Hypokinetic Disorders Research Articles

Identification of the Most Prevalent Hypokinetic Disorders Linked to Sedentary Lifestyles and their Impact on Public Health

Identification of the Most Prevalent Hypokinetic Disorders Linked to Sedentary Lifestyles and their Impact on Public Health

Neurophysiology of hypokinetic movement’s disorders: New insights in daily clinical practice

Hypokinetic movement disorders encompass a group of clinically similar diseases that present challenges in discrimination during neurological examinations. Characterizing a specific hypokinetic disorder is necessary for the diagnosis and treatment in daily clinical practice. Neurophysiological tools, such as electromyography (EMG) combined with accelerometry, motor-evoked potentials (MEPs), electroencephalographic recording (EEG), Bereitschaftspotential (BP), auditory-evoked cognitive potential (P300), blink reflex (BR), and R2 blink reflex recovery cycle (R2BRRC), are useful in the differential diagnosis of movement disorders due to the common clinical features. However, neurophysiological assessments of movement disorders, especially hypokinetic diseases, are currently underutilized in clinical practice as compared to a few decades ago. This review aims to summarize practical insights gleaned from reported studies over the past 5 years (i.e., 2019 – 2023) regarding neurophysiological assessments of hypokinetic movement disorders, emphasizing the importance of their routine application. In particular, the methodology of the electrophysiologic evaluations pertaining to hypokinetic movement disorders is assessed. Moreover, a practical approach for the differential diagnosis of similar movement disorder syndromes based on specific neurophysiological features is proposed. Collectively, this review of the most recent neurophysiological implications in hypokinetic movement disorders highlights the practicality of these methods. Despite the advancement of other diagnostic techniques (e.g., neuroradiological methods), neurophysiological assessments may be a promising tool for clinical diagnoses, due to their high accuracy and ability to categorize and manage movement disorders (e.g., hypokinetic movement disorders) in daily clinical practice.

Neuroprotective Potential of Silymarin against Rotenone induced motor deficits in Wistar Rats

AbstractBackgroundParkinson’s disease is a hypokinetic disorder characterized by selective loss of dopaminergic in substantia nigra pars compacta (SNPc) region of mid‐brain. Dopaminergic degeneration of neurons is considered to be due to oxidative stress, neuroinflammation, neurons mitochondrial dysfunction and glutamate excitotoxicity etc. Silymarin was selected as an investigational drug, due to its numerous activities in current research, it possesses substantial antioxidant and neuroprotective functionalities and it has been reported to produce anti‐oxidant, anti‐inflammatory and neuromodulatory actions in previous studies.MethodIn the current study we have investigated the role of Silymarin against rotenone induced motor deficit and biochemical abnormalities in Wistar rats. Rats were treated with 1.5mg/kg rotenone subcutaneously for 35 days. Silymarin (50,100 and 200 mg/kg i.p.) was administered after 30 minutes of rotenone administration from day 7th to 35th day. Rotenone caused significant reduction in motor functions and body weight and produced elevation in striatal oxidative burden.ResultThe biochemical analysis revealed that there is reduction in the level of anti‐oxidants (GSH, Catalase, and SOD) in the animals following rotenone administration. Whereas Silymarin treated rats were stable and regained their body weight. In addition Silymarin significantly attenuated rotenone induced motor deficit and striatal oxidative stressConclusionOutcomes of the current study suggest neuroprotective potential of Silymarin and its ability to correct movement disability and thus could prove to be useful candidate molecule in the management of motor disorders.

