Reversible encephalitis-like episodes in fragile X-associated tremor/ataxia syndrome: a case report.

BACKGROUND: Fragile X-associated tremor/ataxia syndrome (FXTAS) is a neurodegenerative disorder caused by CGG repeat expansion of FMR1 gene. Both FXTAS and neuronal intranuclear inclusion disease (NIID) belong to polyglycine diseases and present similar clinical, radiological, and pathological features, making it difficult to distinguish these diseases. Reversible encephalitis-like attacks are often observed in NIID. It is unclear whether they are presented in FXTAS and can be used for differential diagnosis of NIID and FXTAS. CASE PRESENTATION: A 63-year-old Chinese male with late-onset gait disturbance, cognitive decline, and reversible attacks of fever, consciousness impairment, dizziness, vomiting, and urinary incontinence underwent neurological assessment and examinations, including laboratory tests, electroencephalogram test, imaging, skin biopsy, and genetic test. Brain MRI showed T2 hyperintensities in middle cerebellar peduncle and cerebrum, in addition to cerebellar atrophy and DWI hyperintensities along the corticomedullary junction. Lesions in the brainstem were observed. Skin biopsy showed p62-positive intranuclear inclusions. The possibilities of hypoglycemia, lactic acidosis, epileptic seizures, and cerebrovascular attacks were excluded. Genetic analysis revealed CGG repeat expansion in FMR1 gene, and the number of repeats was 111. The patient was finally diagnosed as FXTAS. He received supportive treatment as well as symptomatic treatment during hospitalization. His encephalitic symptoms were completely relieved within one week. CONCLUSIONS: This is a detailed report of a case of FXTAS with reversible encephalitis-like episodes. This report provides new information for the possible and rare features of FXTAS, highlighting that encephalitis-like episodes are common in polyglycine diseases and unable to be used for differential diagnosis.

Evaluation and Management of Tremor.

Tremor is a commonly encountered condition in the primary care setting and can manifest at rest, with action, or both. Common causes include Parkinson disease, essential tremor, and drug-induced tremor. In this article, the authors discuss how to examine a patient with tremor and which features of the history and examination can help clue the provider in to the appropriate diagnosis. They also review treatments for varying types of tremor and when referral to a neurologist may be necessary.

Impact of Switching From Immediate- or Prolonged-Release to Once-Daily Extended-Release Tacrolimus (LCPT) on Tremor in Stable Kidney Transplant Recipients: The Observational ELIT Study.

Once-daily extended-release tacrolimus (LCPT) exhibits increased bioavailability versus immediate-release (IR-TAC) and prolonged release (PR-TAC) tacrolimus. Improvements in tremor were previously reported in a limited number of kidney transplant patients who switched to LCPT. We conducted a non-interventional, non-randomized, uncontrolled, longitudinal, prospective, multicenter study to assess the impact of switching to LCPT on tremor and quality of life (QoL) in a larger population of stable kidney transplant patients. The primary endpoint was change in The Essential Tremor Rating Assessment Scale (TETRAS) score; secondary endpoints included 12-item Short Form Survey (SF-12) scores, tacrolimus trough concentrations, neurologic symptoms, and safety assessments. Subgroup analyses were conducted to assess change in TETRAS score and tacrolimus trough concentration/dose (C0/D) ratio by prior tacrolimus formulation and tacrolimus metabolizer status. Among 221 patients, the mean decrease of TETRAS score after switch to LCPT was statistically significant (p < 0.0001 vs. baseline). There was no statistically significant difference in change in TETRAS score after switch to LCPT between patients who had received IR-TAC and those who had received PR-TAC before switch, or between fast and slow metabolizers of tacrolimus. The overall increase of C0/D ratio post-switch to LCPT was statistically significant (p < 0.0001) and from baseline to either M1 or M3 (both p < 0.0001) in the mITT population and in all subgroups. In the fast metabolizers group, the C0/D ratio crossed over the threshold of 1.05 ng/mL/mg after the switch to LCPT. Other neurologic symptoms tended to improve, and the SF-12 mental component summary score improved significantly. No new safety concerns were evident. In this observational study, all patients had a significant improvement of tremor, QoL and C0/D ratio post-switch to LCPT irrespective of the previous tacrolimus formulation administered (IR-TAC or PR-TAC) and irrespective from their metabolism status (fast or slow metabolizers).

