Multisensory mechanisms of gait and balance in Parkinson’s disease:an integrative review

Understanding the neural underpinning of human gait and balance is one of the most pertinent challenges for 21st-century translational neuroscience due to the profound impact that falls and mobility disturbances have on our aging population.Posture and gait control does not happen automatically,as previously believed,but rather requires continuous involvement of central nervous mechanisms.To effectively exert control over the body,the brain must integrate multiple streams of sensory information,including visual,vestibular,and somatosensory signals.The mechanisms which underpin the integration of these multisensory signals are the principal topic of the present work.Existing multisensory integration theories focus on how failure of cognitive processes thought to be involved in multisensory integration leads to falls in older adults.Insufficient emphasis,however,has been placed on specific contributions of individual sensory modalities to multisensory integration processes and cross-modal interactions that occur between the sensory modalities in relation to gait and balance.In the present work,we review the contributions of somatosensory,visual,and vestibular modalities,along with their multisensory intersections to gait and balance in older adults and patients with Parkinson’s disease.We also review evidence of vestibular contributions to multisensory temporal binding windows,previously shown to be highly pertinent to fall risk in older adults.Lastly,we relate multisensory vestibular mechanisms to potential neural substrates,both at the level of neurobiology(concerning positron emission tomography imaging)and at the level of electrophysiology(concerning electroencephalography).We hope that this integrative review,drawing influence across multiple subdisciplines of neuroscience,paves the way for novel research directions and therapeutic neuromodulatory approaches,to improve the lives of older adults and patients with neurodegenerative diseases.

Neurologic complications after liver transplantation

Neurologic complications are relatively common after solid organ transplantation and affect 15%-30%of liver transplant recipients.Etiology is often related to immunosuppressant neurotoxicity and opportunistic infections.Most common complications include seizures and encephalopathy,and occurrence of central pontine myelinolysis is relatively specific for liver transplant recipients.Delayed allograft function may precipitate hepatic encephalopathy and neurotoxicity of calcineurin inhibitors typically manifests with tremor,headaches and encephalopathy.Reduction of neurotoxic immunosuppressants or conversion to an alternative medication usually result in clinical improvement.Standard preventive and diagnostic protocols have helped to reduce the prevalence of opportunistic central nervous system(CNS)infections,but viral and fungal CNS infections still affect 1%of liver transplant recipients,and the morbidity and mortality in the affected patients remain fairly high.Critical illness myopathy may also affect up to 7%of liver transplant recipients.Liver insufficiency is also associated with various neurologic disorders which may improve or resolve after successful liver transplantation.Accurate diagnosis and timely intervention are essential to improve outcomes,while advances in clinical management and extended post-transplant survival are increasingly shifting the focus to chronic post-transplant complications which are often encountered in a community hospital and an outpatient setting.

Steps to consider in the approach and management of critically ill patient with spontaneous intracerebral hemorrhage

Spontaneous intracerebral hemorrhage is a type of stroke associated with poor outcomes. Mortality is elevated, especially in the acute phase. From a pathophysiological point of view the bleeding must traverse different stages dominated by the possibility of re-bleeding, edema, intracranial hypertension, inflammation and neurotoxicity due to blood degradation products, mainly hemoglobin and thrombin. Neurological deterioration and death are common in early hours, so it is a true neurologicalneurosurgical emergency. Time is brain so that action should be taken fast and accurately. The most significant prognostic factors are level of consciousness, location, volume and ventricular extension of the bleeding. Nihilism and early withdrawal of active therapy undoubtedly influence the final result. Although there are no proven therapeutic measures, treatment should be individualized and guided preferably by pathophysiology. The multidisciplinary teamwork is essential. Results of recently completed studies have birth to promising new strategies. For correct management it's important to establish an orderly and systematic strategy based on clinical stabilization, evaluation and establishment of prognosis, avoiding secondary insults and adoption of specific individualized therapies, including hemostatic therapy and intensive control of elevated blood pressure. Uncertainty continues regarding the role of surgery.

