Materiały źródłowe

• #1 Movement disorder – Wikipedia

  https://en.wikipedia.org/wiki/Movement_disorder

  Movement disorders are clinical syndromes with either an excess of movement or a paucity of voluntary and involuntary movements, unrelated to weakness or spasticity. Movement disorders present with extrapyramidal symptoms and are caused by basal ganglia disease. Movement disorders are conventionally divided into two major categories-hyperkinetic and hypokinetic. […] Hyperkinetic movement disorders refer to dyskinesia, or excessive, often repetitive, involuntary movements that intrude upon the normal flow of motor activity. […] Hypokinetic movement disorders fall into one of four subcategories: akinesia (lack of movement), hypokinesia (reduced amplitude of movements), bradykinesia (slow movement), and rigidity. In primary movement disorders, the abnormal movement is the primary manifestation of the disorder. In secondary movement disorders, the abnormal movement is a manifestation of another systemic or neurological disorder. Treatment depends upon the underlying disorder.

• #1 Pathophysiology of the Basal Ganglia and Movement Disorders: Gaining New Insights from Modeling and Experimentation, to Influence the Clinic | Frontiers Research Topic

  https://www.frontiersin.org/research-topics/3875/pathophysiology-of-the-basal-ganglia-and-movement-disorders-gaining-new-insights-from-modeling-and-experimentation-to-influence-the-clinic/magazine

  The basal ganglia constitute a group of subcortical structures, highly interconnected among themselves, as well as with the cerebral cortex, thalamus and other brain areas. These nuclei play a central role in the control of voluntary movement, and their specific pathology comprises the group of diseases known as movement disorders, including Parkinson’s disease, Huntington’s disease, dystonia and Gilles de la Tourette syndrome, among others. Additionally, the presence of a number of circuits within the basal ganglia related to non-motor functions has been acknowledged. Currently, the basal ganglia are thought to participate in cognitive, limbic and learning functions. Moreover, disorders related to the basal ganglia are known to involve a number of complex, non-motor symptoms and syndromes (e.g. compulsive and addictive behavior). In the light of this evidence, it is becoming clear that our knowledge about the basal ganglia needs to be revised, and that new pathophysiological models of movement disorders are needed.

• #1 [Pathophysiology of movement disorders] – PubMed

  https://pubmed.ncbi.nlm.nih.gov/23196562/

  Malfunctions of the basal ganglia cause movement disorders, such as Parkinson’s disease and dystonia. Several models have been proposed to explain the pathophysiology of these disorders: (1) Firing rate model: activity imbalance between the direct and indirect pathways changes the mean firing rate of output nuclei of the basal ganglia and induces hypokinetic or hyperkinetic movement disorders; (2) Firing pattern model: oscillatory and/or synchronized activity observed in the basal ganglia disturbs information processing in the basal ganglia, resulting in motor symptoms; (3) Dynamic activity model: movement-related activity changes through the direct and indirect pathways disrupt balance between movement-related inhibition and surrounding excitation in the output nuclei, and induce motor symptoms. Each model will be critically discussed in this review.

• #1

  https://journals.lww.com/neur/fulltext/2021/69020/post_stroke_movement_disorders__clinical_spectrum,.6.aspx

  Damage to the direct basal ganglia pathway gives rise to hypokinetic movement whereas the involvement of the indirect pathway gives rise to hyperkinetic movement disorder. […] This aspect brings to light the concept of neuronal plasticity wherein there is the formation of a parallel network that overcomes the motor loss, and formation of the pathological circuit gives rise to the abnormal movements. […] The proposed mechanism for this is a compensatory increase in the functioning of structures contralateral to stroke site and thus giving rise to ipsilateral abnormal movements. […] It has been observed that there is no definite relation between the type of abnormal movement and the site of stroke, that is the same type of movement can be seen with lesions at different places. […] The incidence of movement disorders is three times higher with subcortical strokes than cortical strokes, basal ganglia (44%) and thalamus (33%) being involved in most cases. […] In a study by Netravathi et al. on 103 patients of secondary movement disorders, it was found that the most common cause was vascular of which arterial stroke comprised 65% of the cases.

• #1 Parkinson’s disease – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/parkinsons-disease/symptoms-causes/syc-20376055

  Parkinson’s disease is a movement disorder of the nervous system that worsens over time. The nervous system is a network of nerve cells that controls many parts of the body, including movement. […] In Parkinson’s disease, nerve cells in the brain called neurons slowly break down or die. Many Parkinson’s disease symptoms are caused by a loss of neurons that produce a chemical messenger in the brain. This messenger is called dopamine. […] Decreased dopamine leads to irregular brain activity. This causes movement problems and other symptoms of Parkinson’s disease. People with Parkinson’s disease also lose a chemical messenger called norepinephrine that controls many body functions, such as blood pressure. […] Many changes happen in the brains of people with Parkinson’s disease. Researchers are studying why the changes happen and the roles they play. These changes include:

• #1 Movement Disorders – Basal Ganglia

  https://uw.pressbooks.pub/wwamibasalganglia/chapter/pathways/

  Movement disorders are neurologic disorders that cause either an excess or a paucity of movement. These abnormal movements can occur at rest or with action, and can be involuntary or suppressible. […] The main feature of hypokinetic disorders is bradykinesia or slowness of movement. […] In general, many of the hypokinetic disorders have at its core principle reduced dopamine neurotransmission. […] Loss of dopamine (DA) from the substantia nigra effects both the direct and indirect pathways. In the direct pathway, loss of DA leads to decreased stimulation of the striatum, causing a decrease in the inhibition of the GPi. This decreased GPi stimulation then causes an increase in inhibition to the thalamus. Increased inhibition to the thalamus decreases activation of the cortical motor areas, leading to hypokinetic movements.

