RESUMO
Beta-endorphin (ß-E) is an opioid peptide linked to the behavioral effects of ethanol. For example, ß-E provides negative feedback to inhibit the hypothalamic-pituitary-adrenal (HPA) stress axis, and neuroadaptation of this system to ethanol may facilitate sex differences in disordered drinking. Locomotor sensitivity to ethanol may also influence the risk for addiction; however, the role of ß-E in psychomotor effects of ethanol is not fully understood. We examined the role of ß-E and sex on locomotor effects of ethanol using adult male and female wild-type C57BL/6J and ß-E deficient B6.129S2-Pomctm1Low/J mice in a parallel rod floor apparatus following 0.75 or 2.0 g/kg ethanol. Beginning 15 min after intraperitoneal injection, we recorded foot slips, distance traveled, slips per meter, first instance of immobility, and total time spent off-balance (lying on the floor) over 15 min, and collected blood for analysis of ethanol concentration 60 min after injection. Overall, ß-E deficient mice were more sedated and ataxic following ethanol; at the lower dose they slipped more frequently and had a higher rate of slips per meter traveled. At the higher dose, ß-E deficient mice were predominantly sedated, slipping less frequently, and traveling less, as well as spending more time off-balance and becoming immobile sooner. Genotype interacted with sex in that male ß-E deficient mice slipped more frequently than their female counterparts, suggesting that ß-E may elicit sex-dependent effects of ethanol-induced ataxia. Blood ethanol concentration did not differ between any group, suggesting that behavioral differences result from altered sensitivity to ethanol. Our data support the contention that ß-E modulates the locomotor effects of ethanol and may influence ataxia in a sex-dependent manner. These findings help elucidate the role of ß-E in diverging behavioral responses to ethanol and may aid the development of targeted treatments for alcohol use disorders.
Assuntos
Alcoolismo , Hipnóticos e Sedativos , Feminino , Camundongos , Masculino , Animais , Hipnóticos e Sedativos/farmacologia , beta-Endorfina , Alcoolismo/genética , Camundongos Endogâmicos C57BL , Etanol , Ataxia/induzido quimicamenteRESUMO
BACKGROUND: This is an updated version of a Cochrane Review last updated in 2020. Epilepsy is a common neurological disorder, affecting 0.5% to 1% of the population. In nearly 30% of cases, epilepsy is resistant to currently available drugs. Pharmacological treatment remains the first choice to control epilepsy. Lamotrigine is a second-generation antiseizure medication. When used as an add-on (in combination with other antiseizure medications), lamotrigine can reduce seizures, but with some adverse effects. OBJECTIVES: To evaluate the benefits and harms of add-on lamotrigine, compared with add-on placebo or no add-on treatment in people with drug-resistant focal epilepsy. SEARCH METHODS: For this update, we searched the Cochrane Register of Studies (CRS Web) and MEDLINE (Ovid) on 3 October 2022 with no language restrictions. CRS Web includes randomised and quasi-randomised controlled trials from PubMed, Embase, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform (ICTRP), Cochrane Central Register of Controlled Trials (CENTRAL), and the Specialised Registers of Cochrane Review Groups, including Epilepsy. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that investigated add-on lamotrigine versus add-on placebo or no add-on treatment in people of any age with drug-resistant focal epilepsy. We used data from the first period of eligible cross-over trials. DATA COLLECTION AND ANALYSIS: For this update, two review authors independently selected trials and extracted data. Our primary outcome was 50% or greater reduction in seizure frequency. Our secondary outcomes were treatment withdrawal, adverse effects, cognitive effects, and quality of life. Primary analyses were by intention-to-treat. We performed sensitivity best- and worse-case analyses to account for missing outcome data. We calculated pooled risk ratios (RRs) with 95% confidence intervals (95% Cls) for dichotomous outcomes. MAIN RESULTS: We identified no new studies for this update, so the results