Search

Uno de los argumentos más empleados por los radioterapeutas en favor del tratamiento de las lesiones neoplásicas de la laringe por medio de los RX, es la pérdida de la voz que acarrea la cirugía. Sin embargo, esto no es completamente cierto ya que las intervenciones quirúrgicas como la laringofisura o la hemilaringectomía no dan lugar a pérdida de la voz sino más bien a modificaciones de ésta, las cuales en gran número de casos son poco manifiestas. Estas consideraciones son el fruto de una revisión de los trabajos presentados en este sentido por el doctor C. L. Jackson, cuyas conclusiones copio a continuación.

Por considerar de gran interés este asunto, he querido escribir algunas líneas sobre él, sin pretender tratar en estas pocas páginas todos sus aspectos. Únicamente son nociones encaminadas a informar a los estudiantes del curso de órganos de los Sentidos y aquellos especialistas que no se encuentran aun familiarizados con este nuevo sistema de examen. He comenzado por hacer una breve descripción de las antiguas pruebas clásicas, de orden cualitativo y de orden cuantitativo, para luego hacer la crítica de ellas y ver sus inconvenientes y causas de error.

Quiero presentar un instrumento de mi invención el cual he encontrado muy útil en la amigdalectomía porque facilita considerablemente la disección de la amígdala y hace por esta razón más rápida, menos traumatizante y más "perfecta la operación. Como sabemos, las dificultades más frecuentes de la amigdalectomía son: a) El desprendimiento de la glándula de su pilar posterior y de su base por las fuertes adherencias que suelen formarse en aquellos pacientes que han hecho anginas de repetición y sobre todo en los enfermos en los cuales se han presentado flegmones de la amígdala. b) La hemorragia que suele presentarse al hacer la disección, es causa muchas veces de la demora en completar la extracción de la glándula, porque la boca del paciente se llena de sangre, no puede respirar fácilmente, se presenta tos y es necesario suspender la disección para permitir al enfermo que escupa la sangre contenida en la boca, y poder continuar la operación.

An association between hemiplegic migraine (HM) and episodic ataxia type 2 (EA2) has been described; both disorders are linked to mutations in the CACNA1A gene. Although confusion occurs in 21% of patients with HM, we found only one case in the literature of confusional episodes associated with ataxia without hemiplegia. These findings raise the possibility of confusional episodes being part of both the HM and EA2 phenotype. However, a patient with episodic ataxia, confusional spells and CACNA1A gene mutations has not been identified. We describe four individuals, spanning three generations of a family, with episodic ataxia without hemiplegia and confusion, in association with a CACNA1A mutation. We follow with a description of the relationship between the CACNA1A mutations and the three syndromes, suggesting a potential need for a new classification in which the conditions can be subsumed. [ABSTRACT FROM AUTHOR]

Background: Perry syndrome (PS) is a rare and fatal hereditary autosomal dominant neurodegenerative disorder caused by mutations in dynactin (DCTN1). PS brains accumulate inclusions positive for ubiquitin, transactive-response DNA-binding protein of 43 kDa (TDP-43), and to a lesser extent dynactin., Objectives: Little is known regarding the contributions of TDP-43, an RNA binding protein that represses cryptic exon inclusion, in PS. Therefore, we sought to identify the degree of TDP-43 dysfunction in two regions of PS brains., Methods: We evaluated the levels of insoluble pTDP-43 and TDP-43-regulated cryptic RNAs and protein in the caudate nucleus and substantia nigra of 7 PS cases, 12 cases of frontotemporal lobar degeneration (FTLD) with TDP-43 pathology, and 11 cognitively healthy controls without TDP-43 pathology., Results: Insoluble pTDP-43 protein levels were detected in PS brains to a similar extent in the caudate nucleus and substantia nigra but lower than those in FTLD brains. The caudate nucleus of PS showed accumulation of eight TDP-43-regulated cryptic RNAs (ACTL6B, CAMK2B, STMN2, UNC13A, KCNQ2, ATG4B, GPSM2, and HDGFL2) and cryptic protein (HDGFL2) characteristic of FTLD. Conversely, only one cryptic target, UNC13A, reached significance in the substantia nigra despite similar pTDP-43 levels., Conclusion: We detected TDP-43 cryptic RNAs and protein in PS caudate nucleus. Given the importance of cryptic exon biology in the development of biomarkers, and the identification of novel targets for therapeutic intervention, it is imperative we understand the consequences of TDP-43 dysfunction across different brain regions and determine the targets that are specific and common to TDP-43 proteinopathies. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society., (© 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

