mycophenolic-acid and Seizures

The role of neuroinflammatory mediators has been well established in the pathogenesis of temporal lobe epilepsy (TLE) and associated neurobehavioral comorbidities. Mycophenolate mofetil (MMF) is commonly used as an immunosuppressant in organ transplantations. Its neuroprotective effect is well explored in different preclinical and clinical studies. The present study was designed to investigate the effect of MMF in rat model of lithium pilocarpine (LiPc)-induced spontaneous recurrent seizures and its associated neurobehavioral comorbidities. MMF treatment showed a dose-dependent decrease in seizure severity and reduced aggression in epileptic rats. There was marked improvement in spatial and recognition memory functions, along with substantial decrease in depression-like behavior in MMF treated epileptic rats. There was considerable decrease in mossy fiber sprouting in the dentate gyrus and the cornu ammonis 3 regions of the hippocampus, along with reduction in neuronal death in the treated groups. Furthermore, the hippocampal mRNA level of IL-1β, IL-2, PI3K, AKT, HIF-1α, RAPTOR, mTOR, Rps6kb1 and Rps6 was found to be decreased in MMF treated animals. mTOR, S6, pS6 and GFAP protein expression was decreased, whereas NeuN was increased in the rat hippocampus of the treated animals. The results concluded that MMF suppress recurrent seizures, and improves its associated behavioral impairments and cognitive deficit in rat model of TLE. The observed effects of MMF be correlated with the inhibition of IL-2 and IL-1β linked PI3K/AKT/mTOR signaling pathway hyperactivation.

Topics: Animals; Comorbidity; Disease Models, Animal; Epilepsy, Temporal Lobe; Hippocampus; Interleukin-1beta; Interleukin-2; Male; Mycophenolic Acid; Neurons; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Rats; Rats, Wistar; Seizures; Signal Transduction; Temporal Lobe; TOR Serine-Threonine Kinases

Mycophenolate mofetil (MMF) is an effective therapeutic agent with high safety profile in the management of lupus nephritis. This retrospective study was conducted to assess the efficacy and side effect profile of MMF as induction as well as maintenance therapeutic agent along with tapering steroids in neuropsychiatric lupus (NPSLE). Hospital electronic medical records of patients with SLE diagnosed by ACR 1990 and/or SLICC 2012 criteria between January 2005 and May 2015 were retrieved. Among them, patients fulfilling ACR 1999 criteria for NPSLE were identified. Data of NPSLE patients treated with MMF as upfront second line immunosuppressive agent, both for induction and maintenance, were analyzed. Of the 140 patients with NPSLE, 88 fulfilled the inclusion criteria. Mean age of the cohort was 25.51 ± 7.82 years with female to male ratio of 84:4. Median duration of follow-up was 33 months (3-129 months). Seizure was the most common NPSLE manifestation (n = 37, 42.05%). Of the 88 patients, 18 had NPSLE solely due to secondary antiphospholipid syndrome. Of the remaining 70 patients, 61 (87.1%) had improved, 7 remained unchanged with no worsening and 3 patients had worsening or developed new symptoms during follow up after 3 months from baseline. At last follow-up, 55 out of 57 patients (97.1%) with detailed data had improved, while 2 patients had relapsed. Side effects were significantly more common in patients on prednisolone as compared to those on deflazacort. In patients with NPSLE, MMF along with tapering steroids is an efficacious combo in inducing remission and preventing relapse of disease.

Topics: Adolescent; Adult; Age Factors; Antiphospholipid Syndrome; Brain; Electronic Health Records; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; India; Lupus Nephritis; Male; Mycophenolic Acid; Prednisolone; Pregnenediones; Recurrence; Remission Induction; Retrospective Studies; Seizures; Steroids; Tertiary Care Centers; Young Adult

To determine risk factors for early neurologic complications (NCs) after liver transplantation from perspective of recipient, donor, and surgeon.. In all, 295 adult recipients were enrolled consecutively between August 2001 and February 2014 from a single medical center in Taiwan. Any NC in the first 30 d post-liver transplantation, and perioperative variables from multiple perspectives were collected and analyzed. The main outcome was a 30-d NC. Generalized additive models were used to detect the non-linear effect of continuous variables on outcome, and to determine cut-off values for categorizing risk. Risk factors were identified using multiple logistic regression analysis.. In all, 288 recipients were included, of whom 142 (49.3%) experienced at least one NC, with encephalopathy being the most common 106 (73%). NCs prolonged hospital stay (35.15 ± 43.80 d vs 20.88 ± 13.58 d, P < 0.001). Liver recipients' age < 29 or ≥ 60 years, body mass index < 21.6 or > 27.6 kg/m(2), Child-Pugh class C, history of preoperative hepatoencephalopathy or mental disorders, day 7 tacrolimus level > 8.9 ng/mL, and postoperative intra-abdominal infection were more likely associated with NCs. Novel risk factors for NCs were donor age < 22 or ≥ 40 years, male-to-male gender matching, graft-recipient weight ratio 0.9%-1.9%, and sequence of transplantation between 31 and 174.. NCs post- liver transplantation occurs because of factors related to recipient, donor, and surgeon. Our results provide a basis of risk stratification for surgeon to minimize neurotoxic factors during transplantation.