and conclusions of the review are unchanged. We included five parallel-group studies in adults or children, eight cross-over studies in adults or children, and one parallel study with a responder-enriched design in infants. In total, these 14 studies enroled 1806 eligible participants (38 infants, 199 children, 1569 adults). Baseline phases ranged from four to 12 weeks and treatment phases ranged from eight to 36 weeks. We rated 11 studies (1243 participants) at low overall risk of bias and three (697 participants) at unclear overall risk of bias due to lack of information on study design. Four studies (563 participants) reported effective blinding. Lamotrigine compared with placebo probably increases the likelihood of achieving 50% or greater reduction in seizure frequency (RR 1.80, 95% CI 1.45 to 2.23; 12 trials, 1322 participants (adults and children); moderate-certainty evidence). There is probably little or no difference in risk of treatment withdrawal for any reason among people treated with lamotrigine versus people treated with placebo (RR 1.11, 95% CI 0.91 to 1.37; 14 trials; 1806 participants; moderate-certainty evidence). Lamotrigine compared with placebo is probably associated with a greater risk of ataxia (RR 3.34, 99% Cl 2.01 to 5.55; 12 trials; 1525 participants; moderate-certainty evidence), dizziness (RR 1.76, 99% Cl 1.28 to 2.43; 13 trials; 1768 participants; moderate-certainty evidence), nausea (RR 1.81, 99% CI 1.22 to 2.68; 12 studies, 1486 participants; moderate-certainty evidence), and diplopia (RR 3.79, 99% Cl 2.15 to 6.68; 3 trials, 944 participants; moderate-certainty evidence). There is probably little or no difference in the risk of fatigue between lamotrigine and placebo (RR 0.82, 99% CI 0.55 to 1.22; 12 studies, 1552 participants; moderate-certainty evidence). AUTHORS' CONCLUSIONS: Lamotrigine as an add-on treatment for drug-resistant focal seizures is probably effective for reducing seizure frequency. Certain adverse effects (ataxia, dizziness, diplopia, and nausea) are probably more likely to occur with lamotrigine compared with placebo. There is probably little or no difference in the number of people who withdraw from treatment with lamotrigine versus placebo. The trials were of relatively short duration and provided no long-term evidence. In addition, some trials had few participants. Further trials are needed to assess the long-term effects of lamotrigine and to compare lamotrigine with other add-on drugs.
Assuntos
Epilepsia Resistente a Medicamentos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Epilepsias Parciais , Adulto , Criança , Humanos , Lamotrigina/uso terapêutico , Diplopia/induzido quimicamente , Diplopia/tratamento farmacológico , Tontura/induzido quimicamente , Quimioterapia Combinada , Anticonvulsivantes/efeitos adversos , Convulsões/tratamento farmacológico , Epilepsia Resistente a Medicamentos/tratamento farmacológico , Ataxia/induzido quimicamente , Ataxia/tratamento farmacológico , Náusea/induzido quimicamente , Epilepsias Parciais/tratamento farmacológico , Epilepsias Parciais/induzido quimicamenteRESUMO
Amiodarone is an antiarrhythmic drug with a significant adverse effect profile, including neurotoxicity. While ataxia, neuropathy, and tremors are more commonly seen forms of amiodarone neurotoxicity, very few cases of nystagmus are reported. We report the case of an 86-year-old man who presented with abrupt-onset ataxia, dizziness, and inability to ambulate, 10 days after initiating amiodarone for atrial fibrillation. His examination revealed gaze-evoked nystagmus along with features of cerebellar dysfunction. After excluding other etiologies, amiodarone was stopped. His nystagmus resolved, and his ataxia improved within 48 h of stopping amiodarone. Due to the rarity of this drug-induced adverse effect, we performed a systematic review of available case reports in the literature (PubMed and Scopus) using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and presented our findings. Nystagmus is a rarely reported adverse effect of amiodarone, which can occur within days to months of starting the medication. Treatment includes stopping the drug and monitoring for resolution of nystagmus.