A Novel KCNQ2 Variant in a Patient with a Combined Tremor Syndrome.

Background: Tremor disorders have various genetic causes. Case report: A 60-year-old female with a family history of tremor presented a combined tremor syndrome, transient episodes of loss of contact and speech disturbances, as well as distal painful symptoms. Genetic screening revealed a novel heterozygous missense variant in the KCNQ2 gene. Discussion: The KCNQ2 protein regulates action potential firing, and mutations in its gene are associated with epilepsy and neuropathic pain. The identified variant, although of uncertain significance, may disrupt KCNQ2 function and also play a role in tremor pathogenesis. This case highlights the importance of genetic screening in combined tremor disorders.

Clinical characteristics of patients with migraine accompanied by tremor. / åå¤´ç—›ä¼´å‘éœ‡é¢¤æ‚£è€ çš„ä¸´åºŠç‰¹å¾.

OBJECTIVES: Migraine and tremor share some genetic mutation sites, and clinical studies have also confirmed their correlation. This study aims to explore the clinical and electrophysiological characteristics of migraine patients with concomitant tremor, and to analyze the relevant influential factors of tremor occurrence. METHODS: We retrospectively analyzed the clinical data of 217 migraine patients who visited the Third Affiliated Hospital of Qiqihar Medical University from June 2022 to October 2023. The Clinical Rating Scale for Tremor (CRST), Numerical Rating Scale (NRS), Generalized Anxiety Disorder-7 (GAD-7), and Patient Health Questionnaire-9 (PHQ-9) were respectively used to assess the tremor symptoms, degree of headache, anxiety, and depression of patients. All patients underwent routine head MR scanning and electromyography examination, and were divided into a migraine with tremor group and a migraine without tremor group based on the electromyogram examination. RESULTS: The migraine with tremor group and the migraine without tremor group were included 52 patients (23.96%) and 165 patients (76.04%), respectively. Compared with the migraine without tremor group, the migraine with tremor group had a longer course and duration of headache, higher frequency of headache attacks, higher NRS score, GAD-7 score, and PHQ-9 score, and fewer weekly physical exercises. The differences were statistically significant (all P<0.05). There were no statistically significant differences in the presence or absence of prodromal headache and white matter hyperintensities (WMHs) between the 2 groups (both P>0.05). The evaluation results of the CRST showed that out of 217 migraine patients, 39 patients (17.97%) were accompanied by tremors. The electromyographic results showed that all 52 migraine patients with tremors had upper limb tremors, including 28 migraine patients with postural tremors and 24 migraine patients with static tremors. Compared with the migraine patients with static tremors, the migraine patients with postural tremors had lower average frequency, peak frequency, and headache onset frequency (all P<0.05). Multiple linear regression analysis showed that frequency of physical exercise, duration of illness, frequency of headache attacks, NRS score, GAD-7 score, and PHQ-9 score were risk factors for migraine patients with concomitant tremors (all P<0.05). CONCLUSIONS: Patients with migraine mainly experience upper limb postural tremors. Reduced physical exercise, long course of disease, long duration of headache, frequent headache attacks, severe headache, anxiety, and depression are risk factors for migraine patients with concomitant tremors.

The Effects of Hand Tremors on the Shooting Performance of Air Pistol Shooters with Different Skill Levels.

