mycophenolic-acid and Central-Nervous-System-Diseases

To gather data on mycophenolate mofetil (MMF) in paediatric autoimmune/immune-mediated central nervous system (CNS) conditions, focusing on safety and factors that may affect MMF efficacy.. Retrospective, multicentre study based on four paediatric neurology centres.. Forty-four children were included (30 females, 14 males): 19 had proven/suspected autoimmune encephalitis, 14 had inflammatory demyelinating CNS diseases, and 11 had other autoimmune/immune-mediated CNS conditions. Before MMF, all received first-line immune therapies, and 17 had second-line rituximab and/or cyclophosphamide. MMF was started at a median of 9.5 months from disease onset (range 1-127mo) (median age 9y 4mo, range 1y 5mo-16y 5mo), and was used for median 18 months (range 0.3-73mo). On MMF, 31 patients were relapse-free, whereas eight relapsed (excluding patients with chronic-progressive course). Relapses on MMF were associated with medication weaning/cessation, or with suboptimal MMF dosage/duration. Adverse events of MMF occurred in eight patients: six moderate (gastrointestinal, movement disorder, dermatological) and two severe (infectious).. MMF use in paediatric neuroimmunology is heterogeneous, although relatively safe. We have identified factors that may affect MMF efficacy and provide recommendations on MMF usage.. Mycophenolate mofetil (MMF) use was heterogeneous with relatively common adverse events, although mostly not severe. MMF treatment reduced median annualized relapse rate, although 20% of patients relapsed on MMF. A high relapse rate pre-MMF and late MMF start were associated with higher probability of relapsing on MMF. Most relapses were associated with suboptimal MMF dosage, short MMF duration, or concurrent medication weaning/discontinuation.. MICOFENOLATO DE MOFETILO EN ENFERMEDADES PEDIÁTRICAS AUTOINMUNES O INMUNO-MEDIADAS DEL SISTEMA NERVIOSO CENTRAL: EXPERIENCIA CLÍNICA Y RECOMENDACIONES: OBJETIVO: Recolectar información sobre el uso de Micofenolato de mofetilo (MMF) en enfermedades pediátricas del sistema nervioso central (SNC) autoinmunes o inmuno-mediadas, focalizando en la seguridad y otros factores que pudieran afectar la eficacia del MMF. MÈTODO: Estudio retrospectivo, multicéntrico, con base en cuatro centros de neurología infantil. RESULTADOS: Se incluyeron 44 niños (30 sexo femenino, 14 masculino): 19 de ellos tuvieron encefalitis autoimmune confirmada / sospechada, 14 tuvieron enfermedades inflamatorias desmielinizantes del SNC y 11 tuvieron otras condiciones autoinmunes o inmuno-mediadas del SNC. Previo al MMF todos recibieron terapias inmunológicas de primera línea, y 17 recibieron como segunda línea rituximab y / o ciclofosfamida. MMF fue iniciada a una mediana de 9.5 meses desde el comienzo de la enfermedad (rango 1-127 meses) (edad mediana 9 años y 4 meses, rango 1 año y 5 meses a 16 años y 5 meses), y fue utilizada por un tiempo mediana de 18 meses (rango 0.3 a 73 meses). Bajo MMF, 31 pacientes estuvieron libres de recidivas, mientras que 8 recidivaron (excluyendo aquellos con un curso crónico-progresivo). Las recaídas bajo el MMF estuvieron asociadas a suspensión/cese, o dosis de MMF o duración de tratamiento subóptimos. En ocho pacientes se observaron reacciones adversas al MMF: seis moderados (gastrointestinales, trastornos de movimiento o dermatológicos) y dos severos (infecciones). INTERPRETACIÓN: El uso de MMF en neuroinmunología pediátrica es heterogéneo, aunque relativamente seguro. Identificamos factores que pueden afectar la eficacia del MMF y proponemos recomendaciones sobre su uso.. MICOFENOLATO MOFETIL EM DOENÇAS PEDIÁTRICAS AUTO-IMUNES OU IMUNO-MEDIADAS DO SISTEMA NERVOSO CENTRAL: EXPERIÊNCIA CLÍNICA E RECOMENDAÇÕES: OBJETIVO: Reunir dados do micofenolato mofetil (MMF) em condições pediátricas auto-imunes ou imuno-mediadas do sistema nervoso central (SNC), com foco na segurança e nos fatores que podem afetar a eficácia do MMF. MÉTODO: Estudo restrospectivo multicêntrico baseado em quatro centros de neurologia pediátrica. RESULTADOS: Quarenta e quatro crianças foram incluídas (30 do sexo feminino, 14 do sexo masculino): 19 tiveram encefalite auto-imune comprovada/suspeita, 14 tiveram doenças inflamatórias desmielinizantes do SNC, e 11 tiveram outras condições auto-imunes ou imuno-mediadas do SNC. Antes do MMF, todas receberam imuno-terapias de primeira linha, e 17 tiveram rituximab e/ou ciclofosfamida de segunda linha. O MMF foi iniciado em uma mediana de 9.5 meses após o início da doença (variação de 1-127 meses) (idade mediana 9a 4m, variação 1a 5m a 16a 5m), e foi utilizado por uma mediana de 18 meses (variação 0.3-73m). Com MMF, 31 pacientes ficaram livres de recidivas, enquanto oito tiveram recidivas (excluídos os pacientes com curso crônico-progressivo). As recidivas com MMF forma associadas com desmame/descontinuidade da medicação, ou com dosagem/duração do MMF sub-ótimas. Efeitos adversos do MMF ocorreram em oito pacientes: seis moderados (gastrointestinal, desordem motora, dermatológico) e dois severos (infeccioso). INTERPRETAÇÃO: O uso de MMF em neuroimunologia pediátrica é heterogêneo, embora relativamente seguro. Identificamos fatores que podem afetar a eficácia do MMF e fornecemos recomendações sobre o uso de MMF.

