Nasu-Hakola Disease With Stroke-like Attack: A Case Report.

Homozygous mutations in the triggering receptor expressed on myeloid cells 2 (TREM2) gene are known to cause Nasu-Hakola disease, which is a rare cause of progressive presenile dementia. A 36-year-old woman presented with repetitive seizures, a 5-year history of progressive behavioral and cognitive changes, and an affected sibling. Magnetic resonance imaging of the brain revealed an ischemic lesion in the left medial temporal lobe. Extensive evaluation of juvenile stroke revealed that viral and autoimmune encephalitides, serum lactate and pyruvate levels, and cerebrospinal fluid composition were all normal. Brain magnetic resonance imaging was notable of thinning of the corpus callosum and caudate and frontotemporal cortical atrophy, in addition to the ischemic lesion. Whole exome sequencing revealed a homozygous mutation (c.A257T; p.D86V) in TREM2. The present case expands the clinical phenotype of Nasu-Hakola disease and further suggests that TREM2 pathway might have role in vessel wall health.

Scoring Algorithm-Based Genomic Testing in Dystonia: A Prospective Validation Study.

BACKGROUND: Despite the established value of genomic testing strategies, practice guidelines for their use do not exist in many indications. OBJECTIVES: We sought to validate a recently introduced scoring algorithm for dystonia, predicting the diagnostic utility of whole-exome sequencing (WES) based on individual phenotypic aspects (age-at-onset, body distribution, presenting comorbidity). METHODS: We prospectively enrolled a set of 209 dystonia-affected families and obtained summary scores (0-5 points) according to the algorithm. Singleton (N = 146), duo (N = 11), and trio (N = 52) WES data were generated to identify genetic diagnoses. RESULTS: Diagnostic yield was highest (51%) among individuals with a summary score of 5, corresponding to a manifestation of early-onset segmental or generalized dystonia with coexisting non-movement disorder-related neurological symptoms. Sensitivity and specificity at the previously suggested threshold for implementation of WES (3 points) was 96% and 52%, with area under the curve of 0.81. CONCLUSIONS: The algorithm is a useful predictive tool and could be integrated into dystonia routine diagnostic protocols. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson Movement Disorder Society.

Acupuncture in the treatment of HTLV-I-associated myelopathy / tropical spastic Paraparesis.

We investigate the possible effects of acupuncture on the improvement of neurological problems in HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP)disease. Twenty patients with HAM/TSP were studied in this pre and post-test clinical trial. Urinary incontinence, global motor disability, spasticity, and pain severity were evaluated before, one month, and three-month after the intervention. Analyses demonstrated a significant reduction of urinary symptoms one month after acupuncture (P = 0.023). A significant improvement was observed in patients' pain and the spasticity at the upper extremity joints, one and three-month after the intervention (P < 0.05). This study suggests that body acupuncture can be used as a complementary treatment to improve HAM/TSP neurological symptoms.

Five-Year Recurrence Rate and the Predictors Following Stroke in the Mashhad Stroke Incidence Study: A Population-Based Cohort Study of Stroke in the Middle East.

BACKGROUND: Little is known about the risk of recurrent stroke in low- and middle-income countries. This study was designed to identify the long-term risk of stroke recurrence and its associated factors. METHODS: From November 21, 2006 for a period of 1 year, 624 patients with first-ever stroke (FES) were registered from the residents of 3 neighborhoods in Mashhad, Iran. Patients were followed up for the next 5 years after the index event for any stroke recurrence or death. We used competing risk analysis and cause-specific Cox proportional hazard models to estimate the cumulative incidence of stroke recurrence and its associated variables. RESULTS: The cumulative incidence of stroke recurrence was 14.5% by the end of 5 years, with the largest rate during the first year after FES (5.6%). Only advanced age (adjusted hazard ratio [HR] 1.02; 95% CI 1.01-1.04) and severe stroke (National Institutes of Health Stroke Scale score >20; HR 2.23; 95% CI 1.05-4.74) were independently associated with an increased risk of 5-year recurrence. Case fatality at 30 days after first recurrent stroke was 43.2%, which was significantly greater than the case fatality at 30 days after FES of 24.7% (p = 0.001). CONCLUSION: A substantial number of our patients either died or had stroke recurrences during the study period. Advanced age and the severity of the index stroke significantly increased the risk of recurrence. This is an important finding for health policy makers and for designing preventive strategies in people surviving their stroke.