Physiologic hand tremors are a critical factor affecting the aim of air pistol shooters. However, the extent of the effect of hand tremors on shooting performance is unclear. In this study, we aim to explore the relationship between hand tremors and shooting performance scores as well as investigate potential links between muscle activation and hand tremors. In this study, 17 male air pistol shooters from China's national team and the Air Pistol Sports Center were divided into two groups: the elite group and the sub-elite group. Each participant completed 40 shots during the experiment, with shooters' hand tremors recorded using three-axis digital accelerometers affixed to their right hands. Muscle activation was recorded using surface electromyography on the right anterior deltoid, posterior deltoid, biceps brachii (short head), triceps brachii (long head), flexor carpi radialis, and extensor carpi radialis. Our analysis revealed weak correlations between shooting scores and hand tremor amplitude in multiple directions (middle-lateral, ML: r2 = -0.22, p < 0.001; vertical, VT: r2 = -0.25, p < 0.001), as well as between shooting scores and hand tremor complexity (ML: r2 = -0.26, p < 0.001; VT: r2 = -0.28, p < 0.001), across all participants. Notably, weak correlations between shooting scores and hand tremor amplitude (ML: r2 = -0.27, p < 0.001; VT: r2 = -0.33, p < 0.001) and complexity (ML: r2 = -0.31, p < 0.001) were observed in the elite group but not in the sub-elite group. Moderate correlation were found between the biceps brachii (short head) RMS and hand tremor amplitude in the VT and ML directions (ML: r2 = 0.49, p = 0.010; VT: r2 = 0.44, p = 0.025) in all shooters, with a moderate correlation in the ML direction in elite shooters (ML: r2 = 0.49, p = 0.034). Our results suggest that hand tremors in air pistol shooters are associated with the skill of the shooters, and muscle activation of the biceps brachii (long head) might be a factor affecting hand tremors. By balancing the agonist and antagonist muscles of the shoulder joint, shooters might potentially reduce hand tremors and improve their shooting scores.

Potential Prodromal Digital Postural Sway Markers for Fragile X-Associated Tremor/Ataxia Syndrome (FXTAS) Detected via Dual-Tasking and Sensory Manipulation.

FXTAS is a neurodegenerative disorder occurring in some Fragile X Messenger Ribonucleoprotein 1 (FMR1) gene premutation carriers (PMCs) and is characterized by cerebellar ataxia, tremor, and cognitive deficits that negatively impact balance and gait and increase fall risk. Dual-tasking (DT) cognitive-motor paradigms and challenging balance conditions may have the capacity to reveal markers of FXTAS onset. Our objectives were to determine the impact of dual-tasking and sensory and stance manipulation on balance in FXTAS and potentially detect subtle postural sway deficits in FMR1 PMCs who are asymptomatic for signs of FXTAS on clinical exam. Participants with FXTAS, PMCs without FXTAS, and controls underwent balance testing using an inertial sensor system. Stance, vision, surface stability, and cognitive demand were manipulated in 30 s trials. FXTAS participants had significantly greater total sway area, jerk, and RMS sway than controls under almost all balance conditions but were most impaired in those requiring vestibular control. PMCs without FXTAS had significantly greater RMS sway compared with controls in the feet apart, firm, single task conditions both with eyes open and closed (EC) and the feet together, firm, EC, DT condition. Postural sway deficits in the RMS postural sway variability domain in asymptomatic PMCs might represent prodromal signs of FXTAS. This information may be useful in providing sensitive biomarkers of FXTAS onset and as quantitative balance measures in future interventional trials and longitudinal natural history studies.

Prechtl's method to assess general movements: Inter-rater reliability during the preterm period.