Assuntos
Amiodarona , Fibrilação Atrial , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Idoso de 80 Anos ou mais , Humanos , Masculino , Amiodarona/efeitos adversos , Antiarrítmicos/efeitos adversos , Ataxia/induzido quimicamente , Ataxia/diagnóstico , Ataxia/tratamento farmacológico , Fibrilação Atrial/induzido quimicamente , Fibrilação Atrial/tratamento farmacológico , Tontura/induzido quimicamente , Tontura/tratamento farmacológico , Tremor/induzido quimicamente , Relatos de Casos como AssuntoRESUMO
PURPOSE: To investigate the safety of perampanel in different disorders and doses. METHODS: Embase, the Cochrane Library, Medline, and ClinicalTrials.gov were searched from inception to July 2022 for randomized controlled trials (RCTs). The meta-analysis was performed by using Review Manager 5.3 and R 4.2.1 software. RESULTS: A total of 17 RCTs with 5711 subjects were included in the final analysis. The double-blind treatment phase was from 12 weeks to 48 weeks. Our results showed that 11 adverse events (aggression, ataxia, balance disorder, dizziness, fall, fatigue, irritability, rash, somnolence, vertigo, and weight increase) were statistically significantly associated with perampanel, and 4 of them (ataxia, dizziness, fatigue, and somnolence) showed a clear dose-response relationship. Psychiatric adverse events occurred most frequently among serious treatment-emergent adverse events (TEAEs). At 8 mg/day, seven adverse events (aggression, balance disorder, dizziness, fatigue, irritability, vertigo, and weight increase) occurred more frequently in patients with epilepsy than in patients with other disorders, whereas dose discontinuation rates due to adverse events were lower in patients with epilepsy than in patients with other disorders. CONCLUSION: The safety profile of perampanel is dependent on diseases and dose. The risk of adverse events was statistically significantly higher, with doses exceeding 4 mg/day. Despite a higher risk of adverse events, patients with epilepsy had a lower perampanel discontinuation rate than patients with other disorders.
Assuntos
Epilepsias Parciais , Epilepsia , Humanos , Epilepsias Parciais/tratamento farmacológico , Anticonvulsivantes/efeitos adversos , Tontura/induzido quimicamente , Sonolência , Resultado do Tratamento , Epilepsia/tratamento farmacológico , Epilepsia/induzido quimicamente , Piridonas/efeitos adversos , Método Duplo-Cego , Fadiga/induzido quimicamente , Fadiga/tratamento farmacológico , Vertigem/induzido quimicamente , Vertigem/tratamento farmacológico , Ataxia/induzido quimicamente , Quimioterapia Combinada , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
La ataxia es una alteración de la coordinación motora voluntaria y del control postural. Es una entidad poco frecuente en la infancia, siendo la principal causa de ataxia aguda descripta en la bibliografía, de origen inmunológico (post infecciosa), seguida de las intoxicaciones. Para el diagnóstico es fundamental una anamnesis detallada, cronología de los síntomas, antecedentes infecciosos o de contacto con sustancias tóxicas y un examen neurológico completo. El objetivo de nuestro estudio fue analizar retrospectivamente la causa de ataxia aguda como signo neurológico predominante en pacientes que consultaron en el Hospital Juan P. Garrahan. Diseño: Se trata de un estudio descriptivo, observacional, retrospectivo y de corte transversal. Población: niños de 1 a 18 años, con o sin patología previa conocida, que consultaron al servicio de emergencias del hospital por ataxia entre enero de 2013 y octubre de 2018. Método: recolección y análisis de historias clínicas comprendidas en esa fecha, con alteración en la marcha como síntoma de consulta. Resultados: de un total de 237 pacientes, la causa más frecuente de ataxia aguda fue la inmunológica (incluyendo en este grupo a las postinfecciosas y a las no asociadas a infección). Conclusión: En nuestro hospital con tercer nivel de atención, la causa más frecuente de ataxia aguda fue la inmunológica. En segundo lugar, las intoxicaciones y, en tercer lugar, las enfermedades neurológicas. (AU)
