Abnormal Motor Movements Research Articles

Alzheimer’s disease and Parkinson’s disease dementia: Practical tips for physicians

Dementia is a progressive disorder that weakens the intellectual abilities and causes the cognitive, behavioral, and functional decline in occupational and social areas. This research is targeted to extract a profile for the dementia diagnostic and clinical characteristics by evaluating the near-term effects of Alzheimer’s disease (AD) and Parkinson’s disease dementia (PD-D). A total of 240 individuals, including 60 AD patients, 60 PD-D patients, and 120 healthy controls, were included in the study. Data of individuals treated in a local dementia outpatient clinic between 2013 and 2023 were obtained from the clinic database. AD and PD-D diagnoses were made based on the revised National Institute on Aging and Alzheimer’s Association (NIA-AA) criteria and movement disorder society (MDS) clinical diagnostic criteria, respectively. Functional, clinical, and neuropsychological evaluations of the patients were made by the same neurologist. Dementia staging and daily living activities were determined and categorized. In the patient group, functionality and instrumental activities of daily living (ADLs) scores were significantly worse than those of the control group, but there was no difference between the AD and PD-D groups. Calculation, verbal fluency, word list, early learning, and clock drawing test scores were lower in the AD group than in the PD-D group. Apathy, disinhibition, elution, irritability, abnormal motor movements, sleep, and appetite scores were significantly higher in the patient group than in the control group. While depression parameters were not significantly different between all the groups, hallucinations and anxiety parameters were significantly higher in the PD-D group than in the AD group. As an important predictor of independent living and the burden of disease, functional impairment is an important issue in patients with AD compared to those with PD-D. This study also highlights the neuropsychiatric perception disorder in terms of functional loss in AD and significant anxiety disorder for PD-D accompanied by early functional losses.

Microplastic Exposure and the of Parkinson’s Disease

Microplastics (MPs) are small particles or fragments of plastic that have leaked into the environment and ecosystems in recent decades. Numerous animal studies have suggested that an organism’s exposure to microplastics may evoke responses from the body that are similar to the pathogenesis of human diseases. In particular, a collection of evidence has suggested that microplastics exposure may mimic Parkinson’s disease pathology (decreased dopaminergic neurons and interrupted motor function). Parkinson’s disease is an often progressive and fatal neurodegenerative disease that is defined by the degeneration of dopaminergic neurons in the brain; this degeneration leads to decreased motor function and abnormal motor movements. Studies have indicated that, upon entering the body, microplastics may trigger oxidative stress, organ inflammation, neurotoxicity, and transgenerational effects. Parkinson’s disease diagnoses are predicted to greatly increase in upcoming generations while microplastics continue to enter the environment at growing rates, inciting a point of concern for the human population and other organisms. In this review, the possible effects of organisms’ exposure to microplastics are explored through the review of animal studies and the comparison of these findings to the pathogenesis of Parkinson’s disease. By understanding the ways in which MPs affect the body and contribute to PD and other neurodegenerative disorders, the danger that MPs pose toward living organisms can be recognized, necessitate further research, and encourage preventative measures against the leakage of MPs into the environment.

Systemic treatment with the enteric bacterial metabolic product propionic acid results in reduction of social behavior in juvenile rats: Contribution to a rodent model of autism spectrum disorder.

The role of the gut microbiome and its enteric metabolites, such as short-chain fatty acids (SCFAs), in the etiology of autism spectrum disorders (ASDs) has recently received increased attention. Of particular interest has been the SCFA, propionic acid (PPA). Several different rodent models have been developed using PPA treatment to examine behaviors of relevance to ASD. The effects of systemic (intraperitoneal, i.p.) administration of PPA on social behavior, anxiety-related behavior, and locomotor activity in juvenile male rats (age 35days) were examined in this study. Rats received seven i.p. injections of buffered PPA (500mg/kg) or phosphate-buffered saline. Behavior was video-recorded during social interaction in a large open field (first four injections) or assessed in an automated activity system (individual animals, last three injections). PPA treatment significantly reduced social interaction, increased anxiety-related behavior, and produced hypoactivity and increased abnormal motor movements. These findings suggest that PPA alters behaviors of relevance to ASD in juvenile rats. These results contribute to the behavioral validity of the rodent model of ASD with systemic PPA treatment.