Topics: Adrenal Cortex Hormones; Adult; Age Factors; Body Mass Index; Brain Diseases; Case-Control Studies; Consciousness Disorders; Delirium; Female; Graft Rejection; Hepatic Encephalopathy; Humans; Immunosuppressive Agents; Intraabdominal Infections; Length of Stay; Liver Transplantation; Male; Mental Disorders; Middle Aged; Mycophenolic Acid; Myelinolysis, Central Pontine; Neurotoxicity Syndromes; Posterior Leukoencephalopathy Syndrome; Postoperative Complications; Preoperative Period; Psychotic Disorders; Risk Assessment; Risk Factors; Seizures; Sex Factors; Stroke; Tacrolimus; Taiwan; Tissue Donors

We present four cases of confirmed anti-NMDA receptor encephalitis; three presented initially with serious psychiatric symptoms and the other developed significant psychiatric symptoms during the initial phase of illness. Brain biopsy findings of one patient are also described. Psychiatrists should consider anti-NMDA receptor encephalitis in patients presenting with psychosis and additional features of dyskinesias, seizures and catatonia, particularly where there is no previous history of psychiatric disorder.

Topics: Adult; Anti-N-Methyl-D-Aspartate Receptor Encephalitis; Antipsychotic Agents; Autoantibodies; Biopsy; Brain; Delusions; Diagnosis, Differential; Electroencephalography; Female; Humans; Immunoglobulins, Intravenous; Immunosuppressive Agents; Immunotherapy; Lymphocytosis; Mycophenolic Acid; Ovarian Cysts; Plasmapheresis; Psychotic Disorders; Receptors, N-Methyl-D-Aspartate; Recovery of Function; Recurrence; Seizures; Steroids; Ultrasonography; Young Adult

Neurologic complications are a significant cause of morbidity in children after liver transplant. In this study, we sought to evaluate the neurologic complications in children after liver transplant.. All children aged younger than 18 years old who had undergone liver transplant between June 2004 and June 2007 were included in this prospective study. There were 30 boys (62.5%) and 18 girls (37.5%) (mean age, 9.6 -/+ 4.3 years; mean duration of follow-up, 21.6 -/+ 9.4 months). The most common indications for liver transplant were biliary atresia (n=12, 25%), Wilson disease (n=7, 14.6%), tyrosinemia (n=7, 14.6%), progressive familial intrahepatic cholestasis (n=6, 12.5%), and autoimmune cirrhosis (n=5, 10.4%).. Immunosuppressive medication consisted tacrolimus (n=44, 91.7%) or cyclosporine (n=4, 8.3%) combined with mycophenolate mofetil (n=33, 68.7%) and prednisolone (n=18, 37.5%). The most-common neurologic complications were tremor (n=8, 16.7%), convulsions (n=6, 12.5%), insomnia (n=6, 12.5%), headache (n=5, 10.4%), muscle cramps (n=5, 10.4%), paresthesia (n=3, 6.2%), and weakness (n=3, 6.2%).. We conclude that the most-common neurologic complication after liver transplant in children in contrast to other studies is tremor, same as adult patients. This may be due to higher rate of use of tacrolimus in our patients.

Topics: Adolescent; Autoimmune Diseases; Child; Child, Preschool; Cholestasis, Intrahepatic; Cyclosporine; Drug Therapy, Combination; Female; Humans; Immunosuppressive Agents; Incidence; Liver Cirrhosis; Liver Transplantation; Male; Mycophenolic Acid; Prednisolone; Prospective Studies; Retrospective Studies; Seizures; Tacrolimus; Treatment Outcome; Tremor

Topics: Adolescent; Adult; Anticonvulsants; Area Under Curve; Azathioprine; Female; Glucocorticoids; Graft Rejection; Humans; Kidney Transplantation; Male; Methylprednisolone; Mycophenolic Acid; Seizures; Transplantation, Homologous; Valproic Acid