Ataxia is a disorder of voluntary motor coordination and postural control, which is rare in childhood. The main cause of acute ataxia described in the literature is immune-mediated inflammation (postinfectious), followed by intoxication. A detailed anamnesis, chronology of symptoms, history of infection or contact with toxic substances, and a complete neurological examination are essential in the diagnostic work-up. The aim of our study was to retrospectively analyze the cause of acute ataxia as a predominant neurological sign in patients who consulted at Hospital Juan P. Garrahan. Study design: A descriptive, observational, retrospective, cross-sectional study was conducted. Study population: children aged 1 to 18 years, with or without known previous disease, who presented to the hospital emergency department for ataxia between January 2013 and October 2018. Method: collection and analysis of medical records from that period of patients with gait disturbance as the reason for consultation. Results: out of a total of 237 patients, the most frequent cause of acute ataxia was immune-mediated inflammation (both post-infectious and noninfectious). Conclusion: In our tertiary care hospital, the most frequent cause of acute ataxia was immune-mediated inflammation. The second most frequent cause was intoxication and the third neurological diseases (AU)
Assuntos
Humanos , Lactente , Pré-Escolar , Criança , Adolescente , Ataxia/diagnóstico , Ataxia/etiologia , Ataxia/induzido quimicamente , Exame Neurológico , Doença Aguda , Estudos Transversais , Estudos Retrospectivos , Diagnóstico DiferencialRESUMO
Acute ataxia is commonly the chief complaint among patients visiting the emergency department (ED). It has multiple causes including infection and immunity-related, metabolic, vascular, and organic causes. Therefore, treating physicians should consider the severity and timing of onset in relation to the initial screening tests when making a differential diagnosis, and must be careful not to miss cases that require urgent treatment, such as stroke and drug-induced ataxia. In this report, we describe the case of a 53-year-old woman with recurrent acute ataxia. She had a history of epilepsy but had not had a seizure for over 10 years. She presented to the ED with ataxia that had started the previous evening. She reported two previous episodes of acute ataxia 14 and 4 days previously. She had visited two different hospitals, and undergone two head magnetic resonance imaging (MRI) scans which showed no evidence of a stroke, and had been diagnosed with transient ischemic attacks (TIAs) at both hospitals. She underwent a third head MRI during the ED visit, which again revealed no evidence of a stroke. The plasma levels of phenytoin, carbamazepine, and valproic acid were 21.2 µg/mL (normal range: 7-20 µg/mL), 2.1 µg/mL (normal range: 5-10 µg/mL), and 33.5 µg/mL (normal range: 50-100 µg/mL), respectively. She was finally diagnosed with ataxia due to phenytoin toxicity. Her symptoms improved soon after the phenytoin dose was reduced and did not recur during a year of follow-up.
Assuntos
Fenitoína , Acidente Vascular Cerebral , Ataxia/induzido quimicamente , Ataxia/diagnóstico , Carbamazepina , Feminino , Humanos , Pessoa de Meia-Idade , Fenitoína/efeitos adversos , Acidente Vascular Cerebral/diagnóstico , Ácido ValproicoRESUMO
Supplements containing Cannabidiol (CBD) are available for horses, however, few studies have been published on their effects on behavior and health parameters. The purpose of this study was to determine if a daily oral supplement containing CBD would cause sedation, ataxia or alterations in other health parameters during administration for 56 days. Twenty clinically healthy adult Thoroughbred horses were housed in stalls. Before treatment was initiated, a complete physical examination, complete blood count (CBC) and biochemical panel were evaluated. In addition, horses were examined for sedation and ataxia using standard scoring systems. Horses were randomly divided into two treatment groups, treated (supplement pellets containing CBD as Hemp Extract, 150 mg) or control (supplement pellets without CBD). Horses were treated daily and sedation and ataxia scores were assigned by two masked observers once weekly for 56 days. Horses were monitored daily for clinical signs or adverse events and body weights were recorded weekly. A CBC and biochemical panel were repeated on days 28 and 56, two hours after administration of the supplement. The supplement was readily consumed by the horses and no adverse effects were seen over the treatment period. Sedation and ataxia scores ranged from zero to two for all horses during the weekly examinations and there was no statistical difference between treatment groups. There were no treatment effects on blood values, including indicators of anemia and blood proteins, liver enzymes, kidney values, electrolytes or calcium. Body weight significantly increased in all horses, by Day 56 compared to Day zero but no treatment by day effect was noted. The CBD supplement (150 mg) was readily consumed and safe and did not result in changes in mentation, gait, or other health parameters, and no adverse clinical signs were observed during 56 days of oral administration.