Topics: Autoimmune Diseases of the Nervous System; Central Nervous System Diseases; Child; Female; Humans; Immunosuppressive Agents; Male; Mycophenolic Acid; Recurrence; Retrospective Studies; Treatment Outcome

Topics: Autoimmune Diseases; Central Nervous System Diseases; Child; Humans; Immunosuppressive Agents; Mycophenolic Acid

Granulomatosis with polyangiitis (GPA), extremely rare in children, is a disease characterized by granulomatous inflammation and necrotizing vasculitis that involves medium and small vessels. Central nervous system (CNS) involvement in GPA is not common and often appears at a later stage of the disease. The CNS manifestation of pediatric GPA was fragmentally discussed. Herein, we reported a case of relapsing-remitting pediatric GPA with prominent CNS involvement as initial symptoms.. The patient was a 9-year-old female. The first episode manifested as uroclepsia and bilateral lower extremity weakness, resulting from diffused dot-enhanced large lesions within bilateral anterior cerebral artery territory on magnetic resonance (MR). This was followed by three recurring episodes of visual impairment as a result of optic neuritis. MR in the last episode indicated bilateral sphenoid sinus inflammation adjacent to the left optical nerve. All four episodes were combined with upper respiratory tract symptoms and slight urine abnormality. She responded well to large doses of corticosteroids and immunoglobulins. However, the patient had long been suspected of having multiple sclerosis and had not received appropriate maintenance treatment.. After being diagnosed with GPA, the patient received small doses of glucocorticoids and mycophenolate mofetil for maintenance, which generated a favorable outcome.. CNS involvement in pediatric GPA is rare. Single large or multifocal insults involving one or more lobes consistent with the distribution of cerebral arteries could be a typical feature on MR. Early diagnosis and proper treatments help to improve the prognosis.

Topics: Central Nervous System Diseases; Child; Enzyme Inhibitors; Female; Glucocorticoids; Granulomatosis with Polyangiitis; Humans; Magnetic Resonance Imaging; Mycophenolic Acid

To compare the efficacy of methotrexate (MTX) and mycophenolate mofetil (MMF) in the prevention of relapses in neurosarcoidosis.. We conducted a retrospective multicenter study including patients who received MTX or MMF for the treatment of histologically proven neurosarcoidosis. The efficacy of the immunosuppressive drug was assessed by determining the time to relapse.. Forty patients with a diagnosis of neurosarcoidosis (24 men, 16 women, median age at diagnosis 43.5 years) who received at least 3 months of MTX (n = 32) or MMF (n = 14) were included. The immunosuppressive drug was always associated with steroids. The rate of relapse was 47% in the MTX group (0.2 relapses per year of exposure) and 79% in the MMF group (0.6 relapses per year of exposure) (p = 0.058). The median time to relapse was significantly shorter in the MMF group (11 months) compared with the MTX group (28 months) (p = 0.049). Adverse events occurred in 11 patients during MTX therapy and in 1 patient during MMF therapy (p = 0.12).. Relapses of neurosarcoidosis occur frequently, despite the use of an immunosuppressive drug in addition to corticosteroids. MTX significantly increases the survival time without relapse compared to MMF and should be preferred over MMF for the treatment of neurosarcoidosis. This study provides Class IV evidence that for patients with neurosarcoidosis taking steroids, MTX is superior to MMF in reducing the risk of relapse.