Neuroprotective Potential of Limonene in LPS induced Parkinson’s Disease in Rats

AbstractBackgroundParkinson’s disease is a hypokinetic disorder characterized by selective loss of dopaminergic in the substantia nigra pars compacta (SNPc) region of the mid‐brain. Dopaminergic degeneration of neurons is considered to be due to oxidative stress, neuroinflammation, mitochondrial dysfunction, etc.MethodInfusion of LPS induced motor deficit and increased oxidative–nitritive stress in rats. Chronic treatment with limonene (25, 50 and 100 mg/kg/p.o.) for 21 days. LPS induced motor deficit and increase in striatal oxidative burden.ResultChronic treatment with limonene (25, 50 and 100 mg/kg/p.o.) for 21 days, significantly attenuated motor deficit and increased in striatal oxidative burden. Biochemically limonene significantly reduced the oxidative–nitrative stress, as evidenced by the decrease in malondialdehyde (MDA) and nitrite levels, and restored the reduced catalase, glutathione (GSH), and Superoxide dismutase (SOD) levels.ConclusionThe observed beneficial effects of limonene in motor defects may be due to its ability to reduce oxidative burden.

Mitochondrial Bioenergy in Neurodegenerative Disease: Huntington and Parkinson.

Strong evidence suggests a correlation between degeneration and mitochondrial deficiency. Typical cases of degeneration can be observed in physiological phenomena (i.e., ageing) as well as in neurological neurodegenerative diseases and cancer. All these pathologies have the dyshomeostasis of mitochondrial bioenergy as a common denominator. Neurodegenerative diseases show bioenergetic imbalances in their pathogenesis or progression. Huntington's chorea and Parkinson's disease are both neurodegenerative diseases, but while Huntington's disease is genetic and progressive with early manifestation and severe penetrance, Parkinson's disease is a pathology with multifactorial aspects. Indeed, there are different types of Parkinson/Parkinsonism. Many forms are early-onset diseases linked to gene mutations, while others could be idiopathic, appear in young adults, or be post-injury senescence conditions. Although Huntington's is defined as a hyperkinetic disorder, Parkinson's is a hypokinetic disorder. However, they both share a lot of similarities, such as neuronal excitability, the loss of striatal function, psychiatric comorbidity, etc. In this review, we will describe the start and development of both diseases in relation to mitochondrial dysfunction. These dysfunctions act on energy metabolism and reduce the vitality of neurons in many different brain areas.

Humans have a basic physical and psychological need to move the body: Physical activity as a primary drive.

Physical activity, while less necessary for survival in modern times, is still essential for thriving in life, and low levels of movement are related to numerous physical and mental health problems. However, we poorly understand why people move on a day-to-day basis and how to promote greater energy expenditure. Recently, there has been a turn to understand automatic processes with close examination of older theories of behavior. This has co-occurred with new developments in the study of non-exercise activity thermogenesis (NEAT). In this narrative review, it is hypothesized that psycho-physiological drive is important to understand movement in general and NEAT, specifically. Drive, in short, is a motivation state, characterized by arousal and felt tension, energizing the organism to acquire a basic need. Movement is a biological necessity, like food, water, and sleep, but varies across the lifespan and having the greatest impact before adolescence. Movement meets various criteria for a primary drive: (a) deprivation of it produces feelings of tension, such as an urge or craving, known as affectively-charged motivation states, and particularly the feelings of being antsy, restless, hyper or cooped up, (b) provision of the need quickly reduces tension - one can be satiated, and may even over-consume, (c) it can be provoked by qualities of the environment, (d) it is under homeostatic control, (e) there is an appetite (i.e., appetence) for movement but also aversion, and (f) it has a developmental time course. Evidence for drive has mainly come from children and populations with hyperkinetic disorders, such as those with anorexia nervosa, restless legs syndrome, and akathisia. It is also stimulated in conditions of deprivation, such as bed rest, quarantine, long flights, and physical restraint. It seems to be lacking in the hypokinetic disorders, such as depression and Parkinson's. Thus, drive is associated with displeasure and negative reinforcement, subsuming it within the theory of hedonic drive, but it may fit better within new paradigms, such as the WANT model (Wants and Aversions for Neuromuscular Tasks). Recently developed measurement tools, such as the CRAVE scale, may permit the earnest investigation of movement drive, satiation, and motivation states in humans.

