis. RESULTS: The mortality among PD patients and other hospitalized patients was 35.6% and 19.8%, respectively, and the difference between the mortality of these two groups was found to be statistically significant (p-value<0.01). The mean age of PD patients who passed away was 77.06 ± 7.46, and it was not significantly different from that of alive PD patients (p-value>0.05). Alzheimer's disease as an underlying condition was more frequent in deceased PD patients in comparison to survived PD patients, and this difference was found to be statistically significant (p-value<0.01). CONCLUSION: PD patients possess a higher rate of Covid-19 mortality in comparison with other patients hospitalized for Covid-19. PD pathophysiology, advanced age, underlying conditions, and health systems' efficacy may play an essential role in such an outcome.

Neurological Manifestations and their Correlated Factors in COVID-19 Patients; a Cross-Sectional Study.

INTRODUCTION: COVID-19 might present with other seemingly unrelated manifestations; for instance, neurological symptoms. This study aimed to evaluate the neurologic manifestations and their correlated factors in COVID-19 patients. METHODS: This retrospective observational study was conducted from March 17, 2020 to June 20, 2020 in a tertiary hospital in Iran. The study population consisted of adult patients with a positive result for COVID-19 real-time reverse transcriptase polymerase chain reaction (RT-PCR) using nasopharyngeal swabs. Both written and electronic data regarding baseline characteristic, laboratory findings, and neurological manifestations were evaluated and reported. RESULTS: 727 COVID-19 patients with the mean age of 49.94 ± 17.49 years were studied (56.9% male). At least one neurological symptom was observed in 403 (55.4%) cases. Headache (29.0%), and smell (22.3%) and taste (22.0%) impairment were the most prevalent neurological symptoms, while seizure (1.1%) and stroke (2.3%) were the least common ones. Patients with neurological manifestations were significantly older (p = 0.04), had greater body mass index (BMI) (p = 0.02), longer first symptom to admission duration (p < 0.001) and were more frequently opium users (p = 0.03) compared to COVID-19 patients without neurological symptoms. O2 saturation was significantly lower in patients with neurological manifestations (p = 0.04). In addition, medians of neutrophil count (p = 0.006), neutrophil-lymphocyte ratio (NLR) (p = 0.02) and c-reactive protein (CRP) (p = 0.001) were significantly higher and the median of lymphocyte count (p = 0.03) was significantly lower in patients with neurological manifestations. CONCLUSION: The prevalence of neurological manifestations in the studied cases was high (55.4%). This prevalence was significantly higher in older age, grated BMI, longer lasting disease, and opium usage.

Clinical and Epidemiological Characteristics of Postdischarge Patients With COVID-19 in Tehran, Iran: Protocol for a Prospective Cohort Study (Tele-COVID-19 Study).

BACKGROUND: COVID-19 was declared a pandemic on March 11, 2020. Given that the severe shortage of hospital beds has led to early discharge and insufficient patient education on home care routines and isolation protocols, the close follow-up of patients and their immediate relatives is an integral part of transitioning from hospital care to home care for patients with COVID-19. OBJECTIVE: We designed the Tele-COVID-19 prospective cohort to follow-up with COVID-19 patients in Tehran, Iran, and improve health care delivery and the recording of postdischarge patients' clinical profiles. METHODS: All adult patients who were admitted to the COVID-19 wards of teaching hospitals in Tehran, Iran were eligible to participate in this cohort study. At baseline, patients were recruited from 4 major hospitals from March 9, 2020 to May 20, 2020. Telephone follow-ups, which were led by volunteer medical students, were conducted on postdischarge days 1-3, 5, 7, 10, and 14. We collected data on a range of sociodemographic, epidemiological, and clinical characteristics by using a standard questionnaire. RESULTS: Of the 950 patients with confirmed COVID-19 who were approached, 823 (response rate: 86.6%) consented and were enrolled into the cohort. Of the 823 participants, 449 (54.5%) were male. The mean age of participants was 50.1 years (SD 12.6 years). During the initial data collection phase, more than 5000 phone calls were made and over 577 reports of critical patients who were in need of urgent medical attention were recorded. CONCLUSIONS: The Tele-COVID-19 cohort will provide patients with sufficient education on home care and isolation, and medical advice on care and the proper use of drugs. In addition, by preventing unnecessary hospital returns and providing information on household SARS-CoV-2 transmission as early as possible, this cohort will help with effective disease management in resource-limited settings. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/23316.

Clinical Significance of Diffusion-weighted Magnetic Resonance Imaging on Treatment Efficacy in MS Patients With Acute Attacks.

