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.

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.

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

Stereotactic radiosurgery (SRS) is one of the surgical alternatives for drug-resistant essential tremor (ET). Here, we aimed at evaluating whether biologically effective dose (BEDGy2.47) is relevant for tremor improvement after stereotactic radiosurgical thalamotomy in a population of patients treated with one (unplugged) isocenter and a uniform dose of 130 Gy. This is a retrospective longitudinal single center study. Seventy-eight consecutive patients were clinically analyzed. Mean age was 69.1 years (median 71, range 36-88). Mean follow-up period was 14 months (median 12, 3-36). Tremor improvement was assessed at 12 months after SRS using the ET rating assessment scale (TETRAS, continuous outcome) and binary (binary outcome). BED was defined for an alpha/beta of 2.47, based upon previous studies considering such a value for the normal brain. Mean BED was 4573.1 Gy2.47 (median 4612, 4022.1-4944.7). Mean beam-on time was 64.7 min (median 61.4; 46.8-98.5). There was a statically significant correlation between delta (follow-up minus baseline) in TETRAS (total) with BED (p = 0.04; beta coefficient - 0.029) and beam-on time (p = 0.03; beta coefficient 0.57) but also between TETRAS (ADL) with BED (p = 0.02; beta coefficient 0.038) and beam-on time (p = 0.01; beta coefficient 0.71). Fractional polynomial multivariate regression suggested that a BED > 4600 Gy2.47 and a beam-on time > 70 min did not further increase clinical efficacy (binary outcome). Adverse radiation events (ARE) were defined as larger MR signature on 1-year follow-up MRI and were present in 7 out of 78 (8.9%) cases, receiving a mean BED of 4650 Gy2.47 (median 4650, range 4466-4894). They were clinically relevant with transient hemiparesis in 5 (6.4%) patients, all with BED values higher than 4500 Gy2.47. Tremor improvement was correlated with BED Gy2.47 after SRS for drug-resistant ET. An optimal BED value for tremor improvement was 4300-4500 Gy2.47. ARE appeared for a BED of more than 4500 Gy2.47. Such finding should be validated in larger cohorts.

TETRAS Spirals and Handwriting Samples: Determination of Optimal Scoring Examples.

Background: Spiral drawings and handwriting tasks have long been used to assess the severity of essential tremor, but these motor tasks are somewhat less objective as the rules for scoring are not based on firm objective amplitude-based criteria. Publishing the best examples of each of the possible 0-4 ratings for these items could reduce scoring variance. Methods: 21 members of the Tremor Research Group each rated 94 spirals and 64 handwriting samples using TETRAS scoring criteria. For each sample, the most frequently reported score (mode; maximum of 21) was determined. Ratings not adjacent to the mode were subtracted from the number of mode scores, to calculate a total value. For each of the ratings (0, 1, 1.5, 2, 2.5, 3, 3.5, 4), the samples with the highest total value were selected as best examples. Results: In general, rater agreement was good for spirals but poor for handwriting samples. Nevertheless, examples with excellent agreement were identified for all spiral and handwriting ratings, and are presented. Conclusion: Best examples for scoring spirals and handwritings are needed to reduce the variance of TETRAS scores in clinical trials and clinical practice.

Quantifying Tremor in Essential Tremor Using Inertial Sensors-Validation of an Algorithm.

Background Assessment of essential tremor is often done by a trained clinician who observes the limbs during different postures and actions and subsequently rates the tremor. While this method has been shown to be reliable, the inter- and intra-rater reliability and need for training can make the use of this method for symptom progression difficult. Many limitations of clinical rating scales can potentially be overcome by using inertial sensors, but to date many algorithms designed to quantify tremor have key limitations. Methods We propose a novel algorithm to characterize tremor using inertial sensors. It uses a two-stage approach that 1) estimates the tremor frequency of a subject and only quantifies tremor near that range; 2) estimates the tremor amplitude as the portion of signal power above baseline activity during recording, allowing tremor estimation even in the presence of other activity; and 3) estimates tremor amplitude in physical units of translation (cm) and rotation (°), consistent with current tremor rating scales. We validated the algorithm technically using a robotic arm and clinically by comparing algorithm output with data reported by a trained clinician administering a tremor rating scale to a cohort of essential tremor patients. Results Technical validation demonstrated rotational amplitude accuracy better than ±0.2 degrees and position amplitude accuracy better than ±0.1 cm. Clinical validation revealed that both rotation and position components were significantly correlated with tremor rating scale scores. Conclusion We demonstrate that our algorithm can quantify tremor accurately even in the presence of other activities, perhaps providing a step forward for at-home monitoring.

Tremor Research Group Essential Tremor Rating Scale (TETRAS): Assessing Impact of Different Item Instructions and Procedures.

