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.

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.

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.

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.

L-2 hydroxyglutaric aciduria: report of a Mexican-Mayan patient with the mutation c.569C>T and response to vitamin supplements and levocarnitine.

Background: L-2-hydroxyglutaric aciduria (L2HGA) is a rare inherited autosomal recessive neurometabolic disorder caused by pathogenic variants in the L2HGDH gene which encodes mitochondrial 2-hydroxyglutarate dehydrogenase. Here, we report a case of L2HGA in a Mexican-Mayan patient with a homozygous mutation at L2HGDH gene and clinical response to vitamin supplements and levocarnitine. Case report: A 17-year-old, right-handed female patient with long-term history of seizures, developmental delay and ataxia was referred to a movement disorders specialist for the evaluation of tremor. Her brain MRI showed typical findings of L2HGA. The diagnosis was corroborated with elevated levels of 2-hydroxyglutaric acid in urine and genetic test which revealed a homozygous genetic known variant c.569C>T in exon 5 of L2HGDH gene. She was treated with levocarnitine and vitamin supplements, showing improvement in tremor and gait. Discussion: To our knowledge this is the first report of a Mexican patient with L2HGA. This case adds information about a rare condition in a different ethnic group and supports the findings of other authors which encountered symptomatic improvement with the use of flavin adenine dinucleotide (and its precursor riboflavin), and levocarnitine. Highlights: We report the first case of Mexican-Mayan patient with L2HGA showing a missense homozygous mutation in L2HGDH gene, and improvement of symptoms with vitamin supplements and levocarnitine.

A New Wrist-Worn Tool Supporting the Diagnosis of Parkinsonian Motor Syndromes.

To date, clinical expert opinion is the gold standard diagnostic technique for Parkinson's disease (PD), and continuous monitoring is a promising candidate marker. This study assesses the feasibility and performance of a new wearable tool for supporting the diagnosis of Parkinsonian motor syndromes. The proposed method is based on the use of a wrist-worn measuring system, the execution of a passive, continuous recording session, and a computation of two digital biomarkers (i.e., motor activity and rest tremor index). Based on the execution of some motor tests, a second step is provided for the confirmation of the results of passive recording. In this study, fifty-nine early PD patients and forty-one healthy controls were recruited. The results of this study show that: (a) motor activity was higher in controls than in PD with slight tremors at rest and did not significantly differ between controls and PD with mild-to-moderate tremor rest; (b) the tremor index was smaller in controls than in PD with mild-to-moderate tremor rest and did not significantly differ between controls and PD patients with slight tremor rest; (c) the combination of the said two motor parameters improved the performances in differentiating controls from PD. These preliminary findings demonstrate that the combination of said two digital biomarkers allowed us to differentiate controls from early PD.

Autoimmune nodopathy with anti-contactin 1 antibody characterized by cerebellar dysarthria: a case report and literature review.

Background: Autoimmune nodopathy (AN) has emerged as a novel diagnostic category that is pathologically different from classic chronic inflammatory demyelinating polyneuropathy. Clinical manifestations of AN include sensory or motor neuropathies, sensory ataxia, tremor, and cranial nerve involvement. AN with a serum-positive contactin-1 (CNTN1) antibody usually results in peripheral nerve demyelination. In this study, we reported a rare case of AN with CNTN1 antibodies characterized by the presence of CNTN1 antibodies in both serum and cerebrospinal fluid, which is associated with cerebellar dysarthria. Methods: A 25-year-old man was admitted to our hospital due to progressive dysarthria with limb tremors. The patient was initially diagnosed with peripheral neuropathy at a local hospital. Three years after onset, he was admitted to our hospital due to dysarthria, apparent limb tremor, and limb weakness. At that time, he was diagnosed with spinocerebellar ataxia. Eight years post-onset, during his second admission, his condition had notably deteriorated. His dysarthria had evolved to typical distinctive cerebellar characteristics, such as tremor, loud voice, stress, and interrupted articulation. Additionally, he experienced further progression in limb weakness and developed muscle atrophy in the distal limbs. Magnetic resonance imaging (MRI), nerve conduction studies (NCS), and autoimmune antibody tests were performed. Results: The results of the NCS suggested severe demyelination and even axonal damage to the peripheral nerves. MRI scans revealed diffuse thickening of bilateral cervical nerve roots, lumbosacral nerve roots, cauda equina nerve, and multiple intercostal nerve root sheath cysts. Furthermore, anti-CNTN1 antibody titers were 1:10 in the cerebrospinal fluid (CSF) and 1:100 in the serum. After one round of rituximab treatment, the patient showed significant improvement in limb weakness and dysarthria, and the CSF antibodies turned negative. Conclusion: Apart from peripheral neuropathies, cerebellar dysarthria (central nervous system involvement) should not be ignored in AN patients with CNTN1 antibodies.