Introduction: Despite various imaging methods, the accurate diagnosis of numerous neurodegenerative diseases remains controversial. Using advanced imaging techniques, like diffusion-weighted imaging, can help the early detection of Multiple Sclerosis (MS) and evaluation of the treatment efficacy in these patients. Methods: In total, 24 MS patients with acute attack and 30 healthy subjects were considered in our study. Region of Interest (ROI) was defined for acute and chronic plaques and Normal-Appearing White Matter (NAWM) in the patients' group. In the normal group, ROI only was mapped in the white matter in the same regions of the patient. All MS patients were receiving Methylprednisolone for 3 to 5 days. The rate of clinical disability in these patients was also evaluated based on the Expanded Disability Status Scale (EDSS) index. Finally evaluate changes of ADC values of plaques and NAWM before and after treatment. Results: The Apparent Diffusion Coefficient (ADC) values of acute plaques, the ADC values of NAWM, the number of enhancement in T1w, and EDSS values suggested a significant difference after treatment compared to before treatment. However, the ADC values of chronic plaques revealed no significant difference after treatment. There was a significant positive correlation between the difference in EDSS values before and after treatment. Conclusion: The study results demonstrated that using diffusion technique and ADC values analysis is a proper non-invasive method for MS diagnosis and evaluating treatment efficacy in these patients. Highlights: The obtained results suggested that the mean ADC for acute plaques and normal white matter significantly decreased after methylprednisolone treatment.Our study indicated a strong correlation between variations in EDSS, the mean ADC for acute plaques, and normal white matter.The collected results indicated that the number of enhanced plaques decreased after treatment. Besides, there was a positive correlation between its variations and EDSS. Plain Language Summary: Multiple Sclerosis (MS) is a common inflammatory disorder of the central nervous system that could result in physical and mental disabilities in patients. Disease progression usually manifests as a series of attacks. Although there is no proven cure for MS, different treatment strategies aim to modify the cause of the disease, manage its symptoms, and prevent and postpone disability. The most common therapy in acute attacks is using corticosteroid drugs. In addition to the treatment, evaluating the success rate of treatment was also challenging. Historically, clinical assessments method (e.g. EDSS) have been used as the baseline for measuring the therapy's efficiency. Several supplementary methods, including imaging techniques, are introduced to address this issue. Conventional MRI imaging with injection has been widely accepted to assess the treatment. However, because of the modest sensitivity of conventional MRI to detect subtle pathological changes, there is a poor correlation between its findings and patients' disability. This study moved from conventional MRI to advanced techniques, such as DWI and its quantitative index named ADC value. This technique can provide information about microstructural changes in MS patients. This method does not require injection, so there are no probable adverse effects and lower scan time. This study emphasizes changes in ADC value and EDSS before and after treatment with methylprednisolone. Our results suggested s that ADC values and EDSS after treatment are significantly different from their typical values. ADC values can be used as a biomarker to evaluate treatment efficiency, yet it is not objective enough to use it alone. So, the combination of DWI imaging with conventional methods might be beneficial in assessing treatment efficiency in MS patients.

Transverse myelitis after SARS-CoV-2 infection: Report of two cases with COVID-19.

Transverse myelitis has been reported as a complication of COVID-19 in recent studies. Here, we report two cases of transverse myelitis related to COVID-19. Both patients underwent plasma exchange after being treated with antibiotics and corticosteroids which lead to the recovery of one of them.

Incidence of anxiety in epilepsy during coronavirus disease (COVID-19) pandemic.

PURPOSE: The coronavirus disease 2019 (COVID-19) pandemic has affected people globally, and people with chronic diseases are suffering more in maintaining their mental and physical health. METHOD: This cross-sectional, case-control study assessed the anxiety level in people with epilepsy compared with the general population. RESULTS: The results showed that 13.5% of patients had experienced a severe level of anxiety, but the mean anxiety level between groups did not show significant difference. CONCLUSION: Although still many aspects of the pandemic on people with epilepsy are yet to be determined, active investigation of psychological sequels of the pandemic is demanded.

COVID-19-related strokes in adults below 55 years of age: a case series.