Five-Year Case Fatality Following First-Ever Stroke in the Mashhad Stroke Incidence Study: A Population-Based Study of Stroke in the Middle East.

BACKGROUND AND PURPOSE: Despite recent declines in stroke mortality in high-income countries, the incidence and mortality of stroke have increased in many low- and middle-income countries. Population-based information on stroke in such countries is a research priority to address this rising trend. This study was designed to evaluate 5-year stroke mortality and its associated factors. METHODS: During a 12-month period beginning from November 2006, 624 patients with first-ever stroke (FES) living in Mashhad, Iran, were recruited and followed longitudinally. Kaplan-Meier analyses were used to determine the cumulative risk of death. Prognostic variables associated with death were assessed using a Cox proportional hazard, backward logistic regression model. RESULTS: The 5-year cumulative risk of death was 53.8% for women and 60.5% for men (log rank = .1). The most frequent causes of death were stroke (41.2%), myocardial infarction/vascular diseases (16.4%), and pneumonia (14.2%). In multivariable Cox proportional hazard analysis, male gender (hazard ratio [HR]: 1.29, 95% confidence interval [CI]: 1.01-1.64), age (HR: 1.04, 95% CI: 1.03-1.05, per 1-year increase), National Institute of Health Stroke Scale score at admission (HR: 1.11, 95% CI: 1.09-1.12, per 1-point increase), atrial fibrillation (HR: 1.78, CI: 1.24-2.54), and education < 12 years (HR: 1.61, 95% CI: 1.08-2.4) were associated with greater 5-year case fatality. CONCLUSIONS: Long-term case fatality following stroke in Iran is greater than that observed in many high-income countries. Targeting strategies to reduce the poor outcome following stroke, such as treating AF, is likely to reduce this disparate outcome.

Gaps and hurdles deter against following stroke guidelines for thrombolytic therapy in Iran: exploring the problem.

BACKGROUND: Insufficient information is available on the barriers that explain low rates of thrombolytic therapy for acute ischemic stroke (AIS) in developing countries compared with rates in developed societies. By the present study, we aimed to assess the implementation of thrombolytic therapy in the northeast of Iran to explore the gaps and hurdles against thrombolysis as the generally accepted treatment for AIS. METHODS: In a 1-year cohort study among AIS patients admitted to the second largest tertiary neurologic referral center in Iran, those who met the prespecified selection criteria were treated with intravenous recombinant tissue plasminogen activator (rtPA). RESULTS: Among 1,144 patients admitted with AIS, only 14 (1.2%) were treated with rtPA. The mean onset-to-needle and door-to-needle times were 172 and 58 minutes, respectively; 980 (85.6%) patients were initially excluded from the study because of late arrival. Additionally, 60 patients in total were omitted because of either their high age (3.7%) or passing the gold standard time limit for rtPA therapy after preliminary evaluations (1.6%), and 90 more patients (7.9%) were considered not suitable for thrombolysis because of the severity of the symptoms or the higher risk of bleeding on rtPA. CONCLUSIONS: Access to thrombolytic therapy for AIS in Iran is less than in most developed countries but comparable with other developing countries. Awareness campaigns are needed to minimize barriers and improve access to thrombolysis and specialized stroke care in Iran.

Can HTLV-1 infection be a potential risk factor for atherosclerosis?

INTRODUCTION: Chronic inflammations including infectious disorders such as HIV infection are now considered as risk factors for atherosclerosis. In this study, conducted for the first time on human subjects, human T-lymphotropic virus type 1 (HTLV-1) infection was examined as a potential risk factor for atherosclerosis. MATERIALS AND METHODS: This is a matched-pair cross-sectional study on 58 HTLV-1-infected cases and 55 healthy control subjects. The subjects did not have any major cerebrovascular risk factors. Carotid intima-media thickness (IMT) was measured for each patient using the standard protocol of the Atherosclerosis Risk in Communities (ARIC) Study. RESULTS: The mean age of the subjects was 42.9 ± 10.52 years, and males made up 33% of the population. The difference between the mean IMT of the infected case group and that of the healthy control group was significant (p < 0.05). DISCUSSION: This study indicated that the HTLV-infected individuals showed a greater carotid IMT than the age- and sex-matched control subjects. Observing no other known risk factor for atherosclerosis, we concluded that this significant difference in IMT might support the hypothesis that HTLV-1 infection is an independent risk factor for atherogenesis.