Recent advancements in Parkinson's disease (PD) drug development have been significantly driven by genetic research. Importantly, drugs supported by genetic evidence are more likely to be approved. While genome-wide association studies (GWAS) are a powerful tool to nominate genomic regions associated with certain traits or diseases, pinpointing the causal biologically relevant gene is often challenging. Our aim was to prioritize genes underlying PD GWAS signals. The polygenic priority score (PoPS) is a similarity-based gene prioritization method that integrates genome-wide information from MAGMA gene-level association tests and more than 57,000 gene-level features, including gene expression, biological pathways, and protein-protein interactions. We applied PoPS to data from the largest published PD GWAS in East Asian- and European-ancestries. We identified 120 independent associations with P < 5×10 -8 and prioritized 46 PD genes across these loci based on their PoPS scores, distance to the GWAS signal, and presence of non-synonymous variants in the credible set. Alongside well-established PD genes ( e.g., TMEM175 and VPS13C ), some of which are targeted in ongoing clinical trials ( i.e ., SNCA , LRRK2 , and GBA1 ), we prioritized genes with a plausible mechanistic link to PD pathogenesis ( e.g., RIT2, BAG3 , and SCARB2 ). Many of these genes hold potential for drug repurposing or novel therapeutic developments for PD ( i.e., FYN, DYRK1A, NOD2, CTSB, SV2C , and ITPKB ). Additionally, we prioritized potentially druggable genes that are relatively unexplored in PD ( XPO1, PIK3CA, EP300, MAP4K4, CAMK2D, NCOR1 , and WDR43 ). We prioritized a high-confidence list of genes with strong links to PD pathogenesis that may represent our next-best candidates for disease-modifying therapeutics. We hope our findings stimulate further investigations and preclinical work to facilitate PD drug development programs., Competing Interests: Competing interests LML, CCC, JK, AB, SA, GP, MS, NB, DP, SR and CB have nothing to disclose. KH is a former employee of 23andMe, Inc. and a current employee of Bayer AG.

There is now compelling evidence for the presence of pathological forms of Tau in tissues of both patients and animal models of Huntington's disease (HD). While the root cause of this illness is a mutation within the huntingtin gene, a number of studies now suggest that HD could also be considered a secondary tauopathy. However, the contributory role of Tau in the pathogenesis and pathophysiology of this condition, as well as its implications in cellular toxicity and consequent behavioral impairments are largely unknown. We therefore performed intracerebral stereotaxic injections of recombinant human Tau monomers and fibrils into the knock-in zQ175 mouse model of HD. Tau fibrils induced cognitive and anxiety-like phenotypes predominantly in zQ175 mice and increased the number and size of insoluble mutant huntingtin (mHTT) aggregates in the brains of treated animals. To better understand the putative mechanisms through which Tau could initiate and/or contribute to pathology, we incubated StHdh striatal cells, an in vitro model of HD, with the different Tau forms and evaluated the effects on cell functionality and heat shock proteins Hsp70 and Hsp90. Calcium imaging experiments showed functional impairments of HD StHdh cells following treatment with Tau fibrils, as well as significant changes to the levels of both heat shock proteins which were found trapped within mHTT aggregates. The accumulation of Hsp70 and 90 within aggregates was also present in mouse tissue which suggests that alteration of molecular chaperone-dependent protein quality control may influence aggregation, implicating proteostasis in the mHTT-Tau interplay., Competing Interests: Declaration of competing interest The authors declare no competing interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Multiple scientific studies, mostly performed within European populations, have unraveled many of the genetic factors associated with Alzheimer's disease (AD) and Parkinson's disease (PD) etiologies, improving our understanding of the molecular pathways implicated in the pathogenesis of these conditions. However, there is increasing evidence that the genetic architecture of these diseases differs across ancestral populations. This raises concerns about the efficacy of therapeutic interventions crafted around genetic targets prevalent only in European ancestry populations. Such interventions neglect potentially distinctive etiological profiles, including Latino, Black/African American, and East Asian populations. In the current study, we explore Population Attributable Risk (PAR) in AD and PD etiologies and assess the proportion of disease attributed to specific genetic factors across diverse populations. Leveraging data from genome-wide association studies across four ancestries, we explore distinct and universal therapeutic targets across diverse populations. Multi-ancestral genetics research is critical to the development of successful therapeutics and treatments for neurodegenerative diseases. By offering insights into genetic disparities, we aim to inform more inclusive and effective therapeutic strategies, advancing personalized healthcare., Competing Interests: Conflicts of interest: L.J., H.I, M.B.M, and M.A.N.’s participation in this project was part of a competitive contract awarded to DataTecnica LLC by the National Institutes of Health to support open science research. M.A.N. also currently serves on the scientific advisory board at Clover Therapeutics and is an advisor and scientific founder at Neuron23 Inc.