INTRODUCTION: Prechtl's method (GMA) is a test for the functional assessment of the young nervous system. It involves a global and a detailed assessment of the general movements (GMs) and has demonstrated validity. Data on the reliability of both assessments in the preterm period are scarce. This study aimed to evaluate the inter-rater reliability for the global and detailed assessments of the preterm writhing GMA. MATERIALS AND METHODS: The study participants were 69 infants born at <37 gestational weeks and admitted to the neonatal intensive care unit. They were randomly assigned to five pairs of raters. Raters assessed infants' GMs using preterm videos. Outcome variables were (a) the GMs classification (normal versus abnormal; normal versus abnormal subcategories) and (b) the general movements optimality score (GMOS), obtained through the global and detailed assessments. The Gwet's AC1 and the intraclass correlation coefficient (ICC) were calculated for the GMs classification and the GMOS, respectively. RESULTS: The global assessment presented an AC1 = 0.84 [95% CI = 0.54,1] for the GMs binary classification and an AC1 = 0.67 [95% CI = 0.38,0.89] for the GMs classification with abnormal subcategories. The detailed assessment presented an ICC = 0.72 [95% CI = 0.39,0.90] for the GMOS. CONCLUSIONS: Inter-rater reliability was high and substantial for the global assessment and good for the detailed assessment. However, the small sample size limited the precision of these estimates. Future research should involve larger samples of preterm infants to improve estimate precision. Challenging items such as assessing the neck and trunk, poor repertoire GMs, and tremulous movements may impact the preterm writhing GMA's inter-rater reliability. Therefore, ongoing training and calibration among raters is necessary. Further investigation in clinical settings can enhance our understanding of the preterm writhing GMA's reliability.

[Tremor-dominant form of Parkinson's disease]. / Tremor-dominantnaya forma bolezni Parkinsona.

The article is of a review nature and is devoted to tremor, one of the maladaptive and difficult-to-treat symptoms of Parkinson's disease (PD). Along with the classic rest tremor, patients with PD may experience tremor of other modalities: postural tremor, kinetic tremor, which reflects a multimodal mechanism of tremor formation involving multiple neurotransmitter systems. The unpredictable response to therapeutic options, the ambiguous response to levodopa, also reflects the role of multiple underlying pathophysiological processes. Among the drug methods of tremor correction, preference is given to dopamine receptor agonists - due to the spectrum of their pharmaceutical action, high efficiency in relation to all leading motor and a number of non-motor manifestations. The evidence for advanced neurosurgical, non-invasive modalities is mixed, and there are insufficient comparative studies to assess their efficacy in patients with tremor-dominant forms of PD.

Type selective ablation of postnatal slow and fast fatigue-resistant motor neurons in mice induces late onset kinetic and postural tremor following fiber-type transition and myopathy.

Animals on Earth need to hold postures and execute a series of movements under gravity and atmospheric pressure. VAChT-Cre is a transgenic Cre driver mouse line that expresses Cre recombinase selectively in motor neurons of S-type (slow-twitch fatigue-resistant) and FR-type (fast-twitch fatigue-resistant). Sequential motor unit recruitment is a fundamental principle for fine and smooth locomotion; smaller-diameter motor neurons (S-type, FR-type) first contract low-intensity oxidative type I and type IIa muscle fibers, and thereafter larger-diameter motor neurons (FInt-type, FF-type) are recruited to contract high-intensity glycolytic type IIx and type IIb muscle fibers. To selectively eliminate S- and FR-type motor neurons, VAChT-Cre mice were crossbred with NSE-DTA mice in which the cytotoxic diphtheria toxin A fragment (DTA) was expressed in Cre-expressing neurons. The VAChT-Cre;NSE-DTA mice were born normally but progressively manifested various characteristics, including body weight loss, kyphosis, kinetic and postural tremor, and muscular atrophy. The progressive kinetic and postural tremor was remarkable from around 20 weeks of age and aggravated. Muscular atrophy was apparent in slow muscles, but not in fast muscles. The increase in motor unit number estimation was detected by electromyography, reflecting compensatory re-innervation by remaining FInt- and FF-type motor neurons to the orphaned slow muscle fibers. The muscle fibers gradually manifested fast/slow hybrid phenotypes, and the remaining FInt-and FF-type motor neurons gradually disappeared. These results suggest selective ablation of S- and FR-type motor neurons induces progressive muscle fiber-type transition, exhaustion of remaining FInt- and FF-type motor neurons, and late-onset kinetic and postural tremor in mice.

Prasinezumab slows motor progression in rapidly progressing early-stage Parkinson's disease.