• #1 Chorea in Adults: Background, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/1149854-overview

  A simple model of basal ganglia function states that dopaminergic and GABAergic impulses from the substantia nigra and motor cortex, respectively, are funneled through the pallidum into the motor thalamus and motor cortex. These impulses are modulated in the striatum via two segregated, parallel, direct and indirect loops through the medial pallidum and lateral pallidum/subthalamic nucleus. Subthalamic nucleus activity drives the medial pallidum to inhibit cortex-mediated impulses, thereby inducing parkinsonism. Absent subthalamic nucleus inhibition enhances motor activity through the motor thalamus, resulting in abnormal involuntary movements such as dystonia, chorea, and tics. A classic example of loss of subthalamic inhibitory drive is ballism. […] […] Huntington disease is caused by an expanded CAG trinucleotide repeat in the gene that encodes the protein huntingtin. Mutant huntingtin is thought to cause neuronal degeneration through transcription dysregulation as well as mitochondrial impairment. […]

• #1 Chorea in Adults: Background, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/1149854-overview

  Fluctuations in striatal serotonin may play a role in the genesis of many abnormal movements. Selective serotonin reuptake inhibitors, such as fluoxetine, may induce or aggravate parkinsonism, akinesia, myoclonus, or tremor. The role of serotonin (5-hydroxytryptamine [5-HT]) in choreiform movements is less clear since the striatum has a relatively high concentration of serotonin. Pharmacologic attempts to either stimulate or inhibit serotonin receptors in persons with Huntington chorea have shown no effect, indicating that serotonin’s contribution to the pathogenesis of chorea is limited. […] […] The most consistent biochemical lesion in patients with Huntington chorea appears to be a loss of neurons in the basal ganglia that synthesize and contain GABA. The significance of this remains unknown. A variety of pharmacologic techniques have been attempted to increase CNS GABA levels. Valproic acid, which acts in part via a GABAergic mechanism, has, in a limited number of uncontrolled cases, ameliorated not only the agitation sometimes seen in persons with HD but also the movement problem. However, no systematic studies have been conducted on the use of GABAergic agents to treat HD. […]

• #1 Chorea in Adults: Background, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/1149854-overview

  In Huntington chorea, the content of striatal dopamine is normal, indicating that the major pathological alterations lay in the surviving but diseased medium-sized, spiny, striatal dopaminergic neurons. Pharmacologic agents that either deplete dopamine (eg, reserpine and tetrabenazine) or block dopamine receptors (eg, neuroleptic medications) improve chorea, which gives further support to this observation. Given that drugs that decrease the striatal content of dopamine improve chorea, increasing the amount of dopamine worsens chorea, such as in the levodopa-induced chorea seen in persons with Parkinson disease. […] […] The concept that a critical striatal balance between acetylcholine (Ach) and dopamine is essential for normal striatal function received its greatest acceptance in the understanding of PD. In the early days of PD therapy, anticholinergic medications were used frequently, especially when tremor was the predominant symptom. Other PD symptoms, such as bradykinesia and rigidity, often improved as well. […]

• #1 Model systems for understanding dystonia pathogenesis

  https://www.movementdisorders.org/MDS/Scientific-Issues/posts/Model-systems-for-understanding-dystonia-pathogenesis.htm

  These genes encode proteins with distinct biological functions including mitochondrial dysfunction, heavy metals accumulation, endoplasmic reticulum (ER) and nuclear envelope dysfunction, and lipid metabolism. […] Of interest, among the shared biological pathways are defects in dopamine signalling. […] Indeed, multiple mutations causing dystonia to converge, to affect dopamine signal transduction pathways, including GTPCH1, GNAL, and ADCY5, to name a few. […] Several lines of observations emphasize the centrality of a dysregulation of cholinergic transmission at the striatal level, particularly in DYT1 dystonia, with a hypercholinergic tone resulting in an aberrant striatal network activity. […] Elucidation of these and other shared pathways is relevant for understanding the biological basis of dystonia and for designing novel therapeutics that may have a broad potential for distinct types of dystonia.

• #1 Parkinson’s disease – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/parkinsons-disease/symptoms-causes/syc-20376055

  The presence of Lewy bodies. Clumps of proteins in the brain are associated with Parkinson’s disease. These are called Lewy bodies, and researchers believe these proteins hold an important clue to the cause of Parkinson’s disease. […] Alpha-synuclein found within Lewy bodies. Alpha-synuclein is a protein found in all Lewy bodies. It occurs in a clumped form that cells can’t break down. This is currently an important focus among Parkinson’s disease researchers. Alpha-synuclein has been found in the spinal fluid of people who later have Parkinson’s disease. […] Altered mitochondria. Mitochondria are powerhouse compartments inside cells that create most of the body’s energy. Changes to mitochondria can cause cell damage. These changes have been found in the brains of people with Parkinson’s disease.

• #1 Promising Parkinson’s drug decoded

  https://medicalxpress.com/news/2025-05-parkinson-drug-decoded.html

  Impaired quality control of mitochondria plays a central role in Parkinson’s disease. […] The exact cause of nerve cell death remains unclear. However, there are indications that defects in their mitochondria could be responsible. Nerve cells in particular are highly dependent on these organelles, as they require high amounts of energy. […] An important enzyme in mitophagy is the deubiquitinase (DUB) USP30. It removes ubiquitin marks from defective mitochondria that are destined for degradation. […] Using innovative protein engineering, Gersch and his team have now been able to obtain a detailed picture of how an inhibitor binds to USP30 and specifically switches off its activity. […] Elucidating the mechanism of action of this potential Parkinson’s drug will not only help to further develop it, but also lay the foundation for designing new drug molecules against USP30. […] Mitophagy and enzymes from the DUB family also play an important role in other diseases and are associated with a weakened immune system and tumor growth.