Assuntos
Ataxia , Canabidiol , Doenças dos Cavalos , Administração Oral , Animais , Ataxia/induzido quimicamente , Ataxia/veterinária , Canabidiol/uso terapêutico , Suplementos Nutricionais , Eletrólitos/uso terapêutico , Doenças dos Cavalos/induzido quimicamente , CavalosRESUMO
Thyrotropin-releasing hormone (TRH) and the TRH mimetic taltirelin have been used in Japan for the treatment of spinocerebellar degeneration (SCD), a type of progressive ataxia. A TRH mimetic, rovatirelin, ameliorates ataxia symptoms in the rolling mouse Nagoya, a hereditary SCD model. The aim of this study was to verify the effects of oral administration of rovatirelin on a cytosine arabinoside (Ara-C)-induced ataxia rat model, a sporadic SCD model characterized by gait abnormalities and falls because of cerebellar atrophy and investigate the central nervous system mechanism associated with rovatirelin-mediated amelioration of motor dysfunction in these rats. Rovatirelin at ≥3 mg/kg significantly decreased the fall index, which is a primary endpoint of improved motor function calculated by dividing the number of falls by the locomotor activity, in both male and female rats with Ara-C-induced ataxia. Furthermore, rovatirelin caused a significant increase in locomotor activity in a dose-dependent manner. Taltirelin at ≥30 mg/kg ameliorated motor dysfunction in ataxic rats. Moreover, rovatirelin significantly increased acetylcholine (ACh) levels in the medial prefrontal cortex (mPFC) and dopamine (DA) levels in the nucleus accumbens (NAc) at ≥3 mg/kg and significantly increased DA levels in the dorsal striatum at ≥10 mg/kg in normal rats. In conclusion, oral administration of rovatirelin ameliorates motor dysfunction in rats with Ara-C-induced ataxia, owing to its ACh-increasing effects in the mPFC and DA-increasing effects in the dorsal striatum and NAc. Furthermore, the effects of rovatirelin were more potent than those of taltirelin.
Assuntos
Dopamina , Degenerações Espinocerebelares , Acetilcolina , Animais , Ataxia/induzido quimicamente , Citarabina/efeitos adversos , Feminino , Masculino , Camundongos , Oxazolidinonas , Pirrolidinas , Ratos , Transmissão Sináptica , Hormônio Liberador de Tireotropina/efeitos adversosRESUMO
RATIONALE: Miller Fisher syndrome (MFS) is a rare variant of Guillain-Barre syndrome, classically diagnosed based on the clinical triad of ataxia, areflexia, and ophthalmoplegia. MFS is usually preceded by viral infections and febrile illness; however, only a few cases have been reported after vaccinations. PATIENT CONCERNS: A 53-year-old hypertensive male presented with a 2-day history of progressive ascending paralysis of the lower limbs along with diplopia and ataxia, 8 days after the first dose of the Sinovac-Coronavac coronavirus disease 2019 (COVID-19) vaccination, with no prior history of any predisposing infections or triggers. DIAGNOSES: Physical examination showed moderate motor and sensory loss with areflexia in the lower limbs bilaterally. Routine blood investigations and radiological investigations were unremarkable. Cerebrospinal fluid analysis showed albuminocytologic dissociation and nerve conduction studies revealed prolonged latencies with reduced conduction velocities. The diagnosis of MFS was established based on the findings of physical examination, cerebrospinal fluid analysis, and nerve conduction studies. INTERVENTIONS: A management plan was devised based on intravenous immunoglobulins, pregabalin, and physiotherapy. However, due to certain socioeconomic factors, the patient was managed conservatively with regular physiotherapy sessions. OUTCOMES: Follow-up after 6 weeks showed remarkable improvement, with complete resolution of symptoms 10 weeks after the discharge. LESSONS: This case suggests that MFS is a rare adverse effect after COVID-19 vaccination and additional research is required to substantiate a temporal association. Further studies are needed to understand the pathophysiology behind such complications to enhance the safety of COVID-19 vaccinations in the future.
Assuntos
Vacinas contra COVID-19 , COVID-19 , Síndrome de Miller Fisher , Ataxia/induzido quimicamente , COVID-19/diagnóstico , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Diplopia/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Síndrome de Miller Fisher/induzido quimicamente , Síndrome de Miller Fisher/diagnóstico , Vacinação/efeitos adversosRESUMO
INTRODUCTION: The antiseizure medication phenytoin has been associated with changes in the cerebellum, cerebellar signs, and permanent cerebellar damage. We have systematically reviewed the clinical and radiological features, and their correlation. AREAS COVERED: We identified sixty case reports and case series of the effects of phenytoin on the cerebellum by searching Medline and Embase and relevant reference lists. The reports described 92 [median 1, range 1-5] cases, documented median age 28 [2.7-78] years. Eighty-one cases described one or more clinical sign of ataxia (present in 96%), dysarthria (63%), and nystagmus (70%). The neurological outcome (in 76 cases): 10 (13%) recovered by 12 months; 55 (72%) suffered residual disability; and 11 (14%) died. Median serum phenytoin concentration (48 cases) was 50 (interquartile range 31-66) mg/L; only three values were below 20 mg/L. The radiological findings included cerebellar atrophy in 41 of 61 patients (67%) with at least one scan. EXPERT OPINION: Evidence mainly comes from case reports, and is inevitably biased. Most patients with cerebellar dysfunction have phenytoin concentrations above the reference range. Clinical signs of ataxia can persist without radiological evidence of cerebellar atrophy, and cerebellar atrophy is seen without any clinical evidence of cerebellar dysfunction.