Taking central nervous system regenerative therapies to the clinic: curing rodents versus nonhuman primates versus humans

The central nervous system is known to have limited regenerative capacity.Not only does this halt the human body’s reparative processes after central nervous system lesions,but it also impedes the establishment of effective and safe therapeutic options for such patients.Despite the high prevalence of stroke and spinal cord injury in the general population,these conditions remain incurable and place a heavy burden on patients’families and on society more broadly.Neuroregeneration and neural engineering are diverse biomedical fields that attempt reparative treatments,utilizing stem cells-based strategies,biologically active molecules,nanotechnology,exosomes and highly tunable biodegradable systems(e.g.,certain hydrogels).Although there are studies demonstrating promising preclinical results,safe clinical translation has not yet been accomplished.A key gap in clinical translation is the absence of an ideal animal or ex vivo model that can perfectly simulate the human microenvironment,and also correspond to all the complex pathophysiological and neuroanatomical factors that affect functional outcomes in humans after central nervous system injury.Such an ideal model does not currently exist,but it seems that the nonhuman primate model is uniquely qualified for this role,given its close resemblance to humans.This review considers some regenerative therapies for central nervous system repair that hold promise for future clinical translation.In addition,it attempts to uncover some of the main reasons why clinical translation might fail without the implementation of nonhuman primate models in the research pipeline.

The use of hydrogel-delivered extracellular vesicles in recovery of motor function in stroke:a testable experimental hypothesis for clinical translation including behavioral and neuroimaging assessment approaches

Neural tissue engineering,nanotechnology and neuroregeneration are diverse biomedical disciplines that have been working together in recent decades to solve the complex problems linked to central nervous system(CNS)repair.It is known that the CNS demonstrates a very limited regenerative capacity because of a microenvironment that impedes effective regenerative processes,making development of CNS therapeutics challenging.Given the high prevalence of CNS conditions such as stroke that damage the brain and place a severe burden on afflicted individuals and on society,it is of utmost significance to explore the optimum methodologies for finding treatments that could be applied to humans for restoration of function to pre-injury levels.Extracellular vesicles(EVs),also known as exosomes,when derived from mesenchymal stem cells,are one of the most promising approaches that have been attempted thus far,as EVs deliver factors that stimulate recovery by acting at the nanoscale level on intercellular communication while avoiding the risks linked to stem cell transplantation.At the same time,advances in tissue engineering and regenerative medicine have offered the potential of using hydrogels as bio-scaffolds in order to provide the stroma required for neural repair to occur,as well as the release of biomolecules facilitating or inducing the reparative processes.This review introduces a novel experimental hypothesis regarding the benefits that could be offered if EVs were to be combined with biocompatible injectable hydrogels.The rationale behind this hypothesis is presented,analyzing how a hydrogel might prolong the retention of EVs and maximize the localized benefit to the brain.This sustained delivery of EVs would be coupled with essential guidance cues and structural support from the hydrogel until neural tissue remodeling and regeneration occur.Finally,the importance of including nonhuman primate models in the clinical translation pipeline,as well as the added benefit of multi-modal neuroimaging analysis to establish non-invasive,in vivo,quantifiable imagingbased biomarkers for CNS repair are discussed,aiming for more effective and safe clinical translation of such regenerative therapies to humans.

Intracranial Atherosclerosis: The Natural History and Management Strategies

Intracranial atherosclerotic disease (ICAD) represents a major cause of stroke and transient ischemic attacks. The prevalence and natural course of ICAD are closely related to race and ethnicity. The best treatment for ICAD is a crucial issue;data from recent trials indicate that aggressive medical management and life style modifications are better than endovascular treatments for prevention of recurrent stroke in high-risk patients with ICAD. Endovascular treatment is still an option for subgroup of patients who are not responded to optimal medical therapy.

