Degenerative Neurological Diseases Research Articles

Image-recognition-based system for precise hand function evaluation

Hand dysfunction caused by hand injuries, strokes, or other neurological degenerative diseases such as cervical spondylosis is being increasingly reported. Currently, hand function assessments for diagnosis or rehabilitation are primarily based on qualitative scales, which are subjective and may vary considerably depending on the expertise of the attending clinician. Although wearable sensors and computer vision techniques have been proposed to obtain quantitative hand movement information, both have limitations. In this study, a multiview video tracking and recording system was set up using high-speed cameras and mapping of actual hand movements. The state-of-the-art software DeepLabCut was used to obtain precise 2D and 3D finger joint positions. Kinematic parameters, such as movement count, period, phase, and Pearson coefficient were used to characterize hand movement based on the relative distance-time curves of finger joints. Experimental results in a clinical setting showed that this video-based image-recognition neural network method can accurately distinguish healthy from dysfunctional hand movements. The proposed system is inexpensive, easy to set up and use, and exhibits high accuracy. Thus, it can revolutionize medical hand motion analysis and spur the development of automated quantitative systems for early hand-related disorder detection.

Role of selective attention in fatigue in neurological disorders.

Chronic fatigue is a significant symptom in several diseases including traumatic and degenerative neurological disorders. While several studies have investigated the correlates of chronic fatigue, there is as yet no unifying framework to explain chronic fatigue. In this narrative review, I investigate the role of selective attention in the development of chronic fatigue and discuss results within the framework of the sensory attenuation model of fatigue, which posits that fatigue is the phenomenological output of altered attention to sensory input. Following a short introduction of this framework, I present results from investigations that address attentional mechanisms in fatigue in multiple sclerosis, stroke, traumatic brain injury and Parkinson's disease. Attention was quantified in all four disease models using a variety of outcome measures, including behavioural, neurophysiological, structural and functional brain connectivity. The range of measures precluded direct comparison of results across disease conditions; however, in all four disease models there was evidence of poor selective attention that explained levels of chronic fatigue, supporting the sensory attenuation model of fatigue as a disease-independent mechanism of fatigue. Evidence was lacking to draw any conclusions about the direction of causality. The role of selective attention in development of fatigue is indicated. Future studies must focus on establishing causality and exploring attentional circuitry as a potential therapeutic target.

The effects of microglia-associated neuroinflammation on Alzheimer's disease.

Alzheimer's disease (AD) is defined as a severe chronic degenerative neurological disease in human. The pathogenic mechanism of AD has been convincingly elucidated by the "amyloid cascade hypothesis" with the main focus of the pathological accretion of β-amyloid (Aβ) peptides outside the cell. However, increasing evidence suggests that this hypothesis is weak in explaining the pathogenesis of AD. Neuroinflammation is crucial in the development of AD, which is proven by the elevated levels of inflammatory markers and the identification of AD risk genes relevant to the innate immune function. Here, we summarize the effects of microglia-mediated neuroinflammation on AD, focusing on the temporal and spatial changes in microglial phenotype, the interactions among microglia, Aβ, tau, and neurons, and the prospects and recent advances in neuroinflammation as a diagnostic and therapeutic target of AD.

M6A methylation: Critical roles in aging and neurological diseases.

N6-methyladenosine (m6A) is the most abundant internal RNA modification in eukaryotic cells, which participates in the functional regulation of various biological processes. It regulates the expression of targeted genes by affecting RNA translocation, alternative splicing, maturation, stability, and degradation. As recent evidence shows, of all organs, brain has the highest abundance of m6A methylation of RNAs, which indicates its regulating role in central nervous system (CNS) development and the remodeling of the cerebrovascular system. Recent studies have shown that altered m6A levels are crucial in the aging process and the onset and progression of age-related diseases. Considering that the incidence of cerebrovascular and degenerative neurologic diseases increase with aging, the importance of m6A in neurological manifestations cannot be ignored. In this manuscript, we focus on the role of m6A methylation in aging and neurological manifestations, hoping to provide a new direction for the molecular mechanism and novel therapeutic targets.