Application of sensory nerve quantitative tests to analyze the subtypes of motor disorders in Parkinson's disease.

This study investigated the sensory nerve function in people with different subtypes of Parkinson's disease (PD), which included the tremor-dominant (TD) group (n = 30), postural instability and gait disorder (PIGD) group (n = 33), and healthy-controls (HC) group (n = 33). Sural nerve's current perception threshold (CPT) and pain tolerance threshold (PTT) in both feet were measured at different frequencies. Results were evaluated using the mini-mental state examination (MMSE), Hoehn Yahr scale (H-Y) , and 3-meter timed-up-and-go-test (TUGT). The MMSE scores of the TD and HC groups were higher than those of the PIGD group (TD < HC). The 3-meter TUGT scores of the PIGD group were higher than theTD and HC groups (TD > HC). The PIGD patients experienced a significantly shorter disease duration and higher H-Y score than the TD patients ( P  < 0.05). The values of 2 KHz CPT of left-side (CPTL), 2KHz CPT of right-side (CPTR), and 5 Hz CPTR in the PIGD group were significantly higher compared to the TD and HC groups ( P  < 0.05, Bonferroni correction). Additionally, the values of 250 Hz CPTL, 5 Hz CPTL, 250 Hz CPTR, 2 kHz PTT of left-side (PTTL), 250 Hz PTTL, and 5 Hz PTTL in the PIGD group were significantly elevated relative to the TD group ( P  < 0.05, Bonferroni correction). Distinctive current threshold perception and PTT of the sural nerve can be observed in patients with varying PD subtypes, and sensory nerve conduction threshold electrical diagnostic testing can detect these discrepancies in sensory nerve function.

Flapping Tremor: Unraveling Asterixis-A Narrative Review.

Asterixis is a subtype of negative myoclonus characterized by brief, arrhythmic lapses of sustained posture due to involuntary pauses in muscle contraction. We performed a narrative review to characterize further asterixis regarding nomenclature, historical aspects, etiology, pathophysiology, classification, diagnosis, and treatment. Asterixis has been classically used as a synonym for negative myoclonus across the literature and in previous articles. However, it is important to distinguish asterixis from other subtypes of negative myoclonus, for example, epileptic negative myoclonus, because management could change. Asterixis is not specific to any pathophysiological process, but it is more commonly reported in hepatic encephalopathy, renal and respiratory failure, cerebrovascular diseases, as well as associated with drugs that could potentially lead to hyperammonemia, such as valproic acid, carbamazepine, and phenytoin. Asterixis is usually asymptomatic and not spontaneously reported by patients. This highlights the importance of actively searching for this sign in the physical exam of encephalopathic patients because it could indicate an underlying toxic or metabolic cause. Asterixis is usually reversible upon treatment of the underlying cause.

Targeting KRAS G12C Mutation in Colorectal Cancer, A Review: New Arrows in the Quiver.