The effects of Mozart's music on interictal activity in epileptic patients: systematic review and meta-analysis of the literature.

Mozart's music has been shown to have promising effects on nervous system functions. In this study, the effects of Mozart's work on epilepsy were reviewed. Articles were obtained from a variety of sources. The results of 12 studies were extracted. Three different meta-analyses were performed to examine (i) the percentage of patients who had changes in their interictal epileptic discharges (IEDs) by music therapy; and the changes of IEDs (ii) during and (iii) after exposure to Mozart's music. Data analysis indicated that 84% of patients listening to Mozart's music showed a significant decrease in IEDs. In addition, IEDs were decreased during (31.24%) and after (23.74%) listening to Mozart's compositions. A noteworthy response to music therapy in patients with a higher intelligence quotient, generalized or central discharges, and idiopathic epilepsy was demonstrated. The effect of Mozart's music on epilepsy seems to be significant. However, more randomized control studies are needed to determine its clinical efficacy.

Selenium and selenoproteins role in Parkinson's disease: Is there a link between selenoproteins and accumulated alpha-synuclein?

BACKGROUND: While Parkinson's disease (PD) etiology is not clear yet, accumulated alpha-synuclein is proposed to induce neurodegeneration. Selenium (Se) and its functional proteins play a key role in aggregation of misfolded proteins. However, their implications in neurodegenerative process are unclear. AIM: Diagnosing Se and selenoprotein P (SelP), selenoprotein S (SelS) proportions in serum of PD patients to compare with healthy controls, whether the changes in their concentration could be a biomarker for PD. METHODS: Se concentration was investigated in 30 PD patients and 30 controls using atomic absorption spectrometry. Also, alpha-Synuclein, SelP, and SelS levels were evaluated by ELISA. The parameters were compared in PD patients and controls. Also, the variations within the case group according to their age, disorder stage, and drug administration were evaluated. RESULTS: PD subjects had higher Se concentration. The mean SelP in PD patients was lower from controls, whilst SelS levels were higher. Also, the concentration of alpha-synuclein was higher in PD patients. However, age, stage (except UPDRS III), and disorder duration had no influence on the Se and selenoproteins level, whilst there was a direct association between alpha-synuclein levels and disorder stage. Also, alpha-synuclein proportions in subjects using levodopa was significantly higher. CONCLUSION: Our results suggest that serum levels of Se and SelP could be a biomarker or risk factor for PD. Although SelS interferes to reduce aggregated proteins, its pathway in PD is not clearly understood. Future studies could focus on how SelS can reduce on alpha-synuclein aggregation. Thus, other studies should be performed on this issue to induce the selenoproteins in PD.

Changes in speech prosody perception during Parkinson's disease: A comprehensive analysis.

INTRODUCTION: Parkinson's disease (PD) is a progressive neurodegenerative disorder that affects approximately 1%-2% of individuals aged 60 and above. Communication disorders in PD can significantly impact the overall quality of life. As prosody plays a vital role in verbal communication, the present study examines Persian prosody perception in PD, focusing on linguistic and emotional aspects of prosody. METHODS: This cross-sectional study aimed to compare the perception of linguistic and emotional prosody in three groups: middle-aged adults (n = 22; mean age = 50.40 years), healthy older adults (n = 22; mean age = 68.31 years), and individuals with Parkinson's disease (n = 22; mean age = 65years). All individuals with PD were classified in stages 1; 1.5; 2; 2.5, and 3 of the disease using the Hoehn and Yahr scale. All participants had an MMSE score of 24 or above. The Florida Affect Battery (FAB) was used to evaluate prosody perception. This Battery was validated in the Persian language and its reliability and validity were reported as 94 % and 100 % respectively. RESULTS: Participants with PD presented significantly lower scores than the older adults in all subtests of the FAB (p < 0.05), while healthy older adults were significantly different only in linguistic discrimination (ß = -2.14; -3.68 to -0.61), and linguistic naming of prosody (ß = 1.25; 0.17 to 2.33) compared to middle-aged adults. CONCLUSIONS: The present study sheds light on the influence of PD on Persian prosody perception. Given the crucial role of prosody in verbal communication, these findings enhance our understanding of communication disorders in PD and could bring attention to consider prosody perception, among other aspects, when assessing individuals affected by PD.