先天性快速动眼睡眠行为障碍的特征及其与多系统萎缩和帕金森病的关系研究

Objective: To compare the clinical and video-polysomnog-raphic (VPSG) characteristics of idiopathic REM sleep behavior disorder (RBD) vs the RBD seen in multiple system atrophy (MSA) and Parkinson disease (PD). Methods: Clinical features and VPSG measures were evaluated in 110 consecutive nondemented subjects (26 MSA, 45 PD, and 39 idiopathic RBD) free of psychoactive medications referred for suspected RBD to our sleep unit over a 5-year period, with extended follow-up (mean 26.9 ±21.3 months). Results: Across the three groups studied, logistic regression analysis demonstrated that there were no differences in the quality of RBD symptoms (e.g., nature of unpleasant dream recall or behaviors witnessed by bed partners), most PSG variables, abnormal behaviors captured by VPSG, and clinical response to clonazepam. When compared to subjects with PD, however, patients with MSA had a significantly shorter duration of disease, a higher REM sleep without atonia percentage, a greater periodic leg movement index, and less total sleep time. Subjects with idiopathic RBD, as compared to those with either MSA or PD, were more often male, had greater self-reported clinical RBD severity, and were more often aware of their abnormal sleep behaviors. Conclusions: REM sleep behavior disorder (RBD)-related symptoms and neurophysiologic features are qualitatively similar in RBD subjects with the idiopathic form, multiple system atrophy (MSA), and Parkinson disease (PD). Polysomnographic abnormalities associated with RBD in the setting of MSA are greater than in PD, suggesting a more severe dysfunction in the structures that modulate REM sleep.

快动眼睡眠行为异常与钾通道抗体相关边缘脑炎

Of six patients registered in our center with nonparaneoplastic limbic encephalitis associated with antibodies to voltage-gated potassium channels, the five men had rapid eye movement sleep behavior disorder (RBD) coincident with voltage-gated potassium channel antibody-associated limbic encephalitis onset. In three patients, immunosuppression resulted in resolution of RBD in parallel with remission of the limbic syndrome. RBD persisted in two patients with partial resolution of the limbic syndrome. Our findings suggest that RBD is frequent in the setting of voltage-gated potassium channel antibody-associated limbic encephalitis and can be related to autoimmune-mediated mechanisms. In addition, these observations suggest that impairment of the limbic system may play a role in the pathogenesis of RBD.

Clinico-radiological dissociation in multiple sclerosis: Future prospects

Magnetic resonance imaging (MRI) has significantly contributed to our capabilities of diagnosis multiple sclerosis (MS) since it is able to detect demyelinating lesions in almost 100% of patients. However, there are modest correlations between irreversible disability and white matter lesion load, as measured by T2-weighted MRI scans, which represents the clinicoradiological paradox of MS. We report the case of a patient with MS and few neurological manifestations despite extensive T2 visible morphologic abnormalities. The use of non-conventional MRI techniques, which are more specific in the analysis of the pathological substrate of demyelinating lesions and normal appearing brain matter (both white and gray matter), might assist us to overcome this limitation of conventional MRI.

Description of interhemispheric disconnection syndrome in a patient with Marchiafava-Bignami disease

Interhemispheric disconnection syndrome (IDS), described by Sperry, Gazzaniga and Bogen, is characterized by the presence of visual and tactile anomia, absence of interhemispheric transference of unilateral somatosensory stimulation of both hands, hemialexia and unilateral left-side apraxia. Subsequently, changes were also observed in the sensory interhemispheric transfer and in tests of crossed motor control. In Marchiafava-Bignami disease (MBD) there have been descriptions of partial IDS. The aim is to describe the dissociations in IDS that are presented in a patient with MBD, using a specialized assessment methodology. Patient and Method: A 54-year-old patient, righthanded, with 11 years of schooling, presented with antecedent chronic alcoholism. Neuropsychological tests were administered for general assessment along with specific tests of interhemispheric transference. Results: Borderline changes were found in visual memory, visual-constructive abilities and attention and executive functioning. In tasks of interhemispheric transference the patient showed changes in: the imitation of hand poses;inter-manual pressure point localization (tactile stimulation);reading aloud of words by visual hemifield;and movement control. Conclusion: Our patient showed a wide lesion of the Corpus Callosum (CC) with relative preservation of the splenium, accompanied by partial disconnection syndrome in the context of a global cognitive deterioration from his chronic alcoholism.

