Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 167
Filtrar
1.
Physiol Behav ; 281: 114563, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38723388

RESUMEN

Parkinson's Disease (PD) is a neurodegenerative movement disorder characterized by dopamine (DA) cell loss in the substantia nigra pars compacta (SNc). As PD progresses, patients display disruptions in gait such as changes in posture, bradykinesia, and shortened stride. DA replacement via L-DOPA alleviates many PD symptoms, though its effects on gait are not well demonstrated. This study aimed to assess the relationship between DA lesion, gait, and deficit-induced reversal with L-DOPA. To do so, Sprague-Dawley rats (N = 25, 14 males, 11 females) received unilateral medial forebrain bundle (MFB) DA lesions with 6-hydroxydopamine (6-OHDA). An automated gait analysis system assessed spatiotemporal gait parameters pre- and post-lesion, and after various doses of L-DOPA (0, 3, or 6 mg/kg; s.c.). The forepaw adjusting steps (FAS) test was implemented to evaluate lesion efficacy while the abnormal involuntary movements (AIMs) scale monitored the emergence of L-DOPA-induced dyskinesia (LID). High performance liquid chromatography (HPLC) assessed changes in brain monoamines on account of lesion and treatment. Results revealed lesion-induced impairments in gait, inclusive of max-contact area and step-sequence alterations that were not reversible with L-DOPA. However, the emergence of AIMs were observed at higher doses. Post-mortem, 6-OHDA lesions induced a loss of striatal DA and norepinephrine (NE), while prefrontal cortex (PFC) displayed noticeable reduction in NE but not DA. Our findings indicate that hemiparkinsonian rats display measurable gait disturbances similar to PD patients that are not rescued by DA replacement. Furthermore, non-DA mechanisms such as attention-related NE in PFC may contribute to altered gait and may constitute a novel target for its treatment.


Asunto(s)
Trastornos Neurológicos de la Marcha , Levodopa , Oxidopamina , Ratas Sprague-Dawley , Animales , Levodopa/farmacología , Levodopa/efectos adversos , Masculino , Femenino , Ratas , Trastornos Neurológicos de la Marcha/inducido químicamente , Trastornos Neurológicos de la Marcha/tratamiento farmacológico , Trastornos Neurológicos de la Marcha/etiología , Antiparkinsonianos/farmacología , Modelos Animales de Enfermedad , Haz Prosencefálico Medial/efectos de los fármacos , Trastornos Parkinsonianos/inducido químicamente , Trastornos Parkinsonianos/tratamiento farmacológico , Trastornos Parkinsonianos/fisiopatología , Trastornos Parkinsonianos/patología , Dopamina/metabolismo , Relación Dosis-Respuesta a Droga , Lateralidad Funcional/efectos de los fármacos , Enfermedad de Parkinson/tratamiento farmacológico , Enfermedad de Parkinson/patología , Enfermedad de Parkinson/fisiopatología , Marcha/efectos de los fármacos , Discinesia Inducida por Medicamentos
2.
Clin Med (Lond) ; 22(2): 169-171, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-35304379

RESUMEN

Carbamazepine remains a first-line antiepileptic medication for the treatment of partial seizures. Despite its widespread use, carbamazepine has significant neurotoxicity and hypersensitivity reactions. We report a case of a patient post-kidney transplant who was on regular carbamazepine for childhood epilepsy and developed nystagmus, diplopia and a broad-base gait after receiving diltiazem. Understanding of the interaction between diltiazem and carbamazepine is necessary to prevent the neurotoxic effects.


Asunto(s)
Anticonvulsivantes , Carbamazepina , Diltiazem , Trasplante de Riñón , Anticonvulsivantes/efectos adversos , Carbamazepina/efectos adversos , Niño , Diltiazem/efectos adversos , Diplopía/inducido químicamente , Interacciones Farmacológicas , Marcha , Trastornos Neurológicos de la Marcha/inducido químicamente , Humanos , Nistagmo Patológico/inducido químicamente
3.
Proc Natl Acad Sci U S A ; 118(51)2021 12 21.
Artículo en Inglés | MEDLINE | ID: mdl-34911753