Assuntos
Ataxia Cerebelar , Doenças Cerebelares , Adulto , Ataxia/induzido quimicamente , Ataxia/tratamento farmacológico , Ataxia/patologia , Atrofia/tratamento farmacológico , Atrofia/patologia , Ataxia Cerebelar/induzido quimicamente , Ataxia Cerebelar/tratamento farmacológico , Ataxia Cerebelar/patologia , Doenças Cerebelares/induzido quimicamente , Doenças Cerebelares/diagnóstico por imagem , Doenças Cerebelares/tratamento farmacológico , Cerebelo/diagnóstico por imagem , Cerebelo/patologia , Humanos , Fenitoína/efeitos adversosRESUMO
INTRODUCTION: Several overdoses of the antiepileptic drug perampanel have been reported in adults, but very few have been reported in children. We report the case of an observed exploratory ingestion of perampanel in a 2-year-old child that resulted in ataxia and prolonged coma. CASE REPORT: A previously healthy 2-year-old female patient presented to the emergency department (ED) 30 minutes after the witnessed ingestion of 30 mg of perampanel (2 mg/kg). Within minutes of ingestion, she displayed ataxia and inability to walk. Upon ED presentation, she had normal vital signs but was minimally responsive with physical stimulation. Naloxone was given without response. She was intubated because of profound central nervous system depression and transferred to a pediatric tertiary care facility. She remained intubated with no pharmacological sedation. Physical exam showed a horizontal nystagmus. Detailed neurologic examination of ataxia and coordination was not possible, and she did not demonstrate hyperreflexia, clonus, or rigidity. Her mental status gradually improved, and she was extubated approximately 72 hours after exposure. After extubation, the patient still exhibited truncal ataxia and did not return to baseline until 96 hours post ingestion. Serum drawn approximately 16 hours after exposure showed 870 ng/mL perampanel (ref < 20 ng/mL). She remained hemodynamically stable throughout her hospital course, despite protracted depressed mental status. DISCUSSION: Given the severity of our patient's presentation, pediatric patients showing symptoms of perampanel overdose should be triaged to the ED for evaluation in anticipation of a prolonged clinical course with decreased consciousness and hypoventilation.
Assuntos
Anticonvulsivantes/toxicidade , Ataxia/induzido quimicamente , Coma/induzido quimicamente , Overdose de Drogas/tratamento farmacológico , Naloxona/uso terapêutico , Nitrilas/toxicidade , Piridonas/toxicidade , Pré-Escolar , Feminino , Humanos , Resultado do TratamentoRESUMO
This study examined the effects of carbamazepine (CBZ) or levetiracetam (LEV) and sub-therapeutic doses of the combination of the two conventional antiepileptics on some of the markers of motor coordination. Twenty-four male Wistar rats (140 ± 5 g) were randomized into 4 groups (n = 6). Group I rats received physiological saline (0.2 ml), group II were administered CBZ (25.0 mg/kg), group III received LEV (50 mg/kg), while group IV rats were given sub-therapeutic doses of CBZ (12.5 mg/kg) and LEV (25 mg/kg) intraperitoneally for 28 days. Thereafter the animals were subjected to behavioral and biochemical investigations, while the frontal lobe and cerebellar tissue were preserved for histological investigation. Data were subjected to descriptive and inferential statistics, and the results presented as mean ± SEM, analyzed using one-way Analysis of variance (ANOVA) and Student- Newman Keuls post hoc analysis where appropriate. p < 0.05 was considered statistically significant. There was significant alteration in fine and skilled movement after the CBZ, and CBZ + LEV chronic treatment compared with the control. The CBZ, and CBZ + LEV combination treatment increased the frontal lobe and cerebellar activities of acetylcholinesterase, malondialdehyde concentration, tissue necrotic factor alpha and decreased the activities of super oxide dismutase relative to the control. Disorganization of the histoarchitecture of the frontal lobe and cerebellum was characterized by cellular atrophy, chromatolysis and hyalinization. Chronic CBZ, and CBZ + LEV combination treatment produced psychomotor dysfunction and neurotoxicity in this order CBZ + LEV > CBZ > LEV in the rats.