Incidence of first ever stroke during Hajj ceremony.

BACKGROUND: The Hajj Ceremony, the largest annual gathering in the world, is the most important life event for any Muslim. This study was designed to evaluate the incidence of stroke among Iranian pilgrims during the Hajj ceremony. METHODS: We ascertained all cases of stroke occurring in a population of 92,974 Iranian pilgrims between November 27, 2007 and January 12, 2008. Incidence and risk factors of the first ever stroke in Hajj pilgrims were compared, within the same time frame, to those of the Mashhad residents, the second largest city in Iran. Data for the latter group were extracted from the Mashhad Stroke Incidence Study (MSIS) database. RESULTS: During the study period, 17 first-ever strokes occurred in the Hajj pilgrims and 40 first-ever stroke strokes occurred in the MSIS group. Overall, the adjusted incidence rate of first ever stroke in the Hajj cohort was lower than that of the MSIS population (9 vs. 16 per 100,000). For age- and gender-specific subgroups, the Hajj stroke crude rates were in general similar to or lower than the general population of Mashhad, Iran, with the exception of women aged 35 to 44 years and aged >75 years who were at greater risk of having first-ever stroke than the non-pilgrims of the same age. CONCLUSION: The first ever stroke rate among Iranian Hajj pilgrims was lower than that of the general population in Mashhad, Iran, except for females 35-44 or more than 75 years old. The number of events occurring during the Hajj suggests that Islamic countries should consider designing preventive and screening programs for pilgrims.

Enhancing Healthcare Outcomes and Modulating Apoptosis- and Antioxidant-Related Genes through the Nano-Phytosomal Delivery of Phenolics Extracted from Allium ampeloprasum.

The application of nano drug delivery systems, particularly those utilizing natural bioactive compounds with anticancer properties, has gained significant attention. In this study, a novel nano-phytosome-loaded phenolic rich fraction (PRF) derived from Allium ampeloprasum L. was developed. The antitumor activity of the formulation was evaluated in BALB/c mice with TUBO colon carcinoma. The PRF-loaded nano-phytosome (PRF-NPs) exhibited a sphere-shaped structure (226 nm) and contained a diverse range of phenolic compounds. Animal trials conducted on TUBO tumor-bearing mice demonstrated that treatment with PRF-NPs at a dosage of 50 mg TPC/Kg/BW resulted in significant improvements in body weight and food intake, while reducing liver enzymes and lipid peroxidation. The expression of apoptosis-related genes, such as Bax and caspase-3, was upregulated, whereas Bcl2 was significantly downregulated (p < 0.05). Furthermore, the expression of GPx and SOD genes in the liver was notably increased compared to the control group. The findings suggest that the phytosomal encapsulation of the phenolic rich fraction derived from Allium ampeloprasum L. can enhance the bioavailability of natural phytochemicals and improve their antitumor properties. The development of PRF-NPs as a nano drug delivery system holds promise for effective breast cancer treatment.

Copy number analysis from whole-exome sequencing data revealed a novel homozygous deletion in PARK7 leads to severe early-onset Parkinson's disease.