Trastornos del movimiento

Movement disorders encompass nervous system abnormalities responsible for the onset of abnormal involuntary movements both due to an excess of movement (so-called hyperkinetic disorders, which include tics, chorea, dystonia, tremor, and myoclonus) and due to slow, reduced movement (so-called hypokinetic disorders, mainly Parkinsonian syndromes). In all of them, regardless of their cause, an abnormality occurs in the normal functioning of the motor pathway of the basal ganglia. Tremor is a rhythmic, oscillatory movement which, according to its presentation (rest, postural, or kinetic), frequency (Hz), and topographic distribution, is due to different causes which have clinical particularities and different treatment and prognoses. Myoclonus refers to sudden, brief muscle spasms due to a neuronal discharge that cannot be voluntarily suppressed. It has different etiologies and treatments according to the origin, distribution, and form of presentation. This update will describe these aspects of tremor and myoclonus.

Advancing high-resolution manometry: evaluating the use of multiple rapid swallows versus apple viscous swallows in clinical practice.

High-Resolution Manometry (HRM) with provocative maneuvers, such as Multiple Rapid Swallows (MRS) and Apple Viscous Swallows (AVS), is commonly utilized to diagnose esophageal disorders. Increasing standardization in HRM protocol can help save time and reduce patient discomfort. This study assesses AVS and MRS to determine their respective benefits and limitations. Retrospective reviews were performed on 100 patients to analyze their AVS and/or MRS results. Parameters included abnormal motility patterns, tolerance, and DCI. Diagnostic benefits from MRS and AVS were assessed. Based on the previous studies, additional benefit from MRS was defined as detection of good peristaltic reserve, weak peristaltic reserve, or an abnormal motility/pressurization pattern. Additional benefit from AVS was defined as detection of IEM features or abnormal motility/pressurization pattern. When patients completed both MRS and AVS (n = 70), MRS provided additional benefit in assessing 36% of patients, while AVS provided additional benefit in 19% of patients (p < 0.0001). Furthermore, MRS detected significantly more abnormal motility/pressurization patterns than AVS (27% MRS; 8% AVS; p = 0.0005). Two unique strengths of AVS were higher tolerance for test completion (p = 0.009) and better detection of severe hypokinetic disorders in 4% of patients, which were missed by MRS. MRS may uniquely identify abnormal motility/pressurization patterns, such as paradoxical LES response, distal pressurization, hypercontractile, and spasm patterns. These findings argue for a tailored approach when selecting provocative testing. MRS may be more useful for patients with abnormal pathophysiology, while AVS may help to supplement MRS in detecting severe hypokinetic disorders in preoperative management.

Clinical phenomenology and pathophysiology of daytime and nighttime imperative movements

Imperative movements have an intermediate position between voluntary and involuntary movements and are also referred to as semi-voluntary, or induced. Their common characteristic is the urge, forcing the patient to perform an action that can have a different duration and degree of complexity - from a short twitch (with tics) to prolonged episodes of general motor restlessness (for example, akathisia or stereotypes). The ability to slow down this movement for a short or longer period of time by volitional effort is associated with the urge to make a movement, which predetermines the patient's perception of the degree of its imperativeness and arbitrariness. All motor syndromes based on an imperative need to make movements (akathisia, tics, restless legs syndrome, some levodopa-induced dyskinesias, tardive dyskinesia, compulsive disorders, stereotypes), despite their differences, can be conditionally combined by the term «akathisia spectrum disorders». In some cases, violent imperative movements are paradoxically combined with hypokinetic disorders, primarily with parkinsonism, which makes the discomfort experienced by patients particularly severe.