BACKGROUND: Coronavirus infection is a novel respiratory disease affecting people across the world. Although the majority of patients present with fever, dyspnea, cough, or myalgia, various signs and symptoms have been reported for this disease. Recently, neurological symptoms have been noticed in patients with COVID-19 with unknown etiology. However, the occurrence of strokes in young and middle aged patients with COVID-19 is not fully explained. METHODS: In this series, six patients younger than 55 years of age with diagnosis of stroke and a confirmed diagnosis of COVID-19 were evaluated for symptoms, lab data, imaging findings, and outcomes from March 2020 to the end of April 2020 from all stroke cases in a tertiary academic hospital. Patients older than 55 and all others who had evidence of cardiac abnormalities (arrhythmia/valvular) were excluded. RESULTS: Fever, myalgia, cough, and dyspnea were the most common clinical symptoms noted in 66.66% (4/6), 66.66% (4/6), 50% (3/6), and 50% (3/6) of the patients, respectively. The mean ± standard deviation (SD) of National Institutes of Health Stroke Scale (NIHSS) for the patient was 10.16 ± 7.13 (ranged 5-24). The most involved area was middle cerebral artery (MCA) (five in MCA versus one in basal ganglia) and the majority of our patients had a low lung involvement score (mean ± SD: 13.16 ± 6.49 out of 24). Finally, one patient was deceased and rest discharged. CONCLUSION: Stroke may be unrelated to age and the extent of lung involvement. However, different factors may play roles in co-occurrence of stroke and COVID-19 and its outcome. Future studies with long-term follow-up and more cases are needed to assess prognostic factors.

A dissociation between syntactic and lexical processing in Parkinson's disease.

Parkinson's disease (PD), which involves the degeneration of dopaminergic neurons in the basal ganglia, has long been associated with motor deficits. Increasing evidence suggests that language can also be impaired, including aspects of syntactic and lexical processing. However, the exact pattern of these impairments remains somewhat unclear, for several reasons. Few studies have examined and compared syntactic and lexical processing within subjects, so their relative deficits remain to be elucidated. Studies have focused on earlier stages of PD, so syntactic and lexical processing in later stages are less well understood. Research has largely probed English and a handful of other European languages, and it is unclear whether findings generalize more broadly. Finally, few studies have examined links between syntactic/lexical impairments and their neurocognitive substrates, such as measures of basal ganglia degeneration or dopaminergic processes. We addressed these gaps by investigating multiple aspects of Farsi syntactic and lexical processing in 40 Farsi native-speaking moderate-to-severe non-demented PD patients, and 40 healthy controls. Analyses revealed equivalent impairments of syntactic comprehension and syntactic judgment, across different syntactic structures. Lexical processing was impaired only for motor function-related objects (e.g., naming 'hammer', but not 'mountain'), in line with findings of PD deficits at naming action verbs as compared to objects, without the verb/noun confound. In direct comparisons between lexical and syntactic tasks, patients were better at naming words like 'mountain' (but not words like 'hammer') than at syntactic comprehension and syntactic judgment. Performance at syntactic comprehension correlated with the last levodopa equivalent dose. No other correlations were found between syntactic/lexical processing measures and either levodopa equivalent dose or hypokinesia, which reflects degeneration of basal ganglia motor-related circuits. All critical significant main effects, interactions, and correlations yielded large effect sizes. The findings elucidate the nature of syntactic and lexical processing impairments in PD.

Evaluation of iron deposition in brain basal ganglia of patients with Parkinson's disease using quantitative susceptibility mapping.

AIM OF THE STUDY: Parkinson's disease is associated with iron deposition in the brain. The QSM (quantitative susceptibility mapping) is more sensitive than T2-weighted imaging, T2* and R2. Few studies have been used QSM to evaluate the iron in the basal ganglia of patients with Parkinson's disease. Our aim was to evaluate the iron deposition in the basal ganglia using QSM and determination of diagnostic value of this method and evaluation of the association between disease stage with QSM and age with QSM in all nuclei, separately. MATERIALS AND METHODS: Thirty patients were tested using Hoehn and Yahr test in three different stages. Fifteen healthy subjects were considered as control group. MRI sequences were performed using SIEMENS 3 T scanner.The Signal Processing in NMR software was used to process and analyze the images. The QSM in every of the basal ganglia was measured separately. RESULTS: There was a significant difference for QSM in the Subtania Nigera, Red Nucleus, Thalamic Nucleus and Globus Pallidus nucleus between two groups. The relationship between disease stage with QSM was significant in Subtania Nigera, Red Nucleus, and Globus Pallidus nucleus. The QSM values had a significant association with disease stage in all nuclei. The results showed that QSM has a higher accuracy in Subtania Nigera, Globus Pallidus, Red Nucleus and Thalamic Nucleus, respectively. CONCLUSIONS: Using QSM in Red Nucleus, Subtania Nigera, and Globus Pallidus nuclei can help diagnosis and staging the patients with Parkinson's disease. In future, studies with emphasis on the disease stage can be helpful in evaluation the different parts of these three nuclei.