• #1 Model systems for understanding dystonia pathogenesis

  https://www.movementdisorders.org/MDS/Scientific-Issues/posts/Model-systems-for-understanding-dystonia-pathogenesis.htm

  The intracellular stress response pathway appears to be affected in cellular studies of TOR1A and PRKRA gene mutations. […] Thus, cells with a defective ER-mediated stress response appear to be more likely to undergo apoptosis and contribute to the development of dystonia. […] In addition, data from both gene expression studies conducted in neural stem cells derived from humans with different THAP1 mutations and mouse models of THAP1 dystonia, point to abnormalities in expression of genes related to myelination. […] In summary, defects in dopamine synthesis, the ER stress response, and myelin production are implicated in the pathogenesis of dystonia. […] The advances in our understanding of the molecular basis of dystonia have been coming so fast it has been hard to keep up with them. […] The most obvious impact of these findings has been related to diagnostic tools. […] The molecular diagnosis is becoming increasing important, because several specific subtypes now have highly effective interventions, and early treatment produces a better outcome.

• #1 Parkinson’s Disease: What It Is, Causes, Symptoms & Treatment

  https://my.clevelandclinic.org/health/diseases/8525-parkinsons-disease-an-overview

  The buildup of these Lewy bodies (which doesnt happen with some of the genetic problems that cause Parkinsons disease) causes toxic effects and cell damage. […] Several medications can cause a parkinsonism-like effect. […] The Parkinson’s-like effects are often temporary if you stop taking the medication that caused them before the effects become permanent. […] Parkinsons disease can have a familial cause, which means you can inherit it from one or both of your parents. […] Experts have linked at least seven different genes to Parkinsons disease. […] Some genetic mutations also cause unique, distinguishing features. […] Parkinsons disease isnt curable, which means its a permanent, lifelong condition. […] The most common and effective treatment for Parkinsons disease is levodopa. […] Over time, the way your body uses levodopa changes, and levodopa can also lose its effectiveness. […] Parkinsons disease happens for either genetic reasons or unpredictably. […] Parkinsons disease is a degenerative condition, meaning the effects on your brain get worse over time.

• #1 Model systems for understanding dystonia pathogenesis

  https://www.movementdisorders.org/MDS/Scientific-Issues/posts/Model-systems-for-understanding-dystonia-pathogenesis.htm

  Dystonia is one of the most common forms of movement disorder, and yet its pathophysiology is one of the least well understood. […] Over the past 25 years, there has been significant progress in our understanding of the genetics contributing to the development of dystonia, with 300 genes now identified as causative in the development of isolated dystonia or dystonia syndromes. […] Despite this, progress with mechanistic understanding, and by proxy therapeutic development, has been slower and has tended to focus on a limited number of genes. […] The development of several models has contributed to our knowledge on the pathophysiology of dystonia, allowing us to better explore the molecular pathways and neuronal networks underlying the disease. […] At the system level, evidence from clinical, neuroimaging, and neurophysiology studies support the concept of dystonia as a network disorder, including the cortical-thalamic-basal ganglia pathway, and more recently, cerebellar pathways, although the precise role and the relevance of each component have not been elucidated yet.

• #1 Model systems for understanding dystonia pathogenesis

  https://www.movementdisorders.org/MDS/Scientific-Issues/posts/Model-systems-for-understanding-dystonia-pathogenesis.htm

  The phenotypic models have transformed our understanding of the anatomical underpinnings of dystonia. […] The phenotypic animal models provided strong evidence for our modern conceptualization of dystonia as a disorder of a broader motor network, where dystonia may sometimes arise from a defect in the basal ganglia, and other times the defect arises in the cerebellum or elsewhere. […] Despite the absence of overt dystonia, the genetic models have been instrumental in advancing our understanding of the molecular pathogenesis of numerous inherited forms of dystonia, such dopa-responsive dystonia and dystonia associated with the TOR1A and THAP1 genes. […] A relevant contribution to such idea came from genetics, which led to a significant growth in the number of genes associated with dystonia.

• #1 Movement disorders | PPT

  https://www.slideshare.net/slideshow/movement-disorders-53890175/53890175

  Movement disorders disrupt motor function by 1. Abnormal, involuntary, unwanted movements (hyperkinetic movement disorders) 2. Curtailing [restricting] the amount of normal free flowing, fluid movement (hypokinetic movement disorders) hypokinetic movement disorders are accompanied by abnormal states of increased muscle tone Pathology is in basal ganglia […] Parkinson’s disease is a progressive neuro-degenerative disorder that is associated with the loss of dopaminergic neurons in the substantia nigra pars compacta. The hallmarks of the disease are its triad of motor features – resting tremor – rigidity – akinesia/bradykinesia Gait and postural disturbances also characterize the disease. […] The loss of dopamine results in hypokinetic symptoms secondary to overactivity of the STN and Gpi via the indirect path, which increases inhibitory input to the thalamus and then reduces the excitatory thalamocortical activity that ordinarily facilitates motor movements. Hyperkinetic movements, such as levodopa-induced dyskinesias occur with overactivation of the direct pathway.

• #1 Model systems for understanding dystonia pathogenesis

  https://www.movementdisorders.org/MDS/Scientific-Issues/posts/Model-systems-for-understanding-dystonia-pathogenesis.htm

  At the circuit and cellular level, altered synaptic plasticity, caused by an abnormal neurochemical balance between striatal cholinergic and dopaminergic signalling, is consistently implicated in many different forms of dystonia. […] At the molecular level, several novel genes encode proteins with distinct biological functions, including dopamine signalling mitochondrial function, heavy metal accumulation, endoplasmic reticulum and nuclear envelope dysfunction, and lipid metabolism. […] Taken together, genetic models of dystonia and animal models that display overt signs of dystonia both give information regarding pathophysiology. […] These diverse models indicate that dysfunction at one or multiple levels within the nervous system (intracellular defects, neurotransmitter signaling defects and/or in combination with abnormal nerve function) contribute to the development of dystonia.

• #1 Pathogenesis and pathophysiology of functional (psychogenic) movement disorders – PubMed

  https://pubmed.ncbi.nlm.nih.gov/30798005/

  Functional movement disorders (FMDs), known over time as „hysteria”, „dissociative”, „conversion”, „somatoform”, „non-organic” and „psychogenic” disorders, are characterized by having a voluntary quality, being modifiable by attention and distraction but perceived by the patient as involuntary. […] Stressful events, social influences and minor trauma may precede the onset of FMDs, but their pathogenic mechanisms are unclear. Patients with FMDs have several abnormalities in their neurobiology including strengthened connectivity between the limbic and motor networks. Additionally, there is altered top-down regulation of motor activities and increased activation of areas implicated in self-awareness, self-monitoring, and active motor inhibition such as the cingulate and insular cortex. Decreased activation of the supplementary motor area (SMA) and pre-SMA, implicated in motor control and preparation, is another finding. The sense of agency defined as the feeling of controlling external events through one’s own action also seems to be impaired in individuals with FMDs. Correlating with this is a loss of intentional binding, a subjective time compression between intentional action and its sensory consequences. […] Advances in the pathogenesis and pathophysiology of FMDs may be helpful to understand the nature of these disorders and plan further treatment strategies.

• #1 Functional movement disorders – UpToDate

  https://www.uptodate.com/contents/functional-movement-disorders

  FMD, like other functional neurological symptom disorders, is best conceptualized using a biopsychosocial model of predisposing, precipitating, and perpetuating factors. Factors can be biologic, psychological, or social, and the combination of factors is unique to each patient. None of the factors is individually causal; rather, their presence increases risk of developing the disorder. […] FMD is a complex neuropsychiatric condition, and underlying mechanisms are an intense area of study. Processes relevant to FMD include abnormal self-directed attention, abnormal beliefs and expectations, abnormal sense of agency (ie, a subjective sense of control) for self-generated movements, motor learning and plasticity, and abnormal limbic-motor interface. […] Research has sought to understand the neural mechanisms by which functional movement symptoms emerge, using predictive coding models of how the brain generates a sense of agency. At their core, functional motor symptoms are experienced as involuntary, related to a loss of sense of agency due to mismatch between feedforward signals through the „agency network” (involving the right temporoparietal junction) and feedback sensory information once movement is executed. This mismatch arises due to overweighting of the feedforward message, which is strongly influenced by expectation, enhanced attention, and emotion.

• #1 Functional Movement Disorders: Updates and Clinical Overview

  https://www.e-jmd.org/journal/view.php?doi=10.14802/jmd.24126

  Recent fMRI studies have shown that there is decreased functional connectivity between the right temporoparietal junction (TPJ) and bilateral sensorimotor regions and impaired hemodynamic responsiveness of the dorsolateral prefrontal cortex and presupplementary cortex to changes in the loss of movement control in patients with FMD. […] These findings highlight the effects of early-life physical or sexual abuse in the development of FMD, as well as gene-environment interactions that may be relevant. […] Improving accessibility to treatment resources for FMD remains a challenge but is highly important.

• #1

  https://journals.lww.com/neur/fulltext/2021/69020/post_stroke_movement_disorders__clinical_spectrum,.6.aspx

  Involuntary movements develop after 14% of strokes and they have been reported in patients with ischemic and hemorrhagic strokes affecting the basal ganglia, thalamus, and/or their connections. […] Proposed pathophysiological mechanisms include neuronal plasticity, functional diaschisis, and age-related differences in brain metabolism. […] They are often associated with lesions in the basal ganglia, however, there is emerging evidence that in this setting most movement disorders result from a network dysfunction rather than from a single lesion. […] Movement disorders secondary to strokes are diverse and their natural history, prognosis, and treatment differ from their idiopathic counterpart. […] Post-stroke movement disorders can manifest with lesions affecting any segment of the motor circuitry; be it cortical which includes the primary motor, supplementary motor, and premotor cortical areas; or subcortical affecting the basal ganglia, thalamus, internal capsule, diencephalon, and mesencephalon; or cerebellar circuitry.

• #1 Autoimmune Movement Disorders in Adults

  https://practicalneurology.com/articles/2020-sept/autoimmune-movement-disorders-in-adults

  As antibodies to neuronal targets are described, we see the clinical spectrum and pathophysiology of autoimmune movement disorders more clearly. […] Neuroimmunology is a rapidly developing field. With the description of new antibodies and new syndromes, both the clinical spectrum and our insights into disease pathophysiology and treatment expand. These developments also reflect on movement disorders associated with neuronal antibodies, a field that is continuously broadening. […] Movement disorders may be the first or most prominent presentation of autoimmune encephalitis and can present with characteristic phenotypes, with associated red flags or other diagnostic clues. Importantly, they may also be a differential diagnosis of degenerative disease, particularly when signs and symptoms develop slowly.

• #1 Autoimmune Movement Disorders in Adults

  https://practicalneurology.com/articles/2020-sept/autoimmune-movement-disorders-in-adults

  Chorea may occur as a paraneoplastic syndrome, in particular with antibodies to Hu and collapsin response-mediator protein-5 (CRMP5) often combined with other signs. […] Antibodies to phosphodieserase 10A (antiPDE10A) have been recently described as a new marker of paraneoplastic chorea (and other movement disorders) with onset at median age 70 at equal rates in men and women. The full clinical and radiologic spectrum (basal ganglia FLAIR hyperintensities reported) remains to be determined. […] Chorea may also occur with antibodies to neuronal surface antigens (eg, leucine-rich glioma inactivated 1 [LGI1] or contactin-associated protein-like 2 [CASPR2]) with a lower likelihood of an underlying tumour. […] The clinical spectrum of antiCASPR2 includes also limbic encephalitis with cognitive decline, seizures, behavioral change, myoclonus, ataxia, and pain, which can be an important diagnostic clue.

• #1 Manganese and Movement Disorders: A Review

  https://www.e-jmd.org/journal/view.php?doi=10.14802/jmd.20123

  The approach to the management of these groups of disorders differs from disorders caused by environmental and occupational exposure. […] Neurotoxicity due to Mn exposure causes neuronal loss and gliosis in the basal ganglia, with the globus pallidus, the substantia nigra pars reticulata, and the striatum identified as particularly vulnerable structures. […] Mitochondrial dysfunction, along with protein misfolding and neuroinflammation, are hypothesized to reflect Mn toxicity (neurotoxic triad). […] Chronic exposure to Mn leads to manganism, the complex syndrome of Mn neurotoxicity characterized by cognitive, behavioral and extrapyramidal dysfunction. […] Although Mn exposure causes extrapyramidal dysfunction, the clinical features of Mn toxicity are rather different from those observed in patients with idiopathic Parkinsons disease. […] In patients with acquired hepatocerebral degeneration (AHD), toxic substances, primarily Mn, accumulate due to dysfunctional clearance. […] Gene mutations and Mn-related clinical disorders

• #1 Air pollution worsens movement disorder after stroke

  https://bioengineer.org/air-pollution-worsens-movement-disorder-after-stroke/

  Air pollution has been shown to have a negative effect on the prognosis of ischemic stroke, or stroke caused by reduced blood flow to the brain, but the exact mechanism is unknown. […] A team of researchers recently conducted a study to determine whether or not increased inflammation of the brain, also known as neuroinflammation, is the main culprit. […] Mice exposed intranasally to urban aerosols from Beijing, China, for one week demonstrated increased neuroinflammation and worsening movement disorder after ischemic stroke, compared to control mice that were not exposed to air pollution. […] This suggests that PAHs are involved in both neuroinflammation and increased movement disorder associated with air pollution exposure in ischemic stroke. […] They found evidence that intranasal exposure to air pollution from Beijing, China, increased neuroinflammation after ischemic stroke in mice through activation of microglial cells, which are immune cells found in the brain. Movement disorder was also negatively impacted in ischemic stroke mice exposed to the same air pollution.

• #1 Air pollution worsens movement disorder after stroke

  https://bioengineer.org/air-pollution-worsens-movement-disorder-after-stroke/

  Mice lacking the aryl hydrocarbon receptor demonstrated lower microglial cell activation and movement disorder compared to normal mice, suggesting that the PAHs present in Beijing air pollution are responsible for at least some of the neuroinflammation and lower prognosis seen in ischemic stroke mice exposed to air pollution. […] Ultimately, the goal of the research team is to better understand the mechanism by which PM2.5 causes neuroinflammation, since air pollution is inhaled first into the respiratory tract.

• #1 Sleep disturbance in movement disorders: insights, treatments and challenges | Journal of Neurology, Neurosurgery & Psychiatry

  https://jnnp.bmj.com/content/92/7/723

  Sleep and circadian rhythm disturbances are central features of many movement disorders, exacerbating motor and non-motor symptoms and impairing quality of life. […] Understanding these disturbances to sleep is clinically important and may further our understanding of the underlying movement disorder. […] Rapid eye movement sleep behaviour disorder has emerged as the most reliable prodromal biomarker for the alpha synucleinopathies, including Parkinsons disease and multiple system atrophy, often preceding motor symptom onset by several years. […] Abnormal sleep has also been described for many other movement disorders, but further evidence is needed to determine whether this is a primary or secondary phenotypic component of the underlying condition. […] Within the context of movement disorders, there is also some suggestion of a shared underlying mechanism for motor and sleep pathophysiology, with evidence implicating thalamic and brainstem structures and monoaminergic neurotransmission.

• #1

  https://journals.lww.com/neur/fulltext/2020/68002/pediatric_movement_disorders_and_neuromodulation_.9.aspx

  The management of pediatric movement disorders has two main goals 1- management of the etiology if treatable e.g., Wilson’s disease, Glut 1 transporter disease 2- Management of symptomatology. Most of the pediatric movement disorders require symptomatic treatment. […] Neuromodulation Modulation of the pathological brain activity in pediatric movement disorders by deep brain stimulation seems to offer a promising new therapeutic strategy, though not curative or disease specific. […] Deep brain stimulation (DBS) is one of the early invasive brain stimulation techniques described since 1960 for various neurological and psychiatric disorders. […] DBS technique use various continuous frequencies (high 100 Hz and low 60 Hz with various pulse widths (narrow- 6090 microseconds and wide 210-450 microseconds), combination of amplitudes and monopolar or bipolar stimulations. […] The most common targets are STN and GPi. It is associated with symptomatic improvement of disabling symptoms like muscle spasms, various involuntary movements, pain and abnormal postures, respiratory and feeding issues.

• #1 Movement Disorders

  https://www.radiologyinfo.org/en/info/movement-disorders

  Movement disorders are neurological (nervous system) conditions that cause spasms, jerking, or shaking. These conditions may also reduce or slow movement. Disease, genetic conditions, and medications are some of the causes. […] Genetic conditions, traumatic injury, nervous system disease, infections, medication side effects, and other factors may cause a movement disorder. A history of stroke, high blood pressure, and diabetes may increase your risk, which increases with age. […] Movement disorder symptoms can look like those of stroke and vascular disease. Therefore, your doctor may look at the vessels supplying blood to the brain. […] If you have a movement disorder, Deep Brain Stimulation (DBS) may reduce your involuntary movements. A two-part procedure first implants a small electrode in the brain using general anesthesia. The second surgery connects a wire from the electrode to a small battery pack that sends electrical impulses by pushing a button. […] Doctors are studying MR-guided Focused Ultrasound (MRgFUS) as a treatment for some movement disorders. The procedure uses focused beams of sound energy to heat and destroy a small volume of brain tissue without harming adjacent tissue.

• #1 Pathophysiology of the Basal Ganglia and Movement Disorders: Gaining New Insights from Modeling and Experimentation, to Influence the Clinic | Frontiers Research Topic

  https://www.frontiersin.org/research-topics/3875/pathophysiology-of-the-basal-ganglia-and-movement-disorders-gaining-new-insights-from-modeling-and-experimentation-to-influence-the-clinic/magazine

  In this context, the study of the pathophysiology of the basal ganglia and the treatment of their pathology is becoming increasingly interdisciplinary. Nowadays, an appropriate approach to the study of these problems must necessarily involve the use of complex mathematical modeling, computer simulations, basic research (ranging from biomolecular studies to animal experimentation), and clinical research. This research topic aims to bring together the most recent advances related to the pathophysiology of the basal ganglia and movement disorders. We welcome contributions that address any aspect of significance to the field, including but not restricted to: biomolecular aspects, Braak’s hypothesis, electrophysiology, animal models, new technologies and methods of analysis, mathematical modeling, computer simulations, computational theory, neural networks, clinical aspects, deep brain stimulation. We will also welcome papers that analyze various physiological signals (cortical activity, EMG, ECG), as they are related to different aspects of movement disorders (cognitive, autonomic, psychiatric and others). Papers that include an interdisciplinary approach and a discussion at multiple levels (i.e., the relation between experimental results, clinical data and modeling results) are encouraged. Works that describe an effort to translate basic research into clinical achievements will also be given special consideration.

• #1

  https://link.springer.com/article/10.1007/s00702-019-02028-6

  Extrapyramidal movement disorders include hypokinetic rigid and hyperkinetic or mixed forms, most of them originating from dysfunction of the basal ganglia (BG) and their information circuits. […] Pathophysiologic classification of extrapyramidal movement disorder mechanisms distinguish (1) parkinsonian syndromes, (2) chorea and related syndromes, (3) dystonias, (4) myoclonic syndromes, (5) ballism, (6) tics, and (7) tremor syndromes. […] Their etiopathogenesis is still poorly understood, but is suggested to result from an interaction between genetic and environmental factors. […] Multiple etiologies and noxious factors (protein mishandling, mitochondrial dysfunction, oxidative stress, excitotoxicity, energy failure, and chronic neuroinflammation) are more likely than a single factor.

• #1 Pathophysiology of the Basal Ganglia and Movement Disorders: Gaining New Insights from Modeling and Experimentation, to Influence the Clinic | Frontiers Research Topic

  https://www.frontiersin.org/research-topics/3875/pathophysiology-of-the-basal-ganglia-and-movement-disorders-gaining-new-insights-from-modeling-and-experimentation-to-influence-the-clinicundefined

  The basal ganglia constitute a group of subcortical structures, highly interconnected among themselves, as well as with the cerebral cortex, thalamus and other brain areas. These nuclei play a central role in the control of voluntary movement, and their specific pathology comprises the group of diseases known as movement disorders, including Parkinson’s disease, Huntington’s disease, dystonia and Gilles de la Tourette syndrome, among others. […] In the light of this evidence, it is becoming clear that our knowledge about the basal ganglia needs to be revised, and that new pathophysiological models of movement disorders are needed. […] Nowadays, an appropriate approach to the study of these problems must necessarily involve the use of complex mathematical modeling, computer simulations, basic research (ranging from biomolecular studies to animal experimentation), and clinical research. […] This research topic aims to bring together the most recent advances related to the pathophysiology of the basal ganglia and movement disorders.

• #2 Pathogenesis of movement disorders: basic neuroanatomy and pathophysiology (Chapter 2) – Movement Disorders in Neurologic and Systemic Disease

  https://www.cambridge.org/core/books/movement-disorders-in-neurologic-and-systemic-disease/pathogenesis-of-movement-disorders-basic-neuroanatomy-and-pathophysiology/906FC0B1148D64A8B9613B92FA2A153D

  Movement disorders are conditions affecting the ability to produce and control voluntary as well as involuntary movements and comprise a large group of diseases with a wide range of different etiologies and very diverse clinical presentations. […] For many of the conditions, the pathophysiology remains unclear or at least partially unknown. Some of the more common and classical movement disorders, such as Parkinsons disease and Huntingtons disease, arise from disturbances of the basal ganglia. Hence, movement disorders are sometimes also referred to as basal ganglia disorders. […] There is visible evidence of anatomical changes in the basal ganglia in many movement disorders, such as degeneration of the caudate nucleus in Huntingtons disease, or degeneration of the substantia nigra in Parkinsons disease.

• #2 [Pathophysiology of movement disorders] – PubMed

  https://pubmed.ncbi.nlm.nih.gov/23196562/

  Malfunctions of the basal ganglia cause movement disorders, such as Parkinson’s disease and dystonia. Several models have been proposed to explain the pathophysiology of these disorders: (1) Firing rate model: activity imbalance between the direct and indirect pathways changes the mean firing rate of output nuclei of the basal ganglia and induces hypokinetic or hyperkinetic movement disorders; (2) Firing pattern model: oscillatory and/or synchronized activity observed in the basal ganglia disturbs information processing in the basal ganglia, resulting in motor symptoms; (3) Dynamic activity model: movement-related activity changes through the direct and indirect pathways disrupt balance between movement-related inhibition and surrounding excitation in the output nuclei, and induce motor symptoms. Each model will be critically discussed in this review.

• #2 Movement Disorders – Basal Ganglia

  https://uw.pressbooks.pub/wwamibasalganglia/chapter/pathways/

  Movement disorders are neurologic disorders that cause either an excess or a paucity of movement. These abnormal movements can occur at rest or with action, and can be involuntary or suppressible. […] The main feature of hypokinetic disorders is bradykinesia or slowness of movement. […] In general, many of the hypokinetic disorders have at its core principle reduced dopamine neurotransmission. […] Loss of dopamine (DA) from the substantia nigra effects both the direct and indirect pathways. In the direct pathway, loss of DA leads to decreased stimulation of the striatum, causing a decrease in the inhibition of the GPi. This decreased GPi stimulation then causes an increase in inhibition to the thalamus. Increased inhibition to the thalamus decreases activation of the cortical motor areas, leading to hypokinetic movements.

• #2 Hyperkinesia – Wikipedia

  https://en.wikipedia.org/wiki/Hyperkinesia

  Hyperkinesia refers to an increase in muscular activity that can result in excessive abnormal movements, excessive normal movements, or a combination of both. […] Many hyperkinetic movements are the result of improper regulation of the basal gangliathalamocortical circuitry. Overactivity of a direct pathway combined with decreased activity of indirect pathway results in activation of thalamic neurons and excitation of cortical neurons, resulting in increased motor output. […] The causes of the majority of the above hyperkinetic movements can be traced to improper modulation of the basal ganglia by the subthalamic nucleus. In many cases, the excitatory output of the subthalamic nucleus is reduced, leading to a reduced inhibitory outflow of the basal ganglia. Without the normal restraining influence of the basal ganglia, upper motor neurons of the circuit tend to become more readily activated by inappropriate signals, resulting in the characteristic abnormal movements.

• #2 Parkinson’s Disease: What It Is, Causes, Symptoms & Treatment

  https://my.clevelandclinic.org/health/diseases/8525-parkinsons-disease-an-overview

  Parkinsons disease is a condition where a part of your brain deteriorates, causing more severe symptoms over time. […] Parkinsons disease causes a specific area of your brain, the basal ganglia, to deteriorate. As this area deteriorates, you lose the abilities those areas once controlled. Researchers have uncovered that Parkinsons disease causes a major shift in your brain chemistry. […] When you have Parkinsons disease, you dont have enough dopamine, one of the most important neurotransmitters. […] Thats why lack of dopamine causes the slowed movements and tremors symptoms of Parkinsons disease. […] Experts believe idiopathic Parkinsons disease happens because of problems with how your body uses a protein called -synuclein (alpha sy-nu-clee-in). […] When some proteins dont have the correct shape a problem known as protein misfolding your body cant use them and cant break them down.

• #2 Movement Disorders – Basal Ganglia

  https://uw.pressbooks.pub/wwamibasalganglia/chapter/pathways/

  The loss of DA in the indirect pathway leads to a decrease inhibition in the striatum. This leads to an increased inhibition of the GPe, which then reduces inhibition of the STN. This increases STN stimulation of the GPi, which leads to increased inhibition of the thalamus. Decreased output of the thalamus leads to a decrease in cortical activation, and thus suppresses movement. […] The main pathophysiology is degeneration of medium spiny neurons in the striatum (GABAergic efferent projections). […] For chorea management, the goal is to reduce the presumed excess in the basal ganglia output. This is achieved by reducing dopamine transmission. […] Botulinum toxin prevents the release of acetylcholine at the neuromuscular junction preventing neuromuscular transmission. […] Zinc blocks copper uptake.

• #2 Chorea in Adults: Background, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/1149854-overview

  In Huntington chorea, the content of striatal dopamine is normal, indicating that the major pathological alterations lay in the surviving but diseased medium-sized, spiny, striatal dopaminergic neurons. Pharmacologic agents that either deplete dopamine (eg, reserpine and tetrabenazine) or block dopamine receptors (eg, neuroleptic medications) improve chorea, which gives further support to this observation. Given that drugs that decrease the striatal content of dopamine improve chorea, increasing the amount of dopamine worsens chorea, such as in the levodopa-induced chorea seen in persons with Parkinson disease. […] […] The concept that a critical striatal balance between acetylcholine (Ach) and dopamine is essential for normal striatal function received its greatest acceptance in the understanding of PD. In the early days of PD therapy, anticholinergic medications were used frequently, especially when tremor was the predominant symptom. Other PD symptoms, such as bradykinesia and rigidity, often improved as well. […]

• #2 Stages of Parkinson’s | Parkinson’s Foundation

  https://www.parkinson.org/understanding-parkinsons/what-is-parkinsons/stages

  Researchers believe a combination of genetic and environmental factors cause Parkinsons. In 2003, Heiko Braak, MD, hypothesized that an unknown pathogen (a bacteria, virus or other microorganism that causes disease) in the gut could be the cause of PD. […] This is now known as Braaks hypothesis. In this theory, the pathogen enters the body via the nose and/or gets swallowed and reaches the gut. The pathogenic products thus come into contact with the olfactory (smell) and/or enteric (gut) neurons, triggering the aggregation of an abnormal protein called -Synuclein. The aggregated -Synuclein (called Lewy body) then spreads toward the central nervous system (namely the brain), and eventually arriving in and causing the degeneration of the dopaminergic neurons in the area of the brain called the substantia nigra.

• #2 Promising Parkinson’s drug decoded

  https://medicalxpress.com/news/2025-05-parkinson-drug-decoded.html

  Impaired quality control of mitochondria plays a central role in Parkinson’s disease. […] The exact cause of nerve cell death remains unclear. However, there are indications that defects in their mitochondria could be responsible. Nerve cells in particular are highly dependent on these organelles, as they require high amounts of energy. […] An important enzyme in mitophagy is the deubiquitinase (DUB) USP30. It removes ubiquitin marks from defective mitochondria that are destined for degradation. […] Using innovative protein engineering, Gersch and his team have now been able to obtain a detailed picture of how an inhibitor binds to USP30 and specifically switches off its activity. […] Elucidating the mechanism of action of this potential Parkinson’s drug will not only help to further develop it, but also lay the foundation for designing new drug molecules against USP30. […] Mitophagy and enzymes from the DUB family also play an important role in other diseases and are associated with a weakened immune system and tumor growth.

