BACKGROUND

Perampanel is an antagonist of the a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor. It is currently FDA-approved to treat focal and generalized tonic-clonic seizures in epilepsy, but recent evidence suggests its potential in treating severe and refractory tremors.

OBJECTIVES

To determine the safety and efficacy of perampanel in treating tremors via a systematic review of existing literature. 

METHODS

We performed a literature search on five large databases (PubMed, Cochrane, Google Scholar, HERDIN, and Scopus) for clinical studies within the last 10 years and screened a total of 1,539 unique articles for full assessment. We filtered out papers on epilepsy as well as hypokinetic diseases and assessed nine articles for quality assessment and review.

RESULTS

A total of four case reports/series, four open-label trials, and one randomized controlled trial were assessed to be of fair to good quality. All trials showed that low-dose perampanel (2-4 mg/day) was safe and well-tolerated with minor adverse events reported by participants. A net benefit from baseline was observed in patients with essential and primary orthostatic tremors. However, current evidence is weak because the trials employed a non-randomized before-after study design with a small sample size and significant dropout rates.

CONCLUSION

Low-dose perampanel at 2-4 mg/day shows promising potential in treating refractory tremors and myoclonus in recent clinical studies, but current evidence is weak or anecdotal. Additional randomized controlled trials are needed to determine the conclusive benefit of perampanel for hyperkinesia.

Human ; Perampanel ; Receptors, Ampa ; Dystonia ; Tremor ; Myoclonus ; Hyperkinesia ; Hyperkinesis

BACKGROUND

Perampanel is an antagonist of the a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor. It is currently FDA-approved to treat focal and generalized tonic-clonic seizures in epilepsy, but recent evidence suggests its potential in treating severe and refractory tremors.

OBJECTIVES

To determine the safety and efficacy of perampanel in treating tremors via a systematic review of existing literature. 

METHODS

We performed a literature search on five large databases (PubMed, Cochrane, Google Scholar, HERDIN, and Scopus) for clinical studies within the last 10 years and screened a total of 1,539 unique articles for full assessment. We filtered out papers on epilepsy as well as hypokinetic diseases and assessed nine articles for quality assessment and review.

RESULTS

A total of four case reports/series, four open-label trials, and one randomized controlled trial were assessed to be of fair to good quality. All trials showed that low-dose perampanel (2-4 mg/day) was safe and well-tolerated with minor adverse events reported by participants. A net benefit from baseline was observed in patients with essential and primary orthostatic tremors. However, current evidence is weak because the trials employed a non-randomized before-after study design with a small sample size and significant dropout rates.

CONCLUSION

Low-dose perampanel at 2-4 mg/day shows promising potential in treating refractory tremors and myoclonus in recent clinical studies, but current evidence is weak or anecdotal. Additional randomized controlled trials are needed to determine the conclusive benefit of perampanel for hyperkinesia.

Human ; Perampanel ; Receptors, Ampa ; Dystonia ; Tremor ; Myoclonus ; Hyperkinesia ; Hyperkinesis

Mechanistic target of rapamycin (mTOR) signaling governs important physiological and pathological processes key to cellular life. Loss of mTOR negative regulators and subsequent over-activation of mTOR signaling are major causes underlying epileptic encephalopathy. Our previous studies showed that UBTOR/KIAA1024/MINAR1 acts as a negative regulator of mTOR signaling, but whether UBTOR plays a role in neurological diseases remains largely unknown. We therefore examined a zebrafish model and found that ubtor disruption caused increased spontaneous embryonic movement and neuronal activity in spinal interneurons, as well as the expected hyperactivation of mTOR signaling in early zebrafish embryos. In addition, mutant ubtor larvae showed increased sensitivity to the convulsant pentylenetetrazol, and both the motor activity and the neuronal activity were up-regulated. These phenotypic abnormalities in zebrafish embryos and larvae were rescued by treatment with the mTORC1 inhibitor rapamycin. Taken together, our findings show that ubtor regulates motor hyperactivity and epilepsy-like behaviors by elevating neuronal activity and activating mTOR signaling.
Animals ; Hyperkinesis/genetics* ; Mutation/genetics* ; Signal Transduction ; TOR Serine-Threonine Kinases/metabolism* ; Zebrafish/metabolism*