Introduction: The Tremor Research Group Essential Tremor Rating Scale (TETRAS) is a well-validated instrument to assess essential tremor. However, similar to all other tremor rating scales, specific instructions for individual tasks are based mostly on expert opinion and tradition. Several tasks have multiple possible variations that have never been compared to determine if they impact score. Methods: Using blinded, randomized videotapes, a group of tremor experts evaluated multiple ET patients to determine: 1. whether assessments of spirals and writing samples are similar if the rater only sees the end result as opposed to actually watching the task, 2. whether arm tremor ratings (postural and wing-beating) are similar if the subjects hold both hands out concurrently vs. if they only hold one arm out at a time, 3. whether heal to shin tremor scores vary between supine and sitting, and 4. compared cursive vs script writing samples. Results: Intraclass correlation coefficients (ICC) were excellent (>0.95) for all arm assessments. Writing tremor was rated worse if only rating the spiral/writing photos (p < 0.05) rather than also viewing the writing process, arm tremor scores were higher if each arm was rated individually (p < 0.001), heal to shin scores were higher when done sitting (p = 0.01), and cursive writing tended to be rated higher than script (p = 0.08). Discussion: Minor procedure differences when administering the TETRAS can significantly alter results.

Phylogenetic relationships of the neon tetras Paracheirodon spp. (Characiformes: Characidae: Stethaprioninae), including comments on Petitella georgiae and Hemigrammus bleheri

Neon tetras (Paracheirodon spp.) are three colorful characid species with a complicated taxonomic history, and relationships among the species are poorly known. Molecular data resolved the relationships among the three neon tetras, and strongly supported monophyly of the genus and its sister taxon relationship to Brittanichthys. Additionally, the sister-taxon relationship of the rummy-nose tetras Hemigrammus bleheri and Petitella georgiae was strongly supported by molecular and morphological data. Therefore, we propose to transfer the rummy-nose tetras H. bleheri and H. rhodostomus to the genus Petitella. Furthermore, Petitella georgiae is likely to be a species complex comprised of at least two species.(AU)

Os neon tetras (Paracheirodon spp.) são três espécies de caracídeos coloridos com uma complicada história taxonômica e as relações entre suas espécies são pouco conhecidas. Dados moleculares resolveram as relações entre os três neons tetras, suportando fortemente a monofilia do gênero e a relação de grupo-irmão com Brittanichthys. Adicionalmente, a relação de grupo-irmão entre os rodóstomos Hemigrammus bleheri e Petitella georgiae foi fortemente suportada por dados moleculares e morfológicos. Portanto, nós propomos transferir os rodóstomos H. bleheri e H. rhodostomus para o gênero Petitella. Além disso, é possível que Petitella georgiae seja um complexo de espécies composto por, pelo menos, duas espécies.(AU)

A Phase 2, Randomized, Double-Blind, Placebo-Controlled Trial of CX-8998, a Selective Modulator of the T-Type Calcium Channel in Inadequately Treated Moderate to Severe Essential Tremor: T-CALM Study Design and Methodology for Efficacy Endpoint and Digital Biomarker Selection.

Background: Essential tremor (ET) is a common, progressive neurological syndrome with bilateral upper-limb dysfunction of at least 3-year duration, with or without tremor in other body locations. This disorder has a negative impact on daily function and quality of life. A single oral therapy has been approved by FDA for ET. Off-label pharmacotherapies have inadequate efficacy and poor tolerability with high rates of patient dissatisfaction and discontinuation. Safe and efficacious pharmacotherapies are urgently needed to decrease tremor and improve daily living. T-CALM (Tremor-CAv3 modulation) protocol is designed to assess safety and efficacy of CX-8998, a selective modulator of the T-type calcium channel, for ET therapy. Methods/Design: T-CALM is a phase 2, proof of concept, randomized, double-blind, placebo-controlled trial. Titrated doses of CX-8998 to 10 mg BID or placebo will be administered for 28 days to moderate to severe ET patients who are inadequately treated with existing therapies. The primary endpoint will be change from baseline to day 28 of The Essential Tremor Rating Assessment Performance Subscale (TETRAS-PS). Secondary efficacy endpoints for clinician and patient perception of daily function will include TETRAS Activity of Daily Living (ADL), Quality of Life in Essential Tremor Questionnaire (QUEST), Clinical Global Impression-Improvement (CGI-I), Patient Global Impression of Change (PGIC), and Goal Attainment Scale (GAS). Kinesia One, Kinesia 360, and iMotor will biometrically evaluate motor function and tremor amplitude. Safety will be assessed by adverse events, physical and neurological exams and laboratory tests. Sample size of 43 patients per group is estimated to have 90% power to detect a 5.5-point difference between CX-8998 and placebo for TETRAS-PS. Efficacy analyses will be performed with covariance (ANCOVA) and 2-sided test at 0.05 significance level. Discussion: T-CALM has a unique design with physician rating scales, patient-focused questionnaires and scales and objective motor measurements to assess clinically meaningful and congruent efficacy. Patient perception of ET debilitation and therapy with CX-8998 will be key findings. Overall goal of T-CALM is generation of safety and efficacy data to support a go, no-go decision to further develop CX-8998 for ET. Design of T-CALM may guide future clinical studies of ET pharmacotherapies. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT03101241.