Striatal GABAergic interneuron dysfunction in the Q175 mouse model of Huntington's disease.

The pathological hallmark of Huntington's disease (HD) is the massive loss of striatal and cortical neurons. Until recently, it was believed that striatal interneurons were spared from degeneration. This view has changed after the demonstration that parvalbumin (PV)-expressing interneurons also are vulnerable in humans. Here we compared morphological and functional changes of striatal fast-spiking interneurons (FSIs) and low-threshold spiking (LTS) interneurons in the Q175 mouse model of HD at presymptomatic (2months) and symptomatic (12months) stages of the disease. Electrophysiological intrinsic and synaptic properties of FSIs were significantly altered in symptomatic mice compared to wild-type (WT) littermates. Overall, FSIs became more excitable with disease progression. Sholl analysis also revealed a significant loss of dendritic complexity and excitatory synaptic inputs. The basic membrane and synaptic properties of LTS interneurons were similar in Q175 and WT mice regardless of disease stage. The resilience of LTS interneurons could be related to their sparsity of excitatory synaptic inputs compared with FSIs. However, in symptomatic mice, a subpopulation of LTS interneurons displayed an increase in action potential firing within oscillating bursts. Thus, we conclude that while both FSI and LTS interneurons demonstrate increases in excitability, the HD mutation differentially affects their membrane and synaptic properties as well as their ability to respond to compensatory challenges presented during the late stage of the disease. Alterations in GABAergic interneuron intrinsic activity and responsiveness to incoming signals may significantly affect SPN output thus contributing to abnormal motor movements in patients afflicted with HD.

The association between tranexamic acid and convulsive seizures after cardiac surgery: a multivariate analysis in 11 529 patients

Because of a lack of contemporary data regarding seizures after cardiac surgery, we undertook a retrospective analysis of prospectively collected data from 11 529 patients in whom cardiopulmonary bypass was used from January 2004 to December 2010. A convulsive seizure was defined as a transient episode of disturbed brain function characterised by abnormal involuntary motor movements. Multivariate regression analysis was performed to identify independent predictors of postoperative seizures. A total of 100 (0.9%) patients developed postoperative convulsive seizures. Generalised and focal seizures were identified in 68 and 32 patients, respectively. The median (IQR [range]) time after surgery when the seizure occurred was 7 (6-12 [1-216]) h and 8 (6-11 [4-18]) h, respectively. Epileptiform findings on electroencephalography were seen in 19 patients. Independent predictors of postoperative seizures included age, female sex, redo cardiac surgery, calcification of ascending aorta, congestive heart failure, deep hypothermic circulatory arrest, duration of aortic cross-clamp and tranexamic acid. When tested in a multivariate regression analysis, tranexamic acid was a strong independent predictor of seizures (OR 14.3, 95% CI 5.5-36.7; p < 0.001). Patients with convulsive seizures had 2.5 times higher in-hospital mortality rates and twice the length of hospital stay compared with patients without convulsive seizures. Mean (IQR [range]) length of stay in the intensive care unit was 115 (49-228 [32-481]) h in patients with convulsive seizures compared with 26 (22-69 [14-1080]) h in patients without seizures (p < 0.001). Convulsive seizures are a serious postoperative complication after cardiac surgery. As tranexamic acid is the only modifiable factor, its administration, particularly in doses exceeding 80 mg.kg(-1), should be weighed against the risk of postoperative seizures.

Short-chain fatty acid fermentation products of the gut microbiome: implications in autism spectrum disorders

