Manejo multidisciplinario y avances terapéuticos en la esclerosis lateral amiotrófica / Multidisciplinary care and therapeutic advances in amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that mainly affects the motor system, resulting in progressive weakness and muscle wasting. Despite the tremendous advances in physiopathological and clinical characterization, we do not have a curative treatment yet. The progressive and fatal course of ALS makes its management particularly complex and challenging given the diversity of symptoms presenting during the disease progression. The main goal in the treatment of ALS patients is to minimize morbidity and maximize the quality of life. Currently, a series of therapeutic interventions improve the quality of life and prolong survival, including multidisciplinary care, respiratory management, and disease-modifying therapy. Within the supportive interventions, weight maintenance through nutritional and metabolic support is critical. In addition, the management of neuropsychiatric manifestations and preservation of communicative capacity before speech loss are also crucial. Lastly, early palliative care intervention is essential to optimize symptomatic management. Anticipatory guidelines to face the inevitable patient deterioration should be devised. This article updates the main therapeutic strategies used in these patients, including evolving clinical trials with promising novel therapies.

Genetic Profile of Patients with Limb-Girdle Muscle Weakness in the Chilean Population.

Hereditary myopathies are a group of genetically determined muscle disorders comprising more than 300 entities. In Chile, there are no specific registries of the distinct forms of these myopathies. We now report the genetic findings of a series of Chilean patients presenting with limb-girdle muscle weakness of unknown etiology. Eighty-two patients were explored using high-throughput sequencing approaches with neuromuscular gene panels, establishing a definite genetic diagnosis in 49 patients (59.8%) and a highly probable genetic diagnosis in eight additional cases (9.8%). The most frequent causative genes identified were DYSF and CAPN3, accounting for 22% and 8.5% of the cases, respectively, followed by DMD (4.9%) and RYR1 (4.9%). The remaining 17 causative genes were present in one or two cases only. Twelve novel variants were identified. Five patients (6.1%) carried a variant of uncertain significance in genes partially matching the clinical phenotype. Twenty patients (24.4%) did not carry a pathogenic or likely pathogenic variant in the phenotypically related genes, including five patients (6.1%) presenting an autoimmune neuromuscular disorder. The relative frequency of the different forms of myopathy in Chile is like that of other series reported from different regions of the world with perhaps a relatively higher incidence of dysferlinopathy.

[Multidisciplinary care and therapeutic advances in amyotrophic lateral sclerosis]. / Manejo multidisciplinario y avances terapéuticos en la esclerosis lateral amiotrófica.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that mainly affects the motor system, resulting in progressive weakness and muscle wasting. Despite the tremendous advances in physiopathological and clinical characterization, we do not have a curative treatment yet. The progressive and fatal course of ALS makes its management particularly complex and challenging given the diversity of symptoms presenting during the disease progression. The main goal in the treatment of ALS patients is to minimize morbidity and maximize the quality of life. Currently, a series of therapeutic interventions improve the quality of life and prolong survival, including multidisciplinary care, respiratory management, and disease-modifying therapy. Within the supportive interventions, weight maintenance through nutritional and metabolic support is critical. In addition, the management of neuropsychiatric manifestations and preservation of communicative capacity before speech loss are also crucial. Lastly, early palliative care intervention is essential to optimize symptomatic management. Anticipatory guidelines to face the inevitable patient deterioration should be devised. This article updates the main therapeutic strategies used in these patients, including evolving clinical trials with promising novel therapies.

Reliability and reproducibility of visual e-norms plateau identification.

OBJECTIVE: To derive normal values from a lab's own diagnostic studies, the e-norms method relies on the proper identification of the e-norms plateau to derive descriptive statistics of the variable under study. This work was undertaken to compare the inter and intra-rater reliability of visual identification of the plateau by different raters analyzing laboratory nerve conductions study data. METHODS: Twenty raters were asked to visually identify the inflection points delineating an e-norms plateau to derive the Mean value of nerve conduction study laboratory data while blinded to the parameter they were analyzing. After a delay of 1-3 months, the same raters were asked to repeat some of the e-norms plateaus identification to assess delayed intra-rater reproducibility. RESULTS: Mean values derived from the identified plateau data were compared between raters (inter-rater) using a two factor ANOVA without replication. For the immediate inter-rater no statistically significant difference was found between the Means obtained by the different raters. For the delayed intra-rater, differences were found between raters. CONCLUSIONS: This study suggests that visual identification of the e-norms plateau inflection point is reliable between raters but more research is needed to assess reproducibility for the same raters. SIGNIFICANCE: E-norms is a promising method for deriving reference values using data that is available in most electrophysiology laboratories.

[Postural orthostatic tachycardia syndrome (POTS): report of 15 cases]. / Taquicardia postural ortostática en 15 pacientes: disautonomía compleja.

BACKGROUND: Patients with postural orthostatic tachycardia syndrome (POTS) report dizziness, lightheadedness, weakness, blurred vision, and fatigue upon standing. The diagnosis of the syndrome is made when an orthostatic intolerance and tachycardia appear in the standing position. AIM: To report 15 patients with POTS. MATERIAL AND METHODS: Review of Tilt test reports in a period of 15 years. Those reports in which orthostatic postural tachycardia and symptoms compatible with POTS appeared, were selected for analysis. RESULTS: We identified 15 patients (3.1% of all positive Tilt test reports) with compatible signs and symptoms. There was a lag of 8 -10 years between the onset of symptoms and the time of diagnosis. Most patients complained of orthostatic intolerance, dizziness and frequent fainting. Orthostatic tachycardia and symptoms occurred on average after 2.9 and 6.1 minutes, respectively,of staying in the standing position. These patients had a high frequency of family history of syncope orpresyncope (66% frequency) and hyper mobility syndrome (53% prevalence). Only 33% of the patients reported relief of their symptoms after being treated (most of them with fludrocortisone). Most patients that reported little or no relief, did not use medications or were treated for a short period. CONCLUSIONS: POTS syndrome is uncommon but disturbs quality of life of those who suffer it. Its association with hyper mobility syndromes must be investigated.