Prophylactic antireflux procedures are not necessary in neurologically impaired children undergoing gastrostomy placement

Fundoplication is frequently used in children with neurologic impairment even in the absence of reflux due to concerns for future gastric feeding intolerance, but supporting data are lacking. We aimed to determine the incidence of secondary antireflux procedures (fundoplicationor gastrojejunostomy (GJ)) post gastrostomy tube (GT) placement in children with and without neurologic impairment. Children under 18 undergoing a GT placement without fundoplication between 2010 and 2020 were identified utilizing the PearlDiver Mariner national patient claims database. Children with a diagnosis of cerebral palsy or a degenerative neurologic disease were identified and compared to children without these diagnoses. The incidence of delayed fundoplication or conversion to GJ were compared utilizing Kaplan-Meier and Cox proportional hazards regression analyses. A total of 14,965children underwent GT placement, of which 3712 (24.8%) had a diagnosis of neurologic impairment. The rate of concomitant fundoplication was significantly higher among children with a diagnosis of neurologic impairment as compared to those without (9.3% vs 6.4%, p < 0.001). While children with neurologic impairment had a significantly higher rate of fundoplication or GJ conversion at 5years compared to children without (12.6% [95% confidence interval (CI): 11.4%-13.8%] vs 8.6% [95% CI 8.0%-9.2%], p < 0.001), the overall incidence remained low. Although children with neurologic impairment have a higher rate of requiring an antireflux procedure or GJ conversion than other children, the overall rate remains less than 15%. Fundoplication should not be utilized in children without clinical reflux on the basis of neurologic impairment alone.

Multi-targeted anti-inflammatory drugs for the treatment of neurological disorders.

Multi-targeted anti-inflammatory drugs for the treatment of neurological disorders.

Three-dimensional Multi-parameter Mapping of Relaxation Times and Susceptibility Using Partially RF-spoiled Gradient Echo.

MR parameter mapping is a technique that obtains distributions of parameters such as relaxation time and proton density (PD) and is starting to be used for disease quantification in clinical diagnoses. Quantitative susceptibility mapping is also promising for the early diagnosis of brain disorders such as degenerative neurological disorders. Therefore, we developed an MR quantitative parameter mapping (QPM) method to map four tissue-related parameters (T1, T2*, PD, and susceptibility) and B1 simultaneously by using a 3D partially RF-spoiled gradient echo (pRSGE). We verified the accuracy and repeatability of QPM in phantom and volunteer experiments. Tissue-related parameters are estimated by varying four scan parameters of the 3D pRSGE: flip angle, RF-pulse phase increment, TR and TE, performing multiple image scans, and finding a least-squares fit for an intensity function (which expresses the relationship between the scan parameters and intensity values). The intensity function is analytically complex, but by using a Bloch simulation to create it numerically, the least-squares fitting can be used to estimate the quantitative values. This has the advantage of shortening the image-reconstruction processing time needed to estimate the quantitative values than with methods using pattern matching. A 1.1-mm isotropic resolution scan covering the whole brain was completed with a scan time of approximately 12 minutes, and the reconstruction time using a GPU was approximately 1 minute. The phantom experiments confirmed that both the accuracy and repeatability of the quantitative values were high. The volunteer scans also confirmed that the accuracy of the quantitative values was comparable to that of conventional methods. The proposed QPM method can map T1, T2*, PD, susceptibility, and B1 simultaneously within a scan time that can be applied to human subjects.

A Systematic Review of Shoulder Arthroplasty in Parkinson's Disease.

Parkinson's disease is a degenerative neurological disorder that can cause both motor and nonmotor symptoms. Motor symptoms are associated with increasing the patient's falls risk. Shoulder arthroplasty surgery in this patient cohort is associated with more complications than non-Parkinsonian patients. We sought to identify any increase in complications associated with this patient cohort and any surgical considerations that ought to be taken in light of their disease process. We performed a systematic review of articles using PubMed, MEDLINE, Cochrane Central, and Google Scholar. All studies which included any shoulder arthroplasty surgery for patients with Parkinson's disease were included. Complication rates were higher in patients with Parkinson's disease than in the normal arthroplasty cohort in all studies. There was significant heterogeneity between all 8 studies included in the systematic review. Complication rates ranged from 26% to 100%. Complications included subluxation, loosening, malunion, nonunion, scapular notching, stiffness, fracture, baseplate failure, dislocation, and infection. Reoperation rates ranged from 5% to 29%. Compared to patients without Parkinson's disease undergoing shoulder arthroplasty, patients with Parkinson's disease achieved similar reductions in pain but inferior clinical function. The range of movement was less predictable, and complication rates were significantly higher in Parkinson's disease patients. This study will aid the surgeon and patient regarding surgical intervention, informed consent, and allow the surgeon to anticipate potential complications of shoulder arthroplasty in this patient cohort.