RESUMEN

Cancer survivors rank sensorimotor disability among the most distressing, long-term consequences of chemotherapy. Disorders in gait, balance, and skilled movements are commonly assigned to chemotoxic damage of peripheral sensory neurons without consideration of the deterministic role played by the neural circuits that translate sensory information into movement. This oversight precludes sufficient, mechanistic understanding and contributes to the absence of effective treatment for reversing chemotherapy-induced disability. We rectified this omission through the use of a combination of electrophysiology, behavior, and modeling to study the operation of a spinal sensorimotor circuit in vivo in a rat model of chronic, oxaliplatin (chemotherapy)-induced neuropathy (cOIN). Key sequential events were studied in the encoding of propriosensory information and its circuit translation into the synaptic potentials produced in motoneurons. In cOIN rats, multiple classes of propriosensory neurons expressed defective firing that reduced accurate sensory representation of muscle mechanical responses to stretch. Accuracy degraded further in the translation of propriosensory signals into synaptic potentials as a result of defective mechanisms residing inside the spinal cord. These sequential, peripheral, and central defects compounded to drive the sensorimotor circuit into a functional collapse that was consequential in predicting the significant errors in propriosensory-guided movement behaviors demonstrated here in our rat model and reported for people with cOIN. We conclude that sensorimotor disability induced by cancer treatment emerges from the joint expression of independent defects occurring in both peripheral and central elements of sensorimotor circuits.


Asunto(s)
Antineoplásicos/efectos adversos , Trastornos Neurológicos de la Marcha/inducido químicamente , Mecanorreceptores/efectos de los fármacos , Médula Espinal/efectos de los fármacos , Animales , Femenino , Masculino , Neoplasias/tratamiento farmacológico , Propiocepción/efectos de los fármacos , Ratas Endogámicas F344
4.
J Intellect Disabil Res ; 64(10): 793-803, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32885545

RESUMEN

BACKGROUND: Adults with intellectual disabilities (ID) often have polypharmacy and often use antipsychotics. Both polypharmacy and antipsychotics have a negative effect on gait in the general population, but this has not been studied in adults with ID. These negative effects may add to pre-existing gait disturbances in adults with ID and increase the risk for adverse health outcomes in this population. Therefore, the aim of this study is to investigate the difference in gait parameters between adults with ID with and without polypharmacy and between adults with ID using and not using antipsychotics. METHOD: The gait parameters of 31 participants were collected with the GAITRite walkway, a pressure sensitive walkway measuring spatial and temporal gait parameters, in addition to information about personal characteristics, prescribed medication and presence of polypharmacy. RESULTS: After adjustment for sex and body mass index, participants with polypharmacy had a significantly shorter step length [polypharmacy B (SE) = -0.079 (0.034), P = 0.03], shorter stride length [polypharmacy B (SE) = -0.157 (0.069), P = 0.03] and longer double support time [polypharmacy B (SE) = 0.0004 (0.0001), P = 0.047]. Participants using antipsychotics had a significantly longer double support time [antipsychotic use B (SE) = 0.0003 (0.0002), P = 0.019]. CONCLUSION: This study showed for the first time that both polypharmacy and using antipsychotics are associated with gait in adults with ID. The differences seem to resemble a more cautious gait. Further investigation with larger study samples, additional medication types and dosages are needed to acquire more insight in this important topic.


Asunto(s)
Antipsicóticos/efectos adversos , Trastornos Neurológicos de la Marcha/inducido químicamente , Discapacidad Intelectual/tratamiento farmacológico , Polifarmacia , Adulto , Antipsicóticos/uso terapéutico , Estudios Transversales , Femenino , Marcha/efectos de los fármacos , Trastornos Neurológicos de la Marcha/fisiopatología , Humanos , Discapacidad Intelectual/fisiopatología , Masculino , Persona de Mediana Edad
5.
J Parkinsons Dis ; 10(3): 1245-1248, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32417798

RESUMEN

The relation between freezing of gait in Parkinson's disease and levodopa is complex. Here, we describe a new phenotype of freezing of gait, namely levodopa-induced freezing of gait with a biphasic pattern. Our observation supports the idea that freezing of gait might emerge because of a mismatch between cognitive/limbic loops and motor loops involved in gait control. Moreover, it underscores the importance of assessing the influence of dopaminergic medication in daily clinical practice, including objective assessment in all three dopaminergic states. The possibility of biphasic freezing will only emerge after such a comprehensive evaluation, and will have immediate therapeutic consequences.


Asunto(s)
Carbidopa/administración & dosificación , Carbidopa/efectos adversos , Agonistas de Dopamina/administración & dosificación , Agonistas de Dopamina/efectos adversos , Trastornos Neurológicos de la Marcha/inducido químicamente , Levodopa/administración & dosificación , Levodopa/efectos adversos , Enfermedad de Parkinson/tratamiento farmacológico , Anciano , Combinación de Medicamentos , Humanos , Masculino
6.
Neurobiol Aging ; 92: 1-6, 2020 08.
Artículo en Inglés | MEDLINE | ID: mdl-32320836

RESUMEN

There are individual differences in motor deficits, despite a similar degree of dopamine neuronal loss in Parkinson's disease (PD), called motor reserve (MR). Factors enhancing MR have been documented previously, but the influence of initial MR on the long-term prognosis remains unclear. In this longitudinal study, we enrolled 205 patients with de novo PD to estimate individual MR based on initial motor deficits and striatal dopamine depletion using the residual-based approach. We assessed the risk of developing levodopa-induced dyskinesia (LID) or freezing of gait (FOG) and longitudinal increases in levodopa-equivalent dose (LED) according to MR estimates using the Cox regression model and linear mixed model, respectively. Throughout the follow-up period (≥3 years), greater MR estimates were associated with a lower risk for LID and FOG. In addition, patients with high MR received lower LED than those with low MR. These findings suggest that the initial MR, that is, individual's capacity to cope with PD-related pathologies, can be maintained with disease progression and can modulate the risk for LID or FOG.