Parkinson's disease (PD), a neurodegenerative disease characterized by both motor neuron and non-motor neuron symptoms, is the most frequent neurodegenerative disease after Alzheimer's disease. Both genetic and environmental factors take part in disease etiology. Most cases are considered complex multifactorial diseases. About 15% of PD appear in the familial form, and about 5% of all cases arise from a single gene mutation. Among Mendelian causes of PD, PARK7 is one of the autosomal recessive forms due to loss-of-function mutations in both gene alleles. Both single nucleotide variants (SNVs) and copy number variations (CNVs) are observed in PARK7. This study presents an Iranian family with familial PD where some relatives had psychiatric disorders. A homozygous 1617 bp deletion in a female with early-onset PD was detected through copy-number analysis from whole-exome sequencing (WES) data in this consanguineous family. Further investigation by surveying microhomology revealed that the actual size of the deletion is 3,625 bp. This novel CNV that was in the PARK7gene is supposed to co-relation with early-onset PD and infertility in this family.

Lavender essential oil in the treatment of migraine headache: a placebo-controlled clinical trial.

UNLABELLED: Lavender essential oil has been used as an anxiolytic drug, a mood stabilizer, a sedative, spasmolytic, antihypertensive, antimicrobial, analgesic agent as well as a wound healing accelerator. We have studied for the first time the efficacy of lavender essential oil inhalation for the treatment of migraine in a placebo-controlled clinical trial. METHODS: Forty-seven patients with definite diagnosis of migraine headache were divided into cases and controls. Cases inhaled lavender essential oil for 15 min, whereas the control group used liquid paraffin for the same time period. Patients were asked to record their headache severity and associated symptoms in 30-min intervals for a total of 2 h. We matched the two groups for key confounding factors. RESULTS: The mean reduction of headache severity in cases was 3.6 ± 2.8 based on Visual Analogue Scale score. The reduction was 1.6 ± 1.6 in controls. This difference between the controls and cases was statistically significant with p < 0.0001. From 129 headache attacks in cases, 92 responded entirely or partially to lavender. In the control group, 32 out of 68 recorded headache attacks responded to placebo. The percentage of responders was significantly higher in the lavender group than the placebo group (p = 0.001). CONCLUSION: The present study suggests that inhalation of lavender essential oil may be an effective and safe treatment modality in acute management of migraine headaches.

Clinical Spectrum of Tauopathies.

Tauopathies are both clinical and pathological heterogeneous disorders characterized by neuronal and/or glial accumulation of misfolded tau protein. It is now well understood that every pathologic tauopathy may present with various clinical phenotypes based on the primary site of involvement and the spread and distribution of the pathology in the nervous system making clinicopathological correlation more and more challenging. The clinical spectrum of tauopathies includes syndromes with a strong association with an underlying primary tauopathy, including Richardson syndrome (RS), corticobasal syndrome (CBS), non-fluent agrammatic primary progressive aphasia (nfaPPA)/apraxia of speech, pure akinesia with gait freezing (PAGF), and behavioral variant frontotemporal dementia (bvFTD), or weak association with an underlying primary tauopathy, including Parkinsonian syndrome, late-onset cerebellar ataxia, primary lateral sclerosis, semantic variant PPA (svPPA), and amnestic syndrome. Here, we discuss clinical syndromes associated with various primary tauopathies and their distinguishing clinical features and new biomarkers becoming available to improve in vivo diagnosis. Although the typical phenotypic clinical presentations lead us to suspect specific underlying pathologies, it is still challenging to differentiate pathology accurately based on clinical findings due to large phenotypic overlaps. Larger pathology-confirmed studies to validate the use of different biomarkers and prospective longitudinal cohorts evaluating detailed clinical, biofluid, and imaging protocols in subjects presenting with heterogenous phenotypes reflecting a variety of suspected underlying pathologies are fundamental for a better understanding of the clinicopathological correlations.

Corrigendum: Clinical spectrum of tauopathies.

[This corrects the article DOI: 10.3389/fneur.2022.944806.].

Evaluation of curcumin as add-on therapy in patients with Parkinson's disease: A pilot randomized, triple-blind, placebo-controlled trial.