Anaesthetic Management of Patient with Left Atrial Myxoma, Coronary Artery Disease 3 Vessels Disease, and Parkinson’s Disease

Myxomas are the most common primary benign intracavitatory tumour with the incidence of 0.5 per million populations. Myxomas account for 0.3% of all cardiac surgeries performed. Clinically, they are characterized by a triad of embolisation, obstruction of blood flow, and constitutional symptoms (Goodwin’s triad). Meanwhile Parkinson's disease is a degenerative neurologic disorder caused by degeneration of nerve cells in the substantia nigra causing weakness motor coordination. Symptoms include tremor, bradykinesia, rigidity, and postural instability. Achieving a satisfactory hemodynamic performance is the primary objective in the management of cardiac surgery patient. Optimal cardiac function ensures adequate perfusion and oxygenation of other organ systems (in particular vital organs) and improves the chances for an uneventful recovery from surgery. A 61-year old female diagnosed with Coronary Artery Disease 3 Vessel Disease (CAD 3 VD), Parkinson’s disease, and left atrial myxoma was brought to the emergency department with dyspnea. The patient has undergone angiography and the echocardiography result was LVEF 59% with global normokinetic, LA myxoma causing non-significant mitral flow. LA myxoma excision under general anaesthesia on CPB was planned. Balanced general anaesthesia on cardiopulmonary bypass forms the basis of Anaesthetic management of Cardiac myxomas. However specific individual considerations will have to be made regarding drugs, doses, regional anaesthetic choices, anticoagulation and post-operative management. There is no simple anesthetic technique for patients with Parkinson’. Therefore, careful preoperative assessment, administration of drugs during and after anesthesia, as well as avoiding agents that are known to trigger Parkinson's symptoms is a major factor in reducing postoperative morbidity and mortality.

Autoencoder Networks Decipher the Association between Lung Cancer and Alzheimer’s Disease

Lung cancer is the most common malignancy and is responsible for the largest cancer-related mortality worldwide. Alzheimer's disease is a degenerative neurological disease that burdens healthcare worldwide. While the two diseases are distinct, several transcriptomic studies have demonstrated they are linked. However, no concordant conclusion on how they are associated has been drawn. Since these studies utilized conventional bioinformatics methods, such as the differentially expressed gene (DEG) analysis, it is naturally expected that the proportion of DEGs having either the same or inverse directions in lung cancer and Alzheimer's disease is substantial. This raises the inconsistency. Therefore, a novel bioinformatics method capable of determining the direction of association is desirable. In this study, the moderated t-tests were first used to identify DEGs that are shared by the two diseases. For the shared DEGs, separate autoencoder (AE) networks were trained to extract a one-dimensional representation (pseudogene) for each disease. Based on these pseudogenes, the association direction between lung cancer and Alzheimer's disease was inferred. AE networks based on 266 shared DEGs revealed a comorbidity relationship between Alzheimer's disease and lung cancer. Specifically, Spearman's correlation coefficient between the predicted values using the two AE networks for the Alzheimer's disease test set was 0.825 and for the lung cancer test set was 0.316. Novel bioinformatics methods such as an AE network may help decipher how distinct diseases are associated by providing the refined representations of dysregulated genes.