Prasinezumab, a monoclonal antibody that binds aggregated α-synuclein, is being investigated as a potential disease-modifying therapy in early-stage Parkinson's disease. Although in the PASADENA phase 2 study, the primary endpoint (Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) sum of Parts I + II + III) was not met, prasinezumab-treated individuals exhibited slower progression of motor signs than placebo-treated participants (MDS-UPDRS Part III). We report here an exploratory analysis assessing whether prasinezumab showed greater benefits on motor signs progression in prespecified subgroups with faster motor progression. Prasinezumab's potential effects on disease progression were assessed in four prespecified and six exploratory subpopulations of PASADENA: use of monoamine oxidase B inhibitors at baseline (yes versus no); Hoehn and Yahr stage (2 versus 1); rapid eye movement sleep behavior disorder (yes versus no); data-driven subphenotypes (diffuse malignant versus nondiffuse malignant); age at baseline (≥60 years versus <60 years); sex (male versus female); disease duration (>12 months versus <12 months); age at diagnosis (≥60 years versus <60 years); motor subphenotypes (akinetic-rigid versus tremor-dominant); and motor subphenotypes (postural instability gait dysfunction versus tremor-dominant). In these subpopulations, the effect of prasinezumab on slowing motor signs progression (MDS-UPDRS Part III) was greater in the rapidly progressing subpopulations (for example, participants who were diffuse malignant or taking monoamine oxidase B inhibitors at baseline). This exploratory analysis suggests that, in a trial of 1-year duration, prasinezumab might reduce motor progression to a greater extent in individuals with more rapidly progressing Parkinson's disease. However, because this was a post hoc analysis, additional randomized clinical trials are needed to validate these findings.

Mitochondrial dysfunction in Fragile X syndrome and Fragile X-associated tremor/ataxia syndrome: prospect use of antioxidants and mitochondrial nutrients.

Fragile X syndrome (FXS) is a genetic disorder characterized by mutation in the FMR1 gene, leading to the absence or reduced levels of fragile X Messenger Ribonucleoprotein 1 (FMRP). This results in neurodevelopmental deficits, including autistic spectrum conditions. On the other hand, Fragile X-associated tremor/ataxia syndrome (FXTAS) is a distinct disorder caused by the premutation in the FMR1 gene. FXTAS is associated with elevated levels of FMR1 mRNA, leading to neurodegenerative manifestations such as tremors and ataxia.Mounting evidence suggests a link between both syndromes and mitochondrial dysfunction (MDF). In this minireview, we critically examine the intricate relationship between FXS, FXTAS, and MDF, focusing on potential therapeutic avenues to counteract or mitigate their adverse effects. Specifically, we explore the role of mitochondrial cofactors and antioxidants, with a particular emphasis on alpha-lipoic acid (ALA), carnitine (CARN) and Coenzyme Q10 (CoQ10). Findings from this review will contribute to a deeper understanding of these disorders and foster novel therapeutic strategies to enhance patient outcomes.

Cerebrotendinous xanthomatosis with tremor as the main manifestation: A case report.

INTRODUCTION: Cerebrotendinous xanthomatosis (CTX) is an autosomal recessive lipid metabolism disorder. It is caused by a defect in the sterol-27-hydroxylase gene, leading to the deposition of cholesteryl and bile alcohol in large amounts, causing a variety of clinical manifestations; however, tremor as the main manifestation of CTX has not been reported. PATIENTS CONCERNS AND CLINICAL FINDINGS: Herein, we report a 27-year-old woman, who developed head and body tremors at the age of 12 years. Many hospitals misdiagnosed her condition as idiopathic tremor and Parkinson disease, with a poor curative effect. PRIMARY DIAGNOSIS AND INTERVENTION: We diagnosed her with CTX and treated with chenodeoxycholic acid and clonazepam. CONCLUSION: The patient's condition considerably improved. This case could help avoid misdiagnosis and mistreatment in clinical practice.