American journal of neurodegenerative disease最新文献

Introduction: This paper presents 5 cases of neurodegenerative disorders from our tertiary care rural hospital in south India. The purpose of this paper is to generate an emerging common theme by thematic analysis of clinical data from each of these patients. A theme emerged, we identified that there was a common clinical ground in patients with movement disorders and psychiatric symptoms. From this common theme, these patients eventually went on to develop different courses of illnesses.

Methodology: Clinical analysis of a case series of 5 patients with neurodegenerative disorders attending the Medicine or Psychiatry services of our hospital.

Conclusion: A clear & consistent association between movement disorders and psychiatric symptoms was found. Although our data is limited, we conclude that movement disorders can be early clinical markers of organic psychopathology. However, we are aware that this association can be confounded by substance abuse, stress, sleep disruption and even therapeutic interventions, and thus these factors were accounted for and yet we conclude that movement disorders can be early clinical indictors of organic psychopathology.

Background: Multiple Sclerosis (MS) is an autoimmune, inflammatory disease of the central nervous system. Magnetic resonance imaging (MRI) findings are associated with disease clinical activity and response to treatment. This study aimed to evaluate the future value of plaque number and volume in MRI as radiological criteria in determining the treatment response to INF-B in patients with MS.

Methods: This is a cross-sectional study performed in 2016-2021 in Iran on patients with the newly diagnosed (less than one year) relapsing-remitting MS. Brain MRI was taken for all patients. The number and volumes of the MS plaques were evaluated from FLAIR images by the two radiologists. Patients were treated with INF-B1a with a dosage of 12 million units equal to 44 micrograms subcutaneously, three times per week. Patients were visited monthly by neurologists to examine their clinical status. After one year, the brain MRI was conducted with the similar characteristics to the beginning of the study, and the number and volume of MS plaques were measured again.

Results: The study population consisted of 33 males and 90 females with a mean age of 28.37 ± 6.29 years. The mean Expanded Disability Status Scale (EDSS) of the patients was 3.16 ± 0.23 at the beginning of the study. The specificity for a 50% reduction in the number and volume of plaques as two separate criteria was the same and equal to 100%. The sensitivity of the number and volume of plaques were 65.5% and 90.6%, respectively. In addition, considering 10% as the cut-off point of the number of plaques, the sensitivity of the number of plaques as a criterion was equal to the sensitivity of the plaque volume.

Conclusion: The results of this study showed that imaging criteria provide a more objective tool for evaluating the effectiveness of treatment. These findings indicate that the number and volume of plaques could be two reliable MRI imaging criteria for assessing therapy response. The number of plaques was less accurate than the volume of plaques.

Objective: The study aimed to investigate the relationship between menstrual disorders and education in women with intractable epilepsy.

Method: This was a descriptive-analytical study. Statistical population consisted of all female patients with intractable epilepsy in 15-45 age group who visited the third department of epilepsy in Ayatollah Kashani Hospital. The sample size was 380. They were selected using simple random sampling. A questionnaire was distributed among the patients to collect information on education, incidence and type of current menstrual disorder (each type of menstrual disorder was explained to the participants). Then, the relationship between education and prevalence of menstrual disorders in these women was investigated.

Findings: Analysis of Spearman correlation coefficient showed a significant and negative correlation between education and menstrual disorder (P≤0.05). Analysis of multivariate logistic regression also showed a significant relationship between education and types of menstrual disorders. There was also a significant relationship between education and regular and irregular menstruation (P≤0.05).

Conclusion: There is a significant relationship between education and menstrual disorders in women with intractable epilepsy, and the higher education level indicates less prevalent menstrual irregularities.

Clinical data reported a reduction of Multiple sclerosis (MS) symptoms during pregnancy when progesterone levels are high. Medroxyprogesterone acetate (MPA) is a synthetic progestin contraceptive with unknown neuroprotective effects. This study investigated the effect of a contraceptive dose of MPA on microglia polarization and neuroinflammation in the neurotoxic cuprizone (CPZ)-induced demyelinating mouse model of MS. Mice received 1 mg of MPA weekly, achieving similar serum concentrations in human contraceptive users. Results revealed that MPA therapy significantly reduced the demyelination in the corpus callosum. In addition, MPA treatment induced a significant reduction in microglia M1-markers (iNOS, IL-1β and TNF-α) while M2-markers (Arg-1, IL-10 and TGF-β) were significantly increased. Moreover, MPA resulted in a significant decrease in the number of iNOS positive cells (M1), whereas TREM-2 positive cells (M2) significantly increased. Furthermore, MPA decreased the protein expression levels of NF-κB and NLRP3 inflammasome as well as mRNA expression levels of the downstream product IL-18. In summary, MPA reduces the level of demyelination and has an anti-inflammatory role in CNS demyelination by inducing M2 microglia polarization and suppressing the M1 phenotype through the inhibition of NF-κB and NLRP3 inflammasome. Our results suggest that MPA should be a suitable contraceptive pharmacological agent in demyelinating diseases.