Asunto(s)
Discinesias/etiología , Trastornos Neurológicos de la Marcha/inducido químicamente , Levodopa/efectos adversos , Actividad Motora , Enfermedad de Parkinson/tratamiento farmacológico , Enfermedad de Parkinson/fisiopatología , Anciano , Cuerpo Estriado/metabolismo , Progresión de la Enfermedad , Dopamina/metabolismo , Femenino , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/metabolismo , Pronóstico , Factores de Tiempo
7.
Sultan Qaboos Univ Med J ; 20(1): e104-e108, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-32190378

RESUMEN

Proximal muscle weakness is a common presentation in paediatric-orthopaedic clinics and is frequently paired with a vitamin D deficiency diagnosis. Recently, side effects of the extensive use of antiepileptic and antipsychotic drugs such as sodium valproate in childhood disorders are being documented. Sodium valproate causes a time-dependent, drug-induced proximal myopathy. We report a 13-year-old female patient who presented at the Orthopaedic Outpatient Department at Lady Hardinge Medical College, New Delhi, India, in 2019 with an abnormal gait. The patient was taking a combination therapy of sodium valproate, risperidone and trihexyphenidyl for absence seizures and a mood disorder. Following clinical investigations, the patient was diagnosed with proximal myopathy. As a result of elevated serum alkaline phosphatase and creatine kinase myocardial band levels, sodium valproate was replaced with ethosuximide and a carnitine supplementation was prescribed. The patient fully recovered and regained full mobility. Proximal myopathy had been incorrectly managed and assumed to be caused by a vitamin D deficiency.


Asunto(s)
Anticonvulsivantes/efectos adversos , Antipsicóticos/efectos adversos , Trastornos Neurológicos de la Marcha/inducido químicamente , Enfermedades Musculares/inducido químicamente , Ácido Valproico/efectos adversos , Adolescente , Quimioterapia Combinada , Epilepsia Tipo Ausencia/tratamiento farmacológico , Epilepsia Tipo Ausencia/psicología , Femenino , Marcha/efectos de los fármacos , Humanos , India , Trastornos del Humor/complicaciones , Trastornos del Humor/tratamiento farmacológico , Risperidona/efectos adversos , Trihexifenidilo/efectos adversos , Deficiencia de Vitamina D
8.
Toxicol Appl Pharmacol ; 393: 114949, 2020 04 15.
Artículo en Inglés | MEDLINE | ID: mdl-32147541

RESUMEN

Acrylamide (ACR), a potential neurotoxin, is present in diet and drinking water. Dietary exposure contributes to cognitive impairment, but relevant mechanism information is limited. Neuroinflammation plays important roles in neurodegenerative disorders. This study aimed to explore whether chronic acrylamide exposure induced neuronal lesions, microglial activation, NLRP3 inflammasome-mediated neuroinflammation and cognitive impairment. For this purpose, 36 Sprague-Dawley (SD) rats were randomly divided into three groups (n = 12/group) and maintained on treated drinking water providing dosages of 0, 0.5, or 5 mg/kg/day ACR for 12 months. Chronic exposure to ACR caused gait abnormality and cognitive dysfunction, which was associated with neuronal lesions, decrease in synapse associated proteins including synapsin I (SYN1), synaptophysin (SYP) and postsynaptic density protein 95 (PSD95), neurogenesis suppression as shown by reduced brain derived neurotrophic factor (BDNF) and doublecortin (DCX) in the hippocampus and frontal cortex. ACR stimulated glial proliferation and microglial activation by increasing GFAP+, Iba-1+, Iba-1+CD68+ positive cells. ACR markedly upregulated the protein levels of NLRP3 inflammasome constituents NLRP3, caspase-1 and increased pro-IL-1ß and IL-1ß. ACR elevated the protein P62 to suppress NLPR3 inflammasome cleavage. Inflammatory cytokines including TNF-α, IL-6 and Cox-2 were also significantly increased after NF-κB pathway activation, which aggravated neuronal lesions and caused memory deficits. This work helped to propose the possible mechanism of chronic exposure of ACR-induced neurotoxicity.