Вікові особливості перебігу функціональних розладів біліарного тракту в дітей

Актуальність. Функціональні розлади біліарного тракту залишаються поширеною патологією в дітей різного віку. Основними проявами функціональних розладів біліарного тракту в дітей є прояви диспептичного, больового, астеновегетативного та холестатичного синдромів різного ступеня вираженості. Мета дослідження: вивчити особливості проявів функціональних розладів біліарного тракту в дітей різних вікових груп. Матеріали та методи. Під спостереженням перебувало 85 дітей віком від 3 до 17 років із підтвердженим діагнозом функціональних розладів біліарного тракту. Обстеження хворих включало: анамнестичні дані, загальноклінічне обстеження, лабораторні та інструментальні дослідження. Серед обстежених дітей 44 дитини були віком від 3 до 6 років, 41 хворий — від 7 до 17 років. Результати дослідження. Головними причинами захворювання серед дітей дошкільного віку були нераціональне харчування (63,6 %), перенесені гострі інфекції травної системи (29,5 %), наявність вогнищ хронічної інфекції (22,7 %). За результатами аналізу клінічних проявів виявлено, що у 88,6 % дітей дошкільного віку переважали прояви гіпокінетичної форми функціональних розладів біліарного тракту з постійним неінтенсивним болем у животі та диспептичним синдромом. Головними причинами загострення перебігу захворювання серед школярів були нераціональне харчування (92,6 %), психоемоційне навантаження (43,9 %), гіподинамія (34,2 %), дискоординація вегетативної регуляції організму (24,3 %). У 48,7 % дітей шкільного віку діагностовано панкреатичні розлади. Обговорення результатів. Терапевтичну корекцію функціональних розладів біліарного тракту в дітей треба проводити з урахуванням того, що в дітей дошкільного віку переважали прояви гіпокінетичної форми функціональних розладів біліарного тракту, а в шкільному віці частіше діагностовані функціональний панкреатичний розлад сфінктера Одді та функціональний біліарний розлад сфінктера Одді гіперкінетичної форми. Висновки. Урахування вікових особливостей перебігу функціональних розладів біліарного тракту в дітей сприятиме вибору оптимальної схеми терапії для поліпшення стану дитини.

Movement Disorders in Children with a Mitochondrial Disease: A Cross-Sectional Survey from the Nationwide Italian Collaborative Network of Mitochondrial Diseases.

Movement disorders are increasingly being recognized as a manifestation of childhood-onset mitochondrial diseases (MDs). However, the spectrum and characteristics of these conditions have not been studied in detail in the context of a well-defined cohort of patients. We retrospectively explored a cohort of individuals with childhood-onset MDs querying the Nationwide Italian Collaborative Network of Mitochondrial Diseases database. Using a customized online questionnaire, we attempted to collect data from the subgroup of patients with movement disorders. Complete information was available for 102 patients. Movement disorder was the presenting feature of MD in 45 individuals, with a mean age at onset of 11 years. Ataxia was the most common movement disorder at onset, followed by dystonia, tremor, hypokinetic disorders, chorea, and myoclonus. During the disease course, most patients (67.7%) encountered a worsening of their movement disorder. Basal ganglia involvement, cerebral white matter changes, and cerebellar atrophy were the most commonly associated neuroradiological patterns. Forty-one patients harbored point mutations in the mitochondrial DNA, 10 carried mitochondrial DNA rearrangements, and 41 cases presented mutations in nuclear-DNA-encoded genes, the latter being associated with an earlier onset and a higher impairment in activities of daily living. Among our patients, 32 individuals received pharmacological treatment; clonazepam and oral baclofen were the most commonly used drugs, whereas levodopa and intrathecal baclofen administration were the most effective. A better delineation of the movement disorders phenotypes starting in childhood may improve our diagnostic workup in MDs, fine tuning management, and treatment of affected patients.

Exome sequencing in paediatric patients with movement disorders

BackgroundMovement disorders are a group of heterogeneous neurological diseases including hyperkinetic disorders with unwanted excess movements and hypokinetic disorders with reduction in the degree of movements. The objective of our study is to investigate the genetic etiology of a cohort of paediatric patients with movement disorders by whole exome sequencing and to review the potential treatment implications after a genetic diagnosis.ResultsWe studied a cohort of 31 patients who have paediatric-onset movement disorders with unrevealing etiologies. Whole exome sequencing was performed and rare variants were interrogated for pathogenicity. Genetic diagnoses have been confirmed in 10 patients with disease-causing variants in CTNNB1, SPAST, ATP1A3, PURA, SLC2A1, KMT2B, ACTB, GNAO1 and SPG11. 80% (8/10) of patients with genetic diagnosis have potential treatment implications and treatments have been offered to them. One patient with KMT2B dystonia showed clinical improvement with decrease in dystonia after receiving globus pallidus interna deep brain stimulation.ConclusionsA diagnostic yield of 32% (10/31) was reported in our cohort and this allows a better prediction of prognosis and contributes to a more effective clinical management. The study highlights the potential of implementing precision medicine in the patients.

