Diagnostic investigation and multidisciplinary management in motor neuron disease

Rocha, Afonso; Reis, Carina; Simões, F; Fonseca, José Honório de Almeida Palma da; Ribeiro, J Mendes

doi:10.1007/s00415-005-0007-9

Cited by 57 publications

(47 citation statements)

References 98 publications

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“…The clinical failure of minocycline in human ALS [24] may have involved the inadvertent toxicity to motor neurons due to nonselective oral drug administration or the inability to deliver sufficient amounts of drug to the desired site of action. Current treatment for ALS includes only one FDA approved drug (riluzole) that has exhibited modest and variable efficacy [37][38][39][40]. In addition to novel pharmaceutical agents, novel delivery platforms of agents that show efficacy should be evaluated and the findings debated in the literature.…”

Section: Discussionmentioning

confidence: 99%

Lipopolysaccharide Modified Liposomes for Amyotropic Lateral Sclerosis Therapy: Efficacy in SOD1 Mouse Model

Wiley¹,

Madhankumar²,

Mitchell³

et al. 2012

ANP

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Activation of microglia is a histological feature observed in neurodegenerative diseases like ALS. The oral administration of minocycline has been demonstrated to have minimal neuroprotection ability in the animal models and is also associated with inadvertent toxicity due to non-specific oral absorption of the drug. Nonetheless, the drug itself shows promise in a number of disease models suggesting it could be effective if delivered optimally. Thus, we utilized LPS modified liposomes to target TLR4 receptor on the microglia in SOD1 G93A mice and compared its efficacy with nontargeted nanoliposomes. The in vitro results indicate that targeting the TLR4 receptor on microglia significantly increases (p < 0.01) the uptake of drug by 29% compared to non-targeted liposomes. In the SOD1 G93A mouse model of ALS, targeted and non-targeted minocycline treatment significantly increased (p < 0.05) latency to endpoint stages compared to control mice. Targeting liposomes to microglia significantly delayed disease progression. Both targeted and non-targeted liposomes administration in SOD1 mice resulted in decreased TNF-α secretion in activated BV-2 microglial cells as compared to activated cells receiving no treatment. The non-targeted liposomes had a greater effect than the targeted liposomes in reducing the levels of TNF-α released by the BV-2 cells. In SOD1 G93A mice, the nontargeted nanovesicles significantly increased the latency to rotarod failure and both targeted and non-targeted nanovesicles significantly delayed disease endpoints.

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Section: Discussionmentioning

confidence: 99%

Lipopolysaccharide Modified Liposomes for Amyotropic Lateral Sclerosis Therapy: Efficacy in SOD1 Mouse Model

Wiley¹,

Madhankumar²,

Mitchell³

et al. 2012

ANP

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“…Lactulose e polietilenoglicol podem ser usados como agentes osmóticos. (ROCHA et al, 2005) O aumento da frequência urinária é muito comum nos portadores de ELA. Medidas não farmacológicas incluem: evitar cafeína, álcool e uso de sonda de Foley.…”

Section: Terapêutica De Manipulação Celularunclassified

Esclerose lateral amiotrófica

Bertazzi¹,

Martins²,

Saade³

et al. 2017

Rev Pat Tocantins

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A Esclerose Lateral Amiotrófica (ELA) é uma desordem neurodegenerativa dos neurônios motores, invariavelmente progressiva e incapacitante. Sua complexidade e multifatorialidade são determinantes para a dificuldade de tratamentos específicos, embora este cenário tenha mudado nos últimos anos. OBJETIVOS: realizar uma revisão de literatura acerca da ELA, utilizando os agregadores de conteúdo PubMed, BVS e ScieLo. EPIDEMIOLOGIA: A ELA é rara, com predominância de 2:1 em gênero masculino e possui incidência estimada em 1 para 105 habitantes, com prevalência constante. ETIOPATOGÊNESE: Verificadas alterações genéticas em SOD1, FUS, ANG, proteínopatia em TDP-43, dentre outras, que associadas a fatores como exotocicidade, fatores quimiotáxicos de neutrófilos, estresse oxidativo, distúrbios intracelulares do metabolismo do cálcio, lesão mitocondrial, fatores ambientais, infecções e autoimunidade parecem estar implicadas na lesão neuronal. SINTOMATOLOGIA: A entidade progride para perda dos movimentos refinados de prensa, deglutição e fala, acompanhados de miastenia, fasciculações e cãimbras, alentecimento motor, e efeitos pseudobulbares com perda do controle do riso/choro, poupando as funções sensitivas, mantendo a propriocepção do doente. TRATAMENTO: somente o riluzol é aprovado para uso específico, porém outras drogas podem ser usadas: anti-inflamatórios, antiapoptose, anticititóxicos, antioxidantes e mais os inibidores da SOD1. Intervenções cirúrgicas vêm sendo experimentadas, algumas com resultados promissores. O tratamento de suporte deve permear o cuidado com a sialorréia, efeitos pseudobulbares, distúrbios do sono, insuficiência respiratória, fadiga, dor, espasticidade e o laringoespasmo. CONCLUSÃO: Nas últimas décadas, em especial, vimos avanços na determinação dos diferentes elementos da patologia, contudo a terapêutica específica continua restrita. A visibilidade midiática foi importante na implementação de novos estudos. Palavras-chave: Esclerose Amiotrófica Lateral, Doença do Neurônio Motor. ABSTRACT Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disorder of motor neurons, invariably progressive and incapacitating. Your complexity and multifactoriality are determinant for the difficulty of specific treatments, although this scenario has changed in recent years. OBJECTIVES: Make a literature review on ALS using the PubMed, BVS and ScieLo. EPIDEMIOLOGY: ALS is a rare condition, with a predominance of 2:1 in men and has an estimated incidence of 1 to 105 habitants, with a constant prevalence. ETHIOPATHOGENESIS: The presence of genetic alterations in SOD1, FUS, ANG, TDP-43, and others, have been verified, such as exotocicity, neutrophil quimiotaxic factors, oxidative stress, intracellular disorders of calcium metabolism, mitochondrial damage, environmental factors, infections and autoimmunity appear to be implicated in neuronal injury. SYMPTOMATOLOGY: The entity progresses to loss of refined movements of the press, swallowing and speech, accompanied by myasthenia, fasciculations and cramps, motor eningement, and pseudobulbar effects with loss of control of laughter/crying, sparing the sensory functions, preserving the proprioception of the patient. TREATMENT: Only riluzoleis approved for specific use, but other drugs may be used: anti-inflammatories, anti-apoptosis, anti-cytotoxic agents, antioxidants, and SOD1 inhibitors. Surgical interventions have been tried, some with promissory results. The supportive treatment should permeate the care with sialorrhea, pseudobulbar effects, sleep disturbers, respiratory failure, fatigue, pain, spasticity and laryngospasm. CONCLUSION: In the last decades, in particular, we have seen some advances in the determination of the different elements of the pathology, however the specific therapy remains restricted. The media visibility was important in the implementation of new studies. Keywords: Lateral Amyotrophic Sclerosis. Motor Neuron Disease.

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“…Degeneration associated with ALS occurs in the pyramidal neurons (Betz cells, 5 th layer of cerebral cortex) of the precentral gyrus (area 4, motor cortex) and alpha motor neurons from the brainstem and spinal cord. 25 The precise etiology or pathophysiologic mechanism is unknown. For approximately 2/3 of individuals with ALS, degeneration will begin in the limbs (either upper and/or lower extremities).…”

Section: Literature Reviewmentioning

confidence: 99%

Associations Between Laryngeal and Cough Dysfunction in Motor Neuron Disease with Bulbar Involvement

et al. 2014

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Diagnostic investigation and multidisciplinary management in motor neuron disease

Cited by 57 publications

References 98 publications

Lipopolysaccharide Modified Liposomes for Amyotropic Lateral Sclerosis Therapy: Efficacy in SOD1 Mouse Model

Lipopolysaccharide Modified Liposomes for Amyotropic Lateral Sclerosis Therapy: Efficacy in SOD1 Mouse Model

Esclerose lateral amiotrófica

Associations Between Laryngeal and Cough Dysfunction in Motor Neuron Disease with Bulbar Involvement

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