Topics: Adolescent; Adrenal Cortex Hormones; Adult; Aged; Central Nervous System Diseases; Drug Therapy, Combination; Female; Humans; Immunosuppressive Agents; Male; Methotrexate; Middle Aged; Mycophenolic Acid; Recurrence; Retrospective Studies; Sarcoidosis; Treatment Outcome; Young Adult

To describe effectiveness, steroid-sparing effect, and tolerance of the antiproliferative immunosuppressant mycophenolate mofetil (MMF) in neurosarcoidosis.. We describe a retrospective case series of 10 consecutive patients with a diagnosis of neurosarcoidosis who were treated with MMF, alone or in association with corticosteroids, in our teaching hospital.. At the time of our study, the mean duration of MMF treatment was 21 months. All but one patient with CNS involvement (n = 8) were in remission (except for hormonal dysfunction) which was complete in 6 patients. MMF was efficient as single-agent induction therapy in one patient. The 3 patients who received MMF as a maintenance therapy after initial response to corticosteroids did not relapse even though steroids were stopped. Out of 4 subjects who demonstrated insufficient response to prior therapy including corticosteroids and immunosuppressive agents, 3 demonstrated significant clinical and radiologic improvement. However, the 2 patients who presented muscular sarcoidosis did not respond to MMF. Among patients treated with steroids at MMF introduction and after excluding those with sarcoid myopathy, the mean dose of corticosteroids was 6 mg/day at the end of the follow-up while it was 59 mg/day at the initiation of MMF. No significant side effects were observed.. These data suggest that MMF is effective in CNS sarcoidosis but not in sarcoid myopathy, with a corticosteroid sparing effect and a better tolerance profile than other immunosuppressive agents.

Topics: Adult; Aged; Central Nervous System Diseases; Female; Humans; Immunosuppressive Agents; Male; Muscular Diseases; Mycophenolic Acid; Retrospective Studies; Sarcoidosis; Treatment Outcome

Posttransplant lymphoproliferative disorder (PTLD) is one of the life-threatening complications of organ transplantation. PTLD sometimes involves the central nervous system (CNS), but the clinical characteristics are not well recognized. A total of 631 patients received kidney transplantation at Osaka University Hospital between March 1965 and December 2008. Two of the 631 patients (0.32%) developed CNS PTLD. A 40-year-old Japanese woman suffered onset of CNS PTLD 5 years after renal transplantation. After diagnosis based on histological examination by open biopsy, she obtained remission with dose increase of steroid and dose reduction of mycophenolate mofetil. She experienced relapse 20 months after first remission. She underwent second biopsy and the diagnosis was recurrent CNS PTLD. Further reduction of mycophenolate mofetil and increase of steroid led to second remission. The disease remained in complete remission at 60 months after first onset. A 61-year-old woman suffered onset of CNS PTLD 19 years after renal transplantation. After tumor removal, whole brain irradiation was performed. The disease remained in remission at 54 months after onset. Histological examination showed polymorphic-type PTLD in both cases. The first case of polymorphic CNS PTLD was successfully treated by modulation of immunosuppressants without radiation therapy even at recurrence. PTLD should be included in the differential diagnosis of brain tumors in recipients of solid organ transplantation, and histological subtype should be carefully identified to establish the correct treatment strategy.

Topics: Adult; B-Lymphocytes; Central Nervous System Diseases; Dose-Response Relationship, Drug; Female; Humans; Immunosuppressive Agents; Kidney Transplantation; Lymphoproliferative Disorders; Middle Aged; Mycophenolic Acid; Steroids; T-Lymphocytes; Treatment Outcome

To describe the effects of the anti-tumor necrosis factor neutralizing antibody, infliximab, and the antiproliferative immunosuppressant, mycophenolate mofetil, in refractory neurosarcoidosis.. We treated patients with biopsy-proven sarcoidosis and CNS involvement, who had failed treatment with steroids, with infliximab (5 mg/kg on weeks 0, 2, and 6, and then every 6-8 weeks thereafter). Six out of seven patients were co-treated with mycophenolate mofetil (1,000 mg PO BID). Patients underwent a review of symptoms and complete neurologic examination every 3 months and MRI scanning before and after 3-4 infusions of infliximab.. All patients reported significant symptomatic improvement by the fourth infusion of infliximab, including relief of headache and neuropathic pain, reversal of motor, sensory, or coordination deficits, and control of seizure activity. Furthermore, infliximab therapy was universally associated with a decrease in lesion size or suppression of gadolinium enhancement as documented by MRI. A positive treatment response was attained irrespective of location or distribution of CNS involvement by sarcoidosis (dural/leptomeningeal based vs intraparenchymal; cord vs brain; single lesion vs multifocal). There were no serious adverse effects in a follow-up period spanning 6-18 months.. Combination treatment with mycophenolate mofetil and infliximab is a promising therapeutic approach for neurosarcoidosis.

Topics: Adult; Antibodies, Monoclonal; Central Nervous System Diseases; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Infliximab; Male; Middle Aged; Mycophenolic Acid; Sarcoidosis; Treatment Outcome