Asunto(s)
Acrilamida/toxicidad , Disfunción Cognitiva/inducido químicamente , Disfunción Cognitiva/psicología , Inflamasomas/efectos de los fármacos , Activación de Macrófagos/efectos de los fármacos , Proteína con Dominio Pirina 3 de la Familia NLR/biosíntesis , Neuroglía/efectos de los fármacos , Animales , Citocinas/biosíntesis , Citocinas/genética , Proteína Doblecortina , Trastornos Neurológicos de la Marcha/inducido químicamente , Mediadores de Inflamación/metabolismo , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Memoria Espacial/efectos de los fármacos , Regulación hacia Arriba/efectos de los fármacos
9.
Neurochem Int ; 135: 104710, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-32105720

RESUMEN

Schizophrenia is a neuropsychiatric condition that reaches around 1% of people worldwide. Because taurine exerts a neuroprotective role in the brain, this molecule is a promising candidate to reduce schizophrenia-like symptoms. Here, we investigated a possible neuroprotective role of taurine against MK-801-induced memory deficit and hyperlocomotion in zebrafish using the inhibitory avoidance task and the novel tank diving test, respectively. First, we assessed the influence of different MK-801 doses (0.1, 0.3, 0.5, 1 and 2 mg/kg, i.p.) on memory consolidation. Although all MK-801 doses tend to reduce the retention index, only 2 mg/kg MK-801 showed robust amnesic effects. Then, we evaluated whether taurine pretreatments (42, 150 and 400 mg/L for 60 min) prevent MK-801-induced cognitive impairment. Immediately after the training, animals were exposed to non-chlorinated water or taurine and subsequently challenged with 2 mg/kg MK-801, i.p. The test session was performed 24 h after training. Although taurine alone did not change memory retention when compared with control, taurine pretreatments prevented MK-801-induced memory deficit. Importantly, no locomotor changes were observed 24 h after the training session. In the novel tank diving test, MK-801 induced hyperlocomotion and disrupted vertical activity, while 400 mg/L taurine pretreatment prevented these effects. Overall, our novel findings indicate a neuroprotective role of taurine against MK-801-induced memory deficit and hyperlocomotion, reinforcing the growing utility of zebrafish models to investigate the beneficial effects of different compounds against glutamate excitotoxicity.


Asunto(s)
Maleato de Dizocilpina/toxicidad , Trastornos Neurológicos de la Marcha/prevención & control , Trastornos de la Memoria/prevención & control , Fármacos Neuroprotectores/uso terapéutico , Taurina/uso terapéutico , Animales , Relación Dosis-Respuesta a Droga , Antagonistas de Aminoácidos Excitadores/toxicidad , Femenino , Trastornos Neurológicos de la Marcha/inducido químicamente , Trastornos Neurológicos de la Marcha/fisiopatología , Masculino , Trastornos de la Memoria/inducido químicamente , Trastornos de la Memoria/fisiopatología , Fármacos Neuroprotectores/farmacología , Taurina/farmacología , Pez Cebra
11.
Am J Physiol Gastrointest Liver Physiol ; 318(4): G673-G681, 2020 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-32003605

RESUMEN

Impaired manganese (Mn) homeostasis can result in excess Mn accumulation in specific brain regions and neuropathology. Maintaining Mn homeostasis and detoxification is dependent on effective Mn elimination. Specific metal transporters control Mn homeostasis. Human carriers of mutations in the metal transporter ZIP14 and whole body Zip14-knockout (WB-KO) mice display similar phenotypes, including spontaneous systemic and brain Mn overload and motor dysfunction. Initially, it was believed that Mn accumulation due to ZIP14 mutations was caused by impaired hepatobiliary Mn elimination. However, liver-specific Zip14-KO mice did not show systemic Mn accumulation or motor deficits. ZIP14 is highly expressed in the small intestine and is localized to the basolateral surface of enterocytes. Thus, we hypothesized that basolaterally localized ZIP14 in enterocytes provides another route for the elimination of Mn. Using wild-type and intestine-specific Zip14-KO (I-KO) mice, we have shown that ablation of intestinal Zip14 is sufficient to cause systemic and brain Mn accumulation. The lack of intestinal ZIP14-mediated Mn excretion was compensated for by the hepatobiliary system; however, it was not sufficient to maintain Mn homeostasis. When supplemented with extra dietary Mn, I-KO mice displayed some motor dysfunctions and brain Mn accumulation based on both MRI imaging and chemical analysis, thus demonstrating the importance of intestinal ZIP14 as a route of Mn excretion. A defect in intestinal Zip14 expresssion likely could contribute to the Parkinson-like Mn accumulation of manganism.NEW & NOTEWORTHY Mn-induced parkinsonism is recognized as rising in frequency because of both environmental factors and genetic vulnerability; yet currently, there is no cure. We provide evidence in an integrative animal model that basolaterally localized ZIP14 regulates Mn excretion and detoxification and that deletion of intestinal ZIP14 leads to systemic and brain Mn accumulation, providing robust evidence for the indispensable role of intestinal ZIP14 in Mn excretion.