Catatonia in older adults:A systematic review

BACKGROUND Catatonia is a complex psychomotor syndrome that often goes unrecognized and untreated,even though its classification has evolved in recent years.Prompt and correct identification of catatonia allows for highly effective treatment and prevention of possible complications.The underrecognition of catatonia in older patients is also frequent,and research in this population is scarce.AIM To conduct a systematic review of the literature on catatonia in older people to ascertain its clinical characteristics across settings.METHODS Following the PRISMA guidelines,MEDLINE,EMBASE,and PsycINFO databases were searched from inception to December 2021,with a strategy aimed at identifying all articles published on catatonia in older adults.Titles and abstracts were scanned and selected independently by two authors.Papers investigating issues related to catatonia and/or catatonic symptoms in older people,with English abstracts available,were included.References of selected articles were revised to identify other relevant studies.RESULTS In total,1355 articles were retrieved.After removing duplicates,879 remained.Of the 879 identified abstracts,669 were excluded because they did not meet the inclusion criteria.A total of 210 articles underwent full text review,and 51 were eliminated for various reasons.Fourteen more articles were selected from the references.Overall,173 articles were reviewed:108 case reports,35 case series,11 prospective cohort studies,6 case-control studies,3 retrospective cohort studies and 10 reviews.We found several particular aspects of catatonia in this population.Catatonia in older patients is highly prevalent and tends to have a multifactorial etiology.Older patients,compared to younger patients,have a higher risk of developing catatonia with benzodiazepine(BZD)withdrawal,in bipolar disorder,and in the general hospital.Age,together with other risk factors,was significantly associated with the incidence of deep venous thrombosis,neuroleptic malignant syndrome poor outcome,other complications and mortality.Treatment with BZDs and electroconvulsive therapy is safe and effective.Prompt treatment of its cause is essential to ensure a good prognosis.CONCLUSION Catatonia in older patients is highly prevalent and tends to have a multifactorial etiology.The risk of developing catatonia in some settings and conditions,as well as of developing complications,is high in this population.Symptomatic treatment is safe and effective,and timely etiologic treatment is fundamental.

Syncope Beginning in People Over 50 Years Old—Experience in 52 Cases

It is not common to start suffering from syncopes after age 50. They are mainly male patients who present causes other than vasovagal syncope, which predominates at an early age. Orthostatic hypotension is the predominant causal factor, which is attributed in many cases to advanced age, metabolic, cardiovascular or neurological diseases, to failure of baroreflexes, all of the above may be associated with the use of hypotensive drugs alone or in combination with psychotropic drugs. Furthermore, causes such as carotid sinus syncope, postprandial syncope and situational syncope become more frequent. Therefore, as people age, they present a favorable pathological terrain for the production of syncope. The older you are, the more likely you are to start with syncope. Finding the definitive diagnosis for their syncopes can be difficult, given the multiplicity of interacting factors. Their study is more exhaustive and requires a good anamnesis, knowing the drugs used by the patient, concomitant diseases and careful surveillance to get closer to the diagnosis.