Alpha-synuclein promotes dopaminergic neuron death in Parkinson’s disease through microglial and NLRP3 activation

Parkinson’s disease (PD) is a progressive neurodegenerative disorder that involves the death of dopaminergic neurons in the substantia nigra pars compacta (SNpc). After neuronal death, the subsequent reduction of dopamine levels in the brain induces motor deficits characteristic of this hypokinetic disorder. Although there is currently no known cause of PD, alpha-synuclein appears to have a prominent role in both microglial and NLRP3 inflammasome activation. The consequential release of the pro-inflammatory cytokine interleukin-1β (IL-1β) has been demonstrated to be responsible for neuroinflammation and neurodegeneration in PD. The present review highlights the role of alpha-synuclein aggregates in Parkinson’s disease pathogenesis. The PD alpha-synuclein preformed fibril (PFF) animal model permits the specific targeting of alpha-synuclein-mediated microglial and NLRP3 inflammasome activation in newly designed therapies. Studies using this model suggest MCC950 and its analogs as a potential new treatment to prevent neurodegeneration in Parkinson’s disease.

Diagnostic Yield of a Targeted Next-Generation Sequencing Gene Panel for Pediatric-Onset Movement Disorders: A 3-Year Cohort Study.

In recent years, genetic techniques of diagnosis have shown rapid development, resulting in a modified clinical approach to many diseases, including neurological disorders. Movement disorders, in particular those arising in childhood, pose a diagnostic challenge. First, from a purely phenomenological point of view, the correct clinical classification of signs and symptoms may be difficult and require expert evaluation. This is because the clinical picture is often a mixture of hyperkinetic and hypokinetic disorders, and within hyperkinetic movement disorders, combined phenotypes are not unusual. Second, although several genes that cause movement disorders in children are now well-known, many of them have only been described in adult populations or discovered in patients after many years of disease. Furthermore, diseases that alter their mechanisms from childhood to adulthood are still little known, and many phenotypes in children are the result of a disruption of normal neurodevelopment. High-throughput gene screening addresses these difficulties and has modified the approach to genetic diagnosis. In the exome-sequencing era, customized genetic panels now offer the ability to perform fast and low-cost screening of the genes commonly involved in the pathogenesis of the disease. Here, we describe a 3-year study using a customized gene panel for pediatric-onset movement disorders in a selected cohort of children and adolescents. We report a satisfying diagnostic yield, further confirming the usefulness of gene panel analysis.

Hyperkinetic Movement Disorders in Children: A Brief Review.

Movement disorders are common neurologic disturbances in childhood. There are two major types of movement disorders. Hypokinetic disorders are with paucity of voluntary movements and are very uncommon in pediatric age group. Hyperkinetic movement abnormalities are very common in children and defined as abnormal repetitive involuntary movements. Movement disorders in childhood and even in adolescents are different in etiology, timing, treatment and prognosis versus adulthood movement abnormalities. In this brief article, we reviewed common types of hyperkinetic abnormal movements in children and adolescents with emphasis on etiologies, new classifications and recent treatment strategies.

Proportion and spectrum of movement disorders in adolescent and adult patients of autoimmune encephalitis of non-neoplastic aetiology

We aimed to study the proportion of patients with movement disorders in seropositive autoimmune encephalitis of non-neoplastic aetiology and also to describe the spectrum of movement disorders in them.We prospectively screened 362 patients of age >12 years with encephalitis of unknown aetiology for a panel of antibodies for autoimmune encephalitis. Demographic and clinical characteristics with focus on the movement disorders were recorded. We also evaluated the differences in the spectrum of movement disorder based on various age groups and antibody positivity. Patients were treated with immune modulating drugs and were followed up for 6 months.Out of the 41 patients, 21 (51.2%) patients presented with movement disorder as a part of their clinical presentation. The commonest movement disorder encountered in our cohort was orofaciolingual dyskinesia (OFLD) 57.1% followed by tremor (38.1%), choreoathetosis (33.3%), paroxysmal dyskinesia (23.8%) stereotypies (14.3%), bradykinesia (13.1%), followed by dystonia (13.1%), catatonia (4.7%), neuromyotonia (4.7%) ballism (4.7%), ataxia (4.7%) and stiff person phenotype (4.7%). The hyperkinetic movement disorders were more commonly seen compared to hypokinetic disorders. All patients received immunomodulatory therapy. On follow, 17 (80.1%) patients had good response with total remission of the movement disorder. Four patients did not have total remission but significant improvement in the symptoms after 6 months of follow up.Our study shows that >50% of patients with antibody positive autoimmune encephalitis have movement disorder as a part of their clinical feature. Timely institution of immunotherapy leads to good outcome in majority of patients.

Sports for all and its role for maintenance and promotion of physical fitness and wellness

Sports are the physical activities that named according to their respective ways of playing. There is a misleading concept regarding sports that only players can participate in physical or sports activities. But the true is that as the science and technology has made individual to rely on machines, its becomes necessary for all to take part in any kind of physical and sports activities to escape one from the hypo kinetic disorders and to keep physical fitness and wellness. This study has analyzed the role of sports in relation to maintain and promote physical fitness and wellness.

Neuroprotective potential of spermidine against rotenone induced Parkinson's disease in rats

Parkinson's disease is a leading hypokinetic disorder characterized by selective loss of dopaminergic neurons in substantia nigra pars compacta (SNpc) region of mid-brain. Degeneration of dopaminergic neurons is considered to be due to oxidative stress, neuroinflammation, disturbed calcium homeostasis and glutamate excitotoxicity etc. Spermidine is a polyamine which counteracts age associated cell death by scavenging free radical formation, activates authophagic machinery by enhancing formation of autophagosome, and antagonizes NMDA receptor. In the current study we investigated the neuroprotective potential of spermidine against rotenone induced PD in rats. Rats were treated subcutaneously with rotenone 1.5 mg/kg daily for 28 days. Spermidine 5&10 mg/kg was administered orally 1 h prior to rotenone administration from 15 to 28. Rotenone caused significant reduction in motor functioning and elevated levels of oxidative stress markers and proinflammatory cytokines levels (IL-1β, IL6 and TNF-α). The neurochemical analysis revealed a significant decrease in serotonin, norepinephrine, dopamine and their metabolites accompanied by a significant loss of dopaminergic neurons in the SNpc following ROT injection. However, treatment with spermidine rescued DAergic neurons in SNpc and nerve terminals in the striatum following ROT insult. Spermidine treatment also attenuated oxidative stress, neuroinflammation and restored striatal neurochemistry. Results of our study suggest that spermidine has promising neuroprotective effect against degenerative changes in experimental PD, and the protective effects are mediated through its antioxidant and anti-inflammatory properties.

Pediatric movement disorders.

Pediatric movement disorders are commonly encountered clinical entities in the pediatric outpatient department. These disorders are a heterogenous group of disorders and may represent an underlying genetic disorder, a metabolic disorder or a hypoxic-ischemic insult during the perinatal period. Hyperkinetic movement disorders are more common as compared to hypokinetic disorders. This is unlike the situation in adult movement disorders where hypokinetic disorders are more often seen. A child's nervous system is more prone to hypoxic-ischemic insults due to its higher metabolic demands and the presence of an immature blood-brain barrier. The commonest movement disorders seen are tics, dystonia and chorea. Myoclonus is commonly associated with epilepsy syndromes. The aetiology of paediatric movement disorders depends on their course, their static or progressive nature, and whether an isolated symptom or an association with other neurological symptoms is present. The clue to the diagnosis is the proper recognition of the movement prevalent in the disorder.

The role of Dopamine in Preparatory Inhibition: What can we learn from Parkinson’s disease?

The role of Dopamine in Preparatory Inhibition: What can we learn from Parkinson’s disease?