Asunto(s)
Proteínas de Transporte de Catión/metabolismo , Trastornos Neurológicos de la Marcha/inducido químicamente , Mucosa Intestinal/metabolismo , Manganeso/toxicidad , Animales , Transporte Biológico , Encéfalo/metabolismo , Encéfalo/patología , Proteínas de Transporte de Catión/genética , Relación Dosis-Respuesta a Droga , Genotipo , Inflamación/inducido químicamente , Manganeso/administración & dosificación , Ratones , Ratones Noqueados , Membrana Serosa/metabolismo
12.
Behav Brain Res ; 378: 112279, 2020 01 27.
Artículo en Inglés | MEDLINE | ID: mdl-31606429

RESUMEN

Parkinson's disease (PD) is a progressive neuropathology characterized by motor and non-motor alterations. ß-sitosterol ß-d-glucoside (BSSG) is a neurotoxin whose prolonged oral administration in rats has been proposed as a new PD model. Herein, we demonstrate that a single, unilateral, and intranigral administration of BSSG also elicits bilateral sensorimotor alterations in the rat. Six behavioral tests evaluated the effect of different concentrations of BSSG (3, 6, 9, and 12 µg/µL DMSO) from 15 to 120 days after administration. The first behavioral alterations, which appeared on day 15, were unbalanced and uncoordinated gaits and a decrease in the sensorimotor cortex activity, as evidenced by the beam-walking and the vibrissae tests, respectively. After 30 days, the corridor test revealed hyposmia and a decreased locomotor activity in the open field. The last alteration was a depressive-like behavior, as shown by the forced swim test on days 60 and 120. According to the cylinder test, no locomotor asymmetry was observed over time with any BSSG concentrations tested. Also, a mesencephalic TH(+) cell loss (p < 0.05) was shown on day 30 when compared with the mock condition, and such a loss was even higher on day 120. At this time, the presence of pathological α-synuclein aggregates in the mesencephalon was documented. Our results show that the stereotaxic intranigral administration of BSSG reproduces some characteristics of oral administration, such as the progression of behavioral alterations, dopaminergic neurons loss, and the presence of Lewy body-like synuclein aggregations, in less time and resources.


Asunto(s)
Anosmia , Depresión , Neuronas Dopaminérgicas , Trastornos Neurológicos de la Marcha , Locomoción , Mesencéfalo , Neurotoxinas/farmacología , Enfermedad de Parkinson Secundaria/inducido químicamente , Enfermedad de Parkinson , Corteza Sensoriomotora , Sitoesteroles/farmacología , Animales , Anosmia/inducido químicamente , Anosmia/patología , Anosmia/fisiopatología , Depresión/inducido químicamente , Depresión/patología , Depresión/fisiopatología , Modelos Animales de Enfermedad , Neuronas Dopaminérgicas/efectos de los fármacos , Neuronas Dopaminérgicas/patología , Trastornos Neurológicos de la Marcha/inducido químicamente , Trastornos Neurológicos de la Marcha/etiología , Trastornos Neurológicos de la Marcha/patología , Trastornos Neurológicos de la Marcha/fisiopatología , Locomoción/efectos de los fármacos , Locomoción/fisiología , Masculino , Mesencéfalo/efectos de los fármacos , Mesencéfalo/patología , Mesencéfalo/fisiopatología , Neurotoxinas/administración & dosificación , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/patología , Enfermedad de Parkinson/fisiopatología , Ratas , Ratas Wistar , Corteza Sensoriomotora/fisiopatología , Sitoesteroles/administración & dosificación , Sustancia Negra/efectos de los fármacos
13.
J Pharm Pharmacol ; 72(1): 149-160, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31713882

RESUMEN

OBJECTIVES: A botanical drug derived from the ethanolic extract composed of Clematis chinensis Osbeck (Ranunculaceae), Trichosanthes kirilowii Maximowicz (Cucurbitaceae) and Prunella vulgaris Linné (Lamiaceae) has been used to ameliorate rheumatoid arthritis as an ethical drug in Korea. In our study, we investigated the effect of this herbal complex extract (HCE) on schizophrenia-like behaviours induced by MK-801. METHODS: HCE (30, 100 or 300 mg/kg, p.o) was orally administered to male ICR mice to a schizophrenia-like animal model induced by MK-801. We conducted an acoustic startle response task, an open-field task, a novel object recognition task and a social novelty preference task. KEY FINDINGS: We found that a single administration of HCE (100 or 300 mg/kg) ameliorated MK-801-induced abnormal behaviours including sensorimotor gating deficits and social or object recognition memory deficits. In addition, MK-801-induced increases in phosphorylated Akt and GSK-3ß expression levels in the prefrontal cortex were reversed by HCE (30, 100 or 300 mg/kg). CONCLUSIONS: These results imply that HCE ameliorates MK-801-induced dysfunctions in prepulse inhibition, social interactions and cognitive function, partly by regulating the Akt and GSK-3ß signalling pathways.