Lithium as a Protective Factor against Dementia in Bipolar Patients—A Retrospective Cohort Study

Background: Controversial research has indicated potential neuroprotective qualities of lithium in the prevention of dementia, but it did not lead to a definite conclusion. Aim: We seek to examine whether lithium has a protective effect in an elderly population suffering from bipolar disorder. Patients and Methods: Of a retrospective cohort including 433 patient files that met inclusion criteria (age over 65 years and bipolar disease coded by ICD), 147 files contained enough relevant data. The patients’ files were divided into lithium users (LU) for those who used lithium for at least a minimum of 3 months and non-users (LNU) for those who did not use lithium at all or used it for a period of less than 3 months. We searched for dementia incidence in these two groups. Results: 433 files were collected initially through a computerized search using ICD10 code for bipolar affective disorder. One hundred twenty three files were excluded due to age (younger than 65 years), 7 were excluded due to neurological background, and 49 were excluded due to either a secondary or a not strictly bipolar psychiatric diagnosis. One hundred and seven were excluded due to insufficient/uncertain data. The remainders of 147 files were included in the final analysis. Twenty five of the 147 bipolar patients were diagnosed with dementia (17%). Amongst the 92 LNU patients, 16 developed dementia (17.4%) and of the 55 LU patients, 9 developed dementia (16.4%);Pearson’s χ2(1) = 0.026, p Conclusions: No cognitive protective qualities of lithium treatment in elderly bipolar patients were demonstrated by our study.

Anterior Choroidal Artery Territory Stroke in Young Patient

Introduction: Stroke incidence in young patients is about 10 cases in 100.000, according to several European studies. In this age group arterial dissection is one of the main pathological mechanisms involved. The internal carotid’s artery (ICA) main supraclinoid branch is the anterior choroidal artery (AChA). The occurrence of infarction in its territory due to internal carotid dissection is considered to be a rare event and may have different clinical presentations due to anatomical variability. Clinical case: A 31-year-old male patient, without any known cardiovascular risk factors or chronic medication, presented with acute onset of stabbing right sided headache while practicing football. Visual disturbances and hemiparesis with hypesthesia of his left arm were also mentioned. On admission left homonymous hemianopsia, left hemiparesis and left extensor plantar reflex were present. Brain magnetic resonance showed hyperintensity of T2 and FLAIR signals and restricted diffusion pattern suggested acute/subacute infarctions in the thalamic and subcapsular area, corpus callosum, splenium and subcortical parietal right region. Magnetic resonance angiography (MRA) of the brain showed reduction of the right ICA’s caliber, mainly of its supraclinoid segment in which a marked irregular stenosis was visualized, suggestive of arterial dissection. This stenotic segment included the origin of the AChA and of the posterior communicating cerebral artery with an exchange in their territories. Lumbar puncture results were normal as were analytical investigations which included CBC, sedimentation rate, syphilis serology and immunologic and prothrombotic screen. There were no phenotype characteristics suggestive of connective tissue disease. Conclusion: Trauma seems to be the most probable lesion mechanism for the occurrence of intracranial carotid’s dissection in this particular case, as the patient was practicing vigorous sports at time of onset. In view of great anatomic variability and multiple anatomical sites supplied by the AChA its occlusion will induce a wide range of clinical manifestations.

Ocular Manifestations among HIV Infected Children in Ouagadougou, Burkina Faso

Ocular manifestations among HIV infected children are diverse and global incidence varies from 7% to 75%. At this age, eye lesions are often unnoticed because of the incapacity to express eye discomfort. The purpose of this study is to describe ocular manifestations among HIV-infected children and hence associated factors in the Department of Paediatrics at the Yalgado Ouédraogo Teaching Hospital. This was a cross-sectional descriptive and analytical study conducted between July 2014 and December 2014. A complete ophthalmic examination was systematically done to all HIV-positive children attending the clinic, as part of their routine medical visit. The most recent socio-demographic, clinical, biological and treatment data were registered. Seventy-nine children had an ocular examination and among them 92.4% were on ARV treatment. The incidence of ocular manifestations was 46.7%. Median age was 8 years old (interquartile 6 - 12 years old). Sex ratio was 1.3. The risk of ocular manifestations involvement among boys was twice than that of girls. More than half (59.5%) of children who had ocular problems had not expressed ocular discomfort. Ocular adnexal lesions were more common (35.4%) compared to eye segments (8.9%) lesions. Anterior segment and posterior segment lesions were statistically associated with immune system depression (p = 0.003 and 0.001). However, this relationship was not statistically significant (p = 0.15). Five out of seven children who had eye fundus lesions had CD4 count 3. Ocular manifestations were very common among HIV infected children in our context. Ophthalmic examination should be systematic at admission and regularly repeated during follow-up.