Kirsten rat sarcoma virus oncogene homolog (KRAS) is the most frequently mutated oncogene in human cancer. In colorectal cancer (CRC), KRAS mutations are present in more than 50% of cases, and the KRAS glycine-to-cysteine mutation at codon 12 (KRAS G12C) occurs in up to 4% of patients. This mutation is associated with short responses to standard chemotherapy and worse overall survival compared to non-G12C mutations. In recent years, several KRAS G12C inhibitors have demonstrated clinical activity, although all patients eventually progressed. The identification of negative feedback through the EGFR receptor has led to the development of KRAS inhibitors plus an anti-EGFR combination, thus boosting antitumor activity. Currently, several KRAS G12C inhibitors are under development, and results from phase I and phase II clinical trials are promising. Moreover, the phase III CodeBreaK 300 trial demonstrates the superiority of sotorasib-panitumumab over trifluridine/tipiracil, establishing a new standard of care for patients with colorectal cancer harboring KRAS G12C mutations. Other combinations such as adagrasib-cetuximab, divarasib-cetuximab, or FOLFIRI-panitumumab-sotorasib have also shown a meaningful response rate and are currently under evaluation. Nonetheless, most of these patients will eventually relapse. In this setting, liquid biopsy emerges as a critical tool to characterize the mechanisms of resistance, consisting mainly of acquired genomic alterations in the MAPK and PI3K pathways and tyrosine kinase receptor alterations, but gene fusions, histological changes, or conformational changes in the kinase have also been described. In this paper, we review the development of KRAS G12C inhibitors in colorectal cancer as well as the main mechanisms of resistance.

WHIGET and TETRAS Ratings of Action Tremor in Patients with Essential Tremor: Substantial Association and Agreement.

Background: Evaluating tremor severity is a critical component of diagnosing and clinically managing patients with essential tremor (ET). We examined the comparability of tremor severity ratings derived from two frequently used tremor rating scales: the Washington Heights-Inwood Genetic Study of Essential Tremor (WHIGET) rating scale and the Tremor Research Group Essential Tremor Rating Scale (TETRAS). Methods: A trained assistant administered and videotaped a neurological examination, including eight items assessing upper limb action tremor (arms outstretched, arms in the wingbeat position, finger-nose-finger maneuver, and drawing of Archimedes spirals). An experienced movement disorders neurologist reviewed the videos and assigned WHIGET and TETRAS ratings. We calculated associations between TETRAS and WHIGET ratings using Spearman rank order correlations. Subsequently, we collapsed these ratings into four tremor severity categories (absent, mild, moderate, severe) and then two broader tremor severity categories (absent/mild, moderate/severe). We calculated weighted Kappa coefficients to assess agreement between category assignments based on the TETRAS and the WHIGET. Results: Spearman's r' s were significant for all items (p's ≤ 0.001, mean r = 0.89). Weighted Kappa's revealed substantial to near perfect agreement for all eight items (mean k = 0.86, range = 0.64 to 1.00). Conclusion: Analyses revealed substantial strength of association and substantial to near perfect agreement between items rated with the WHIGET and TETRAS scales. These data indicated that ratings provided by each scale are highly comparable.

Unmethylated Mosaic Full Mutation Males without Fragile X Syndrome.

Fragile X syndrome (FXS) is the leading inherited cause of intellectual disability (ID) and single gene cause of autism. Although most patients with FXS and the full mutation (FM) have complete methylation of the fragile X messenger ribonucleoprotein 1 (FMR1) gene, some have mosaicism in methylation and/or CGG repeat size, and few have completely unmethylated FM alleles. Those with a complete lack of methylation are rare, with little literature about the cognitive and behavioral phenotypes of these individuals. A review of past literature was conducted regarding individuals with unmethylated and mosaic FMR1 FM. We report three patients with an unmethylated FM FMR1 alleles without any behavioral or cognitive deficits. This is an unusual presentation for men with FM as most patients with an unmethylated FM and no behavioral phenotypes do not receive fragile X DNA testing or a diagnosis of FXS. Our cases showed that mosaic males with unmethylated FMR1 FM alleles may lack behavioral phenotypes due to the presence of smaller alleles producing the FMR1 protein (FMRP). However, these individuals could be at a higher risk of developing fragile X-associated tremor/ataxia syndrome (FXTAS) due to the increased expression of mRNA, similar to those who only have a premutation.

Case of tizanidine withdrawal showing hallucination, decorticate posture and tremor, with hypersympathetic vital signs.