Asunto(s)
Antipsicóticos/farmacología , Conducta Animal/efectos de los fármacos , Cognición/efectos de los fármacos , Disfunción Cognitiva/prevención & control , Trastornos Neurológicos de la Marcha/prevención & control , Extractos Vegetales/farmacología , Corteza Prefrontal/efectos de los fármacos , Esquizofrenia/prevención & control , Filtrado Sensorial/efectos de los fármacos , Animales , Clematis , Disfunción Cognitiva/inducido químicamente , Disfunción Cognitiva/fisiopatología , Disfunción Cognitiva/psicología , Modelos Animales de Enfermedad , Maleato de Dizocilpina , Trastornos Neurológicos de la Marcha/inducido químicamente , Trastornos Neurológicos de la Marcha/fisiopatología , Trastornos Neurológicos de la Marcha/psicología , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Locomoción/efectos de los fármacos , Masculino , Ratones Endogámicos ICR , Fosforilación , Corteza Prefrontal/metabolismo , Corteza Prefrontal/fisiopatología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Prunella , Reconocimiento en Psicología/efectos de los fármacos , Reflejo de Sobresalto/efectos de los fármacos , Esquizofrenia/inducido químicamente , Psicología del Esquizofrénico , Conducta Social , Trichosanthes
14.
J Neurol ; 267(2): 422-429, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31655888

RESUMEN

INTRODUCTION: In recent years, there has been a sharp increase in the number of patients with neurological disorders associated with recreational use of nitrous oxide (N2O) in China. Here, we summarize the clinical characteristics of patients with neurological disorders associated with N2O abuse diagnosed in our Hospital. Further, we conducted a literature search on recent cases reported in mainland China to improve the awareness of the outbreak of neurological disorders associated with N2O abuse. METHODS: We retrospectively collected data of patients diagnosed with neurological disorders associated with recreational use of N2O in Shengjing Hospital of China Medical University from January 2018 to June 2019, and performed a literature search using the "nitrous oxide" and "neurological disorder" as keywords in the Chinese literature databases of WANFANG and CNKI and the English literature databases of Pubmed and Web of Science RESULTS: We enrolled 43 patients (average age: 21.9 ± 3.3 years). The main clinical manifestations were weakness and paresthesia in the four extremities and unsteady gait. Further, most patients showed significantly lower levels of serum vitamin B12 (169.4 ± 79.1 pg/mL) and increased homocysteine levels (78.1 ± 32.2 µmol/L). MRI of the spinal cord showed longitudinal high T2 signal lesions in the dorsal spinal cord in some patients. Moreover, electromyography showed sensory and motor nerve axonal damage combined with demyelination, which was relatively more severe in the lower limbs. There was rapid improvement of the symptoms after treatment with intramuscular injections of vitamin B12 and the overall prognosis was good. The literature search indicated that the number of published papers and related patients showed a rapid annual increase since the first Chinese case reported in 2016 CONCLUSION: Recreational use of N2O is an emerging public health problem in China that needs prompt action from the society and government. Early diagnosis and treatment allow a good overall prognosis.


Asunto(s)
Drogas Ilícitas/efectos adversos , Enfermedades del Sistema Nervioso/inducido químicamente , Óxido Nitroso/efectos adversos , Trastornos Relacionados con Sustancias/complicaciones , Adolescente , Adulto , China , Enfermedades Desmielinizantes/inducido químicamente , Femenino , Trastornos Neurológicos de la Marcha/inducido químicamente , Homocisteína/efectos de los fármacos , Humanos , Masculino , Debilidad Muscular/inducido químicamente , Enfermedades del Sistema Nervioso/sangre , Enfermedades del Sistema Nervioso/patología , Parestesia/inducido químicamente , Estudios Retrospectivos , Enfermedades de la Columna Vertebral/inducido químicamente , Enfermedades de la Columna Vertebral/patología , Vitamina B 12/sangre , Adulto Joven
15.
Rev Med Interne ; 41(2): 126-129, 2020 Feb.
Artículo en Francés | MEDLINE | ID: mdl-31796339

RESUMEN

INTRODUCTION: Vitamin B6 is contained in a number of over-the-counter drugs and vitamin supplements. It may cause severe neurological troubles in case of overdosage. CASE REPORT: We report the case of a 92-year-old women with gait disorders. A diagnosis of peripheral neuropathy with both motor and sensitive deficits was established and investigated. Blood level of vitamin B6 was measured to investigate a potential deficiency. Unexpectedly, the results showed hypervitaminosis B6, which appears to be due to self-administration of an over-the-counter drug containing vitamin B6. Discontinuation of this drug was associated with decrease in vitamin B6 level as well as gait improvement. We also discuss the toxicity of vitamin B6. CONCLUSION: Hypervitaminosis B6 remains a possible cause of peripheral neuropathy and it may be caused by self-administration of over-the-counter vitamin-containing drugs.