Hyperglycemia-induced hemichorea (HGHC) is a rare but characteristic hyperkinetic movement disorder involving limbs on one side of the body. In a 75-year-old woman with a left-sided HGHC, conventional brain MR imaging showed very subtle T1-hyperintensity and unique gadolinium enhancement in the basal ganglia contralateral to movements. Multi-parametric MRI was acquired using pulse sequence with quantification of relaxation times and proton density by multi-echo acquisition. Myelin map was reconstructed based on new tissue classification modeling. In this case report of multi-parametric MRI, quantitative measurement of myelin change related to HGHC in brain structures and its possible explanations are presented. This is the first study to demonstrate myelin loss related to hyperglycemic insult in multi-parametric quantitative MR imaging.
Aged ; Basal Ganglia ; Brain ; Classification ; Extremities ; Female ; Gadolinium ; Humans ; Hyperglycemia ; Hyperkinesis ; Magnetic Resonance Imaging ; Movement Disorders ; Myelin Sheath ; Protons ; Relaxation

Abnormal eye movements are commonly observed in movement disorders. Ocular motility examination should include bedside evaluation and laboratory recording of ocular misalignment, involuntary eye movements, including nystagmus and saccadic intrusions/oscillations, triggered nystagmus, saccades, smooth pursuit (SP), and the vestibulo-ocular reflex. Patients with Parkinson's disease (PD) mostly show hypometric saccades, especially for the self-paced saccades, and impaired SP. Early vertical saccadic palsy is characteristic of progressive supranuclear palsy-Richardson's syndrome. Patients with cortico-basal syndrome typically show a delayed onset of saccades. Downbeat and gaze-evoked nystagmus and hypermetric saccades are characteristic ocular motor findings in ataxic disorders due to cerebellar dysfunction. In this review, we discuss various ocular motor findings in movement disorders, including PD and related disorders, ataxic syndromes, and hyperkinetic movement disorders. Systemic evaluation of the ocular motor functions may provide valuable information for early detection and monitoring of movement disorders, despite an overlap in the abnormal eye movements among different movement disorders.
Ataxia ; Cerebellar Diseases ; Eye Movements ; Humans ; Hyperkinesis ; Movement Disorders ; Paralysis ; Parkinson Disease ; Parkinsonian Disorders ; Pursuit, Smooth ; Reflex, Vestibulo-Ocular ; Saccades

Takotsubo cardiomyopathy (TC) is a transient form of acute heart failure that most often occurs in postmenopausal women, typically triggered by a preceding emotional or physical stressor. A 74-year-old woman who suffered from chronic psychiatric stress visited National Medical Center for dyspnea. Acute emotional or physical stress could not be identified despite careful history taking. An electrocardiogram showed diffuse T-wave inversions with prolonged QT interval, and the echocardiogram showed akinesia of mid and apical segments of the left ventricle with hyperkinesia at the base. There was no significant stenosis on coronary angiography. Differing from the typical case of TC, which follows acute stress triggers, our case indicates that underlying chronic psychiatric illness exacerbation can lead to TC. We suggest that cardiologists and psychiatrists be aware of this predisposition to TC, especially in the circumstances of acute heart failure.
Aged* ; Cardiomyopathies ; Constriction, Pathologic ; Coronary Angiography ; Depressive Disorder, Major* ; Dyspnea ; Electrocardiography ; Female ; Heart Failure ; Heart Ventricles ; Humans ; Hyperkinesis ; Psychiatry ; Takotsubo Cardiomyopathy*

Stress cardiomyopathy (SCMP) is characterized by a transient left ventricular dysfunction associated with apical ballooning and compensatory hyperkinesias of the basal segments after emotional or physical stress, but inverted or mid-ventricular variants of SCMP have also been described. Although catecholamine excess has been suggested as a possible pathophysiologic mechanism of SCMP, the etiology of SCMP is still unknown. Here, we report a case of inverted type of SCMP with clinical presentation mimicking acute coronary syndromes. The cause or precipitating stressor was unclear initially, but pheochromocytoma has been demonstrated as a cause of SCMP during clinical follow-up at out-patient clinic in the present case. Catecholamine-producing tumors should be included in the evaluation or management of SCMP, even though initial clinical manifestations are not suggestive for pheochromocytoma.
Acute Coronary Syndrome ; Cardiomyopathies ; Follow-Up Studies ; Humans ; Hyperkinesis ; Outpatients ; Pheochromocytoma* ; Takotsubo Cardiomyopathy* ; Ventricular Dysfunction, Left

OBJECTIVETo investigate the method and mechanism for exercise-related immunosuppression via the inhibitor of NADPH oxidase diphenyleneiodonium(DPI) and glutamine supplementation and on the function of neutrophils after overtraining.