Background: Various articles show the high prevalence of sleep disorders and especially excessive daytime sleepiness (EDS) in patients with refractory epilepsy and the importance of personal and social burden of this complication on individuals. Considering the insufficient evidence to draw efficacy and safety of modafinil and methylphenidate to treat EDS in the patient with intractable seizures, we decided to compare the effect of methylphenidate and modafinil with the control group. It is hoped that this study will pave the way for further studies.

Methods: This study is a clinical trial (IRCT20171030037093N22) (URL: https://www.irct.ir/trial/42485). The study population was patients with refractory epilepsy referred to the neurology clinic of Al-Zahra Hospital, Isfahan, Iran, from 2019 to 2020. The patients were randomly divided into three groups. The first group was treated with methylphenidate, the second group was treated with modafinil, and the third group was not received any medication such as modafinil and methylphenidate. Methylphenidate dosage was 10-20 mg/day. The patients were treated with modafinil at a dose of 200-600 mg/day. EPWORTH sleepiness scale (ESS) and Total Sleep Time (TST) were calculated before and 8 weeks after the intervention for the patients.

Results: 47 patients were included and divided into 3 groups, methylphenidate (10 males and 9 females), modafinil (7 males and 13 females), and control (4 males and 4 females). There was no significant difference among the groups based on ESS before and after intervention and TST after the intervention (P>0.05), but the mean of TST was significantly lower in the control group than in methylphenidate and modafinil groups before the intervention (P=0.003). The change of ESS and TST before compared to after intervention in the methylphenidate and modafinil group were significant (P<0.001), but the changes of ESS and TST in the control group were not significant (P>0.05). The frequency of complications (P=0.74) and outcomes (P=0.07) were similar in both groups.

Conclusion: Modafinil and methylphenidate are two effective and safe drugs to increase the quality of sleep in the patients. Additionally, ESS and TST scores are better in the patients who used modafinil and methylphenidate.

Introduction: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a chronic autoimmune demyelinating peripheral neuropathy that leads to symmetrical muscular weakness, sensory deficit, hyporeflexia, chronic fatigue, and impaired quality of life (QoL). The current study aims to investigate the effects of gabapentin versus pregabalin on pain, sleep disturbances, and QoL in CIDP patients.

Methods: This clinical trial was conducted on 40 patients diagnosed with CIDP randomly allocated to treatment with 100-500 mg gabapentin (n=20) or 50-300 mg pregabalin (n=20) both co-medicated with 37.5 mg venlafaxine. The dose of gabapentin/pregabalin was adjusted based on the patient's tolerability/response to the treatment. Visual analogue scale (VAS), Pittsburg Sleep Quality Questionnaire and Short Form Health Survey (SF-36) were filled at baseline, within three, six, nine and 12 months after the interventions to assess pain severity, sleep quality and QoL, respectively. The Iranian Registry of Clinical Trials (IRCT) code: IRCT20200217046523N16, https://fa.irct.ir/search/result?query=IRCT20200217046523N16.

Results: Gabapentin revealed a dose-dependent efficacy in pain severity (P-value =0.004, r=0.287), sleep quality (P-value <0.001, r=0.387) and QoL (P-value =0.001, r=-0.378), but pregabalin (P-value >0.05). Co-medication of gabapentin plus venlafaxine could significantly improve sleep quality (P-value =0.009) and QoL (P-value =0.004), but pain severity (P-value =0.796). Pregabalin plus venlafaxine showed statistically significant improvement in pain (P-value =0.046), sleep quality (P-value <0.001) and QoL (P-value <0.001). The comparison of the two medications revealed the superiority of pregabalin in pain relief (P-value >0.001) and QoL (P-value =0.03) to pregabalin.

Conclusion: Based on this study, the co-medication of pregabalin and venlafaxine led to remarkable superior outcomes compared to venlafaxine plus gabapentin in the management of pain, sleep quality, and QoL due to CIDP.

Parsonage Turner Syndrome (syn. idiopathic brachial plexopathy, neurologic amyotrophy) is a rare syndrome of poorly understood etiology with a reported incidence of 1.64 in 1 lakh persons per year. It affects men more often than women with a highest incidence in the third and seventh decades of life. Its pathophysiology is obscure and the syndrome has been reported in the postoperative, post infectious and recent viral illness, and post-vaccination settings. Trauma from manipulation of tissues and various positioning techniques used to facilitate surgical techniques, or immune-mediated inflammation remains the most common associated risk factor. It mostly remains under diagnosed for lack of clinical suspicion and specific diagnostic tools. Herein, we share a personal experience of this uncommon disorder by the first author, a healthy 67-year-old man, having no significant medical or surgical disorder and presenting with several weeks of weakness of right shoulder. The diagnosis was made after its aggravation following stretch injury sustained from a fall with upper limbs in full abduction. Treatment with high dose dexamthasone (100 mg in 200 ml 5% dextrose given once by slow i.v. infusion), NSAIDs (as needed) and physiotherapy given over 12 months was remittive.