Assuntos
Ataxia/fisiopatologia , Ataxia Cerebelar/fisiopatologia , Atividade Motora/efeitos dos fármacos , Animais , Anticonvulsivantes/farmacologia , Ataxia/induzido quimicamente , Carbamazepina/farmacologia , Cerebelo/metabolismo , Cerebelo/fisiopatologia , Quimioterapia Combinada/métodos , Levetiracetam/farmacologia , Masculino , Atividade Motora/fisiologia , Piracetam/farmacologia , Ratos , Ratos WistarRESUMO
BACKGROUND: A low level of response (low LR) to alcohol correlates with the later development of alcohol-related problems. Although some of the underpinnings of LR are understood, little is known about the potential relationship between LR and acute tolerance. The current analyses tested the hypothesis that a low LR will be explained in part by more intense acute tolerance to alcohol during a drinking session. METHODS: Data were generated through a reanalysis of data from 120 individuals who were 18- to 25-year-old, sex-matched pairs of low and high LR drinkers who at baseline did not meet criteria for an alcohol use disorder. Each subject participated in an oral alcohol challenge in which they consumed about 0.7 ml ethanol per kg and acute tolerance was measured as the differences in alcohol's effects at similar breath alcohol levels (BrACs) during the rising and falling breath alcohol concentration (BrAC) curve. Measures included aspects of the Subjective High Assessment Scale (SHAS) and body sway. RESULTS: Contrary to our hypothesis, but similar to results with other alcohol measures, acute tolerance was significantly attenuated in low LR compared with high LR individuals on most SHAS scores. Neither LR group demonstrated acute tolerance to alcohol for sleepiness or body sway. Men and women did not differ on any of these measures. CONCLUSION: These data do not support a role of acute tolerance in the low LR to alcohol as measured by subjective feelings of intoxication or body sway in these subjects, findings that were similar across males and females. In addition, consistent with the literature, the analyses demonstrated differences across measures such that acute tolerance was observed for most measures of subjective effects but not for body sway. Among the subjective effects, acute tolerance was observed for alcohol's intoxicating effect but not for feeling sleepy.
Assuntos
Consumo de Bebidas Alcoólicas/fisiopatologia , Intoxicação Alcoólica/diagnóstico , Tolerância a Medicamentos/fisiologia , Etanol/administração & dosagem , Adolescente , Adulto , Intoxicação Alcoólica/fisiopatologia , Ataxia/induzido quimicamente , Testes Respiratórios , Etanol/análise , Feminino , Humanos , Masculino , Fatores Sexuais , Inquéritos e Questionários , Adulto JovemRESUMO
A 73-year-old man who presented with fever and abdominal discomfort was diagnosed to have a liver abscess. He was treated with antimicrobials which included metronidazole. One month into treatment, he developed neurological symptoms and signs that were suggestive of cerebellar pathology. MRI of the brain showed T2/fluid attenuated inversion recovery hyperintensities involving bilateral dentate, fastigial and interpositus nuclei. After excluding common aetiologies, the possibility of metronidazole-induced neurotoxicity was considered. After stopping metronidazole, his symptoms and signs resolved. A subsequent MRI scan of the brain showed reversal of changes. Neurotoxicity caused by metronidazole is an uncommon adverse effect of a commonly used antimicrobial drug and should be considered in the appropriate clinical scenario.
Assuntos
Antibacterianos/efeitos adversos , Doenças Cerebelares/induzido quimicamente , Núcleos Cerebelares/diagnóstico por imagem , Abscesso Hepático/tratamento farmacológico , Metronidazol/efeitos adversos , Idoso , Ataxia/induzido quimicamente , Ataxia/fisiopatologia , Doenças Cerebelares/diagnóstico por imagem , Doenças Cerebelares/fisiopatologia , Duração da Terapia , Disartria/induzido quimicamente , Disartria/fisiopatologia , Humanos , Abscesso Hepático/diagnóstico por imagem , Imageamento por Ressonância Magnética , Masculino , Síndromes Neurotóxicas/diagnóstico por imagem , Síndromes Neurotóxicas/etiologiaRESUMO
Amiodarone therapy is widely prescribed in patients with atrial fibrillation. The higher prevalence of this arrhythmic heart disease, and the specific age-related issues of homeostasis in the elderly population, makes this group particularly exposed to its adverse effects. Among the many described side-effects, neurological impairments are the less documented and studied. Because amiodarone can be responsible for severe complications, as described in the case below, a close monitoring is necessary throughout its prescription. Awareness should be brought on the amiodarone-induced neurological side-effects as they could be overlooked.