Tizanidine, an α2-adrenergic receptor agonist commonly prescribed as a muscle relaxant, has been associated with limited cases of acute intoxication or withdrawal. Here, we present a case of tizanidine withdrawal in a woman in her 40s who presented with an unusual combination of systemic and neurological symptoms. These included hallucinations, decorticate posture, limb and eyelid tremors, along with hypertension, tachycardia and tachypnoea. The diagnosis of tizanidine withdrawal was established by a comprehensive assessment of the patient's medical history and the systematic exclusion of other potential diseases. Our approach to managing the withdrawal symptoms was to initiate symptomatic treatment with a combination of a beta-blocker and a calcium channel blocker. Remarkably, this intervention successfully resolved both vital signs and neurological manifestations by the following day. In conclusion, tizanidine withdrawal is associated with a distinct and diagnostically significant neurological syndrome characterised by hallucinations, decorticate posture, tremors and hypersympathetic vital signs.

On Multiscaling of Parkinsonian Rest Tremor Signals and Their Classification.

Self-similar stochastic processes and broad probability distributions are ubiquitous in nature and in many man-made systems. The brain is a particularly interesting example of (natural) complex system where those features play a pivotal role. In fact, the controversial yet experimentally validated "criticality hypothesis" explaining the functioning of the brain implies the presence of scaling laws for correlations. Recently, we have analyzed a collection of rest tremor velocity signals recorded from patients affected by Parkinson's disease, with the aim of determining and hence exploiting the presence of scaling laws. Our results show that multiple scaling laws are required in order to describe the dynamics of such signals, stressing the complexity of the underlying generating mechanism. We successively extracted numeric features by using the multifractal detrended fluctuation analysis procedure. We found that such features can be effective for discriminating classes of signals recorded in different experimental conditions. Notably, we show that the use of medication (L-DOPA) can be recognized with high accuracy.

Pearls & Oy-sters: AARS2 Leukodystrophy-Tremor and Tribulations.

A 35-year-old woman with a progressive, bilateral upper limb tremor, personality change, behavioral disturbance, and primary ovarian insufficiency was found to have AARS2-related leukodystrophy. She had congenital nystagmus which evolved to head titubation by age 8 years and then developed an upper limb tremor in her mid-teens. These symptoms stabilized during her 20s, but soon after this presentation at age 35 years, neurologic and behavioral disturbances progressed rapidly over a 12-month period requiring transition to an assisted living facility with care support (4 visits/day) and assistance for all activities of daily living. MRI of the brain demonstrated confluent white matter changes predominantly involving the frontal lobes consistent with a leukodystrophy. All other investigations were unremarkable. Nongenetic causes of a leukodystrophy including sexually transmitted diseases and recreational drug use were excluded. Family history was negative for similar symptoms. Gene panel testing identified compound heterozygous pathogenic AARS2 mutations. This case highlights the importance of MRI brain imaging in progressive tremor syndromes, the utility of gene panels in simultaneous testing of multiple disorders with overlapping phenotypes, and the need for awareness of comorbid endocrinological disorders in many of the genetic leukodystrophies, whose identification may aid in clinical diagnosis.

Impact of biologically effective dose on tremor decrease after stereotactic radiosurgical thalamotomy for essential tremor: a retrospective longitudinal analysis.

This letter to the editor critiques a recent study evaluating the role of biologically effective dose (BED) in stereotactic radiosurgical thalamotomy for essential tremor (ET). The study, conducted retrospectively on 78 ET patients, demonstrates a significant correlation between BED and tremor improvement post-SRS. Moreover, the study suggests adjusting the prescribed dose rather than changing cobalt-60 sources to maintain treatment efficacy while minimizing toxicity. This suggestion aligns with previous research indicating an annual decrease in BED due to cobalt-60 decay. The letter emphasizes the importance of considering BED and cobalt-60 decay in optimizing treatment outcomes for ET patients undergoing stereotactic radiosurgery. Further research is recommended to explore innovative techniques for dose modulation in response to cobalt-60 decay and validate findings in larger cohorts.