Background: Hypertension has been reported to cause impaired cardiovagal modulation and a wide variety of cognitive loss. However, the link cardiovagal modulation to neurocognitive impairment has not been studied yet. The present study has compared the link cardiovagal modulation to neurocognitive impairment between prehypertension and newly diagnosed hypertension in young adults.

Methods: One hundred forty-seven subjects (42 normotensives, 54 prehypertensives and 51 newly diagnosed hypertensives) aged between 18-44 years were included in this case-control study. The demographic, anthropometric, basal parameters, heart rate variability (HRV), cardiovascular autonomic function tests (CAFTs), event-related potential P300 and biochemical parameters were recorded in all the groups. Association of various parameters with neurocognitive deficit was studied by Pearson correlation analysis and independent contribution of various factors to cognitive deficit was assessed by multiple regression analysis in the study groups.

Results: Total power (TP) of HRV, the marker of cardiovagal modulation was reduced in both prehypertensives and hypertensives compared to controls. Among CAFTs, the ΔDBP_IHG was increased, and 30:15 ratio and E:I ratio were decreased in both study groups. The latency of P300 (the marker of neurocognition) was significantly prolonged in prehypertensives and hypertensives and P300 latency was significantly associated with reduction in TP in both the groups. HOMA-IR was increased, and total oxidant capacity was decreased in prehypertensives and hypertensives, and both these parameters had independent contribution to P300.

Conclusion: Prehypertensives had considerable autonomic imbalance, reduced cardiovagal modulation and neurocognitive deficit that were comparable to newly diagnosed hypertensives. Though the causal relationship between cardiovagal modulation and neurocognitive impairment can't be established from the findings of the present study, it appears that neurocognitive deficit might have some possible link to the decreased cardiovagal modulation and metabolic derangements in young prehypertensives and hypertensives.

The second most prevalent neurodegenerative disorder worldwide in the elderly is Parkinson's disease (PD). It is a major risk factor for aging. Objectives: Currently the involvement of miRNAs in the disease is mainly unclear. Additionally, the disease aetiology is complex and there are no available disease-modifying medications. Therefore, more evidence is required concerning its pathogenesis and developing new treatment modalities. Methods: Here, we studied the expression profiles of about 900 miRNAs in PD patients prior to and following deep brain stimulation (DBS) both on and following 1 hour off electrical stimulation and as compared with age and gender matched healthy control (HC) donor samples, using Affymetrix miRNA microarrays. We analysed statistically the data using Affymetrix expression console software. Results: We detected significantly altered miRNAs pre and post DBS treatment. Conclusions: Our findings indicate the involvement of miRNAs in PD. Future studies can enlarge the number of samples and use RNA sequencing platform to quantify further miRNAs in PD samples. We may also use the expression levels of miRNAs as biomarkers for PD in the blood.

From the early stages of any neurodegenerative-disease mitochondrial functionality has been mortally extricated, though the exact timeline of these events is still unclear, it is likely to represent a progressive neurons-decline and cognitive-functions. Hence strategies suggested by herbal extract to restore mitochondrial functions may be a remedial approach to chronic neurodegenerative disorder like Alzheimer's disease (AD). This research was designed to evaluate if Aβ_1-40 induced oxidative stress and mitochondrial dysfunction could be inhibited by Allium Sativum (AS) supplementation. AD was induced by a single intra-hippocampal injection of Aβ_1-40 (5 μg/4 μl), while herbal supplementation was given orally (100, 250, 500 mg/kg body weight, daily) for 3 weeks. Morris water maze was used to assess cognitive function shows deficits in Aβ_1-40 treated animals, there is no significant alteration in locomotor function as examined by actophotometer. This was accompanied by enhancement in oxidative stress indicating by accentuated ROS and protein carbonyl levels. Concomitantly, decrease in activity of antioxidant enzymes was observed in diseased animals; as expressed by reduced superoxide-dismutase and catalase activity, as well as reduction in GSH levels and impaired mitochondrial functions. Medium dose of AS has been found effective in restoring the memory impairment along with antioxidant levels but high dose is more efficient as observed in the Aβ_1-40 treated rats. High dose of AS, on the other hand significantly ameliorates the mitochondrial-dysfunction in comparison to medium dose. Taken together, the findings reveal that AS reverses Aβ_1-40 induced brain alteration, it could be an efficient clinical mitigation action against AD growth.