BACKGROUND AND OBJECTIVE: Preclinical studies suggest that curcumin might be a potential neuroprotective agent in Parkinson's disease (PD). This clinical trial aimed to evaluate the efficacy of adding nanomicelle curcumin on improving the motor and non-motor symptoms of PD patients and their quality of life. MATERIAL AND METHODS: Idiopathic PD patients aged ≥30≥ 30 whose symptoms were under control were included in this pilot, randomized, triple-blind, placebo-controlled, add-on trial. Eligible patients were randomly assigned to either the curcumin (n = 30, 80 mg/day) or placebo (n = 30) groups and were followed for nine months. Primary outcomes were the Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) and Parkinson's Disease Questionnaire (PDQ-39). These variables, along with demographic data, drug history, and possible side effects of curcumin, were gathered at the beginning of the study and every three months. A mixed effects model was used to compare the group-by-time interaction, followed by post hoc analysis. RESULTS: Although the mean MDS-UPDRS and PDQ-39 scores were not significantly different between the curcumin and placebo groups at any time points, MDS-UPDRS part III (P = 0.04) showed a significant difference in its overall trend between the study groups. However, post hoc analysis failed to spot this difference at study time points. The most common side effects of curcumin were nausea and vomiting (P = 0.25) and gastroesophageal reflux (P = 0.42). CONCLUSION: While curcumin is a well-tolerated natural compound, this trial was unsuccessful in showing its efficacy in quality of life and clinical symptoms of PD patients.

Whole-Exome Sequencing Study of Consanguineous Parkinson's Disease Families and Related Phenotypes: Report of Twelve Novel Variants.

Parkinson's disease (PD) is a common progressive neurodegenerative disorder with motor and nonmotor symptoms. Recent studies demonstrate various susceptibility loci and candidate genes for familial forms of the disease. However, the genetic basis of the familial form of early-onset PD (EOPD) is not widely studied in the Iranian population. Therefore, the present study aimed to investigate the possible causative genetic variants responsible for developing EOPD among Iranian patients. Iranian patients with a clinical diagnosis of Parkinson's disease were evaluated, and 12 consanguineous families with at least two affected individuals with early-onset PD (EOPD) were chosen to enroll in the present study. An expert neurologist group examined these families. Whole-exome sequencing (WES) was performed on PD patients, and the possible causative genetic variants related to the development of PD were reported. Exome sequencing (WES) was performed on every PD patient and revealed that patients had novel genetic variants in PRKN, PARK7, and PINK1 genes. All the genetic variants were in homozygous status and none of these variants were previously reported in the literature. Moreover, these genetic variants were "pathogenic" based on bioinformatic studies and according to the American College of Medical Genetics (ACMG). The present research revealed some novel variants for EOPD among the Iranian population. Further functional studies are warranted to confirm the pathogenicity of these novel variants and establish their clinical application for the early diagnosis of EOPD.

Brain proton magnetic resonance spectroscopy in patients with Parkinson's disease.

Background: The accuracy of current laboratory and imaging studies for diagnosis and monitoring of Parkinson's disease (PD) severity is low and diagnosis is mainly dependent on clinical examination. Proton magnetic resonance spectroscopy (MRS) is a non-invasive technique that can assess the chemical profile of the brain. In this study, we evaluated the utility of proton MRS in diagnosis of PD and determination of its severity. Methods: Patients with PD and healthy age-matched controls were studied using proton MRS. The level of N-acetylaspartate (NAA), total creatine (Cr), and total choline (Cho), and their ratios were calculated in substantia nigra (SN), putamen (Pu), and motor cortex. PD severity was assessed by the Unified Parkinson's Disease Rating Scale (UPDRS) and the Hoehn and Yahr scale. Results: Compared to 25 healthy controls (18 men, age: 59.00 ± 8.39 years), our 30 patients with PD (24 men, age: 63.80 ± 12.00 years, 29 under treatment) showed no significant difference in the metabolite ratios in SN, Pu, and motor cortex. Nigral level of NAA/Cr was significantly correlated with total UPDRS score in patients with PD (r = -0.35, P = 0.08). Moreover, patients with PD with Hoehn and Yahr scale score ≥ 2 had a lower NAA/Cr level in SN compared to patients with a lower stage. Conclusion: This study shows that 1.5 tesla proton MRS is unable to detect metabolite abnormalities in patients with PD who are under treatment. However, the NAA/Cr ratio in the SN might be a useful imaging biomarker for evaluation of disease severity in these patients.