Parkinson's disease (PD) is a global health challenge, yet historically studies of PD have taken place predominantly in European populations. Recent genetics research conducted in non-European populations has revealed novel population-specific genetic loci linked to PD risk, highlighting the importance of studying PD globally. These insights have broadened our understanding of PD etiology, which is crucial for developing disease-modifying interventions. This review comprehensively explores the global genetic landscape of PD, emphasizing the scientific rationale for studying underrepresented populations. It underscores challenges, such as genotype-phenotype heterogeneity and inclusion difficulties for non-European participants, emphasizing the ongoing need for diverse and inclusive research in PD. ANN NEUROL 2024;95:831-842., (© 2024 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Introduction: A marked response to L-Dopa and L-Dopa-induced dyskinesia (LID) make the diagnosis of Parkinson's disease (PD) highly likely. This paper evaluates response to L-Dopa in Perry syndrome (PS), parkinsonism with distinct molecular and neuropathologic characteristics., Methods: Six patients with PS with a mean follow-up of 5 years (0.5-12) were assessed by movement disorder specialists and video recorded in states off and on. Additionally, DATSCAN-SPECT was performed in 3 subjects., Results: Four patients displayed a marked and sustained response to L-Dopa and LID. Additionally, we observed a distinct pattern of off-state predominant craniocervical dystonia responsive to L-Dopa in 4 patients, truncal dystonia in one, and dystonic head tremor in another. DATSCAN-SPECT was abnormal in 3 patients., Conclusions: Patients with PS may present PD-like parkinsonism with a marked and sustained response to L-Dopa and LID. The characteristic pattern of craniocervical dystonia may be a helpful clue to the diagnosis of PS., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background and Purpose: Perry disease (or Perry syndrome) is an autosomal dominant neurodegenerative disorder characterized by parkinsonism, neuropsychiatric symptoms, central hypoventilation, weight loss and distinct TDP-43 pathology. It is caused by mutations of the DCTN1 gene encoding an essential component of axonal transport. The objectives were to provide the current state of knowledge on clinical, pathological and genetic aspects of Perry disease, as well as practical suggestions for the management of the disease., Methods: Data on new patients from New Zealand, Poland and Colombia were collected, including autopsy report. Also all of the published papers since the original work by Perry in 1975 were gathered and analyzed., Results: Parkinsonism was symmetrical, progressed rapidly and was poorly responsive to L-Dopa; nonetheless, a trial with high doses of L-Dopa is warranted. Depression was severe, associated with suicidal ideations, and benefited from antidepressants and L-Dopa. Respiratory symptoms were the leading cause of death, and artificial ventilation or a diaphragm pacemaker prolonged survival. Weight loss occurred in most patients and was of multifactorial etiology. Autonomic dysfunction was frequent but underdiagnosed. There was a clinical overlap with other neurodegenerative disorders. An autopsy showed distinctive pallidonigral degeneration with TDP-43 pathology. Genetic testing provided evidence of a common founder for two families. There was striking phenotypic variability in DCTN1-related disorders. It is hypothesized that oligogenic or polygenic inheritance is at play., Conclusions: Perry disease and other DCTN1-related diseases are increasingly diagnosed worldwide. Relatively effective symptomatic treatments are available. Further studies are needed to pave the way toward curative/gene therapy., (© 2021 European Academy of Neurology.)