Recent evidence suggests potential, but unproven, links between dietary, metabolic, infective, and gastrointestinal factors and the behavioral exacerbations and remissions of autism spectrum disorders (ASDs). Propionic acid (PPA) and its related short-chain fatty acids (SCFAs) are fermentation products of ASD-associated bacteria (Clostridia, Bacteriodetes, Desulfovibrio). SCFAs represent a group of compounds derived from the host microbiome that are plausibly linked to ASDs and can induce widespread effects on gut, brain, and behavior. Intraventricular administration of PPA and SCFAs in rats induces abnormal motor movements, repetitive interests, electrographic changes, cognitive deficits, perseveration, and impaired social interactions. The brain tissue of PPA-treated rats shows a number of ASD-linked neurochemical changes, including innate neuroinflammation, increased oxidative stress, glutathione depletion, and altered phospholipid/acylcarnitine profiles. These directly or indirectly contribute to acquired mitochondrial dysfunction via impairment in carnitine-dependent pathways, consistent with findings in patients with ASDs. Of note, common antibiotics may impair carnitine-dependent processes by altering gut flora favoring PPA-producing bacteria and by directly inhibiting carnitine transport across the gut. Human populations that are partial metabolizers of PPA are more common than previously thought. PPA has further bioactive effects on neurotransmitter systems, intracellular acidification/calcium release, fatty acid metabolism, gap junction gating, immune function, and alteration of gene expression that warrant further exploration. These findings are consistent with the symptoms and proposed underlying mechanisms of ASDs and support the use of PPA infusions in rats as a valid animal model of the condition. Collectively, this offers further support that gut-derived factors, such as dietary or enteric bacterially produced SCFAs, may be plausible environmental agents that can trigger ASDs or ASD-related behaviors and deserve further exploration in basic science, agriculture, and clinical medicine.

Clinical variability in early speech-language development in females with Rett syndrome

For clinicians treating children with developmental disorders, the paper by Marschik et al. has significant relevance.1 The study reported on pre-regression verbal development with a preserved speech variant and underscores what has been suspected regarding females with Rett syndrome. Those with preserved speech showed atypical development of vocalizations and communication as infants and young children, which contradicts the idea of ‘normal early development’. It is logical that mutations of the MECP-2 gene, which is expressed in the brain at different developmental periods, result in emerging abnormalities of speech and language development. Hence it is not surprising to find the subtle abnormalities of vocalizations and oral motor function, along with poor control of respiratory rhythm, that have been teased out diligently with hours of observations of videos provided by families. It would be useful for clinicians to request infant videos of the children in their care, so as to obtain added information on not only their communicative development but their gross movements2 which would add further to our understanding of their early abnormalities. Marschik et al. emphasize the early abnormalities in pre-linguistic communicative behaviours (intermittent and rapidly alternating character of expected and unexpected behaviours) and propose using this finding as a diagnostic marker. Perhaps it would be informative to focus on the poor oral motor control and involuntary movements affecting the orofacial muscles, which are more likely to be recognized. This may provide an opportunity to discuss with the family the lack of development of mature patterns of chewing and feeding, and how these movements affect speech articulation. The brief discussion regarding poor control of respiratory rhythm appears to be a crucial early finding which may alert the clinician to consider the diagnosis of Rett syndrome. It is true that infants and young children with Rett syndrome often remain undiagnosed. Marschik et al. suggest using subtle atypical vocalizations and behaviours as a diagnostic marker, but this recommendation places the clinicians on shaky ground. One is cognizant of the fact that raising the possibility of a serious neurological disorder with the family on clinically nebulous evidence is a difficult task for any clinician, who may then consider deferring the diagnosis until clinical findings are more obvious. Although a limited number of clinicians worldwide have experience in evaluating and following children with Rett syndrome, it is timely that we identify the specific types of dysfunctions. Einspieler et al.2 described abnormal general movements in females with Rett syndrome in the first 4 months and Marschik et al.’s earlier description of one female3,4 have obviously provided a foundation for more detailed study of abnormal motor movements. Although this study2 includes a very small sample of children with preserved speech who had Rett syndrome, it is commendable that the authors were able to access and study videos from six females ages 6–24 months. The six participants studied all had different mutations. These results are consistent with published data on the genotype-phenotype.5–8 Finally, as a challenge to clinicians, it would be important to document whether we can identify early abnormal oral motor dysfunction in children and how one would differentiate an oral motor disorder due to cerebral palsy versus Rett syndrome. I believe that the answer lies in the poor control of respiratory rhythm affecting abnormal inspiratory vocalizations.

Neuroinflammation in Huntington’s disease

Huntington's disease (HD) is a monogenic neurodegenerative disease characterized by abnormal motor movements, personality changes and early death. In contrast to other neurodegenerative diseases, very little is known about the role of neuroinflammation in HD. While the current data clearly demonstrate the existence of inflammatory processes in HD pathophysiology, the question of whether neuroinflammation is purely reactive or might actively participate in disease pathogenesis is currently a matter of ongoing research and debate. This review will try to shed some light on the current state of research in this area and provide an outlook on potential future developments.