Asunto(s)
Trastornos Neurológicos de la Marcha/inducido químicamente , Trastornos Nutricionales/inducido químicamente , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Automedicación/efectos adversos , Vitamina B 6/toxicidad , Anciano de 80 o más Años , Suplementos Dietéticos/toxicidad , Sobredosis de Droga/complicaciones , Sobredosis de Droga/diagnóstico , Femenino , Trastornos Neurológicos de la Marcha/sangre , Humanos , Síndromes de Neurotoxicidad/diagnóstico , Síndromes de Neurotoxicidad/etiología , Trastornos Nutricionales/diagnóstico , Enfermedades del Sistema Nervioso Periférico/diagnóstico , Vitamina B 6/administración & dosificación , Vitamina B 6/efectos adversos , Vitamina B 6/sangre
17.
BMJ Case Rep ; 12(7)2019 Jul 22.
Artículo en Inglés | MEDLINE | ID: mdl-31337633

RESUMEN

Freezing of gait (FOG) and postural instability are challenging motor symptoms that present a serious therapeutic dilemma in Parkinson's disease. Appropriate distinction between FOG subtypes may be difficult during routine clinical visits, as shown in the case we present. The patient was examined in three different states in relation to levodopa (L-DOPA) and apomorphine subcutaneous (sc) tests with video documentation: (1) 'overnight-off', after 12 hours without medication; (2)'on', 60 min after intake of regular levodopa dose (200 mg) and 20 min after 2 mg of apomorphine sc; and (3) 'supra-on', after 350 mg of L-DOPA and 3 mg of apomorphine sc. The patient clearly showed a dose-dependent paradoxical response to L-DOPA treatment with the emergence of severe FOG and postural instability. The tendency to develop these axial symptoms was less pronounced with apomorphine at doses that achieved similar improvements of other Parkinsonian features.


Asunto(s)
Antiparkinsonianos/efectos adversos , Inhibidores de Catecol O-Metiltransferasa/uso terapéutico , Trastornos Neurológicos de la Marcha/inducido químicamente , Levodopa/efectos adversos , Oxadiazoles/uso terapéutico , Enfermedad de Parkinson/tratamiento farmacológico , Equilibrio Postural , Trastornos de la Sensación/inducido químicamente , Anciano , Antiparkinsonianos/administración & dosificación , Relación Dosis-Respuesta a Droga , Humanos , Levodopa/administración & dosificación , Masculino , Enfermedad de Parkinson/fisiopatología
18.
J Med Case Rep ; 13(1): 147, 2019 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-31092289

RESUMEN

BACKGROUND: Mirtazapine has a good tolerability and safety profile that demonstrates several benefits over other antidepressants and it is associated with few fatalities. Boric acid is an odorless white powder that is generally not recognized as a poisonous substance. We report a case of cardiac arrest induced by the intentional ingestion of mirtazapine, boric acid, and sennosides, by a patient who required percutaneous cardiopulmonary bypass. CASE PRESENTATION: Our patient was a 49-year-old Japanese woman with a history of depression; she was found in an unconscious state after ingesting boric acid (unknown amount), mirtazapine (1950 mg), and sennosides (780 mg). On arrival, she was in a deep coma with marked hypotension induced by atrial fibrillation, tachycardia, and diffuse hypokinetic cardiac motion. She had systemic diffuse erythema. Her serum concentrations of boric acid and mirtazapine on arrival were 560.49 mg/L and 1270 ng/mL, respectively. She experienced repeated cardiac arrest, and was therefore treated with tracheal intubation, mechanical ventilation, percutaneous cardiopulmonary bypass, and continuous hemodialysis filtration. Stable circulation and respiration and a normal kidney function were finally obtained and she was transferred to a local medical facility in a persistent unconscious state. CONCLUSIONS: This is the first case of a return of spontaneous circulation after cardiac arrest induced by the intentional ingestion of boric acid and mirtazapine, requiring percutaneous cardiopulmonary bypass for survival. To maintain cerebral perfusion during percutaneous cardiopulmonary bypass, even in a prolonged state of cardiac arrest induced by overdose, is medically, ethically, and economically challenging.