Objective: Perry syndrome (PS) is a rare neurodegenerative disorder with autosomal dominant inheritance caused by point mutations in DCTN1 and characterized by parkinsonism, hypoventilation, weight loss, and psychiatric symptoms. Even though behavioral manifestation is a main feature of PS, detailed neuropsychological assessment was not performed in this cohort. In this study, the neuropsychological profile of individuals from one Polish and one Colombian family are presented., Methods: Detailed clinical and neuropsychological data were obtained from Polish and Colombian families. Clinical and neuropsychological examinations on the proband from the Polish family were performed 6 times over 11 years. Each of 3 individuals from the Colombian family received a clinical and neuropsychological assessment., Results: The neurologic examination showed severe parkinsonism, levodopa-induced motor fluctuations, and dyskinesias in all cases. Respiratory insufficiency was observed in 2 patients and weight loss in 1 individual. Neuropsychological assessment revealed predominant deterioration of working memory and learning capacity in the Polish patient. He also demonstrated compulsive behaviors, such as excessive shopping and eating, but only in the "on" phase. In the Colombian family, attentional deficits were present in 2 out of 3 cases. Out of 4 reported cases apathy and depressed mood were present in 2 individuals. Two cases demonstrated impulsivity and one had episodes of hypomania., Conclusions: Both of these families revealed relatively similar neurologic and neuropsychological profiles. The Polish patient's behavioral and neuropsychological profile was mostly compatible with a behavioral variant of frontotemporal dementia. Of note, not only depression and apathy, but also impulsivity can occur in PS., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: The incidences of dystonic reactions to metoclopramide and prochlorperazine have not been well characterized in children., Methods: Medical record data were reviewed for patients at a tertiary care pediatric hospital who received metoclopramide or prochlorperazine for treatment of headache., Results: A total of 4588 clinical encounters were identified, 2542 with prochlorperazine and 2046 with metoclopramide. One patient had a dystonic reaction with metoclopramide (0.049%). Eleven patients had a dystonic reaction with prochlorperazine (0.43%). The relative risk of a dystonic reaction with prochlorperazine over metoclopramide is 8.85 (95% confidence interval 1.15 to 68.5). There were differences between groups of patients who received metoclopramide versus prochlorperazine in terms of age, number of doses, and coadministration of diphenhydramine. In a logistic regression, administration of prochlorperazine over metoclopramide (P = 0.019) and greater number of doses (P < 0.001) remained associated with acute dystonic reactions., Conclusions: Dystonic reactions are rare events among pediatric patients treated for acute headache, but are more common with prochlorperazine than metoclopramide., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Headache is the third leading cause of referral to a pediatric emergency room. It is imperative for providers to be able to rule out rare but possible life-threatening disorders, such as meningitis, intracranial hemorrhage, brain tumor, or hydrocephalus. Most of the presenting headaches are secondary to viral illnesses followed by primary headache and migraine. A detailed initial evaluation is essential to guide toward necessary testing as well as diagnosis., (Copyright 2010 Elsevier Inc. All rights reserved.)

Telcagepant is an oral calcitonin-gene related peptide (CGRP) receptor antagonist that is being developed by Merck & Co Inc for the treatment of migraine. This compound blocks CGRP receptors and may block the dilation of dural vessels and reduce neurotransmission in the CNS, resulting in pain relief. Telcagepant does not cause vasoconstriction, one of the major limitations in the use of triptans, which are considered to be the standard of care for migraine. Data from phase II and III clinical trials suggest that the use of telcagepant for the acute treatment of migraine was comparable with the use of triptan compounds and was superior to placebo in all primary endpoints, including pain relief and freedom from pain at 2 h. However, recent data reported elevated transaminase levels when telcagepant was dosed daily rather than acutely. It was concluded that, if these hepatic toxicities are not observed in ongoing/future trials of the acute use of telcagepant, then this agent may offer an alternative to triptan therapy for the treatment of migraine.

Patent foramen ovale (PFO) appears to be associated with migraine with aura (MA), probably through cardiac shunting. PFOs may also be comorbid with cryptogenic strokes. Although multiple open-label, retrospective, and case-controlled studies have noted sometimes dramatic reductions of MA after PFO closure, the only prospective sham-controlled study of PFO closure for MA, MIST, was negative for all primary and secondary measures of migraine improvement. MIST did demonstrate an association between MA and severe PFO shunts prospectively. Difficulty with recruitment closed the MIST II and ESCAPE trials; the PREMIUM and PRIMA randomized controlled trials are ongoing at the time of this writing.

Sumatriptan 85 mg with naproxen sodium 500 mg, a combination tablet for the acute treatment of migraine, is approved in the USA. It is likely that triptan/NSAID combination benefits are a class effect, although the majority of data are on sumatriptan and naproxen sodium. The combination tablet demonstrated superior effectiveness over its individual components or placebo in two Phase III regulatory trials on six coprimary end points. The pharmacokinetic shifts in the combination tablet result in an earlier T(max) for sumatriptan, a later T(max) for naproxen sodium and a reduction of the C(max) by 36% for naproxen sodium compared with the components alone. In addition, the 85 mg dose of sumatriptan in the combination tablet has an area under the curve similar to 100 mg of sumatriptan alone. The clinical advantage of the sumatriptan and naproxen sodium combination is likely to be prolonged benefit per attack, that is, a sustained pain-free response.