Description of a new species of Moenkhausia (Characiformes: Characidae) from the upper Paraguay basin, Central Brazil, with comments on its phylogenetic relationships

A new species of Moenkhausia is described from tributaries of the upper rio Sepotuba, Paraguay basin, Brazil. The new species is distinguished from its congeners by a combination of characters, including an inconspicuous oval-shaped vertically elongated humeral blotch, extending horizontally from third through five lateral-line scales, and vertically from third row above lateral line to first row below it, followed by a diffuse field of dark chromatophores in the flank, combined with a well-defined dark line at the base of the anal fin. Furthermore, the phylogenetic position of the new species is presented based on molecular data, showing a close relationship among species of Moenkhausia and Hemigrammus that have a well-defined dark line at the base of the anal fin. Until this moment, this species is only known from in the upper rio Sepotuba basin.(AU)

Uma nova espécie de Moenkhausia é descrita nos afluentes do rio Sepotuba, bacia do Paraguai, no Brasil. A nova espécie se distingue dos seus congêneres por uma combinação de caracteres, incluindo uma mancha umeral discreta de forma oval, alongada verticalmente, que se estende horizontalmente da terceira a quinta escamas da linha lateral e, verticalmente, da terceira fila de escamas acima da linha lateral até a primeira fila abaixo da linha lateral; seguida por escassos cromatóforos no flanco, combinado com uma linha escura bem definida na base da nadadeira anal. Além disso, a posição filogenética da nova espécie é apresentada com base em dados moleculares, mostrando um relacionamento próximo entre as espécies de Moenkhausia e Hemigrammus que possuem uma linha escura bem definida na base da nadadeira anal. Até o momento, essa espécie é conhecida apenas da bacia do Alto Sepotuba.(AU)

Thayeria tapajonica (Characiformes: Characidae), a new species from rio Tapajós basin, Brazil.

A new species of penguin tetra, Thayeria tapajonica, is described from the rio Tapajós basin. It is most similar to T. boehlkei by presenting a straight midlateral stripe running anteriorly to immediately posterior to the head, while in T. ifati and T. obliqua the midlateral stripe is restricted to the caudal peduncle, merging with an anterodorsal oblique stripe. The new species is restricted to the rio Tapajós basin downriver of the confluence of the rio Juruena and rio Teles Pires, and lower rio Teles Pires, where its distribution overlaps with T. boehlkei.

Hemigrammus ataktos: a new species from the rio Tocantins basin, central Brazil (characiformes: characidae)

A new species of hemigrammus is described from the middle rio Tocantins basin, central Brazil. The new species can be distinguished from all congeners by having a black midlateral stripe on the body extending from the posterior margin of the eye to the median caudal-fin rays. Mature males possess dorsal-, pelvic-, and anal-fin rays elongate, features that also help to recognize the new species. Although the new species is described in Hemigrammus, some specimens present a complete series of pored scales in the lateral line. A discussion about the generic allocation of the new species is presented.

Uma espécie nova de hemigrammus é descrita da bacia do médio rio Tocantins, Brasil central. A espécie nova distingue-se de seus congêneres por apresentar uma faixa mediana negra na lateral do corpo desde a margem posterior do olho até os raios medianos da nadadeira caudal. Machos maduros apresentam os raios das nadadeiras dorsal, pélvica e anal alongados, características que também auxiliam o reconhecimento da espécie. Apesar da espécie nova ser descrita em Hemigrammus, alguns exemplares possuem série completa de escamas perfuradas na linha lateral. Uma discussão sobre o posicionamento genérico da espécie nova é apresentada.

Occurrence of intersexuality in "Lambaris", Astyanax scabripinnis (Jenyns, 1842), small characids from the Brazilian streams

During studies carried out with a small characid (Astyanax scabripinnis), from the Brazilian streams located in Cerrado biome, some gonads of fishes exhibited sparse oocytes in perinucleolar stage embedded in normally developing testicular tissues. Another pattern of gonad intersex with vitellogenic oocytes and mature lobules was observed in the gonads of fishes collected from a reservoir supplied by the Atlantic Forest stream. These gonads in different stages of maturation were examined histologically. The results revealed the patterns occurring in fishes of the same species, from four different populations.

Durante estudos efetuados com pequenos caracídeos (Astyanax scabripinnis) de riachos do Cerrado brasileiro, localizados nos Estados de Minas Gerais e de São Paulo, foram encontrados alguns peixes com gônadas exibindo oócitos em estágio perinucleolar dispersos, embebidos em tecidos testiculares em desenvolvimento. Em exemplares da mesma espécie, provenientes de um riacho situado na Mata Atlântica do Estado de São Paulo, outro padrão de gônadas intersexuadas foi registrado, mostrando oócitos vitelogênicos e lóbulos maduros presentes na mesma gônada. As gônadas em diferentes estágios de maturação foram submetidas a análises histológicas. Os resultados obtidos mostram os padrões morfológicos e as freqüências de ocorrência dos intersexos encontrados em peixes do " complexo" A. scabripinnis provenientes de quatro diferentes populações. São discutidas as prováveis causas ambientais responsáveis por estas alterações.