An insight into the immunomodulatory potential of wood oil of Aquilaria malaccensis Lam. with an emphasis into related phytomedicine, biomarkers, pharmacology, and toxicity

Critically endangered Aquilaria malaccensis Lam. is known for highly expensive agarwood with unique aroma. Agarwood has been used as a phytomedicine in chronic degenerative neurological disorders, paralysis, rheumatism, asthma, and others. Its production is dependent naturally or artificially on interaction of endophytic fungi, and by nailing, drilling, and microbial inoculation respectively. The majorly produced biomarkers of terpenes, fatty acids, alkanes, chromones, and flavonoids exhibited several biological activities in congruence to their ethnomedicinal claims. During the pandemic, several in-silico , studies showed the potential of a few sesquiterpene hydrocarbons against covid-19. The review aimed to deliver a comprehensive outline of the immunomodulatory potential of agarwood oil with allied traditional medicinal use, biomarkers, pharmacological evaluation, toxicity, and mechanistic action . The review eventually showed the agarwood oil, extracts, and major biomarkers viz., aromadendrene II, valencene, phytol, octacosane, caryophyllene oxide, β-caryophyllene, hinesol, agarospirol, with immunomodulatory, anti-inflammatory, and allied neural, antidiabetic, antimicrobial activity, toxicity, along with molecular target binding potential against 3CLpro, RDRP, Mpro, PLpro, Spike protein S1 of SARS-CoV2 through in-vitro, in-vivo, in silico studies and limited human clinical trials. The expression of HMGR, ASS, ADXPS, ADXPR, FPS , and WRKY genes of sesquiterpenoid biosynthetic pathways were upregulated for signature aroma and immunomodulatory markers viz., δ-guaiene, dodecane, tetracosane, agarospirol, farnesol, and geranylgeraniol acetate as a defensive response. The review would ignite future research on potential immunomodulatory markers viz., caryophyllene oxide, octacosane, heneicosane, agarospirol, n-hexadecanoic acid, α-eudesmol, α-santalol and inoculum guided in-vitro agarwood production restoring the prized aroma, therapeutic efficacy, and wild population. Phytomedicinal uasge, biomarkers, immunomodulatory and related biological activities of Aquilaria malaccensis . • Critically endangered Aquilaria malaccensis Lam. is globally known for unique aroma. • High value agarwood oil is traditionally used as a phytomedicine in several chronic degenerative ailments. • Biomarkers exhibited pharmacological evaluation and in-silico immunomodulatory potential against SARS-CoV2. • Several genes WRKY, PAL, GLU were expressed during formation of agarwood as response to fungal infection, mechanical damage, and stress. • Futuristic scope on gene expression and marker-driven agarwood production with immunomodulatory potential.

Verification of the association between cognitive decline and olfactory dysfunction using a DEmentia screening kit in subjects with Alzheimer's dementia, mild cognitive impairment, and normal cognitive function (DESK study): A multicenter, open-label, interventional study.

Olfactory dysfunction may be an early symptom of degenerative neurological disorders such as mild cognitive impairment (MCI), which may progress to cognitive decline and Alzheimer's disease (AD). We investigated the relationship between cognitive decline and olfactory dysfunction in healthy controls and patients with MCI or AD using the DEmentia Screening Kit (DESK), an olfactory identification assessment tool designed for Japanese populations. In this multicenter, open-label, interventional study conducted from 16 September 2020 to 30 April 2021, participants underwent olfactory tests using the DESK tool. This included 10 odorants at two concentrations (weak/strong) including toothpaste, butter, and India ink. Among 223 participants, 100, 61, and 62 were healthy controls, MCI patients, and AD patients (mean ages, 57.4, 72.8, and 76.3years; total DESK olfaction scores, 18.4, 14.7, and 7.4), respectively. Significant differences in total olfaction scores were observed between groups (healthy controls vs MCI, healthy controls vs AD, and MCI vs AD). Significant between-group total score differences were shown for olfaction scores with both the 10 strong and 10 weak odorant varieties. The DESK tool may discriminate between healthy individuals and those with MCI or AD, facilitating early screening for cognitive decline among Japanese patients, although the effect of age on DESK olfaction scores has not been fully explored.

Analysis of Massage Treatment Mechanism of Parkinson’s Disease

Parkinson’s disease as a common neurological degenerative disease, there is no clear cure, now approved treatment can only alleviate symptoms, and cannot effectively prevent the further development of the disease and the emergence of side reaction, massage as complementary and alternative medical means one of the most commonly used form, its improve Parkinson’s disease motor symptoms and nonmotor symptoms have a good advantage, but its potential treatment mechanism has not been further discussed. Therefore, this paper will deeply explore the potential action mechanism of massage therapy to improve the symptoms of Parkinson’s disease from multiple angles, in order to provide theoretical support for the rationality of massage treatment of Parkinson’s disease, so that massage therapy can be better used in clinical practice.