Asunto(s)
Antidepresivos/envenenamiento , Ácidos Bóricos/administración & dosificación , Puente Cardiopulmonar , Trastornos Neurológicos de la Marcha/inducido químicamente , Paro Cardíaco/inducido químicamente , Mirtazapina/envenenamiento , Ácidos Bóricos/efectos adversos , Depresión , Evaluación de la Discapacidad , Sobredosis de Droga , Femenino , Trastornos Neurológicos de la Marcha/fisiopatología , Paro Cardíaco/fisiopatología , Paro Cardíaco/terapia , Humanos , Persona de Mediana Edad , Intento de Suicidio , Resultado del Tratamiento
19.
Annu Int Conf IEEE Eng Med Biol Soc ; 2019: 3279-3285, 2019 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-31946584

RESUMEN

Intoxicated driving causes 10,000 deaths annually. Smartphone sensing of user gait (walk) to identify intoxicated users in order to prevent drunk driving, have recently emerged. Such systems gather motion sensor (accelerometer and gyroscope) data from the users' smartphone as they walk and classify them using machine or deep learning. Standard Field Sobriety Tests (SFSTs) involve various types of walks designed to cause an intoxicated person to lose their balance. However, SFSTs were designed to make intoxication apparent to a trained law enforcement officer who manually proctors them. No prior work has explored which types of walk yields the most accurate results when assessed autonomously by a smartphone intoxicated gait assessment system. In this paper, we compare how accurately Long Short Term Memory (LSTM), Convolution Neural Network (CNN), Random Forest, Gradient Boosted Machines (GBM) and neural network classifiers are able to detect intoxication levels of drunk subjects who performed normal, walk-and-turn and standing on one foot SFST walks. We also compared the accuracy of intoxication detection on the ascending (increasing intoxication) vs descending (decreasing intoxication) limbs of drinking sessions (bi-phasic). We found smartphone intoxication sensing more accurate on the descending limb of the drinking episode and that intoxication detection on the normal walks of subjects were just as accurate as the SFSTs.


Asunto(s)
Intoxicación Alcohólica , Conducción de Automóvil , Trastornos Neurológicos de la Marcha/inducido químicamente , Teléfono Inteligente , Intoxicación Alcohólica/diagnóstico , Marcha , Trastornos Neurológicos de la Marcha/diagnóstico , Humanos , Aprendizaje Automático
20.
Behav Brain Res ; 360: 120-127, 2019 03 15.
Artículo en Inglés | MEDLINE | ID: mdl-30521934

RESUMEN

This study aims to investigate the contribution of nigral dopaminergic (DA) cell loss, repeated exposure to DA medication and the combination of both to the development of neuropsychiatric symptoms observed in Parkinson's disease (PD). A bilateral 6-OHDA lesion of the substantia nigra pars compacta (SNc) was performed in rats. A set of animals was repeatedly administered with L-dopa (20 mg/kg/day) and benserazide (5 mg/kg/day) over 10 days starting from day 11 post-lesion. Behavioural testing was performed in week 3 post-lesion: novel object recognition (NOR), elevated plus maze (EPM) social interaction (SI) tests, and amphetamine-induced hyperlocomotion (AIH). Immunohistochemical analysis revealed a significant partial lesion (48%) in 6-OHDA versus sham rats. This lesion was not associated with motor impairment. However, lesioned rats displayed a significant deficit in the NOR, which was reversed by acute treatment with l-dopa/benserazide (12.5 mg/kg and 15 mg/kg respectively). Lesioned rats also displayed a deficit in the EPM which was not reversed by acute treatment with l-dopa. No difference was observed in the SI test or in the AIH assay. In all assays, no effect of chronic l-dopa exposure was observed. This study provides new insights into the neuropathophysiology associated with neuropsychiatric symptoms of PD. Our data strongly emphasises a not previously clearly identified critical role in cognition for the SNc. The results suggest that DA pathways were less directly involved in lesion-induced anxiety-like behaviour. We did not report any effect of chronic l-dopa exposure in the context of partial nigral cell loss.


Asunto(s)
Antiparkinsonianos/efectos adversos , Dopamina/metabolismo , Levodopa/efectos adversos , Trastornos de la Memoria/inducido químicamente , Enfermedad de Parkinson Secundaria/tratamiento farmacológico , Sustancia Negra/metabolismo , Anfetamina/toxicidad , Animales , Ansiedad/inducido químicamente , Benserazida/efectos adversos , Modelos Animales de Enfermedad , Miembro Anterior/fisiopatología , Trastornos Neurológicos de la Marcha/inducido químicamente , Relaciones Interpersonales , Locomoción/efectos de los fármacos , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Oxidopamina/toxicidad , Enfermedad de Parkinson Secundaria/inducido químicamente , Ratas , Ratas Sprague-Dawley , Reconocimiento en Psicología/efectos de los fármacos , Sustancia Negra/efectos de los fármacos , Simpaticolíticos/toxicidad , Tirosina 3-Monooxigenasa/metabolismo
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA