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1.
J Neurol Neurosurg Psychiatry ; 89(6): 566-571, 2018 06.
Artículo en Inglés | MEDLINE | ID: mdl-29549192

RESUMEN

OBJECTIVE: To ascertain demographic and clinical features of Parkinson disease (PD) associated with functional neurological features. METHODS: A standardised form was used to extract data from electronic records of 53 PD patients with associated functional neurological disorders (PD-FND) across eight movement disorders centres in the USA, Canada and Europe. These subjects were matched for age, gender and disease duration to PD patients without functional features (PD-only). Logistic regression analysis was used to compare both groups after adjusting for clustering effect. RESULTS: Functional symptoms preceded or co-occurred with PD onset in 34% of cases, nearly always in the most affected body side. Compared with PD-only subjects, PD-FND were predominantly female (68%), had longer delay to PD diagnosis, greater prevalence of dyskinesia (42% vs 18%; P=0.023), worse depression and anxiety (P=0.033 and 0.025, respectively), higher levodopa-equivalent daily dose (972±701 vs 741±559 mg; P=0.029) and lower motor severity (P=0.019). These patients also exhibited greater healthcare resource utilisation, higher use of [(123)I]FP-CIT SPECT and were more likely to have had a pre-existing psychiatric disorder (P=0.008) and family history of PD (P=0.036). CONCLUSIONS: A subtype of PD with functional neurological features is familial in one-fourth of cases and associated with more psychiatric than motor disability and greater use of diagnostic and healthcare resources than those without functional features. Functional manifestations may be prodromal to PD in one-third of patients.


Asunto(s)
Enfermedades del Sistema Nervioso/epidemiología , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/fisiopatología , Anciano , Antiparkinsonianos/uso terapéutico , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedades del Sistema Nervioso/diagnóstico , Enfermedad de Parkinson/tratamiento farmacológico , Prevalencia , Factores de Riesgo
3.
J Clin Med ; 9(11)2020 Nov 16.
Artículo en Inglés | MEDLINE | ID: mdl-33207828

RESUMEN

SRX246 is a vasopressin (AVP) 1a receptor antagonist that crosses the blood-brain barrier. It reduced impulsive aggression, fear, depression and anxiety in animal models, blocked the actions of intranasal AVP on aggression/fear circuits in an experimental medicine fMRI study and demonstrated excellent safety in Phase 1 multiple-ascending dose clinical trials. The present study was a 3-arm, multicenter, randomized, placebo-controlled, double-blind, 12-week, dose escalation study of SRX246 in early symptomatic Huntington's disease (HD) patients with irritability. Our goal was to determine whether SRX246 was safe and well tolerated in these HD patients given its potential use for the treatment of problematic neuropsychiatric symptoms. Participants were randomized to receive placebo or to escalate to 120 mg twice daily or 160 mg twice daily doses of SRX246. Assessments included standard safety tests, the Unified Huntington's Disease Rating Scale (UHDRS), and exploratory measures of problem behaviors. The groups had comparable demographics, features of HD and baseline irritability. Eighty-two out of 106 subjects randomized completed the trial on their assigned dose of drug. One-sided exact-method confidence interval tests were used to reject the null hypothesis of inferior tolerability or safety for each dose group vs. placebo. Apathy and suicidality were not affected by SRX246. Most adverse events in the active arms were considered unlikely to be related to SRX246. The compound was safe and well tolerated in HD patients and can be moved forward as a candidate to treat irritability and aggression.

4.
Mov Disord Clin Pract ; 2(1): 29-32, 2015 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-25961068

RESUMEN

OBJECTIVE: To determine the diagnostic value of effort-associated behaviors ("huffing and puffing" spectrum) in patients with psychogenic movement disorders. METHODS: Three blinded clinicians rated presence, severity, and duration of effort-associated features during standing and walking tasks on edited videos of 131 patients with psychogenic gait disorders and 37 patients with organic gait disorders. RESULTS: Huffing, grunting, grimacing, and breath holding were the most common effort-associated behaviors in patients with psychogenic gait disorders, with a combined prevalence of 44% and disproportionate to the severity of gait impairment compared to organic gait disorders. The presence of "huffing and puffing"-type behaviors yielded a relatively low sensitivity but high specificity for the diagnosis of psychogenic movement disorders, increasing the odds of diagnosis 13-fold (95%, CI: 4.2-43.8) compared to organic gait disorders. CONCLUSIONS: Demonstration of effort-associated behaviors during standing and walking strongly supports the psychogenic nature of disorders when gait is involved.

6.
Cell Biol Int ; 31(12): 1470-81, 2007 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-17716930

RESUMEN

Rb/E2F regulates many genes that encode proteins required for the cell cycle. Using affymetrix microarrays we previously identified genes regulated by the Rb proteins p130 and p107, many of which are involved in the cell cycle. Several genes with unknown functions were also repressed by p130 and p107, of which some have recently been found to have various roles in mitosis, the spindle checkpoint and cytokinesis. This study focuses on the regulation of borealin/dasra/cdca8, which encodes a recently discovered member of the chromosomal passenger complex. It is recorded that borealin is a cell cycle regulator, down-regulated in response to p53/Rb-signaling, and up-regulated in many types of cancerous tissues.


Asunto(s)
Proteínas de Ciclo Celular/metabolismo , Regulación de la Expresión Génica/fisiología , Genes p53/fisiología , Neoplasias/genética , Proteína de Retinoblastoma/metabolismo , Transducción de Señal/fisiología , Proteína p53 Supresora de Tumor/metabolismo , Empalme Alternativo/genética , Biomarcadores de Tumor/metabolismo , Ciclo Celular , Proteínas de Ciclo Celular/genética , División Celular/genética , Factores de Transcripción E2F/genética , Factores de Transcripción E2F/metabolismo , Silenciador del Gen , Células HCT116 , Humanos , Neoplasias/metabolismo , Proteína de Retinoblastoma/genética , Proteína p107 Similar a la del Retinoblastoma/genética , Proteína p107 Similar a la del Retinoblastoma/metabolismo , Proteína p130 Similar a la del Retinoblastoma/genética , Proteína p130 Similar a la del Retinoblastoma/metabolismo , Transcripción Genética , Proteína p53 Supresora de Tumor/genética
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