Assuntos
Amiodarona/efeitos adversos , Ataxia/induzido quimicamente , Doenças Cerebelares/induzido quimicamente , Idoso de 80 Anos ou mais , Humanos , MasculinoRESUMO
BACKGROUND: The mu-opioid agonist methadone is administered orally and used in opioid detoxification and in the treatment of moderate-to-severe pain. Acute oral methadone-use and -abuse have been associated with inflammatory and toxic central nervous system (CNS) damage in some cases and cognitive deficits can develop in long-term methadone users. In contrast, reports of intravenous methadone adverse effects are rare. CASE PRESENTATION: Here, we report a patient who developed acute bilateral hearing loss, ataxia and paraparesis subsequently to intravenous methadone-abuse. While the patient gradually recovered from these deficits, widespread magnetic resonance imaging changes progressed and delayed-onset encephalopathy with signs of cortical dysfunction persisted. This was associated with changes in the composition of monocyte and natural killer cell subsets in the cerebrospinal fluid. CONCLUSION: This case suggests a potential bi-phasic primary toxic and secondary inflammatory CNS damage induced by intravenous methadone.
Assuntos
Analgésicos Opioides/intoxicação , Ataxia/induzido quimicamente , Encefalopatias/induzido quimicamente , Disfunção Cognitiva/induzido quimicamente , Perda Auditiva Bilateral/induzido quimicamente , Metadona/intoxicação , Paraparesia/induzido quimicamente , Abuso de Substâncias por Via Intravenosa , Administração Intravenosa , Ataxia/fisiopatologia , Encéfalo/diagnóstico por imagem , Encefalopatias/diagnóstico por imagem , Encefalopatias/imunologia , Encefalopatias/fisiopatologia , Edema Encefálico/induzido quimicamente , Edema Encefálico/diagnóstico por imagem , Edema Encefálico/imunologia , Edema Encefálico/fisiopatologia , Disfunção Cognitiva/imunologia , Disfunção Cognitiva/fisiopatologia , Imagem de Difusão por Ressonância Magnética , Perda Auditiva Bilateral/fisiopatologia , Humanos , Inflamação/imunologia , Células Matadoras Naturais/imunologia , Imageamento por Ressonância Magnética , Masculino , Monócitos/imunologia , Síndromes Neurotóxicas/diagnóstico por imagem , Síndromes Neurotóxicas/etiologia , Síndromes Neurotóxicas/imunologia , Síndromes Neurotóxicas/fisiopatologia , Paraparesia/fisiopatologia , Adulto JovemRESUMO
BACKGROUND: Lamotrigine (LMT) is a phenyltriazine derivative that was originally described as an antiepileptic drug. OBJECTIVE: This literature review aims to evaluate the clinical epidemiological profile, pathological mechanisms, and management of lamotrigine-associated movement disorders. METHODS: Relevant reports in six databases were identified and assessed by two reviewers without language restriction. Reports that the individuals only developed tremor or ataxia after LMT use were not included. RESULTS: In total 48 reports of 108 cases from 19 countries were assessed. The movement disorders associated with LMT found were 29 tics, 21 dyskinesias, 14 myoclonus, 13 parkinsonism, 10 dystonia, and 1 stuttering. The not clearly defined cases included 10 akathisia, 4 myoclonus, 4 cerebellar syndromes, 1 hypertonia, 1 dyskinesia, and an unknown number of dystonia cases. The mean reported age was 33.34 years (range: 1.574 years). The male was the predominant sex and the most common LMT indication was epilepsy. The mean LMT-dose at the movement disorder onset was 228 mg. The time from LMT start to the onset of movement disorder was within 6 months in 81%. The time from LMT withdrawal to complete recovery was within 1 month in 83%. The most common management was LMT withdrawal. CONCLUSIONS: In the literature, the majority of the cases did not give a clear picture of the individual, and the times of movement disorder onset and recovery are not described. We believe that before withdrawal LMT, a dose adjustment based on the benefits and adverse events with careful evaluation case-by-case can be done.