• #2 Movement disorders – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/movement-disorders/symptoms-causes/syc-20363893

  Movement disorders are a group of nervous system conditions that affect movement. They can cause either increased movements or reduced or slow movements. These movements may be under the person’s control, known as voluntary. Or the movements may not be under the person’s control, known as involuntary. […] There are many types of movement disorders that cause different symptoms. For example, dystonia causes muscle contractions that lead to twisting of the body. Another movement disorder called chorea causes brief periods of quick involuntary movements that happen over and over. Parkinsonism causes slowness of movement with stiffness, tremors or loss of balance. […] A wide variety of factors can cause movement disorders, including: […] Some types of movement disorders can be caused by an altered gene. The altered gene is passed down from a parent to a child. This is called an inherited condition. Huntington’s disease and Wilson’s disease are two movement disorders that can be inherited.

• #2 Model systems for understanding dystonia pathogenesis

  https://www.movementdisorders.org/MDS/Scientific-Issues/posts/Model-systems-for-understanding-dystonia-pathogenesis.htm

  The phenotypic models have transformed our understanding of the anatomical underpinnings of dystonia. […] The phenotypic animal models provided strong evidence for our modern conceptualization of dystonia as a disorder of a broader motor network, where dystonia may sometimes arise from a defect in the basal ganglia, and other times the defect arises in the cerebellum or elsewhere. […] Despite the absence of overt dystonia, the genetic models have been instrumental in advancing our understanding of the molecular pathogenesis of numerous inherited forms of dystonia, such dopa-responsive dystonia and dystonia associated with the TOR1A and THAP1 genes. […] A relevant contribution to such idea came from genetics, which led to a significant growth in the number of genes associated with dystonia.

• #2 Model systems for understanding dystonia pathogenesis

  https://www.movementdisorders.org/MDS/Scientific-Issues/posts/Model-systems-for-understanding-dystonia-pathogenesis.htm

  These genes encode proteins with distinct biological functions including mitochondrial dysfunction, heavy metals accumulation, endoplasmic reticulum (ER) and nuclear envelope dysfunction, and lipid metabolism. […] Of interest, among the shared biological pathways are defects in dopamine signalling. […] Indeed, multiple mutations causing dystonia to converge, to affect dopamine signal transduction pathways, including GTPCH1, GNAL, and ADCY5, to name a few. […] Several lines of observations emphasize the centrality of a dysregulation of cholinergic transmission at the striatal level, particularly in DYT1 dystonia, with a hypercholinergic tone resulting in an aberrant striatal network activity. […] Elucidation of these and other shared pathways is relevant for understanding the biological basis of dystonia and for designing novel therapeutics that may have a broad potential for distinct types of dystonia.

• #2 Parkinson’s disease – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/parkinsons-disease/symptoms-causes/syc-20376055

  Parkinson’s disease is a movement disorder of the nervous system that worsens over time. The nervous system is a network of nerve cells that controls many parts of the body, including movement. […] In Parkinson’s disease, nerve cells in the brain called neurons slowly break down or die. Many Parkinson’s disease symptoms are caused by a loss of neurons that produce a chemical messenger in the brain. This messenger is called dopamine. […] Decreased dopamine leads to irregular brain activity. This causes movement problems and other symptoms of Parkinson’s disease. People with Parkinson’s disease also lose a chemical messenger called norepinephrine that controls many body functions, such as blood pressure. […] Many changes happen in the brains of people with Parkinson’s disease. Researchers are studying why the changes happen and the roles they play. These changes include:

• #2 Pathophysiology of the Basal Ganglia and Movement Disorders: Gaining New Insights from Modeling and Experimentation, to Influence the Clinic | Frontiers Research Topic

  https://www.frontiersin.org/research-topics/3875/pathophysiology-of-the-basal-ganglia-and-movement-disorders-gaining-new-insights-from-modeling-and-experimentation-to-influence-the-clinic/magazine

  In this context, the study of the pathophysiology of the basal ganglia and the treatment of their pathology is becoming increasingly interdisciplinary. Nowadays, an appropriate approach to the study of these problems must necessarily involve the use of complex mathematical modeling, computer simulations, basic research (ranging from biomolecular studies to animal experimentation), and clinical research. This research topic aims to bring together the most recent advances related to the pathophysiology of the basal ganglia and movement disorders. We welcome contributions that address any aspect of significance to the field, including but not restricted to: biomolecular aspects, Braak’s hypothesis, electrophysiology, animal models, new technologies and methods of analysis, mathematical modeling, computer simulations, computational theory, neural networks, clinical aspects, deep brain stimulation. We will also welcome papers that analyze various physiological signals (cortical activity, EMG, ECG), as they are related to different aspects of movement disorders (cognitive, autonomic, psychiatric and others). Papers that include an interdisciplinary approach and a discussion at multiple levels (i.e., the relation between experimental results, clinical data and modeling results) are encouraged. Works that describe an effort to translate basic research into clinical achievements will also be given special consideration.

• #3 Movement Disorders – Basal Ganglia

  https://uw.pressbooks.pub/wwamibasalganglia/chapter/pathways/

  The loss of DA in the indirect pathway leads to a decrease inhibition in the striatum. This leads to an increased inhibition of the GPe, which then reduces inhibition of the STN. This increases STN stimulation of the GPi, which leads to increased inhibition of the thalamus. Decreased output of the thalamus leads to a decrease in cortical activation, and thus suppresses movement. […] The main pathophysiology is degeneration of medium spiny neurons in the striatum (GABAergic efferent projections). […] For chorea management, the goal is to reduce the presumed excess in the basal ganglia output. This is achieved by reducing dopamine transmission. […] Botulinum toxin prevents the release of acetylcholine at the neuromuscular junction preventing neuromuscular transmission. […] Zinc blocks copper uptake.

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