The role of tonifying kidney decoction and acupuncture in the treatment of Alzheimer's disease: A network meta-analysis.

As one of the chronic neurological degenerative diseases with the highest incidence of amnesia and dementia, Alzheimer's disease (AD) carried out the clinical treatment based on the 2 traditional Chinese medicine (TCM) of Chinese herbal compound and acupuncture (AP). With the vigorous development of TCM, doctors are facing the problem of choosing TCM or western medicine in clinical work. Hence there is an urge to make pairwise comparisons among these interventions to provide evidence for clinical practice. The used efficacy of the 2 TCM methods and combined with donepeziline were compared to compile the best treatment through network meta-analysis. Patients diagnosed with AD were included in the randomized clinical trial, who were treated with tonifying kidney decoction (TKD) or AP combined with donepezil hydrochloride (DH) as an intervention measure, while the control group was treated with DH. The total effective rate was the primary outcome, and mini-mental state examination (MMSE) score and activities of daily living (ADCS-ADL) scores were the secondary indicators. Eventually 30 studies reporting 2236 patients underwent TKD or AP combined with DH were enrolled. In terms of total efficiency, compared with TKD and DH, TKD + DH was significantly preferable. In addition, TKD were classified into 2 categories, namely tonifying kidney with reducing phlegm formulas (TKRP) and tonifying kidney with filling lean marrow (TKFLM). Regarding to MMSE score of TKD, of the 3 interventions, only TKRP + DH (standard mean difference [SMD] = 4.84, 95% confidence interval [CI]: 0.86-8.82) and TKFLM + DH (SMD = 3.93, 95% CI: 1.06-6.80) had significant efficacy over TKFLM (SMD = 4.25, 95%CI: -2.58 to 11.08). Although no difference between TKRP and other groups, its effectiveness was higher than TKFLM + DH and TKFLM (surface under the cumulative ranking curve (SUCRA) = 61.5%). For the ADL score, compared with TKFLM + DH and DH, TKRP + DH had more effective (SUCRA = 70.2%). Regarding to the total effective rates, AP + DH was more statistically better than AP, and AP was statistically better than DH. TKD or AP in combination with DH are significantly superior in treating AD.

Discovery of Taxus chinensis fruit wine as potentially functional food against Alzheimer's disease by UHPLC-QE-MS/MS, network pharmacology and molecular docking.

Nowadays, there is no specific cure for Alzheimer's disease (AD), but the progression of AD can be improved by preventive interventions. The wine of Taxus chinensis fruit (TCFW) has the effect of improving human immunity and anti-aging as a long history of health care wine in folk, especially popular in the longevity villages in China, which may be potentially effective dietary products to improve AD. However, the chemical constituents and molecular mechanisms of TCFW still remain unknown. In this study, chemical profiling with UHPLC-QE-MS/MS, network pharmacology and molecular docking were integrated to fastly explore the potential chemicals and mechanisms of TCFW against AD. A total of 31 chemical components in TCFW were detected and identified compared with the solvent wine of TCFW by UHPLC-QE-MS/MS. Then, 27 potential key targets and 14 chemical compounds of TCFW were uncovered for the improvement of AD by network pharmacology and molecular docking. These 14 compounds were reported to have diverse bioactivities such as neuroprotective activity, antifibrotic activity, anticancer activity, antiviral activity and effectiveness in the treatment of neuronal injury, Alzheimer's disease, etc. Among these 27 targets affected by TCFW predicted by our approach, AKT1, PTGS2, NOS3, NOS2, INS, ESR1, ESR2, BDNF, IL6, IL1B, DRD2 and ACHE were significantly altered in AD. The GO and KEGG enrichment analyses revealed that TCFW mainly acted on oxidative response, inflammatory response, insulin secretion, amyloid fibril formation, neurodegenerative pathway-multiple diseases, Alzheimer's disease, longevity regulation pathway, PI3K-Akt signaling pathway, MAPK signaling pathway, etc, which were the main pathogenesis of AD. PRACTICAL APPLICATIONS: Alzheimer's disease (AD) is a degenerative neurological disorder characterized by cognitive and behavioral dysfunction. Nowadays, there is no specific cure for AD, but the progression of AD can be improved by preventive interventions. The wine of Taxus chinensis fruit (TCFW) has the effect of improving human immunity and anti-aging as a long history of health care wine in folk, especially popular in the longevity villages in China, which may be potentially effective dietary products to improve AD. This study proposed a fastly integrated method to explore the potential chemicals and mechanisms of TCFW against AD by UHPLC-QE-MS/MS, network pharmacology and molecular docking. Here, we found that TCFW may ameliorate AD by reversing many biological events, including oxidative stress, inflammatory response, neuronal apoptosis, insulin secretion, amyloid fibril formation, and T cell co-stimulation, which may provide some insights for the development and research of anti-AD drugs.

SLC20A2-Associated Idiopathic basal ganglia calcification (Fahr disease): a case family report

BackgroundIdiopathic basal ganglia calcification (IBGC) is a genetic disorder of the nervous system commonly known as Fahr disease. IBGC patients with a genetic background are considered to have primary familial brain calcification (PFBC), also known as familial basal ganglia calcification (FBGC), or familial Fahr disease. It is a rare degenerative neurological disorder characterized by extensive bilateral basal ganglia calcification that can lead to a range of extrapyramidal symptoms and neuropsychiatric manifestations. Studies have suggested that more than 50 variants of SLC20A2 gene mutations account for approximately 50% of IBGC cases. There is a wide spectrum of mutation types, including frameshift, nonsense, and splice site mutations in addition to deletion and missense mutations. Here we report a case of familial basal ganglia calcification caused by a frameshift mutation in the SLC20A2 gene. We identified a heterozygous mutation in the SLC20A2 gene, c.1097delG (p.G366fs*89). To our knowledge, this mutation site has not been reported before.Case presentationA 57-year-old male patient was admitted to the hospital with “unstable walking and involuntary movements between the eyes and eyebrows for 6 months”. Based on the patient’s family history, symmetrical calcification foci in the bilateral caudate nucleus head, thalamus, cerebellum and parietal lobe indicated by head CT, and gene test results, the diagnosis of familial Fahr disease caused by mutations in the SLC20A2 gene, c.1097delG p.G366fs*89) was confirmed.ConclusionFor the first time, we identified c.1097delG (p.G366fs*89) as a frameshift mutation in the IBGC family. This frameshift mutation caused the condition in this family of patients. This mutation not only broadens the range of known SLC20A2 mutations but also aids in the genetic diagnosis of IBGC.

Salivary Gene Expression of RANK, RANKL, and OPG in Type 1 Diabetes Mellitus and Periodontal Disease Patients.

The relationship between type 1 diabetes mellitus (T1DM) and periodontal disease may exhibit by the alteration of bone metabolism. However, evidence for this relationship is scarce and inconclusive. Thus, the aims of the present study were to investigate salivary receptor activator of nuclear factor kappa-β (RANK), receptor activator of nuclear factor kappa-β ligand (RANKL), osteoprotegerin (OPG) gene expression and the RANKL:OPG ratio in T1DM and non-T1DM. Secondary objective was to determine the relationships of RANK, RANKL and OPG gene expression to clinical parameters of T1DM and periodontal disease. Twenty patients with T1DM and twenty age-matched non-T1DM were recruited. Clinical periodontal parameters were measured. Total RNA was isolated from non-stimulated saliva, and the relative gene expressions of RANK, RANKL, OPG and RANKL:OPG ratio were determined by quantitative real-time polymerase chain reaction. The T1DM group had significantly higher mean periodontal parameters than the non-T1DM group, while the mean plaque scores of both groups were not significantly different. There was a trend of higher relative gene expression of RANK, RANKL, and the RANKL:OPG ratio and lower expression of OPG in T1DM group but no statistic significant different when compared to non-T1DM. In the T1DM group, RANKL:OPG correlated with the percentage of bleeding sites, whereas RANK, RANKL, and HbA1c levels correlated with pocket depth. Bone metabolisms demonstrating by decreased OPG gene expression and upregulated of RANK, RANKL, RANKL:OPG with higher pocket depth and bleeding in T1DM may play an important role in periodontal destruction in T1DM.