Chronic bilirubin encephalopathy: diagnosis and outcome

Chronic bilirubin encephalopathy (kernicterus) can be diagnosed using semi-objective criteria based on history, physical and neurological examination and laboratory findings including auditory brainstem responses and magnetic resonance imaging. Classical kernicterus is a well-described clinical tetrad of (i) abnormal motor control, movements and muscle tone, (ii) an auditory processing disturbance with or without hearing loss, (iii) oculomotor impairments, especially impairment of upward vertical gaze, and (iv) dysplasia of the enamel of deciduous teeth. Subtle kernicterus or bilirubin-induced neurologic dysfunction (BIND) refers to individuals with subtle neurodevelopmental disabilities without classical findings of kernicterus that, after careful evaluation and consideration, appear to be due to bilirubin neurotoxicity. Kernicterus can be further classified as auditory predominant or motor predominant and characterized based on the severity of clinical sequelae. Proposed research definitions for kernicterus diagnosis in infants from 3 to 18 months are reviewed, as are treatments of auditory and motor deficits and other complications of bilirubin encephalopathy.

Justinus Kerners wagemutige Experimente mit Botulinumtoxin

The 19th century German romantic poet and medical officer Justinus Kerner (1786-1862) provided the first detailed clinical description of botulism and its associations with faulty sausage production. He collected data on 230 cases of botulism and published 2 important monographs in 1820 and 1822. Kerner gave a remarkably complete and accurate description of clinical botulism: its symptoms, time course, and physical findings - 70 years before this was identified as being caused by anaerobic microbes. He drank an extract of the faulty sausage poison to study the symptoms in a very dangerous self-experiment. Thereby he could describe that it was sour and could produce early stages of the „sausage poisoning”. Treating this disease he described the use of a gastric tube, 50 years before such experiments were recorded officially. Beyond of that he applied an extracorporal „pacemaker” - 100 years before this was introduced into clinical medicine. Finally, Kerner suggested the potential therapeutic use of botulinum toxin to block abnormal motor movements, such as chorea, and speculated on its use in other disorders such as hypersecretion, for example. His first description of „botulismus” is a highlight and up to now an example of pure natural science and shows that he was an excellent clinician, too.

Mood and Behavioral Dysfunction With Opsoclonus-Myoclonus Ataxia

Opsoclonus-myoclonus ataxia syndrome is a paraneoplastic syndrome of cerebellar damage associated with neuroblastoma. The authors assessed psychiatric symptoms of opsoclonus-myoclonus ataxia syndrome in 17 children, who were 16 months to 12(1/2) years of age. Psychiatric symptoms examined included disruptive behavior, affective dysregulation, irritability, impulsivity, cognitive impairment, and poor attention.

A primate model of Huntington's disease: functional neural transplantation and CT-guided stereotactic procedures.

In this article, we show that 1) computed tomographic (CT)-guided stereotactic infusion of an excitotoxin into the striatum of a nonhuman primate provides a useful neuropathologic and behavioral model for Huntington's disease. 2) High-resolution positron emission tomography (PET) can be used to image the decreased glucose utilization and the preservation of dopaminergic terminals in the lesioned striatum by using 2-fluoro-deoxy-D-glucose (2FDG) and N-(C-11)-methyl-2-beta-carbomethoxy-3-beta-phenyl tropane (CPT) as tracers. 3) Transplantation of cross-species striatal fetal tissue into the lesioned caudate-putamen reduces many of the abnormal motor movements and behavioral changes seen in the Huntington's disease primate model. 4) Graft rejection results in the return of the abnormal signs of the pregrafted state. These results indicate that treatment of the neuronal deficit in Huntington's disease can involve intervention at the local neuronal circuit level. CT-guided stereotactic implantation of cells that might protect or replace this defective circuitry may eventually provide an effective treatment for Huntington's disease.

Regional, reversible ultrastructural changes in rat brain with chronic neuroleptic treatment

Administration of the dopamine receptor antagonist (neuroleptic, antipsychotic), haloperidol, resulting in an increase in the number of dopamine binding sites in the striatum and nucleus accumbens, has been well established. These increases disappear following withdrawal of treatment. Ultrastructurally, we found an increase in the number of synapses containing perforated postsynaptic densities (PSDs) following haloperidol administration within the caudate nucleus but not within the nucleus accumbens. The effect in the caudate reversed following cessation of treatment. We speculate that the terminals undergoing the change are not dopaminergic but may originate from the cerebral cortex. This reversible morphological increase associated with dopamine antagonist drug therapy may be reflective of the tolerance developed to neuroleptic drug-induced extrapyramidal syndromes and/or may be associated with abnormal motor movements of tardive dyskinesia that occur following long-term treatment.