METHODSFifty male Wistar rats were randomly divided into five groups: a negative control group (C), an overtraining group (E), an overtraining + DPI intervention group (D), an overtraining+ glutamine supplementation group(G) and combined glutamine + DPI intervention group(DG). After 36 - 40 h from the last training, eight rats were randomly selected from each group, and blood was sampled from the orbital vein. ELISAs were used to measure serum cytokine levels and lipid peroxidation in blood plasma. Flow cytometry was used to measure neutrophil respiratory burst and phagocytosis. The activity of NADPH oxidase was assessed by chemiluminescence and the gene expression of gp91(phox) and p47(phox) of the NADPH-oxidase subunit was checked by Western blot.

RESULTSCompared with group C, the plasma concentrations of NO increased in group G, and the NO, cytokine-induced neutrophil chemoattractant (CINC) concentrations in group DG increased significantly. The respiratory burst and phagocytosis function of neutrophils were decreased in group E, but in group DG were increased when compared with those of group E. After overtraining the expression of gp91(phox) and p47(phox) was up regulated in group E. There were no significant changes in other groups except group DG, in which the expression of gp91(phox) was down regulated. Compared with group E, the expression of gp91(phox) and p47(phox) was up regulated in group D, group G and group DG.

CONCLUSIONThe activation of NADPH oxidase is responsible for the production of superoxide anions, which may be related to the decrease in neutrophil function after over training and is the mechanism of exercise-related immunosuppression. The DPI treatment combined glutamine supplementation can reverse the decrease neutrophils function after overtraining in vitro.

Animals ; Dietary Supplements ; Glutamine ; pharmacology ; Hyperkinesis ; physiopathology ; Male ; Membrane Glycoproteins ; metabolism ; NADPH Oxidase 2 ; NADPH Oxidases ; antagonists & inhibitors ; metabolism ; Neutrophils ; metabolism ; physiology ; Onium Compounds ; pharmacology ; Oxidation-Reduction ; Rats ; Rats, Wistar ; Respiratory Burst ; physiology

Fluvoxamine is a selective serotonin reuptake inhibitor that is approved for psychiatric disorders such as major depressive episodes and obsessive-compulsive disorder. Beside inhibition of serotonin reuptake, fluvoxamine is also a potent agonist of endoplasmic reticulum (ER) protein sigma-1 receptors, which play a role in the pathophysiology of a number of psychiatric and neurodegenerative disorders. This report presents beneficial effects of sigma-1 agonist fluvoxamine on hyperkinetic movement disorders such as tardive dyskinesia and tardive akathisia. Fluvoxamine might be a novel treatmet approach in the treatment of hyperkinetic movement disorders.
Akathisia, Drug-Induced* ; Dyskinesias ; Endoplasmic Reticulum ; Fluvoxamine* ; Humans ; Hyperkinesis ; Movement Disorders* ; Neurodegenerative Diseases ; Obsessive-Compulsive Disorder ; Psychomotor Agitation ; Receptors, sigma ; Schizophrenia* ; Serotonin

Tardive dyskinesia (TD) is a hyperkinetic movement disorder associated with the prolonged use of antipsychotic drugs. Since prostate apoptosis response 4 (Par-4) is a key ligand of the dopamine D2 receptor, the Par-4 gene (PAWR) is a good candidate gene to study in the context of TD susceptibility. We examined the association between PAWR gene polymorphisms and TD. Three single nucleotide polymorphisms of PAWR were selected for the analysis: rs7979987, rs4842318, and rs17005769. Two hundred and eighty unrelated Korean schizophrenic patients participated in this study (105 TD and 175 non-TD patients). Genotype/allele-wise and haplotype-wise analyses were performed. There were no significant differences in genotype and allele frequencies between the two groups. Haplotype analysis also did not reveal a difference between the two groups. Within the limitations imposed by the size of the clinical sample, these findings suggest that PAWR gene variants do not significantly contribute to an increased risk of TD.
Antipsychotic Agents ; Apoptosis ; Gene Frequency ; Genotype ; Haplotypes ; Humans ; Hyperkinesis ; Movement Disorders ; Polymorphism, Single Nucleotide ; Prostate ; Receptors, Dopamine D2 ; Schizophrenia