Advancement of biomolecular engineering in Parkinson disease

Parkinson's Condition (PD) is the second most common degenerative neurological disease, affecting 10 million people globally. Nigrostriatal degeneration is linked to decreased motor and non-motor functioning in this chronic illness. Resting tremor, stiffness, akinesia (or bradykinesia), and postural instability are the four cardinal symptoms of Parkinson's disease. Because the symptoms of Parkinson's disease are similar to those of other age-related disorders like SWEDD (scans without evidence of dopaminergic deficit), essential tremors, and Parkinson's disease, early diagnosis is difficult. A synucleinopathy is Parkinson's disease (PD) with Lewy Bodies (DLB).Although both genetic and environmental variables are assumed to play a role in Parkinson's disease (PD), there was no direct evidence to support either as a causal component until recently. Six distinct genes have been discovered as producing familial PD in the last eight years. They back up the idea that similar pathogenetic pathways exist across the spectrum of Parkinson's disease etiologies. Mutations in α-synuclein, parkin, UCHL1, DJ1, PINK1, and LRRK2 cause.Parkinson's disease, which is inherited in a Mendelian form. Overexpression of α- synuclein and parkin causes mitochondrial issues, but DJ1 and PINK1 are mitochondrial proteins. These same proteins regulate proteasomal function and play a role in the oxidative stress response.Doped carbon nanotubes, especially phosphorus-doped carbon nanotubes, can efficiently prevent the formation of α- synuclein amyloid, suggesting that they could be utilized to treat Parkinson's disease. More in vitro and clinical research is, however, necessary. As previously stated, αsynuclein could be a therapeutic target for Parkinson's disease and other synucleinopathies. The most promising option would be small chemicals that may modify the structure of protofibrillar forms of α-synuclein and render them nonpathogenic. Given the pathogenic consequences of αsynuclein's feed-forward amplification loops, a range of therapeutic options will almost certainly be required.

Atypical idiopathic NBIA (neurodegeneration with brain iron accumulation) associated with treatment-resistant bipolar mania responding to clozapine.

Management of treatment-resistant bipolar mania has not been discussed much in the literature. The underlying degenerative neurological disorders could be one of the reasons for treatment resistance. A 27-year-old single male presented with 13 years of episodic illness characterised by typical manic symptoms with poor interepisodic recovery. His neurological examination was normal. Most of the commonly used antipsychotics, mood stabilizers and their combination failed to sustain the response to manic symptoms, including when psychotropics were combined with electroconvulsive therapy. Severe adverse effects such as pancreatitis with valproate and hyponatremia with oxcarbamazepine further challenged the management of treatment-resistant bipolar mania. Radiological evaluation revealed the presence of brain mineralisation in bilateral dentate, substantia nigra, red nuclei, globus pallidi and posterolateral putamen. Based on the clinical and radiological findings, a possibility of atypical idiopathic Neurodegeneration with Brain Iron Accumulation (NBIA) associated with treatment-resistant bipolar mania was made. Clozapine was initiated and titrated up to 300mg. Clinically significant improvement was seen in manic symptoms, and the response was sustained over two years. The presence of atypical idiopathic NBIA could be one of the factors for treatment resistance in bipolar mania. Clozapine has a good response in treatment-resistant bipolar disorder and can be effective even in the presence of the underlying neurodegenerative condition.

Testing of Motor Coordination in Degenerative Neurological Diseases.

Parkinson’s disease (PD) is a progressive movement disorder caused by the death of dopamine-producing cells in the midbrain. PD is the most prevalent movement disorder of the central nervous system and affects more than 6.3 million people in the world. The changes in the motor functions of patients are not easy to be clearly and on-time observed by the clinicians and to make the most well-informed decisions for the treatment. The aim of this paper is the monitoring PD by designing, developing, and evaluating a prototype mobile App using a pressure pen, which collects quantitative and objective information about PD patients, thus allowing clinicians to understand better and make assumptions about the severity and the stage of Parkinson’s disease. This study presents a dynamic spiral test that can only be performed with tablet and pen pressure. Furthermore, the handwriting samples by PD patients and healthy controls individuals are collected by a computerized system, and the measurements of Spiral Deviation, Total Time, and Pen Pressure are processed. The results showed an accurate evaluation of the stage of Parkinson’s disease. Thus, the clinician may use the proposed PD telemonitoring system as a screening test, storing the history of all the patient’s measurements.