Clozapine, Chlorpromazine, and Placebo in Newly Hospitalized, Acutely Schizophrenic Patients

Clozapine is a unique compound belonging to a relatively new group of antipsychotic agents, the dibenzazepines. To our knowledge, the present study represents the first double-blind, controlled comparison recorded in the United States. The data suggest that clozapine in the present population of newly admitted, acutely psychotic schizophrenic individuals, and in the doses employed, was more effective in overall improvement response, discharge rate, and ameliorating discrete symptoms across the different objective rating scales used than was chlorpromazine (Thorazine) hydrochloride. Placebo was ineffective. Unlike chlorpromazine, no extrapyramidal reactions occurred in those patients ingesting clozapine. Clozapine was also beneficial in reversing abnormal involuntary motor movements. It is an excellent anxiolytic and hypnotic agent. Sedation, hypotension, and hypersalivation are among the more common side effects observed.

Alterations in dopaminergic receptors in Huntington's disease

To detect variations in dopaminergic receptors and cholinergic activity in regions of postmortem Huntington's diseased brains, 3H-spiroperidol binding assays and choline acetyltransferase (ChAc) activities were carried out. A significant reduction in 3H-spiroperidol binding in the caudate nucleus, putamen and frontal cortex of choreic brains was detected which appeared to be due to a decrease in the total number of binding sites rather than to a decrease in affinity of 3H-spiroperidol for the dopaminergic receptor. In choreic brains, there were also significant reductions in ChAc activity in the caudate nucleus and putamen. The decreases of both 3H-spiroperidol binding and ChAc activity in the neostriatum suggest that the dopaminergic receptors are localized postsynaptically on cholinergic interneurons. Dopaminergic receptor alterations in the basal ganglia may be one of the causes of the abnormal motor movements found in HD while alterations of these receptors in the frontal cortex may be associated with the neuronal degeneration found in that area of choreic brains.

Changes in dopamine agonist and antagonist activity following temporary inactivation of the neostraitum.

Changes in drug-induced catalepsy and stereotyped behaviour were investigated in the rat following the intrastriatal application of 1 μl 25% w/v KCl which was shown to reduce striatal electrical activity. The unilateral or bilateral application of KCl to normal animals caused contralateral circling or stereotyped biting and gnawing respectively. These effects were differentiated from injection artifact. The cataleptic actions of haloperidol, fluphenazine, loxapine, oxypertine or metaclopramide were modified biphasically by bilateral intrastriatal KCl: catalepsy was initially reversed and stereotypy developed but, subsequently, catalepsy was intensified. Unilateral injections of KCl also reversed catalepsy and marked contralateral circling activity developed. These actions of intrastriatal KCl, both in normal and cataleptic animals, were abolished by lesions of the substantia nigra. RS 86 catalepsy was potentiated both by uni-and bilateral intrastriatal injections of KCl whilst similar injections failed to modify the depressant effects of IB 503, chloral hydrate, diazepam, clozapine or a combination of reserpine/α-methyl-ptyrosine. Morphine catalepsy was modified by intrastriatal KCl more in the manner of the stereotypic agents (D-and L-amphetamine, apomorphine, methylphenidate, ET 495), this being the production of ipsilateral circling following unilateral KCl or the induction of a state of immobility following bilateral injections (concomitant with antagonism of stereotypy or enhancement of morphine catalepsy). The mild stereotypic and tremorogenic activities of amantadine and NBT I were unmodified by intrastriatal KCl. Similarly, bilateral KCl failed to modify the abnormal motor movements observed after an L-Dopa/nialamide pretreatment, although a contralateral asymmetry was recorded following unilateral injections. The actions of intrastriatal KCl upon D-amphetamine stereotypy were mimicked by the cortical application of KCl at times prior to passage of the ‘spreading depression’ to the striatal area. However, at similar times, the effects of intrastriatal KCl on normal animal behaviour or upon haloperidol catalepsy were not reproduced by KCl applied to the cortex.

Abnormal motor movements during divinyl ether anesthesia.

Abnormal motor movements during divinyl ether anesthesia.