伊拉克自由行动中的神经病学:疾病转诊、临床表现和发病率的危险因素

Six hundred and sixteen patients were referred for consultation to the author who served as the neurologist on the 252nd Neurosurgical Team in Kuwait in support of Operation Iraqi Freedom between April and October, 2003. Demographic and military data were collected. The cohort of neurologic patients showed significant differences from the total population of the United States Army contemporarily deployed to Operation Iraqi Freedom. Versus the deployed personnel, the neurologic cohort was older in age (p < 0.001), had a greater percentage of females (p < 0.00001), had an excessive representation for the military rank of sergeant (p < 0.00001), with a deficit of other ranks (junior enlisted and officers), and were more likely to soldiers from the Reserves (p < 0.00001) and National Guard (p = 0.0021) than from the Regular Army. Seven categories of chief complaints and ten categories of diagnoses constituted some 80% of patients. The incidence of neurologic disease was calculated to be 634 per 100,000 people/year. This information provides valuable information for military neurologists concerning their anticipated duties in future deployments and for non-neurologists by focusing their skills in the evaluation of common neurologic presentations, yet further research is needed to optimize the neurologist’s role in a field environment.

左乙拉西坦对特发性震颤的疗效

The effect of a single dose of 1,000 mg of levetiracetam on essential tremor was investigated in 24 patients in a double-blind,placebo-controlled trial. The re was a significant reduction of hand tremor for at least 2 hours as measured by accelerometry and functional tests.

The Tower of Hanoi for Evaluating Dysexecutive Syndrome in Patients with Parkinson’s:Standardization Values

Objective: The Tower of Hanoi measures executive functions using non-verbal content and requires perception of position in space. The main objective of this study is to standardize the use of the TOH as a measurement tool in Parkinson’s disease. Patients and Methods: Of the Control Group subjects, 192 (59.6%) were women, 223 subjects (69.25%) were able to perform the TOH with 3 discs. In the Parkinson’s Group, there were 57 women (39.3%), and 66 subjects (45.5%) did not get past that level. Results: If we take the TOH (with 3 or 4 discs) as a tool for discriminating between those who have dysexecutive syndrome and those who do not, we find that the Parkinson’s Group presents dysexecutive syndrome significantly more frequently than the Control Group (p ≤ 0.0064). Conclusion: We can conclude that dysexecutive syndrome is frequent in Parkinson’s patients and it is more prevalent than in the general population.

Properties of the Apathy Scale(AS)for use on Parkinson’s patients

Parkinson’s disease is a neurodegenerative disorder characterized by motor, autonomic, and neuropsychiatric symptoms, among the latter, apathy has been found to be present in up to 70% of patients. The main objective of the present study was to assess the psychometric properties of the Apathy Scale for evaluation of Ecuadorian patients with Parkinson’s. This was a cross sectional study, with re-test. There were 73 women (34.5%) in the final sample of 211 patients. Mean age was 67.5 ± 10.2 years, mean length of illness was 7.1 ± 5.5 years, and the mean ldopa dose was 656.1 ± 292.7 mg/day. The mean Apathy Scale score was 12.7 ± 7.1. Reliability: The Guttman’s λ obtained was 0.89. The SEM was 2.34 for the AS. The ICC using an absolute agreement definition was: ICC = 0.78 [(95% IC 0.73?- 0.82) f = 4.96;p ≤ 0.000]. Discriminative validity, analyzed with the Kruskal-Wallis statistic and using H&Y stages as segmentation variable registered an X(2) value of p 0.0001. In conclusion the Apathy Scale proved to have suitable metric attributes in this specific PD patient sample: internal consistency, reliability, stability, and convergent and known-groups validity.